BioPAX pathway converted from "Liganded Gi-activating GPCR acts as a GEF for Gi" in the Reactome database. LEFT-TO-RIGHT Liganded Gi-activating GPCR acts as a GEF for Gi The liganded receptor undergoes a conformational change, generating a signal that is propagated in a manner that is not completely understood to the the G-protein. This stimulates the exchange of GDP for GTP in the G-protein alpha subunit, activating the G-protein. This event is negatively regulated by some Activators of G protein signaling (AGS) proteins, a class of proteins identified in yeast functional screens for proteins able to activate G protein signaling in the absence of a G protein–coupled receptor (GPCR) (Cismowski et al. 1999, Takesono et al. 1999). AGS proteins contain G protein regulatory (GPR) motifs (also referred to as the GoLoco motif) that bind and stabilize the Galpha subunit in its GDP-bound conformation (Mochizuki et al. 1996, Peterson et al. 2000, Cao et al. 2004, Blumer & Lanier 2014). Some RGS proteins similarly bind to Galpha preventing the exchange of GDP for GTP (Soundararajan et al. 2008). Authored: Jassal, Bijay, 2008-11-07 Reviewed: D'Eustachio, P, 2008-11-29 18:33:05 Ligand:GPCR complexes that activate Gi:Heterotrimeric G-protein Gi (inactive) Reactome DB_ID: 749455 plasma membrane GENE ONTOLOGY GO:0005886 Converted from EntitySet in Reactome Ligand:GPCR complexes that activate Gi Reactome DB_ID: 380091 C3AR1:C3a C3a receptor:C3a Reactome DB_ID: 444688 C3a C3(672-748) Reactome DB_ID: 166828 extracellular region GENE ONTOLOGY GO:0005576 UniProt:P01024 C3 C3 CPAMD1 FUNCTION C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.FUNCTION Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. In chronic inflammation, acts as a chemoattractant for neutrophils (By similarity). It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.SUBUNIT C3 precursor is first processed by the removal of 4 Arg residues, forming two chains, beta and alpha, linked by a disulfide bond. C3 convertase activates C3 by cleaving the alpha chain, releasing C3a anaphylatoxin and generating C3b (beta chain + alpha' chain). Forms the pro-C3-convertase enzyme complex by interacting with Complement factor B Bb fragment (Bb), which is then stabilized by binding CFP, allowing the complex to become active (PubMed:28264884, PubMed:31507604). The interaction with Bb is dependent on Mg2+ (PubMed:31507604). C3b interacts with CR1 (via Sushi 8 and Sushi 9 domains) (PubMed:8175757, PubMed:2972794). C3b interacts with CFH (PubMed:21285368). C3d interacts with CFH (PubMed:21285368, PubMed:21317894). C3dg interacts with CR2 (via the N-terminal Sushi domains 1 and 2). During pregnancy, C3dg exists as a complex (probably a 2:2:2 heterohexamer) with AGT and the proform of PRG2. Interacts with VSIG4. Interacts (both C3a and ASP) with C5AR2; the interaction occurs with higher affinity for ASP, enhancing the phosphorylation and activation of C5AR2, recruitment of ARRB2 to the cell surface and endocytosis of GRP77.SUBUNIT (Microbial infection) C3b interacts with herpes simplex virus 1 (HHV-1) and herpes simplex virus 2 (HHV-2) envelope glycoprotein C; this interaction inhibits the activation of the complement system.SUBUNIT (Microbial infection) Interacts with Staphylococcus aureus immunoglobulin-binding protein Sbi; this interaction prevents the association between C3dg and CR2.SUBUNIT (Microbial infection) Interacts with Staphylococcus aureus protein Fib.TISSUE SPECIFICITY Plasma. The acylation stimulating protein (ASP) is expressed in adipocytes and released into the plasma during both the fasting and postprandial periods.PTM C3b is rapidly split in two positions by factor I and a cofactor to form iC3b (inactivated C3b) and C3f which is released. Then iC3b is slowly cleaved (possibly by factor I) to form C3c (beta chain + alpha' chain fragment 1 + alpha' chain fragment 2), C3dg and C3f. Other proteases produce other fragments such as C3d or C3g. C3a is further processed by carboxypeptidases to release the C-terminal arginine residue generating the acylation stimulating protein (ASP). Levels of ASP are increased in adipocytes in the postprandial period and by insulin and dietary chylomicrons.PTM (Microbial infection) C3 is cleaved by Staphylococcus aureus aureolysin; this cleavage renders C3a and C3b inactive. C3b is rapidly degraded by host factors CFH and CFI preventing its deposition on the bacterial surface while C3a is further inactivated by aureolysin.PTM Phosphorylated by FAM20C in the extracellular medium.POLYMORPHISM There are two alleles: C3S (C3 slow), the most common allele in all races and C3F (C3 fast), relatively frequent in Caucasians, less common in Black Americans, extremely rare in Orientals.DISEASE Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage.CAUTION An article reported the interaction surface between C3 and CR2 (PubMed:11387479). According to a another paper, it is however an artifact and can be ascribed to the presence of zinc acetate in the buffer (PubMed:21527715).CAUTION The difference between allele C3S (C3 slow) and allele C3F (C3 fast) was reported to be caused by a an Asn at position 1216 instead of an Asp (PubMed:2473125). The paper was however retracted (PubMed:2584723). Homo sapiens NCBI Taxonomy 9606 UniProt P01024 672 EQUAL 748 EQUAL Reactome Database ID Release 78 166828 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=166828 Reactome R-HSA-166828 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-166828.1 Reactome http://www.reactome.org 1 C3AR1 C3a anaphylatoxin chemotactic receptor C3AR_HUMAN Reactome DB_ID: 444727 UniProt:Q16581 C3AR1 C3AR1 AZ3B C3R1 HNFAG09 FUNCTION Receptor for the chemotactic and inflammatory peptide anaphylatoxin C3a. This receptor stimulates chemotaxis, granule enzyme release and superoxide anion production.SUBUNIT Interacts with VGF-derived peptide TLQP-21 (By similarity).TISSUE SPECIFICITY Widely expressed in several differentiated hematopoietic cell lines, in the lung, spleen, ovary, placenta, small intestine, throughout the brain, heart, and endothelial cells. Mostly expressed in lymphoid tissues.PTM Among the sulfation sites Tyr-174 is essential for binding of C3a anaphylatoxin.PTM O-glycosylated.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q16581 1 EQUAL 482 EQUAL Reactome Database ID Release 78 444727 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444727 Reactome R-HSA-444727 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444727.1 1 Reactome Database ID Release 78 444688 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444688 Reactome R-HSA-444688 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444688.2 AGTR2:AGT(34-41) Reactome DB_ID: 389873 AGT AGT(34-41) Angiotensin-2 Angiotensin-(1-8) Angiotensin II ANGT_HUMAN ANG1-8 Reactome DB_ID: 374187 UniProt:P01019 AGT AGT SERPINA8 FUNCTION Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.SUBUNIT During pregnancy, exists as a disulfide-linked 2:2 heterotetramer with the proform of PRG2 and as a complex (probably a 2:2:2 heterohexamer) with pro-PRG2 and C3dg.TISSUE SPECIFICITY Expressed by the liver and secreted in plasma.PTM Beta-decarboxylation of Asp-34 in angiotensin-2, by mononuclear leukocytes produces alanine. The resulting peptide form, angiotensin-A, has the same affinity for the AT1 receptor as angiotensin-2, but a higher affinity for the AT2 receptor.PTM In response to low blood pressure, the enzyme renin/REN cleaves angiotensinogen to produce angiotensin-1. Angiotensin-1 is a substrate of ACE (angiotensin converting enzyme) that removes a dipeptide to yield the physiologically active peptide angiotensin-2. Angiotensin-1 and angiotensin-2 can be further processed to generate angiotensin-3, angiotensin-4. Angiotensin 1-9 is cleaved from angiotensin-1 by ACE2 and can be further processed by ACE to produce angiotensin 1-7, angiotensin 1-5 and angiotensin 1-4. Angiotensin 1-7 has also been proposed to be cleaved from angiotensin-2 by ACE2 or from angiotensin-1 by MME (neprilysin).PTM The disulfide bond is labile. Angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized disulfide-bonded form, which preferentially interacts with receptor-bound renin.SIMILARITY Belongs to the serpin family.CAUTION It is uncertain whether Met-1 or Met-10 is the initiator. UniProt P01019 34 EQUAL 41 EQUAL Reactome Database ID Release 78 374187 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374187 Reactome R-HSA-374187 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374187.1 1 AGTR2 Type-2 angiotensin II receptor AGTR2_HUMAN Reactome DB_ID: 374130 UniProt:P50052 AGTR2 AGTR2 FUNCTION Receptor for angiotensin II. Cooperates with MTUS1 to inhibit ERK2 activation and cell proliferation.SUBUNIT Interacts with MTUS1.TISSUE SPECIFICITY In adult, highly expressed in myometrium with lower levels in adrenal gland and fallopian tube. Expressed in the cerebellum. Very highly expressed in fetal kidney and intestine.SIMILARITY Belongs to the G-protein coupled receptor 1 family.CAUTION Although AGTR2 has been reported to be involved in X-linked mental retardation (PubMed:12089445), its pathological role is questionable (PubMed:23871722). UniProt P50052 1 EQUAL 363 EQUAL Reactome Database ID Release 78 374130 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374130 Reactome R-HSA-374130 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374130.1 1 Reactome Database ID Release 78 389873 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389873 Reactome R-HSA-389873 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-389873.2 APLNR:Apelin peptides Apelin receptor:apelin peptides Reactome DB_ID: 374316 APLNR Apelin receptor APJ_HUMAN AGTRL1 Reactome DB_ID: 374259 UniProt:P35414 APLNR APLNR AGTRL1 APJ FUNCTION Receptor for apelin receptor early endogenous ligand (APELA) and apelin (APLN) hormones coupled to G proteins that inhibit adenylate cyclase activity (PubMed:11090199, PubMed:25639753, PubMed:28137936). Plays a key role in early development such as gastrulation, blood vessels formation and heart morphogenesis by acting as a receptor for APELA hormone (By similarity). May promote angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis (By similarity). Promotes sinus venosus (SV)-derived endothelial cells migration into the developing heart to promote coronary blood vessel development (By similarity). Plays also a role in various processes in adults such as regulation of blood vessel formation, blood pressure, heart contractility and heart failure (PubMed:25639753, PubMed:28137936).FUNCTION (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection; may be involved in the development of AIDS dementia (PubMed:11090199).TISSUE SPECIFICITY Expressed in heart, brain, kidney, stomach, spleen, thymus, lung, ovary, small intestine and colon, adipose tissues and pancreas (PubMed:8294032, PubMed:25639753). Expressed in glial cells, astrocytes and neuronal subpopulations (PubMed:8294032). Expressed in embryonic (ESCs) and induced (iPSCs) pluripotent stem cells (PubMed:25639753).SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P35414 1 EQUAL 380 EQUAL Reactome Database ID Release 78 374259 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374259 Reactome R-HSA-374259 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374259.1 1 Converted from EntitySet in Reactome Apelin peptides Reactome DB_ID: 374317 APLN APLN(65-77) Apelin-13 APEL_HUMAN Reactome DB_ID: 374315 UniProt:Q9ULZ1 APLN APLN APEL FUNCTION Endogenous ligand for the apelin receptor (APLNR) (PubMed:10525157). Drives internalization of the apelin receptor (By similarity). Apelin-36 dissociates more hardly than (pyroglu)apelin-13 from APLNR (By similarity). Hormone involved in the regulation of cardiac precursor cell movements during gastrulation and heart morphogenesis (By similarity). Has an inhibitory effect on cytokine production in response to T-cell receptor/CD3 cross-linking; the oral intake of apelin in the colostrum and the milk might therefore modulate immune responses in neonates (By similarity). Plays a role in early coronary blood vessels formation (By similarity). Mediates myocardial contractility in an ERK1/2-dependent manner (By similarity). May also have a role in the central control of body fluid homeostasis by influencing vasopressin release and drinking behavior (By similarity).FUNCTION (Microbial infection) Endogenous ligand for the apelin receptor (APLNR), an alternative coreceptor with CD4 for HIV-1 infection (PubMed:11090199). Inhibits HIV-1 entry in cells coexpressing CD4 and APLNR (PubMed:11090199). Apelin-36 has a greater inhibitory activity on HIV infection than other synthetic apelin derivatives (PubMed:11090199).TISSUE SPECIFICITY Expressed in the brain with highest levels in the frontal cortex, thalamus, hypothalamus and midbrain (PubMed:10617103). Secreted by the mammary gland into the colostrum and the milk.PTM Several active peptides may be produced by proteolytic processing of the peptide precursor.SIMILARITY Belongs to the apelin family. UniProt Q9ULZ1 65 EQUAL 77 EQUAL Reactome Database ID Release 78 374315 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374315 Reactome R-HSA-374315 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374315.1 APLN APLN(50-77) Apelin-28 APEL_HUMAN Reactome DB_ID: 374318 50 EQUAL 77 EQUAL Reactome Database ID Release 78 374318 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374318 Reactome R-HSA-374318 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374318.1 APLN APLN(47-77) Apelin-31 APEL_HUMAN Reactome DB_ID: 374320 47 EQUAL 77 EQUAL Reactome Database ID Release 78 374320 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374320 Reactome R-HSA-374320 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374320.1 APLN APLN(42-77) Apelin-36 APEL_HUMAN Reactome DB_ID: 374319 42 EQUAL 77 EQUAL Reactome Database ID Release 78 374319 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374319 Reactome R-HSA-374319 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374319.1 Reactome Database ID Release 78 374317 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374317 Reactome R-HSA-374317 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374317.1 1 Reactome Database ID Release 78 374316 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374316 Reactome R-HSA-374316 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374316.2 Bradykinin receptor:Bradykinin Reactome DB_ID: 374321 Converted from EntitySet in Reactome BDKRB1,BDKRB2 Bradykinin receptor Reactome DB_ID: 374323 BDKRB1 B1 bradykinin receptor BKRB1_HUMAN Reactome DB_ID: 374257 UniProt:P46663 BDKRB1 BDKRB1 BRADYB1 FUNCTION This is a receptor for bradykinin. Could be a factor in chronic pain and inflammation.SIMILARITY Belongs to the G-protein coupled receptor 1 family. Bradykinin receptor subfamily. BDKRB1 sub-subfamily. UniProt P46663 1 EQUAL 353 EQUAL Reactome Database ID Release 78 374257 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374257 Reactome R-HSA-374257 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374257.1 BDKRB2 B2 bradykinin receptor BKRB2_HUMAN Reactome DB_ID: 374255 UniProt:P30411 BDKRB2 BDKRB2 BKR2 FUNCTION Receptor for bradykinin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system.SUBUNIT Forms a complex with PECAM1 and GNAQ. Interacts with PECAM1.TISSUE SPECIFICITY Ubiquitous. Widespread in normal smooth muscle tissue and neurons.SIMILARITY Belongs to the G-protein coupled receptor 1 family. Bradykinin receptor subfamily. BDKRB2 sub-subfamily. UniProt P30411 1 EQUAL 391 EQUAL Reactome Database ID Release 78 374255 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374255 Reactome R-HSA-374255 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374255.1 Reactome Database ID Release 78 374323 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374323 Reactome R-HSA-374323 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374323.2 1 Bradykinin KNG1(381-389) Reactome DB_ID: 158344 UniProt:P01042 KNG1 KNG1 BDK KNG FUNCTION (1) Kininogens are inhibitors of thiol proteases; (2) HMW-kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; (3) HMW-kininogen inhibits the thrombin- and plasmin-induced aggregation of thrombocytes; (4) the active peptide bradykinin that is released from HMW-kininogen shows a variety of physiological effects: (4A) influence in smooth muscle contraction, (4B) induction of hypotension, (4C) natriuresis and diuresis, (4D) decrease in blood glucose level, (4E) it is a mediator of inflammation and causes (4E1) increase in vascular permeability, (4E2) stimulation of nociceptors (4E3) release of other mediators of inflammation (e.g. prostaglandins), (4F) it has a cardioprotective effect (directly via bradykinin action, indirectly via endothelium-derived relaxing factor action); (5) LMW-kininogen inhibits the aggregation of thrombocytes; (6) LMW-kininogen is in contrast to HMW-kininogen not involved in blood clotting.TISSUE SPECIFICITY Secreted in plasma. T-kinin is detected in malignant ovarian, colon and breast carcinomas, but not in benign tumors.PTM Bradykinin is released from kininogen by plasma kallikrein.PTM Hydroxylation of Pro-383 occurs prior to the release of bradykinin.PTM Phosphorylated by FAM20C in the extracellular medium.PTM N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans.POLYMORPHISM The T-kinin peptide is missing residues 378 to 380, probably as a result of a naturally occurring variant. The complete sequence of the T-kinin peptide is therefore ISRPPGFSPFR. This peptide is associated with malignant tumors but not with benign ones. UniProt P01042 381 EQUAL 389 EQUAL Reactome Database ID Release 78 158344 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=158344 Reactome R-HSA-158344 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-158344.2 1 Reactome Database ID Release 78 374321 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374321 Reactome R-HSA-374321 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374321.1 C5AR1:C5a Reactome DB_ID: 375354 C5a C5(678-751) Reactome DB_ID: 173677 UniProt:P01031 C5 C5 CPAMD4 FUNCTION Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled.FUNCTION Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. Binding to the receptor C5AR1 induces a variety of responses including intracellular calcium release, contraction of smooth muscle, increased vascular permeability, and histamine release from mast cells and basophilic leukocytes (PubMed:8182049). C5a is also a potent chemokine which stimulates the locomotion of polymorphonuclear leukocytes and directs their migration toward sites of inflammation.SUBUNIT C5 precursor is first processed by the removal of 4 basic residues, forming two chains, beta and alpha, linked by a disulfide bond. C5 convertase activates C5 by cleaving the alpha chain, releasing C5a anaphylatoxin and generating C5b (beta chain + alpha' chain). The C5a anaphylatoxin interacts with C5AR1. Interacts with tick complement inhibitor.SUBUNIT (Microbial infection) Interacts with Staphylococcus aureus protein SSL5.POLYMORPHISM C5 variants are responsible for poor response to eculizumab [MIM:615749]. Eculizumab is a monoclonal antibody highly effective in reducing intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria. It specifically binds to the terminal complement protein C5, inhibits its cleavage into C5a and C5b, and prevents the formations of the cytolytic complement pore (PubMed:24521109).DISEASE An association study of C5 haplotypes and genotypes in individuals with chronic hepatitis C virus infection shows that individuals homozygous for the C5_1 haplotype have a significantly higher stage of liver fibrosis than individuals carrying at least 1 other allele. UniProt P01031 678 EQUAL 751 EQUAL Reactome Database ID Release 78 173677 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=173677 Reactome R-HSA-173677 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-173677.1 1 C5AR1 C5a anaphylatoxin chemotactic receptor C5AR_HUMAN Reactome DB_ID: 375356 UniProt:P21730 C5AR1 C5AR1 C5AR C5R1 FUNCTION Receptor for the chemotactic and inflammatory peptide anaphylatoxin C5a (PubMed:1847994, PubMed:8182049, PubMed:7622471, PubMed:9553099, PubMed:10636859, PubMed:15153520, PubMed:29300009). The ligand interacts with at least two sites on the receptor: a high-affinity site on the extracellular N-terminus, and a second site in the transmembrane region which activates downstream signaling events (PubMed:8182049, PubMed:7622471, PubMed:9553099). Receptor activation stimulates chemotaxis, granule enzyme release, intracellular calcium release and superoxide anion production (PubMed:10636859, PubMed:15153520).SUBUNIT Homodimer. May also form higher-order oligomers (PubMed:12835319). Interacts (when phosphorylated) with ARRB1 and ARRB2; the interaction is associated with internalization of C5aR (PubMed:12464600). Interacts (via N-terminal domain) with S.aureus chemotaxis inhibitory protein (CHIPS); the interaction blocks the receptor and may thus inhibit the immune response (PubMed:15153520, PubMed:15542591, PubMed:21706042).PTM Sulfation plays a critical role in the association of C5aR with C5a, but no significant role in the ability of the receptor to transduce a signal and mobilize calcium in response to a small a small peptide agonist (PubMed:11342590). Sulfation at Tyr-14 is important for CHIPS binding (PubMed:21706042).PTM Phosphorylated on serine residues in response to C5a binding, resulting in internalization of the receptor and short-term desensitization to the ligand. The key residues involved in this process are Ser-334 and Ser-338.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P21730 1 EQUAL 350 EQUAL Reactome Database ID Release 78 375356 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=375356 Reactome R-HSA-375356 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-375356.1 1 Reactome Database ID Release 78 375354 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=375354 Reactome R-HSA-375354 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-375354.2 GPER1:ESTG GPER1:Estrogen Reactome DB_ID: 374150 ESTG estrogen Reactome DB_ID: 374146 estrogen [ChEBI:50114] estrogen ChEBI CHEBI:50114 Reactome Database ID Release 78 374146 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374146 Reactome R-ALL-374146 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-374146.3 1 GPER1 G-protein coupled estrogen receptor 1 GPER_HUMAN Reactome DB_ID: 374191 UniProt:Q99527 GPER1 GPER1 CEPR CMKRL2 DRY12 GPER GPR30 FUNCTION G-protein coupled estrogen receptor that binds to 17-beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Stimulates cAMP production, calcium mobilization and tyrosine kinase Src inducing the release of heparin-bound epidermal growth factor (HB-EGF) and subsequent transactivation of the epidermal growth factor receptor (EGFR), activating downstream signaling pathways such as PI3K/Akt and ERK/MAPK. Mediates pleiotropic functions among others in the cardiovascular, endocrine, reproductive, immune and central nervous systems. Has a role in cardioprotection by reducing cardiac hypertrophy and perivascular fibrosis in a RAMP3-dependent manner. Regulates arterial blood pressure by stimulating vasodilation and reducing vascular smooth muscle and microvascular endothelial cell proliferation. Plays a role in blood glucose homeostasis contributing to the insulin secretion response by pancreatic beta cells. Triggers mitochondrial apoptosis during pachytene spermatocyte differentiation. Stimulates uterine epithelial cell proliferation. Enhances uterine contractility in response to oxytocin. Contributes to thymic atrophy by inducing apoptosis. Attenuates TNF-mediated endothelial expression of leukocyte adhesion molecules. Promotes neuritogenesis in developing hippocampal neurons. Plays a role in acute neuroprotection against NMDA-induced excitotoxic neuronal death. Increases firing activity and intracellular calcium oscillations in luteinizing hormone-releasing hormone (LHRH) neurons. Inhibits early osteoblast proliferation at growth plate during skeletal development. Inhibits mature adipocyte differentiation and lipid accumulation. Involved in the recruitment of beta-arrestin 2 ARRB2 at the plasma membrane in epithelial cells. Functions also as a receptor for aldosterone mediating rapid regulation of vascular contractibility through the PI3K/ERK signaling pathway. Involved in cancer progression regulation. Stimulates cancer-associated fibroblast (CAF) proliferation by a rapid genomic response through the EGFR/ERK transduction pathway. Associated with EGFR, may act as a transcription factor activating growth regulatory genes (c-fos, cyclin D1). Promotes integrin alpha-5/beta-1 and fibronectin (FN) matrix assembly in breast cancer cells.SUBUNIT Homodimer (Probable). Heterodimer; heterodimerizes with other G-protein-coupled receptor (GPCRs) like CRHR1, HTR1A and PAQR8. Interacts (via C-terminus tail motif) with DLG4 (via N-terminus tandem pair of PDZ domains); the interaction is direct and induces the increase of GPER1 protein levels residing at the plasma membrane surface in a estradiol-independent manner (By similarity). Interacts with RAMP3. Interacts with KRT7 and KRT8. Interacts with EGFR; the interaction increases after agonist-induced stimulation in cancer-associated fibroblasts (CAF). Interacts with EGFR and ESR1.TISSUE SPECIFICITY Expressed in placenta, endothelial and epithelial cells, non laboring and laboring term myometrium, fibroblasts and cancer-associated fibroblasts (CAF), prostate cancer cells and invasive adenocarcinoma (at protein level). Ubiquitously expressed, but is most abundant in placenta. In brain regions, expressed as a 2.8 kb transcript in basal forebrain, frontal cortex, thalamus, hippocampus, caudate and putamen.INDUCTION Up-regulated by EGF and TGF-alpha in endometrial, ovarian and breast tumor cells. Up-regulated by progestin and by phorbol 12-myristate 13-acetate (PMA) in breast cancer cell lines.PTM Ubiquitinated; ubiquitination occurs at the plasma membrane and leads to proteasome-mediated degradation.PTM Glycosylated.MISCELLANEOUS Does not bind estradiol according to PubMed:18566127 and PubMed:16645038.SIMILARITY Belongs to the G-protein coupled receptor 1 family.CAUTION Data is conflicting regarding whether it fulfills the criteria of a membrane-bound estrogen receptor (PubMed:15705806, PubMed:17379646). Other reports suggest that it is not (PubMed:16645038, PubMed:18566127).CAUTION Data is conflicting regarding whether it is localized either at the cell membrane (PM) (PubMed:15539556, PubMed:21427217, PubMed:21540189, PubMed:21354433, PubMed:21149639 and PubMed:23674134). Other reports suggest that it localizes at the endoplasmic reticulum (ER) (PubMed:15705806, PubMed:18566127). UniProt Q99527 1 EQUAL 375 EQUAL Reactome Database ID Release 78 374191 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374191 Reactome R-HSA-374191 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374191.2 1 Reactome Database ID Release 78 374150 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374150 Reactome R-HSA-374150 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374150.4 Neuropeptides B/W receptor:neuropeptides B/W Reactome DB_ID: 374779 Converted from EntitySet in Reactome Neuropeptides B/W receptors Reactome DB_ID: 374798 NPBWR1 Neuropeptides B/W receptor type 1 NPBW1_HUMAN Reactome DB_ID: 374780 UniProt:P48145 NPBWR1 NPBWR1 GPR7 FUNCTION Interacts specifically with a number of opioid ligands. Receptor for neuropeptides B and W, which may be involved in neuroendocrine system regulation, food intake and the organization of other signals. Has a higher affinity for neuropeptide B.TISSUE SPECIFICITY Found in cerebellum and frontal cortex. Detected at high levels in hippocampus, amygdala and trachea; at moderate levels in fetal brain, pituitary gland and prostate. Not in caudate, accumbens, kidney or liver. Also detected at high levels in lung carcinoma.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P48145 1 EQUAL 328 EQUAL Reactome Database ID Release 78 374780 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374780 Reactome R-HSA-374780 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374780.1 NPBWR2 Neuropeptides B/W receptor type 2 NPBW2_HUMAN Reactome DB_ID: 374797 UniProt:P48146 NPBWR2 NPBWR2 GPR8 FUNCTION Interacts specifically with a number of opioid ligands. Receptor for neuropeptides B and W, which may be involved in neuroendocrine system regulation, food intake and the organization of other signals.TISSUE SPECIFICITY Detected at high levels in caudate nucleus, hyppocampus and amygdala; at moderate levels in the adult brain, thalamus, parietal cortex, pituitary gland, adrenal gland and lymph nodes.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P48146 1 EQUAL 333 EQUAL Reactome Database ID Release 78 374797 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374797 Reactome R-HSA-374797 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374797.1 Reactome Database ID Release 78 374798 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374798 Reactome R-HSA-374798 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374798.1 1 Converted from EntitySet in Reactome Neuropeptides B/W Reactome DB_ID: 374796 NPB NPB(25-48) Neuropeptide B-23 NPB_HUMAN Reactome DB_ID: 374794 UniProt:Q8NG41 NPB NPB PPL7 PPNPB FUNCTION May be involved in the regulation of feeding, neuroendocrine system, memory, learning and in the afferent pain pathway.TISSUE SPECIFICITY Widely expressed in the central nervous system. High levels are found in substantia nigra, hypothalamus, hyppocampus, spinal cord, placenta and fetal brain; lower levels are found in testis, uterus and ovary. Also detected at high levels in colorectal adenocarcinoma.SIMILARITY Belongs to the neuropeptide B/W family. UniProt Q8NG41 25 EQUAL 48 EQUAL Reactome Database ID Release 78 374794 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374794 Reactome R-HSA-374794 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374794.1 NPB NPB(25-53) Neuropeptide B-29 NPB_HUMAN Reactome DB_ID: 374790 25 EQUAL 53 EQUAL Reactome Database ID Release 78 374790 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374790 Reactome R-HSA-374790 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374790.1 NPW NPW(33-55) Neuropeptide W-23 NPW_HUMAN Reactome DB_ID: 374802 UniProt:Q8N729 NPW NPW PPL8 PPNPW FUNCTION Plays a regulatory role in the organization of neuroendocrine signals accessing the anterior pituitary gland. Stimulates water drinking and food intake. May play a role in the hypothalamic response to stress (By similarity). NPW23 activates GPR7 and GPR8 more efficiently than NPW30.TISSUE SPECIFICITY Detected at high levels in the substantia nigra, fetal kidney and trachea; at lower levels in testis, uterus, ovary and placenta. Not detectable in many regions of the central nervous system. Also detected at high levels in lymphoblastic leukemia and colorectal adenocarcinoma.SIMILARITY Belongs to the neuropeptide B/W family. UniProt Q8N729 33 EQUAL 55 EQUAL Reactome Database ID Release 78 374802 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374802 Reactome R-HSA-374802 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374802.1 NPW NPW(33-62) Neuropeptide W-30 NPW_HUMAN Reactome DB_ID: 374804 33 EQUAL 62 EQUAL Reactome Database ID Release 78 374804 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374804 Reactome R-HSA-374804 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374804.1 Reactome Database ID Release 78 374796 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374796 Reactome R-HSA-374796 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374796.1 1 Reactome Database ID Release 78 374779 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374779 Reactome R-HSA-374779 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374779.1 Nociceptin receptor:Nociceptin Reactome DB_ID: 374725 OPRL1 Nociceptin receptor OPRX_HUMAN Reactome DB_ID: 374731 UniProt:P41146 OPRL1 OPRL1 OOR ORL1 FUNCTION G-protein coupled opioid receptor that functions as receptor for the endogenous neuropeptide nociceptin. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling via G proteins mediates inhibition of adenylate cyclase activity and calcium channel activity. Arrestins modulate signaling via G proteins and mediate the activation of alternative signaling pathways that lead to the activation of MAP kinases. Plays a role in modulating nociception and the perception of pain. Plays a role in the regulation of locomotor activity by the neuropeptide nociceptin.TISSUE SPECIFICITY Detected in blood leukocytes.INDUCTION By phytohemagglutinin (PHA).PTM Phosphorylation at Ser-363 requires GRK3.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P41146 1 EQUAL 370 EQUAL Reactome Database ID Release 78 374731 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374731 Reactome R-HSA-374731 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374731.1 1 PNOC PNOC(130-146) Nociceptin PNOC_HUMAN Reactome DB_ID: 374749 UniProt:Q13519 PNOC PNOC OFQ TISSUE SPECIFICITY Predominantly expressed in the brain and spinal cord. Also expressed and secreted by peripheral blood neutrophils following degranulation.PTM Specific enzymatic cleavages at paired basic residues probably yield other active peptides besides nociceptin.PTM The N-terminal domain contains 6 conserved cysteines thought to be involved in disulfide bonding and/or processing.SIMILARITY Belongs to the opioid neuropeptide precursor family. UniProt Q13519 130 EQUAL 146 EQUAL Reactome Database ID Release 78 374749 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374749 Reactome R-HSA-374749 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374749.1 1 Reactome Database ID Release 78 374725 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374725 Reactome R-HSA-374725 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374725.1 Opioid receptor:opioid ligand Reactome DB_ID: 374302 Converted from EntitySet in Reactome Opioid ligands Reactome DB_ID: 374370 POMC(237-267) Beta-endorphin Reactome DB_ID: 167405 UniProt:P01189 POMC POMC TISSUE SPECIFICITY ACTH and MSH are produced by the pituitary gland.PTM Specific enzymatic cleavages at paired basic residues yield the different active peptides.PTM O-glycosylated; reducing sugar is probably N-acetylgalactosamine.SIMILARITY Belongs to the POMC family. UniProt P01189 237 EQUAL 267 EQUAL Reactome Database ID Release 78 167405 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=167405 Reactome R-HSA-167405 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-167405.1 POMC(237-241) Met-enkephalin Reactome DB_ID: 167407 237 EQUAL 241 EQUAL Reactome Database ID Release 78 167407 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=167407 Reactome R-HSA-167407 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-167407.1 Converted from EntitySet in Reactome Dynorphins Reactome DB_ID: 374372 PDYN PDYN(207-238) Big dynorphin PDYN_HUMAN Reactome DB_ID: 374380 UniProt:P01213 PDYN PDYN FUNCTION Leu-enkephalins compete with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress (By similarity).FUNCTION Dynorphin peptides differentially regulate the kappa opioid receptor. Dynorphin A(1-13) has a typical opiod activity, it is 700 times more potent than Leu-enkephalin (By similarity).FUNCTION Leumorphin has a typical opiod activity and may have anti-apoptotic effect.PTM The N-terminal domain contains 6 conserved cysteines thought to be involved in disulfide bonding and/or processing.SIMILARITY Belongs to the opioid neuropeptide precursor family. UniProt P01213 207 EQUAL 238 EQUAL Reactome Database ID Release 78 374380 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374380 Reactome R-HSA-374380 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374380.1 PDYN PDYN(207-223) Dynorphin-A PDYN_HUMAN Reactome DB_ID: 374388 207 EQUAL 223 EQUAL Reactome Database ID Release 78 374388 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374388 Reactome R-HSA-374388 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374388.1 PDYN PDYN(226-238) Dynorphin-B PDYN_HUMAN Reactome DB_ID: 374383 226 EQUAL 238 EQUAL Reactome Database ID Release 78 374383 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374383 Reactome R-HSA-374383 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374383.1 PDYN PDYN(175-184) alpha-neoendorphin PDYN_HUMAN Reactome DB_ID: 374378 175 EQUAL 184 EQUAL Reactome Database ID Release 78 374378 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374378 Reactome R-HSA-374378 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374378.1 PDYN PDYN(175-183) beta-neoendorphin PDYN_HUMAN Reactome DB_ID: 374387 175 EQUAL 183 EQUAL Reactome Database ID Release 78 374387 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374387 Reactome R-HSA-374387 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374387.1 Reactome Database ID Release 78 374372 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374372 Reactome R-HSA-374372 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374372.1 PENK PENK(230-234) Leu-enkephalin PENK_HUMAN Reactome DB_ID: 374376 UniProt:P01210 PENK PENK PTM The N-terminal domain contains 6 conserved cysteines thought to be involved in disulfide bonding and/or processing.PTM Proenkephalin-A is cleaved by CTSL to generate Met-enkephalin.SIMILARITY Belongs to the opioid neuropeptide precursor family. UniProt P01210 230 EQUAL 234 EQUAL Reactome Database ID Release 78 374376 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374376 Reactome R-HSA-374376 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374376.1 PENK PENK(210-214) Met-enkephalin (210-214) PENK_HUMAN Reactome DB_ID: 374379 210 EQUAL 214 EQUAL Reactome Database ID Release 78 374379 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374379 Reactome R-HSA-374379 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374379.1 PENK PENK(136-140) Met-enkephalin (136-140) PENK_HUMAN Reactome DB_ID: 374392 136 EQUAL 140 EQUAL Reactome Database ID Release 78 374392 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374392 Reactome R-HSA-374392 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374392.1 PENK PENK(107-111) Met-enkephalin (107-111) PENK_HUMAN Reactome DB_ID: 374375 107 EQUAL 111 EQUAL Reactome Database ID Release 78 374375 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374375 Reactome R-HSA-374375 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374375.1 PENK PENK(100-104) Met-enkephalin (100-104) PENK_HUMAN Reactome DB_ID: 374371 100 EQUAL 104 EQUAL Reactome Database ID Release 78 374371 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374371 Reactome R-HSA-374371 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374371.1 Reactome Database ID Release 78 374370 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374370 Reactome R-HSA-374370 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374370.1 1 Converted from EntitySet in Reactome Opioid receptors Reactome DB_ID: 374277 OPRD1 Delta-type opioid receptor OPRD_HUMAN Reactome DB_ID: 374265 UniProt:P41143 OPRD1 OPRD1 OPRD FUNCTION G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.SUBUNIT May form homooligomers. Forms a heterodimer with OPRM1 (By similarity). Interacts with GPRASP1 (PubMed:12142540, PubMed:15086532). Interacts with RTP4; the interaction promotes cell surface localization of the OPRD1-OPRM1 heterodimer (By similarity).TISSUE SPECIFICITY Detected in oocytes (at protein level). Detected in brain cortex, hypothalamus, hippocampus and olfactory bulb. Detected in oocytes.PTM N-glycosylated.PTM Ubiquitinated. A basal ubiquitination seems not to be related to degradation. Ubiquitination is increased upon formation of OPRM1:OPRD1 oligomers leading to proteasomal degradation; the ubiquitination is diminished by RTP4.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P41143 1 EQUAL 372 EQUAL Reactome Database ID Release 78 374265 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374265 Reactome R-HSA-374265 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374265.1 OPRM1 Mu-type opioid receptor MOR-1 Reactome DB_ID: 60951 UniProt:P35372 OPRM1 OPRM1 MOR1 FUNCTION Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:7905839, PubMed:7957926, PubMed:7891175, PubMed:12589820, PubMed:9689128). Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors (PubMed:7905839). The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:12068084). They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects (PubMed:20525224). Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity (PubMed:16580639).SUBUNIT Forms homooligomers and heterooligomers with other GPCRs, such as OPRD1, OPRK1, OPRL1, NPFFR2, ADRA2A, SSTR2, CNR1 and CCR5 (probably in dimeric forms) (PubMed:12413885, PubMed:15778451, PubMed:15967873, PubMed:17224450). Interacts with heterotrimeric G proteins; interaction with a heterotrimeric complex containing GNAI1, GNB1 and GNG2 stabilizes the active conformation of the receptor and increases its affinity for endomorphin-2, the synthetic opioid peptide DAMGO and for morphinan agonists (By similarity). Interacts with PPL; the interaction disrupts agonist-mediated G-protein activation (PubMed:12810704). Interacts (via C-terminus) with DNAJB4 (via C-terminus) (PubMed:16542645). Interacts with calmodulin; the interaction inhibits the constitutive activity of OPRM1; it abolishes basal and attenuates agonist-stimulated G-protein coupling (PubMed:10419536, PubMed:10899953). Interacts with FLNA, PLD2, RANBP9 and WLS and GPM6A (PubMed:12519790, PubMed:14573758, PubMed:19788913, PubMed:20214800). Interacts with RTP4 (By similarity). Interacts with SYP and GNAS (By similarity). Interacts with RGS9, RGS17, RGS20, RGS4, PPP1R9B and HINT1 (By similarity).TISSUE SPECIFICITY Expressed in brain. Isoform 16 and isoform 17 are detected in brain.PTM Phosphorylated. Differentially phosphorylated in basal and agonist-induced conditions. Agonist-mediated phosphorylation modulates receptor internalization. Phosphorylated by GRK2 in a agonist-dependent manner. Phosphorylation at Tyr-168 requires receptor activation, is dependent on non-receptor protein tyrosine kinase Src and results in a decrease in agonist efficacy by reducing G-protein coupling efficiency. Phosphorylated on tyrosine residues; the phosphorylation is involved in agonist-induced G-protein-independent receptor down-regulation. Phosphorylation at Ser-377 is involved in G-protein-dependent but not beta-arrestin-dependent activation of the ERK pathway (By similarity).PTM Ubiquitinated. A basal ubiquitination seems not to be related to degradation. Ubiquitination is increased upon formation of OPRM1:OPRD1 oligomers leading to proteasomal degradation; the ubiquitination is diminished by RTP4.POLYMORPHISM Variant Asp-40 does not show altered binding affinities for most opioid peptides and alkaloids tested, but it binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately 3 times more tightly than the most common allelic form.MISCELLANEOUS OPRM1 is the main physiological target for most clinically important opioid analgesics. OPRM1-mediated inhibition of voltage-gated calcium channels on central presynaptic terminals of primary afferent nociceptors is thought to be one of the primary mechanisms mediating analgesia at the spinal level. Opioid-induced hyperalgesic responses are observed following both acute and chronic dosing associated with cellular excitation.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P35372 1 EQUAL 400 EQUAL Reactome Database ID Release 78 60951 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=60951 Reactome R-HSA-60951 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-60951.1 OPRK1 Kappa-type opioid receptor OPRK_HUMAN Reactome DB_ID: 374286 UniProt:P41145 OPRK1 OPRK1 OPRK FUNCTION G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.SUBUNIT Interacts with SLC9A3R1. Interacts with GABARAPL1.TISSUE SPECIFICITY Detected in brain and placenta.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P41145 1 EQUAL 380 EQUAL Reactome Database ID Release 78 374286 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374286 Reactome R-HSA-374286 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374286.1 Reactome Database ID Release 78 374277 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374277 Reactome R-HSA-374277 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374277.1 1 Reactome Database ID Release 78 374302 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374302 Reactome R-HSA-374302 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374302.1 CCR1,2,8:CCL16 Reactome DB_ID: 373268 CCL16 C-C motif chemokine 16 CCL16_HUMAN Reactome DB_ID: 373103 UniProt:O15467 CCL16 CCL16 ILINCK NCC4 SCYA16 FUNCTION Shows chemotactic activity for lymphocytes and monocytes but not neutrophils. Also shows potent myelosuppressive activity, suppresses proliferation of myeloid progenitor cells. Recombinant SCYA16 shows chemotactic activity for monocytes and THP-1 monocytes, but not for resting lymphocytes and neutrophils. Induces a calcium flux in THP-1 cells that were desensitized by prior expression to RANTES.TISSUE SPECIFICITY Mainly expressed in liver, also found in spleen and thymus. Highly expressed in LPS- and IFN-gamma-activated monocytes, weakly in some lymphocytes, including natural killer cells, gamma-delta T-cells, and some T-cell clones.INDUCTION By IL10/interleukin-10.SIMILARITY Belongs to the intercrine beta (chemokine CC) family. UniProt O15467 24 EQUAL 120 EQUAL Reactome Database ID Release 78 373103 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373103 Reactome R-HSA-373103 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373103.1 1 Converted from EntitySet in Reactome CCR1,2,8 Reactome DB_ID: 373229 CCR1 C-C chemokine receptor type 1 CCR1_HUMAN Reactome DB_ID: 373107 UniProt:P32246 CCR1 CCR1 CMKBR1 CMKR1 SCYAR1 FUNCTION Receptor for a C-C type chemokine. Binds to MIP-1-alpha, MIP-1-delta, RANTES, and MCP-3 and, less efficiently, to MIP-1-beta or MCP-1 and subsequently transduces a signal by increasing the intracellular calcium ions level. Responsible for affecting stem cell proliferation.SUBUNIT Interacts with CREB3.TISSUE SPECIFICITY Widely expressed in different hematopoietic cells.INDUCTION Up-regulated by CREB3.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P32246 1 EQUAL 355 EQUAL Reactome Database ID Release 78 373107 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373107 Reactome R-HSA-373107 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373107.1 CCR8 C-C chemokine receptor type 8 CCR8_HUMAN Reactome DB_ID: 373237 UniProt:P51685 CCR8 CCR8 CKRL1 CMKBR8 CMKBRL2 FUNCTION Receptor for the chemokine CCL1/SCYA1/I-309. May regulate monocyte chemotaxis and thymic cell line apoptosis. Alternative coreceptor with CD4 for HIV-1 infection.SIMILARITY Belongs to the G-protein coupled receptor 1 family.CAUTION Was originally thought to be a receptor for SCYA3 and SCYA17. UniProt P51685 1 EQUAL 355 EQUAL Reactome Database ID Release 78 373237 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373237 Reactome R-HSA-373237 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373237.1 CCR2 C-C chemokine receptor type 2 CCR2_HUMAN Reactome DB_ID: 2976755 UniProt:P41597 CCR2 CCR2 CMKBR2 FUNCTION Key functional receptor for CCL2 but can also bind CCL7 and CCL12 (PubMed:8146186, PubMed:8048929, PubMed:23408426). Its binding with CCL2 on monocytes and macrophages mediates chemotaxis and migration induction through the activation of the PI3K cascade, the small G protein Rac and lamellipodium protrusion (Probable). Also acts as a receptor for the beta-defensin DEFB106A/DEFB106B (PubMed:23938203). Regulates the expression of T-cell inflammatory cytokines and T-cell differentiation, promoting the differentiation of T-cells into T-helper 17 cells (Th17) during inflammation (By similarity). Facilitates the export of mature thymocytes by enhancing directional movement of thymocytes to sphingosine-1-phosphate stimulation and up-regulation of S1P1R expression; signals through the JAK-STAT pathway to regulate FOXO1 activity leading to an increased expression of S1P1R (By similarity). Plays an important role in mediating peripheral nerve injury-induced neuropathic pain (By similarity). Increases NMDA-mediated synaptic transmission in both dopamine D1 and D2 receptor-containing neurons, which may be caused by MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B (By similarity). Mediates the recruitment of macrophages and monocytes to the injury site following brain injury (By similarity).FUNCTION (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection.SUBUNIT Interacts with ARRB1 (PubMed:9501202). Interacts (via extracellular N-terminal region) with beta-defensin DEFB106A/DEFB106B; this interaction may preferentially require specific tyrosine sulfation on CCR2 (PubMed:23938203). Interacts with NUP85; the interaction is required for CCR2 clusters formation on the cell membrane and CCR2 signaling (PubMed:15995708, PubMed:25283965).SUBUNIT (Microbial infection) Binds to HIV-1 Tat.TISSUE SPECIFICITY Expressed by monocytes and IL2-activated NK cells.INDUCTION Up-regulated by CREB3 (PubMed:18587271). In NK cells, induced by IL2 (PubMed:9058802).PTM N-glycosylated.PTM Sulfation increases the affinity for both monomeric and dimeric CCL2 with stronger binding to the monomeric form (PubMed:11046064, PubMed:23408426). Binding of sulfated CCR2 to CCL2 promotes conversion of CCL2 from dimer to monomer (PubMed:11046064, PubMed:23408426).POLYMORPHISM Variations in CCR2 are associated with relative resistance to immunodeficiency virus type 1 (resistance to HIV-1) [MIM:609423].SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P41597 1 EQUAL 374 EQUAL Reactome Database ID Release 78 2976755 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2976755 Reactome R-HSA-2976755 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2976755.1 Reactome Database ID Release 78 373229 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373229 Reactome R-HSA-373229 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373229.1 1 Reactome Database ID Release 78 373268 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373268 Reactome R-HSA-373268 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373268.1 CCR3,4,5:CCL5(24-91) Reactome DB_ID: 373299 Converted from EntitySet in Reactome CCR3,4,5 Reactome DB_ID: 373259 CCR3 C-C chemokine receptor type 3 CCR3_HUMAN Reactome DB_ID: 373106 UniProt:P51677 CCR3 CCR3 CMKBR3 FUNCTION Receptor for C-C type chemokine. Binds and responds to a variety of chemokines, including CCL11, CCL26, CCL7, CCL13, RANTES(CCL5) and CCL15 (PubMed:7622448, PubMed:8642344, PubMed:8676064). Subsequently transduces a signal by increasing the intracellular calcium ions level (PubMed:8676064). In addition acts as a possible functional receptor for NARS1 (PubMed:30171954).FUNCTION (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection.SUBUNIT (Microbial infection) Interacts with HIV-1 protein Tat.TISSUE SPECIFICITY In eosinophils as well as trace amounts in neutrophils and monocytes.MISCELLANEOUS Overexpression of CCR3 together with its ligands appears to be a characteristic of ulcerative colitis (UC). The production of CCR3 ligands by human colonic epithelial cells suggests further that the epithelium can play a role in modulating pathological T-cell-mediated mucosal inflammation (PubMed:21077277).SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P51677 1 EQUAL 355 EQUAL Reactome Database ID Release 78 373106 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373106 Reactome R-HSA-373106 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373106.1 CCR4 C-C chemokine receptor type 4 CCR4_HUMAN Reactome DB_ID: 373090 UniProt:P51679 CCR4 CCR4 CMKBR4 FUNCTION High affinity receptor for the C-C type chemokines CCL17/TARC, CCL22/MDC and CKLF isoform 1/CKLF1. The activity of this receptor is mediated by G(i) proteins which activate a phosphatidylinositol-calcium second messenger system. Can function as a chemoattractant homing receptor on circulating memory lymphocytes and as a coreceptor for some primary HIV-2 isolates. In the CNS, could mediate hippocampal-neuron survival.TISSUE SPECIFICITY Predominantly expressed in the thymus, in peripheral blood leukocytes, including T-cells, mostly CD4+ cells, and basophils, and in platelets; at lower levels, in the spleen and in monocytes. Detected also in macrophages, IL-2-activated natural killer cells and skin-homing memory T-cells, mostly the ones expressing the cutaneous lymphocyte antigen (CLA). Expressed in brain microvascular and coronary artery endothelial cells.PTM In natural killer cells, CCL22 binding induces phosphorylation on yet undefined Ser/Thr residues, most probably by beta-adrenergic receptor kinases 1 and 2.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P51679 1 EQUAL 360 EQUAL Reactome Database ID Release 78 373090 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373090 Reactome R-HSA-373090 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373090.1 CCR5 C-C chemokine receptor type 5 Reactome DB_ID: 171279 UniProt:P51681 CCR5 CCR5 CMKBR5 FUNCTION Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation. Participates in T-lymphocyte migration to the infection site by acting as a chemotactic receptor (PubMed:30713770).FUNCTION (Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) of human immunodeficiency virus-1/HIV-1.SUBUNIT Interacts with PRAF2 (PubMed:15757671). Efficient ligand binding to CCL3/MIP-1alpha and CCL4/MIP-1beta requires sulfation, O-glycosylation and sialic acid modifications. Glycosylation on Ser-6 is required for efficient binding of CCL4 (PubMed:11733580, PubMed:8663314, PubMed:8699119, PubMed:10383387). Interacts with GRK2 (PubMed:10085131). Interacts with ARRB1 and ARRB2 (PubMed:11448957, PubMed:16144840). Interacts with CNIH4 (PubMed:24405750). Interacts with S100A4; this interaction stimulates T-lymphocyte chemotaxis (PubMed:30713770).SUBUNIT (Microbial infection) Interacts with HIV-1 surface protein gp120.SUBUNIT (Microbial infection) May interact with human cytomegalovirus/HHV-5 protein UL78.TISSUE SPECIFICITY Highly expressed in spleen, thymus, in the myeloid cell line THP-1, in the promyeloblastic cell line KG-1a and on CD4+ and CD8+ T-cells. Medium levels in peripheral blood leukocytes and in small intestine. Low levels in ovary and lung.INDUCTION (Microbial infection) May be down-regulated by human cytomegalovirus/HHV-5 protein UL78.PTM Sulfated on at least 2 of the N-terminal tyrosines. Sulfation contributes to the efficiency of HIV-1 entry and is required for efficient binding of the chemokines, CCL3 and CCL4.PTM O-glycosylated, but not N-glycosylated. Ser-6 appears to be the major site. Also sialylated glycans present which contribute to chemokine binding. Thr-16 and Ser-17 may also be glycosylated and, if so, with small moieties such as a T-antigen.PTM Palmitoylation in the C-terminal is important for cell surface expression, and to a lesser extent, for HIV entry.PTM Phosphorylation on serine residues in the C-terminal is stimulated by binding CC chemokines especially by APO-RANTES.POLYMORPHISM Variations in CCR5 are associated with resistance or susceptibility to immunodeficiency virus type 1 (resistance or susceptibility to HIV-1) [MIM:609423]. Variations in CCR5 gene also influence the rate of progression to AIDS after infection.POLYMORPHISM Ser-60 variant, a naturally occurring mutation in a conserved residue in the first intracellular domain of CCR5, results in reduced amounts of the protein in the membrane and consequently may be associated with reduced susceptibility to infection by microbes that depend on these molecules as their receptors.POLYMORPHISM Variations in CCR5 are associated with susceptibility to West Nile virus (WNV) infection [MIM:610379].SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P51681 1 EQUAL 352 EQUAL Reactome Database ID Release 78 171279 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=171279 Reactome R-HSA-171279 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-171279.1 Reactome Database ID Release 78 373259 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373259 Reactome R-HSA-373259 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373259.1 1 CCL5 CCL5(24-91) C-C motif chemokine 5 CCL5_HUMAN Reactome DB_ID: 373108 UniProt:P13501 CCL5 CCL5 D17S136E SCYA5 FUNCTION Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. May activate several chemokine receptors including CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second processed form RANTES(4-68) exhibits reduced chemotactic and HIV-suppressive activity compared with RANTES(1-68) and RANTES(3-68) and is generated by an unidentified enzyme associated with monocytes and neutrophils (PubMed:16791620, PubMed:1380064, PubMed:8525373, PubMed:9516414, PubMed:15923218). May also be an agonist of the G protein-coupled receptor GPR75, stimulating inositol trisphosphate production and calcium mobilization through its activation. Together with GPR75, may play a role in neuron survival through activation of a downstream signaling pathway involving the PI3, Akt and MAP kinases. By activating GPR75 may also play a role in insulin secretion by islet cells (PubMed:23979485).TISSUE SPECIFICITY Expressed in the follicular fluid (at protein level). T-cell and macrophage specific.INDUCTION By mitogens.PTM N-terminal processed form RANTES(3-68) is produced by proteolytic cleavage, probably by DPP4, after secretion from peripheral blood leukocytes and cultured sarcoma cells.PTM The identity of the O-linked saccharides at Ser-27 and Ser-28 are not reported in PubMed:1380064. They are assigned by similarity.SIMILARITY Belongs to the intercrine beta (chemokine CC) family. UniProt P13501 24 EQUAL 91 EQUAL Reactome Database ID Release 78 373108 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373108 Reactome R-HSA-373108 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373108.1 1 Reactome Database ID Release 78 373299 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373299 Reactome R-HSA-373299 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373299.2 CCR10:CCL27,28 Reactome DB_ID: 373236 CCR10 C-C chemokine receptor type 10 CCR10_HUMAN Reactome DB_ID: 373126 UniProt:P46092 CCR10 CCR10 GPR2 FUNCTION Receptor for chemokines SCYA27 and SCYA28. Subsequently transduces a signal by increasing the intracellular calcium ions level and stimulates chemotaxis in a pre-B cell line.TISSUE SPECIFICITY Expressed at high levels in adult testis, small intestine, fetal lung, fetal kidney. Weaker expression was observed in many other adult tissues including spleen, thymus, lymph node, Peyer patches, colon, heart, ovary, peripheral blood lymphocytes, thyroid and spinal cord. Also expressed by melanocytes, dermal fibroblasts, dermal microvascular endothelial cells. Also detected in T-cells and in skin-derived Langerhans cells.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P46092 1 EQUAL 362 EQUAL Reactome Database ID Release 78 373126 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373126 Reactome R-HSA-373126 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373126.1 1 Converted from EntitySet in Reactome CCL27,28 Reactome DB_ID: 373322 CCL27 C-C motif chemokine 27 CCL27_HUMAN Reactome DB_ID: 373098 UniProt:Q9Y4X3 CCL27 CCL27 ILC SCYA27 FUNCTION Chemotactic factor that attracts skin-associated memory T-lymphocytes. May play a role in mediating homing of lymphocytes to cutaneous sites. Binds to CCR10.SUBUNIT Monomer, dimer, and tetramer. Heparin avidly promotes oligomerization.TISSUE SPECIFICITY Testis, thymus, placenta, ovary and skin.SIMILARITY Belongs to the intercrine beta (chemokine CC) family. UniProt Q9Y4X3 25 EQUAL 112 EQUAL Reactome Database ID Release 78 373098 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373098 Reactome R-HSA-373098 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373098.1 CCL28 C-C motif chemokine 28 CCL28_HUMAN Reactome DB_ID: 373300 UniProt:Q9NRJ3 CCL28 CCL28 SCYA28 FUNCTION Chemotactic activity for resting CD4, CD8 T-cells and eosinophils. Binds to CCR3 and CCR10 and induces calcium mobilization in a dose-dependent manner.TISSUE SPECIFICITY Preferentially expressed by epithelial cells of diverse tissues including normal and pathological colon, salivary gland, mammary gland, trachea and rectum. Also found in prostate, spleen, thyroid, psoriasis skin and in lower levels in peripheral blood leukocytes, small intestine, Peyer patches, stomach and normal skin.SIMILARITY Belongs to the intercrine beta (chemokine CC) family. UniProt Q9NRJ3 20 EQUAL 127 EQUAL Reactome Database ID Release 78 373300 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373300 Reactome R-HSA-373300 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373300.1 Reactome Database ID Release 78 373322 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373322 Reactome R-HSA-373322 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373322.1 1 Reactome Database ID Release 78 373236 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373236 Reactome R-HSA-373236 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373236.1 CCR6:CCL20 Reactome DB_ID: 373235 CCR6 C-C chemokine receptor type 6 CCR6_HUMAN Reactome DB_ID: 373089 UniProt:P51684 CCR6 CCR6 CKRL3 CMKBR6 GPR29 STRL22 FUNCTION Receptor for the C-C type chemokine CCL20 (PubMed:9169459). Binds to CCL20 and subsequently transduces a signal by increasing the intracellular calcium ion levels (PubMed:20068036). Although CCL20 is its major ligand it can also act as a receptor for non-chemokine ligands such as beta-defensins (PubMed:25585877). Binds to defensin DEFB1 leading to increase in intracellular calcium ions and cAMP levels. Its binding to DEFB1 is essential for the function of DEFB1 in regulating sperm motility and bactericidal activity (PubMed:25122636). Binds to defensins DEFB4 and DEFB4A/B and mediates their chemotactic effects (PubMed:20068036). The ligand-receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendritic cells (DC), effector/ memory T-cells and B-cells and plays an important role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and various autoimmune diseases. CCR6-mediated signals are essential for immune responses to microbes in the intestinal mucosa and in the modulation of inflammatory responses initiated by tissue insult and trauma (PubMed:21376174). CCR6 is essential for the recruitment of both the proinflammatory IL17 producing helper T-cells (Th17) and the regulatory T-cells (Treg) to sites of inflammation. Required for the normal migration of Th17 cells in Peyers-patches and other related tissue sites of the intestine and plays a role in regulating effector T-cell balance and distribution in inflamed intestine. Plays an important role in the coordination of early thymocyte precursor migration events important for normal subsequent thymocyte precursor development, but is not required for the formation of normal thymic natural regulatory T-cells (nTregs). Required for optimal differentiation of DN2 and DN3 thymocyte precursors. Essential for B-cell localization in the subepithelial dome of Peyers-patches and for efficient B-cell isotype switching to IgA in the Peyers-patches. Essential for appropriate anatomical distribution of memory B-cells in the spleen and for the secondary recall response of memory B-cells (By similarity). Positively regulates sperm motility and chemotaxis via its binding to CCL20 (PubMed:23765988).TISSUE SPECIFICITY Sperm. Mainly localized in the tail and in the postacrosomal region but is also found in the midpiece and basal region in a small percentage of sperm cells. Reduced levels found in the sperms of asthenozoospermia and leukocytospermia patients (at protein level). Spleen, lymph nodes, appendix, and fetal liver. Expressed in lymphocytes, T-cells and B-cells but not in natural killer cells, monocytes or granulocytes.INDUCTION By IL2/interleukin-2.SIMILARITY Belongs to the G-protein coupled receptor 1 family.CAUTION It is uncertain whether Met-1 or Met-6 is the initiator. UniProt P51684 1 EQUAL 374 EQUAL Reactome Database ID Release 78 373089 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373089 Reactome R-HSA-373089 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373089.1 1 CCL20 CCL20(27-96) C-C motif chemokine 20 CCL20_HUMAN Reactome DB_ID: 373097 UniProt:P78556 CCL20 CCL20 LARC MIP3A SCYA20 FUNCTION Acts as a ligand for C-C chemokine receptor CCR6. Signals through binding and activation of CCR6 and induces a strong chemotactic response and mobilization of intracellular calcium ions (PubMed:11352563, PubMed:11035086, PubMed:20068036). The ligand-receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendritic cells (DC), effector/memory T-cells and B-cells and plays an important role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and various autoimmune diseases (PubMed:21376174). CCL20 acts as a chemotactic factor that attracts lymphocytes and, slightly, neutrophils, but not monocytes (PubMed:9038201, PubMed:11352563). Involved in the recruitment of both the proinflammatory IL17 producing helper T-cells (Th17) and the regulatory T-cells (Treg) to sites of inflammation. Required for optimal migration of thymic natural regulatory T cells (nTregs) and DN1 early thymocyte progenitor cells (By similarity). C-terminal processed forms have been shown to be equally chemotactically active for leukocytes (PubMed:11035086). Positively regulates sperm motility and chemotaxis via its binding to CCR6 which triggers Ca2+ mobilization in the sperm which is important for its motility (PubMed:23765988, PubMed:25122636). Inhibits proliferation of myeloid progenitors in colony formation assays (PubMed:9129037). May be involved in formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells (By similarity). Possesses antibacterial activity towards E.coli ATCC 25922 and S.aureus ATCC 29213 (PubMed:12149255).TISSUE SPECIFICITY Expressed in the seminal plasma, endometrial fluid and follicular fluid (at protein level). Expressed predominantly in the liver, lymph nodes, appendix, peripheral blood lymphocytes, and fetal lung. Low levels seen in thymus, prostate, testis, small intestine and colon.INDUCTION By bacterial lipopolysaccharides (LPS), TNF and IFNG/IFN-gamma. Induced by phorbol myristate acetate (PMA) in U-937 cell line and bowes melanoma. Repressed by IL10/interleukin-10.PTM C-terminal processed forms which lack 1, 3 or 6 amino acids are produced by proteolytic cleavage after secretion from peripheral blood monocytes.SIMILARITY Belongs to the intercrine beta (chemokine CC) family. UniProt P78556 27 EQUAL 96 EQUAL Reactome Database ID Release 78 373097 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373097 Reactome R-HSA-373097 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373097.1 1 Reactome Database ID Release 78 373235 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373235 Reactome R-HSA-373235 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373235.1 CCR7:CCL19,21 Reactome DB_ID: 373319 Converted from EntitySet in Reactome CCL19,21 Reactome DB_ID: 373283 CCL19 C-C motif chemokine 19 CCL19_HUMAN Reactome DB_ID: 373094 UniProt:Q99731 CCL19 CCL19 ELC MIP3B SCYA19 FUNCTION May play a role not only in inflammatory and immunological responses but also in normal lymphocyte recirculation and homing. May play an important role in trafficking of T-cells in thymus, and T-cell and B-cell migration to secondary lymphoid organs. Binds to chemokine receptor CCR7. Recombinant CCL19 shows potent chemotactic activity for T-cells and B-cells but not for granulocytes and monocytes. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4.TISSUE SPECIFICITY Expressed at high levels in the lymph nodes, thymus and appendix. Intermediate levels seen in colon and trachea, while low levels found in spleen, small intestine, lung, kidney and stomach.SIMILARITY Belongs to the intercrine beta (chemokine CC) family. UniProt Q99731 22 EQUAL 98 EQUAL Reactome Database ID Release 78 373094 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373094 Reactome R-HSA-373094 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373094.1 CCL21 C-C motif chemokine 21 CCL21_HUMAN Reactome DB_ID: 373116 UniProt:O00585 CCL21 CCL21 SCYA21 UNQ784/PRO1600 FUNCTION Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Shows preferential activity towards naive T-cells. May play a role in mediating homing of lymphocytes to secondary lymphoid organs. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4.SUBUNIT Monomer. Binds to CCR7. Interacts with PDPN; relocalizes PDPN to the basolateral membrane (PubMed:14978162).TISSUE SPECIFICITY Highly expressed in high endothelial venules of lymph nodes, spleen and appendix. Intermediate levels found in small intestine, thyroid gland and trachea. Low level expression in thymus, bone marrow, liver, and pancreas. Also found in tonsil, fetal heart and fetal spleen.SIMILARITY Belongs to the intercrine beta (chemokine CC) family. UniProt O00585 24 EQUAL 134 EQUAL Reactome Database ID Release 78 373116 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373116 Reactome R-HSA-373116 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373116.1 Reactome Database ID Release 78 373283 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373283 Reactome R-HSA-373283 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373283.1 1 CCR7 C-C chemokine receptor type 7 CCR7_HUMAN Reactome DB_ID: 373125 UniProt:P32248 CCR7 CCR7 CMKBR7 EBI1 EVI1 FUNCTION Receptor for the MIP-3-beta chemokine. Probable mediator of EBV effects on B-lymphocytes or of normal lymphocyte functions.TISSUE SPECIFICITY Expressed in various lymphoid tissues and activated B- and T-lymphocytes, strongly up-regulated in B-cells infected with Epstein-Barr virus and T-cells infected with herpesvirus 6 or 7.INDUCTION By Epstein-Barr virus (EBV).SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P32248 25 EQUAL 378 EQUAL Reactome Database ID Release 78 373125 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373125 Reactome R-HSA-373125 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373125.1 1 Reactome Database ID Release 78 373319 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373319 Reactome R-HSA-373319 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373319.1 CCR9:CCL25 Reactome DB_ID: 373329 TECK CCL25 C-C motif chemokine 25 CCL25_HUMAN Reactome DB_ID: 373096 UniProt:O15444 CCL25 CCL25 SCYA25 TECK FUNCTION Potentially involved in T-cell development. Recombinant protein shows chemotactic activity on thymocytes, macrophages, THP-1 cells, and dendritics cells but is inactive on peripheral blood lymphocytes and neutrophils. Binds to CCR9. Isoform 2 is an antagonist of isoform 1. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4.TISSUE SPECIFICITY Specifically expressed by thymic dendritic cells. High levels in thymus and small intestine.SIMILARITY Belongs to the intercrine beta (chemokine CC) family. UniProt O15444 24 EQUAL 150 EQUAL Reactome Database ID Release 78 373096 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373096 Reactome R-HSA-373096 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373096.1 1 CCR9 C-C chemokine receptor type 9 CCR9_HUMAN Reactome DB_ID: 2976763 UniProt:P51686 CCR9 CCR9 GPR28 FUNCTION Receptor for chemokine SCYA25/TECK. Subsequently transduces a signal by increasing the intracellular calcium ions level.FUNCTION (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection.TISSUE SPECIFICITY Highly expressed in the thymus and low in lymph nodes and spleen.MISCELLANEOUS EC50 of SCYA25/TECK for isoform 1 is lower than for isoform 2.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P51686 1 EQUAL 369 EQUAL Reactome Database ID Release 78 2976763 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2976763 Reactome R-HSA-2976763 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2976763.1 1 Reactome Database ID Release 78 373329 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373329 Reactome R-HSA-373329 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373329.1 CXCR1:CXCR1 ligands Reactome DB_ID: 373801 Converted from EntitySet in Reactome CXCR1 ligands Reactome DB_ID: 373823 CXCL6 CXCL6(38-114) C-X-C motif chemokine 6 CXCL6_HUMAN Reactome DB_ID: 373784 UniProt:P80162 CXCL6 CXCL6 GCP2 SCYB6 FUNCTION Chemotactic for neutrophil granulocytes. Signals through binding and activation of its receptors (CXCR1 and CXCR2). In addition to its chemotactic and angiogenic properties, it has strong antibacterial activity against Gram-positive and Gram-negative bacteria (90-fold-higher when compared to CXCL5 and CXCL7).SIMILARITY Belongs to the intercrine alpha (chemokine CxC) family. UniProt P80162 38 EQUAL 114 EQUAL Reactome Database ID Release 78 373784 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373784 Reactome R-HSA-373784 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373784.1 IL8 Interleukin-8 IL8_HUMAN CXCL8 Reactome DB_ID: 447095 UniProt:P10145 CXCL8 CXCL8 IL8 FUNCTION IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus. IL-8(6-77) has a 5-10-fold higher activity on neutrophil activation, IL-8(5-77) has increased activity on neutrophil activation and IL-8(7-77) has a higher affinity to receptors CXCR1 and CXCR2 as compared to IL-8(1-77), respectively.SUBUNIT Homodimer (PubMed:31235521). Dimer formation is disrupted by tick evasin-3 (PubMed:31235521).INDUCTION By ER stress in a DDIT3/CHOP-dependent manner.PTM Several N-terminal processed forms are produced by proteolytic cleavage after secretion from at least peripheral blood monocytes, leukcocytes and endothelial cells. In general, IL-8(1-77) is referred to as interleukin-8. IL-8(6-77) is the most promiment form.PTM Citrullination at Arg-27 prevents proteolysis, and dampens tissue inflammation, it also enhances leukocytosis, possibly through impaired chemokine clearance from the blood circulation.SIMILARITY Belongs to the intercrine alpha (chemokine CxC) family. UniProt P10145 23 EQUAL 99 EQUAL Reactome Database ID Release 78 447095 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=447095 Reactome R-HSA-447095 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-447095.1 Reactome Database ID Release 78 373823 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373823 Reactome R-HSA-373823 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373823.1 1 CXCR1 IL8RA High affinity interleukin-8 receptor A Reactome DB_ID: 373805 UniProt:P25024 CXCR1 CXCR1 CMKAR1 IL8RA FUNCTION Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activate a phosphatidylinositol-calcium second messenger system. This receptor binds to IL-8 with a high affinity and to MGSA (GRO) with a low affinity.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P25024 1 EQUAL 350 EQUAL Reactome Database ID Release 78 373805 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373805 Reactome R-HSA-373805 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373805.1 1 Reactome Database ID Release 78 373801 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373801 Reactome R-HSA-373801 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373801.1 CXCR2:CXCR2 ligands Reactome DB_ID: 373773 Converted from EntitySet in Reactome CXCR2 ligands Reactome DB_ID: 373814 CXCL1 CXCL1(35-107) Growth-regulated alpha protein precursor GROA_HUMAN Reactome DB_ID: 373778 UniProt:P09341 CXCL1 CXCL1 GRO GRO1 GROA MGSA SCYB1 FUNCTION Has chemotactic activity for neutrophils. May play a role in inflammation and exerts its effects on endothelial cells in an autocrine fashion. In vitro, the processed forms GRO-alpha(4-73), GRO-alpha(5-73) and GRO-alpha(6-73) show a 30-fold higher chemotactic activity.PTM N-terminal processed forms GRO-alpha(4-73), GRO-alpha(5-73) and GRO-alpha(6-73) are produced by proteolytic cleavage after secretion from peripheral blood monocytes.SIMILARITY Belongs to the intercrine alpha (chemokine CxC) family. UniProt P09341 35 EQUAL 107 EQUAL Reactome Database ID Release 78 373778 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373778 Reactome R-HSA-373778 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373778.1 CXCL2 CXCL2(35-107) Macrophage inflammatory protein 2-alpha MIP2A_HUMAN Reactome DB_ID: 373777 UniProt:P19875 CXCL2 CXCL2 GRO2 GROB MIP2A SCYB2 FUNCTION Produced by activated monocytes and neutrophils and expressed at sites of inflammation. Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cell proliferation. GRO-beta(5-73) shows a highly enhanced hematopoietic activity.PTM The N-terminal processed form GRO-beta(5-73) is produced by proteolytic cleavage after secretion from bone marrow stromal cells.PHARMACEUTICAL GRO-beta(5-73) is available under the name Garnocestim as immunomodulator. It is used prior to hematopoietic transplantation for peripheral blood stem cell mobilization and reduction of incidence, duration, and/or severity of chemotherapy induced cytopenias.SIMILARITY Belongs to the intercrine alpha (chemokine CxC) family. UniProt P19875 35 EQUAL 107 EQUAL Reactome Database ID Release 78 373777 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373777 Reactome R-HSA-373777 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373777.1 CXCL3 CXCL3(35-107) Macrophage inflammatory protein 2-beta MIP2B_HUMAN Reactome DB_ID: 373774 UniProt:P19876 CXCL3 CXCL3 GRO3 GROG SCYB3 FUNCTION Ligand for CXCR2 (By similarity). Has chemotactic activity for neutrophils. May play a role in inflammation and exert its effects on endothelial cells in an autocrine fashion. In vitro, the processed form GRO-gamma(5-73) shows a fivefold higher chemotactic activity for neutrophilic granulocytes.PTM N-terminal processed form GRO-gamma(5-73) is produced by proteolytic cleavage after secretion from peripheral blood monocytes.SIMILARITY Belongs to the intercrine alpha (chemokine CxC) family. UniProt P19876 35 EQUAL 107 EQUAL Reactome Database ID Release 78 373774 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373774 Reactome R-HSA-373774 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373774.1 CXCL4 homotetramer Reactome DB_ID: 373835 PF4(48-101) Low-affinity platelet factor IV Reactome DB_ID: 114629 UniProt:P02776 PF4 PF4 CXCL4 SCYB4 FUNCTION Released during platelet aggregation. Neutralizes the anticoagulant effect of heparin because it binds more strongly to heparin than to the chondroitin-4-sulfate chains of the carrier molecule. Chemotactic for neutrophils and monocytes. Inhibits endothelial cell proliferation, the short form is a more potent inhibitor than the longer form.SUBUNIT Homotetramer.SIMILARITY Belongs to the intercrine alpha (chemokine CxC) family. UniProt P02776 48 EQUAL 101 EQUAL Reactome Database ID Release 78 114629 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=114629 Reactome R-HSA-114629 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-114629.1 4 Reactome Database ID Release 78 373835 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373835 Reactome R-HSA-373835 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373835.1 CXCL5 CXCL5(37-114) C-X-C motif chemokine 5 CXCL5_HUMAN Reactome DB_ID: 373815 UniProt:P42830 CXCL5 CXCL5 ENA78 SCYB5 FUNCTION Involved in neutrophil activation. In vitro, ENA-78(8-78) and ENA-78(9-78) show a threefold higher chemotactic activity for neutrophil granulocytes.SUBUNIT Monomer (PubMed:24695525). Homodimer (PubMed:24695525).PTM N-terminal processed forms ENA-78(8-78) and ENA-78(9-78) are produced by proteolytic cleavage after secretion from peripheral blood monocytes.SIMILARITY Belongs to the intercrine alpha (chemokine CxC) family. UniProt P42830 37 EQUAL 114 EQUAL Reactome Database ID Release 78 373815 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373815 Reactome R-HSA-373815 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373815.1 PPBP PPBP(35-128) Beta-thromboglobulin Reactome DB_ID: 114573 UniProt:P02775 PPBP PPBP CTAP3 CXCL7 SCYB7 TGB1 THBGB1 FUNCTION LA-PF4 stimulates DNA synthesis, mitosis, glycolysis, intracellular cAMP accumulation, prostaglandin E2 secretion, and synthesis of hyaluronic acid and sulfated glycosaminoglycan. It also stimulates the formation and secretion of plasminogen activator by human synovial cells. NAP-2 is a ligand for CXCR1 and CXCR2, and NAP-2, NAP-2(73), NAP-2(74), NAP-2(1-66), and most potent NAP-2(1-63) are chemoattractants and activators for neutrophils. TC-1 and TC-2 are antibacterial proteins, in vitro released from activated platelet alpha-granules. CTAP-III(1-81) is more potent than CTAP-III desensitize chemokine-induced neutrophil activation.SUBUNIT Beta-thromboglobulin is a homotetramer.PTM Proteolytic removal of residues 1-9 produces the active peptide connective tissue-activating peptide III (CTAP-III) (low-affinity platelet factor IV (LA-PF4)).PTM Proteolytic removal of residues 1-13 produces the active peptide beta-thromboglobulin, which is released from platelets along with platelet factor 4 and platelet-derived growth factor.PTM NAP-2(1-66) is produced by proteolytical processing, probably after secretion by leukocytes other than neutrophils.PTM NAP-2(73) and NAP-2(74) seem not be produced by proteolytical processing of secreted precursors but are released in an active form from platelets.SIMILARITY Belongs to the intercrine alpha (chemokine CxC) family. UniProt P02775 35 EQUAL 128 EQUAL Reactome Database ID Release 78 114573 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=114573 Reactome R-HSA-114573 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-114573.1 Reactome Database ID Release 78 373814 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373814 Reactome R-HSA-373814 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373814.1 1 CXCR2 High affinity interleukin-8 receptor B IL8RB Reactome DB_ID: 373796 UniProt:P25025 CXCR2 CXCR2 IL8RB FUNCTION Receptor for interleukin-8 which is a powerful neutrophil chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Binds to IL-8 with high affinity. Also binds with high affinity to CXCL3, GRO/MGSA and NAP-2.PTM Phosphorylated upon ligand binding; which is required for desensitization.PTM (Microbial infection) Proteolytically cleaved by Staphylococcus aureus staphopain A/SspP. This cleavage inhibits CXCR2-dependent neutrophil activation and chemotaxis.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P25025 1 EQUAL 360 EQUAL Reactome Database ID Release 78 373796 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373796 Reactome R-HSA-373796 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373796.1 1 Reactome Database ID Release 78 373773 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373773 Reactome R-HSA-373773 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373773.1 CXCR3:CXCR3 ligands Reactome DB_ID: 374141 CXCR3 C-X-C chemokine receptor type 3 CXCR3_HUMAN Reactome DB_ID: 2980699 UniProt:P49682 CXCR3 CXCR3 GPR9 SUBUNIT Homomer. Forms heteromers with ACKR4.TISSUE SPECIFICITY Isoform 1 and isoform 2 are mainly expressed in heart, kidney, liver and skeletal muscle. Isoform 1 is also expressed in placenta. Isoform 2 is expressed in endothelial cells. Expressed in T-cells (at protein level).PTM Sulfation on Tyr-27 and Tyr-29 is essential for CXCL10 binding and subsequent signal transduction induction.PTM N-glycosylated.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P49682 1 EQUAL 368 EQUAL Reactome Database ID Release 78 2980699 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2980699 Reactome R-HSA-2980699 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2980699.1 1 Converted from EntitySet in Reactome CXCR3 ligands Reactome DB_ID: 374233 CXCL9 C-X-C motif chemokine 9 CXCL9_HUMAN Reactome DB_ID: 373856 UniProt:Q07325 CXCL9 CXCL9 CMK MIG SCYB9 FUNCTION Cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory response. Chemotactic for activated T-cells. Binds to CXCR3.INDUCTION By IFNG/IFN-gamma. The induction is enhanced by TNF in dermal fibroblasts and vein endothelial cells.SIMILARITY Belongs to the intercrine alpha (chemokine CxC) family. UniProt Q07325 23 EQUAL 125 EQUAL Reactome Database ID Release 78 373856 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373856 Reactome R-HSA-373856 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373856.1 CXCL10 CXCL10(22-98) C-X-C motif chemokine 10 CXL10_HUMAN Reactome DB_ID: 373853 UniProt:P02778 CXCL10 CXCL10 INP10 SCYB10 FUNCTION Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modulation of angiostatic effects (PubMed:7540647, PubMed:11157474, PubMed:22652417). Plays thereby an important role during viral infections by stimulating the activation and migration of immune cells to the infected sites (By similarity). Mechanistically, binding of CXCL10 to the CXCR3 receptor activates G protein-mediated signaling and results in downstream activation of phospholipase C-dependent pathway, an increase in intracellular calcium production and actin reorganization (PubMed:12750173, PubMed:19151743). In turn, recruitment of activated Th1 lymphocytes occurs at sites of inflammation (PubMed:12750173, PubMed:12663757). Activation of the CXCL10/CXCR3 axis plays also an important role in neurons in response to brain injury for activating microglia, the resident macrophage population of the central nervous system, and directing them to the lesion site. This recruitment is an essential element for neuronal reorganization (By similarity).SUBUNIT Monomer, dimer, and tetramer (PubMed:12737818). Interacts with CXCR3 (via N-terminus) (PubMed:19151743).TISSUE SPECIFICITY Mainly secreted by monocytes, endothelial cells as well as fibroblasts. Expressed by epithelial cells in thymus (PubMed:11157474). Microglial cells produce CXCL10 in response to viral stimulation (PubMed:12663757).INDUCTION By IFNG/IFN-gamma. A diverse population of cell types rapidly increases transcription of mRNA encoding this protein. This suggests that gamma-induced protein may be a key mediator of the IFNG/IFN-gamma response.PTM Several proteases can mediate post-secretion cleavages. DPP4 cleaves CXCL10 on its N-terminal 2 amino acids leading to an antagonist form of CXCL10. This dominant negative form is capable of binding CXCR3 but does not induce signaling. MMP9 cleaves 9 amino acids instead.SIMILARITY Belongs to the intercrine alpha (chemokine CxC) family. UniProt P02778 22 EQUAL 98 EQUAL Reactome Database ID Release 78 373853 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373853 Reactome R-HSA-373853 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373853.1 CXCL11 C-X-C motif chemokine 11 CXL11_HUMAN Reactome DB_ID: 373852 UniProt:O14625 CXCL11 CXCL11 ITAC SCYB11 SCYB9B FUNCTION Chemotactic for interleukin-activated T-cells but not unstimulated T-cells, neutrophils or monocytes. Induces calcium release in activated T-cells. Binds to CXCR3. May play an important role in CNS diseases which involve T-cell recruitment. May play a role in skin immune responses.TISSUE SPECIFICITY High levels in peripheral blood leukocytes, pancreas and liver astrocytes. Moderate levels in thymus, spleen and lung. Low levels in placenta, prostate and small intestine. Also found in epidermal basal layer keratinocytes in skin disorders.INDUCTION By IFNG/IFN-gamma and IFNB1/IFN-beta. Induction by IFNG/IFN-gamma is enhanced by TNF in monocytes, dermal fibroblasts and endothelial cells, and by IL1/interleukin-1 in astrocytes.SIMILARITY Belongs to the intercrine alpha (chemokine CxC) family. UniProt O14625 22 EQUAL 94 EQUAL Reactome Database ID Release 78 373852 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373852 Reactome R-HSA-373852 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373852.1 Reactome Database ID Release 78 374233 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374233 Reactome R-HSA-374233 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374233.1 1 Reactome Database ID Release 78 374141 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374141 Reactome R-HSA-374141 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374141.1 CXCR4,7:CXCL12 Reactome DB_ID: 374203 Converted from EntitySet in Reactome CXCR4,7 Reactome DB_ID: 374120 CXCR7 C-X-C chemokine receptor type 7 CXCR7_HUMAN Reactome DB_ID: 373859 UniProt:P25106 ACKR3 ACKR3 CMKOR1 CXCR7 GPR159 RDC1 FUNCTION Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Acts as coreceptor with CXCR4 for a restricted number of HIV isolates.SUBUNIT Homodimer. Can form heterodimers with CXCR4; heterodimerization may regulate CXCR4 signaling activity. Interacts with ARRB1 and ARRB2.TISSUE SPECIFICITY Expressed in monocytes, basophils, B-cells, umbilical vein endothelial cells (HUVEC) and B-lymphoblastoid cells. Lower expression detected in CD4+ T-lymphocytes and natural killer cells. In the brain, detected in endothelial cells and capillaries, and in mature neurons of the frontal cortex and hippocampus. Expressed in tubular formation in the kidney. Highly expressed in astroglial tumor endothelial, microglial and glioma cells. Expressed at low levels in normal CD34+ progenitor cells, but at very high levels in several myeloid malignant cell lines. Expressed in breast carcinomas but not in normal breast tissue (at protein level).INDUCTION Up-regulated during cell differentiation in glioma cells.DOMAIN The C-terminal cytoplasmic tail, plays a key role in: correct trafficking to the cell membrane, recruitment of beta-arrestin, ubiquitination, and in chemokine scavenging and signaling functions. The Ser/Thr residues and the Lys residues in the C-terminal cytoplasmic tail are essential for beta-arrestin recruitment and ubiquitination respectively.PTM The Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated.PTM Ubiquitinated at the Lys residues in its C-terminal cytoplasmic tail and is essential for correct trafficking from and to the cell membrane. Deubiquitinated by CXCL12-stimulation in a reversible manner.SIMILARITY Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.CAUTION Was originally thought to be the receptor for VIP. UniProt P25106 1 EQUAL 362 EQUAL Reactome Database ID Release 78 373859 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373859 Reactome R-HSA-373859 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373859.1 CXCR4 C-X-C chemokine receptor type 4 CXCR4_HUMAN Reactome DB_ID: 2980772 UniProt:P61073 CXCR4 CXCR4 FUNCTION Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:28978524, PubMed:18799424, PubMed:24912431). Involved in the AKT signaling cascade (PubMed:24912431). Plays a role in regulation of cell migration, e.g. during wound healing (PubMed:28978524). Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels (PubMed:20228059). Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival (By similarity).FUNCTION (Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) for human immunodeficiency virus-1/HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus (PubMed:8849450, PubMed:8929542, PubMed:9427609, PubMed:10074122, PubMed:10756055).SUBUNIT Monomer. Can form homodimers (PubMed:20929726). Interacts with CD164 (PubMed:17077324). Interacts with ARRB2; the interaction is dependent on the C-terminal phosphorylation of CXCR4 and allows activation of MAPK1 and MAPK3. Interacts with ARR3; the interaction is dependent on the C-terminal phosphorylation of CXCR4 and modulates calcium mobilization (PubMed:20048153). Interacts with RNF113A; the interaction, enhanced by CXCL12, promotes CXCR4 ubiquitination and subsequent degradation (PubMed:28978524). Interacts (via the cytoplasmic C-terminal) with ITCH (via the WW domains I and II); the interaction, enhanced by CXCL12, promotes CXCR4 ubiquitination and leads to its degradation. Interacts with extracellular ubiquitin. Interacts with DBN1; this interaction is enhanced by antigenic stimulation. Following LPS binding, may form a complex with GDF5, HSP90AA1 and HSPA8.SUBUNIT (Microbial infection) Interacts with HIV-1 surface protein gp120 and Tat.SUBUNIT (Microbial infection) Interacts with HHV-8 protein ORF K4 (PubMed:25612609).SUBUNIT (Microbial infection) May interact with human cytomegalovirus/HHV-5 protein UL78.SUBUNIT (Microbial infection) Interacts with Staphylococcus aureus protein SSL10.TISSUE SPECIFICITY Expressed in numerous tissues, such as peripheral blood leukocytes, spleen, thymus, spinal cord, heart, placenta, lung, liver, skeletal muscle, kidney, pancreas, cerebellum, cerebral cortex and medulla (in microglia as well as in astrocytes), brain microvascular, coronary artery and umbilical cord endothelial cells. Isoform 1 is predominant in all tissues tested.INDUCTION (Microbial infection) May be down-regulated by Human cytomegalovirus/HHV-5.INDUCTION (Microbial infection) May be down-regulated by HIV-1 tat.DOMAIN The amino-terminus is critical for ligand binding. Residues in all four extracellular regions contribute to HIV-1 coreceptor activity.PTM Phosphorylated on agonist stimulation. Rapidly phosphorylated on serine and threonine residues in the C-terminal. Phosphorylation at Ser-324 and Ser-325 leads to recruitment of ITCH, ubiquitination and protein degradation.PTM Ubiquitinated after ligand binding, leading to its degradation (PubMed:28978524). Ubiquitinated by ITCH at the cell membrane on agonist stimulation. The ubiquitin-dependent mechanism, endosomal sorting complex required for transport (ESCRT), then targets CXCR4 for lysosomal degradation. This process is dependent also on prior Ser-/Thr-phosphorylation in the C-terminal of CXCR4. Also binding of ARRB1 to STAM negatively regulates CXCR4 sorting to lysosomes though modulating ubiquitination of SFR5S.PTM Sulfation on Tyr-21 is required for efficient binding of CXCL12/SDF-1alpha and promotes its dimerization. Tyr-7 and Tyr-12 are sulfated in a sequential manner after Tyr-21 is almost fully sulfated, with the binding affinity for CXCL12/SDF-1alpha increasing with the number of sulfotyrosines present. Sulfotyrosines Tyr-7 and Tyr-12 occupy clefts on opposing CXCL12 subunits, thus bridging the CXCL12 dimer interface and promoting CXCL12 dimerization.PTM O- and N-glycosylated. Asn-11 is the principal site of N-glycosylation. There appears to be very little or no glycosylation on Asn-176. N-glycosylation masks coreceptor function in both X4 and R5 laboratory-adapted and primary HIV-1 strains through inhibiting interaction with their Env glycoproteins. The O-glycosylation chondroitin sulfate attachment does not affect interaction with CXCL12/SDF-1alpha nor its coreceptor activity.DISEASE CXCR4 mutations play a role in the pathogenesis of Waldenstroem macroglobulinemia (WM) and influence disease presentation and outcome, as well as response to therapy. WM is a B-cell lymphoma characterized by accumulation of malignant lymphoplasmacytic cells in the bone marrow, lymph nodes and spleen, and hypersecretion of monoclonal immunoglobulin M (IgM). Excess IgM production results in serum hyperviscosity, tissue infiltration, and autoimmune-related pathology.MISCELLANEOUS Plerixafor (AMD3100), an antagonist of CXCR4 activity, blocks HIV-1 entry, interaction with CXCL12 and subsequent CXCR4 signaling.SIMILARITY Belongs to the G-protein coupled receptor 1 family.CAUTION Was originally thought to be a receptor for neuropeptide Y type 3 (NPY3R) (NPY3-R) (PubMed:8329116 and PubMed:8234909). Later reports showed that it acts as a receptor for the C-X-C chemokine CXCL12/SDF-1 (PubMed:9427609, PubMed:10825158, PubMed:12034737). UniProt P61073 1 EQUAL 352 EQUAL Reactome Database ID Release 78 2980772 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2980772 Reactome R-HSA-2980772 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2980772.1 Reactome Database ID Release 78 374120 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374120 Reactome R-HSA-374120 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374120.1 1 CXCL12 CXCL12(22-93) Stromal cell-derived factor 1 SDF1_HUMAN Reactome DB_ID: 2980693 UniProt:P48061 CXCL12 CXCL12 SDF1 SDF1A SDF1B FUNCTION Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Binds to the allosteric site (site 2) of integrins and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a CXCR4-independent manner (PubMed:29301984). Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of ACKR3 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. Stimulates the proliferation of bone marrow-derived B-cell progenitors in the presence of IL7 as well as growth of stromal cell-dependent pre-B-cells (By similarity).SUBUNIT Monomer or homodimer; in equilibrium. Dimer formation is induced by non acidic pH and the presence of multivalent anions, and by binding to CXCR4 or heparin. Monomeric form is required for full chemotactic activity and resistance to ischemia/reperfusion injury, whereas the dimeric form acts as a partial agonist of CXCR4, stimulating Ca2+ mobilization but with no chemotactic activity and instead acts as a selective antagonist that blocks chemotaxis induced by the monomeric form. Interacts with the N-terminus of ACKR3. Interacts with integrin subunit ITGB3 (via the allosteric site (site 2)) (PubMed:29301984).SUBUNIT (Microbial infection) Interacts with molluscum contagiosum virus protein MC148.TISSUE SPECIFICITY Isoform Alpha and isoform Beta are ubiquitously expressed, with highest levels detected in liver, pancreas and spleen. Isoform Gamma is mainly expressed in heart, with weak expression detected in several other tissues. Isoform Delta, isoform Epsilon and isoform Theta have highest expression levels in pancreas, with lower levels detected in heart, kidney, liver and spleen.DEVELOPMENTAL STAGE Isoform Alpha is ubiquitously expressed in fetal tissues. Isoform Beta and isoform Delta have more limited expression patterns, with highest levels detected in fetal spleen and fetal liver, respectively. Isoform Gamma and isoform Theta are weakly detected in fetal kidney.PTM Processed forms SDF-1-beta(3-72) and SDF-1-alpha(3-67) are produced after secretion by proteolytic cleavage of isoforms Beta and Alpha, respectively. The N-terminal processing is probably achieved by DPP4. Isoform Alpha is first cleaved at the C-terminus to yield a SDF-1-alpha(1-67) intermediate before being processed at the N-terminus. The C-terminal processing of isoform Alpha is reduced by binding to heparin and, probably, cell surface proteoglycans.SIMILARITY Belongs to the intercrine alpha (chemokine CxC) family. UniProt P48061 22 EQUAL 93 EQUAL Reactome Database ID Release 78 2980693 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2980693 Reactome R-HSA-2980693 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2980693.1 1 Reactome Database ID Release 78 374203 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374203 Reactome R-HSA-374203 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374203.1 CXCR5:CXCL13 Reactome DB_ID: 444551 BLR1 CXCR5 C-X-C chemokine receptor type 5 CXCR5_HUMAN CD185 Reactome DB_ID: 444505 UniProt:P32302 CXCR5 CXCR5 BLR1 MDR15 FUNCTION Cytokine receptor that binds to B-lymphocyte chemoattractant (BLC). Involved in B-cell migration into B-cell follicles of spleen and Peyer patches but not into those of mesenteric or peripheral lymph nodes. May have a regulatory function in Burkitt lymphoma (BL) lymphomagenesis and/or B-cell differentiation.TISSUE SPECIFICITY Expression in mature B-cells and Burkitt lymphoma cells.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P32302 1 EQUAL 372 EQUAL Reactome Database ID Release 78 444505 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444505 Reactome R-HSA-444505 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444505.1 1 BLC CXCL13 C-X-C motif chemokine 13 CXL13_HUMAN Reactome DB_ID: 444506 UniProt:O43927 CXCL13 CXCL13 BCA1 BLC SCYB13 FUNCTION Chemotactic for B-lymphocytes but not for T-lymphocytes, monocytes and neutrophils. Does not induce calcium release in B-lymphocytes. Binds to BLR1/CXCR5.TISSUE SPECIFICITY Highest levels in liver, followed by spleen, lymph node, appendix and stomach. Low levels in salivary gland, mammary gland and fetal spleen.SIMILARITY Belongs to the intercrine alpha (chemokine CxC) family. UniProt O43927 23 EQUAL 109 EQUAL Reactome Database ID Release 78 444506 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444506 Reactome R-HSA-444506 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444506.1 1 Reactome Database ID Release 78 444551 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444551 Reactome R-HSA-444551 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444551.1 CXCR6:CXCL16 Reactome DB_ID: 373797 CXCL16 C-X-C motif chemokine 16 CXL16_HUMAN Reactome DB_ID: 373826 UniProt:Q9H2A7 CXCL16 CXCL16 SCYB16 SRPSOX UNQ2759/PRO6714 FUNCTION Acts as a scavenger receptor on macrophages, which specifically binds to OxLDL (oxidized low density lipoprotein), suggesting that it may be involved in pathophysiology such as atherogenesis (By similarity). Induces a strong chemotactic response. Induces calcium mobilization. Binds to CXCR6/Bonzo.TISSUE SPECIFICITY Expressed in T-cell areas. Expressed in spleen, lymph nodes, lung, kidney, small intestine and thymus. Weak expression in heart and liver and no expression in brain and bone marrow.PTM Glycosylated.SIMILARITY Belongs to the intercrine alpha (chemokine CxC) family. UniProt Q9H2A7 30 EQUAL 254 EQUAL Reactome Database ID Release 78 373826 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373826 Reactome R-HSA-373826 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373826.1 1 CXCR6 C-X-C chemokine receptor type 6 CXCR6_HUMAN Reactome DB_ID: 373825 UniProt:O00574 CXCR6 CXCR6 BONZO STRL33 TYMSTR FUNCTION Receptor for the C-X-C chemokine CXCL16. Used as a coreceptor by SIVs and by strains of HIV-2 and m-tropic HIV-1.TISSUE SPECIFICITY Expressed in lymphoid tissues and activated T cells.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt O00574 1 EQUAL 342 EQUAL Reactome Database ID Release 78 373825 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373825 Reactome R-HSA-373825 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373825.1 1 Reactome Database ID Release 78 373797 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=373797 Reactome R-HSA-373797 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-373797.1 Somatostatin receptor:somatostatin Reactome DB_ID: 374763 Converted from EntitySet in Reactome Somatostatin receptors Reactome DB_ID: 374746 SSTR1 Somatostatin receptor type 1 SSR1_HUMAN Reactome DB_ID: 374741 UniProt:P30872 SSTR1 SSTR1 FUNCTION Receptor for somatostatin with higher affinity for somatostatin-14 than -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and Na(+)/H(+) exchanger via pertussis toxin insensitive G proteins.SUBUNIT Interacts with SKB1.TISSUE SPECIFICITY Fetal kidney, fetal liver, and adult pancreas, brain, lung, jejunum and stomach.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P30872 1 EQUAL 391 EQUAL Reactome Database ID Release 78 374741 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374741 Reactome R-HSA-374741 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374741.1 SSTR2 Somatostatin receptor type 2 SSR2_HUMAN Reactome DB_ID: 374757 UniProt:P30874 SSTR2 SSTR2 FUNCTION Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and PLC via pertussis toxin insensitive as well as sensitive G proteins. Inhibits calcium entry by suppressing voltage-dependent calcium channels. Acts as the functionally dominant somatostatin receptor in pancreatic alpha- and beta-cells where it mediates the inhibitory effect of somatostatin-14 on hormone secretion. Inhibits cell growth through enhancement of MAPK1 and MAPK2 phosphorylation and subsequent up-regulation of CDKN1B. Stimulates neuronal migration and axon outgrowth and may participate in neuron development and maturation during brain development. Mediates negative regulation of insulin receptor signaling through PTPN6. Inactivates SSTR3 receptor function following heterodimerization.SUBUNIT Homodimer and heterodimer with SSTR3 and SSTR5. Heterodimerization with SSTR3 inactivates SSTR3 receptor function. Heterodimerization with SSTR5 is enhanced by agonist stimulation of SSTR2 and increases SSTR2 cell growth inhibition activity. Following agonist stimulation, homodimers dissociate into monomers which is required for receptor internalization. Interacts with beta-arrestin; this interaction is necessary for receptor internalization and is destabilized by heterodimerization with SSTR5 which results in increased recycling of SSTR2 to the cell surface. Interacts (via C-terminus) with SHANK1 (via PDZ domain).TISSUE SPECIFICITY Expressed in both pancreatic alpha- and beta-cells (at protein level). Expressed at higher levels in the pancreas than other somatostatin receptors. Also expressed in the cerebrum and kidney and, in lesser amounts, in the jejunum, colon and liver. In the developing nervous system, expressed in the cortex where it is located in the preplate at early stages and is enriched in the outer part of the germinal zone at later stages. In the cerebellum, expressed in the deep part of the external granular layer at gestational week 19. This pattern persists until birth but disappears at adulthood.PTM Phosphorylated on serine and threonine residues in response to agonist stimulation, leading to receptor desensitization and rapid internalization. Phosphorylated to a greater extent on serine than threonine residues. Threonine phosphorylation is required for arrestin binding and receptor endocytosis but is not necessary for desensitization (By similarity).SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P30874 1 EQUAL 369 EQUAL Reactome Database ID Release 78 374757 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374757 Reactome R-HSA-374757 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374757.1 SSTR3 Somatostatin receptor type 3 SSR3_HUMAN Reactome DB_ID: 374732 UniProt:P32745 SSTR3 SSTR3 FUNCTION Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase.SUBUNIT Homodimer and heterodimer with SSTR2. Heterodimerization with SSTR2 inactivates SSTR3 receptor function (By similarity).TISSUE SPECIFICITY Brain, pituitary and pancreas.PTM Phosphorylated. Phosphorylation increases upon somatostatin binding (By similarity).SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P32745 1 EQUAL 418 EQUAL Reactome Database ID Release 78 374732 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374732 Reactome R-HSA-374732 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374732.1 SSTR4 Somatostatin receptor type 4 SSR4_HUMAN Reactome DB_ID: 374745 UniProt:P31391 SSTR4 SSTR4 FUNCTION Receptor for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. It is functionally coupled not only to inhibition of adenylate cyclase, but also to activation of both arachidonate release and mitogen-activated protein (MAP) kinase cascade. Mediates antiproliferative action of somatostatin in tumor cells.TISSUE SPECIFICITY Specifically expressed in fetal and adult brain, lung tissue, stomach, and in lesser quantities in the kidney, pituitary and adrenals.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P31391 1 EQUAL 388 EQUAL Reactome Database ID Release 78 374745 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374745 Reactome R-HSA-374745 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374745.1 SSTR5 Somatostatin receptor type 5 SSR5_HUMAN Reactome DB_ID: 374753 UniProt:P35346 SSTR5 SSTR5 FUNCTION Receptor for somatostatin 28 and to a lesser extent for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Increases cell growth inhibition activity of SSTR2 following heterodimerization.SUBUNIT Heterodimer with SSTR2. Heterodimerization with SSTR2 increases cell growth inhibition activity of SSTR2.TISSUE SPECIFICITY Adult pituitary gland, heart, small intestine, adrenal gland, cerebellum and fetal hypothalamus. No expression in fetal or adult kidney, liver, pancreas, uterus, spleen, lung, thyroid or ovary.PTM Palmitoylated by ZDHHC5, but not ZDHHC3, nor ZDHHC8. Palmitoylation creates an additional intracellular loop which is thought to be important for efficient coupling to G-proteins and may target the protein to lipid rafts.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P35346 1 EQUAL 364 EQUAL Reactome Database ID Release 78 374753 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374753 Reactome R-HSA-374753 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374753.1 Reactome Database ID Release 78 374746 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374746 Reactome R-HSA-374746 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374746.1 1 Converted from EntitySet in Reactome Somatostatin, cortistatin Reactome DB_ID: 8849391 Converted from EntitySet in Reactome Somatostatin Reactome DB_ID: 374714 SST SST(103-116) Somatostatin-14 SMS_HUMAN Reactome DB_ID: 374738 UniProt:P61278 SST SST PTM C-terminal amidation of the neuronostatin peptide is required for its biological activity, including for the regulation of mean arterial pressure.PHARMACEUTICAL A synthetic analog known as octreotide or SMS 201-995 is available under the name Sandostatin (Novartis). It is used for the treatment of a variety of disorders including acromegaly and the symptomatic treatment of carcinoid tumors and vasoactive intestinal peptide tumors.SIMILARITY Belongs to the somatostatin family. UniProt P61278 103 EQUAL 116 EQUAL Reactome Database ID Release 78 374738 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374738 Reactome R-HSA-374738 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374738.1 SST SST(89-116) Somatostatin-28 SMS_HUMAN Reactome DB_ID: 374710 89 EQUAL 116 EQUAL Reactome Database ID Release 78 374710 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374710 Reactome R-HSA-374710 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374710.1 Reactome Database ID Release 78 374714 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374714 Reactome R-HSA-374714 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374714.1 CORT_HUMAN CORT(89-105) Cortistatin-17 Reactome DB_ID: 8849392 UniProt:O00230 CORT CORT UNQ307/PRO350 FUNCTION Binds to all human somatostatin receptor (SSTR) subtypes. It also inhibits cAMP production induced by forskolin through SSTRs.TISSUE SPECIFICITY Expressed in a subset of GABAergic cells in the cortex and hippocampus.SIMILARITY Belongs to the somatostatin family. UniProt O00230 89 EQUAL 105 EQUAL Reactome Database ID Release 78 8849392 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8849392 Reactome R-HSA-8849392 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8849392.1 Reactome Database ID Release 78 8849391 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8849391 Reactome R-HSA-8849391 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8849391.1 1 Reactome Database ID Release 78 374763 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374763 Reactome R-HSA-374763 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-374763.2 HTR1B,D,E,F,HTR5A:5HT 5-HT1AB-F/5 receptor:serotonin Reactome DB_ID: 390955 Converted from EntitySet in Reactome HTR1B,D,E,F,HTR5A 5-HT1B-F/5 receptor Reactome DB_ID: 390959 HTR1B 5-HT1B receptor RecName: Full=5-hydroxytryptamine receptor 1B; AltName: Full=5-HT-1D-beta; Short=5-HT-1B; Short=5-HT1B; AltName: Full=Serotonin receptor 1B; AltName: Full=Serotonin 1D beta receptor; AltName: Full=S12;<br>GN Name=HTR1B; Synonyms=HTR1DB;<br>OS Homo sapiens 5HT1B_HUMAN Reactome DB_ID: 390934 UniProt:P28222 HTR1B HTR1B HTR1DB FUNCTION G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances, such as lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.SUBUNIT Homodimer. Heterodimer with HTR1D.TISSUE SPECIFICITY Detected in cerebral artery smooth muscle cells (at protein level). Detected in brain cortex, striatum, amygdala, medulla, hippocampus, caudate nucleus and putamen.DOMAIN Ligands are bound in a hydrophobic pocket formed by the transmembrane helices.PTM Phosphorylated. Desensitization of the receptor may be mediated by its phosphorylation.PTM Palmitoylated.MISCELLANEOUS A residue in the 7th transmembrane region (Thr-355 in human, 'Asn-351' in mouse and rat) is important for species-specific sensitivity to various agonists.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P28222 1 EQUAL 390 EQUAL Reactome Database ID Release 78 390934 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390934 Reactome R-HSA-390934 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390934.1 HTR1D 5-HT1D receptor RecName: Full=5-hydroxytryptamine receptor 1D; Short=5-HT-1D; AltName: Full=5-HT-1D-alpha; AltName: Full=Serotonin receptor 1D;<br>GN Name=HTR1D; Synonyms=HTR1DA, HTRL;<br>OS Homo sapiens 5HT1D_HUMAN Reactome DB_ID: 390940 UniProt:P28221 HTR1D HTR1D HTR1DA HTRL FUNCTION G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction.SUBUNIT Homodimer. Heterodimer with HTR1B.TISSUE SPECIFICITY Detected in brain neocortex and caudate nucleus (at protein level).SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P28221 1 EQUAL 377 EQUAL Reactome Database ID Release 78 390940 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390940 Reactome R-HSA-390940 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390940.1 HTR1E 5-HT1E receptor RecName: Full=5-hydroxytryptamine receptor 1E; Short=5-HT-1E; Short=5-HT1E; AltName: Full=Serotonin receptor 1E; AltName: Full=S31;<br>GN Name=HTR1E;<br>OS Homo sapiens 5HT1E_HUMAN Reactome DB_ID: 390960 UniProt:P28566 HTR1E HTR1E FUNCTION G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.TISSUE SPECIFICITY Detected in brain.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P28566 1 EQUAL 365 EQUAL Reactome Database ID Release 78 390960 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390960 Reactome R-HSA-390960 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390960.1 HTR1F 5-HT1F receptor RecName: Full=5-hydroxytryptamine receptor 1F; Short=5-HT-1F; AltName: Full=Serotonin receptor 1F;<br>GN Name=HTR1F; Synonyms=HTR1EL;<br>OS Homo sapiens 5HT1F_HUMAN Reactome DB_ID: 390979 UniProt:P30939 HTR1F HTR1F HTR1EL FUNCTION G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P30939 1 EQUAL 366 EQUAL Reactome Database ID Release 78 390979 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390979 Reactome R-HSA-390979 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390979.1 HTR5A 5-HT5A receptor RecName: Full=5-hydroxytryptamine receptor 5A; Short=5-HT-5A; Short=5-HT-5; AltName: Full=Serotonin receptor 5A;<br>GN Name=HTR5A;<br>OS Homo sapiens 5HT5A_HUMAN Reactome DB_ID: 391007 UniProt:P47898 HTR5A HTR5A FUNCTION This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P47898 1 EQUAL 357 EQUAL Reactome Database ID Release 78 391007 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=391007 Reactome R-HSA-391007 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-391007.1 Reactome Database ID Release 78 390959 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390959 Reactome R-HSA-390959 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390959.4 1 5HT 5-Hydroxytryptamine serotonin 3-(2-Aminoethyl)-1H-indol-5-ol Enteramine Reactome DB_ID: 114523 serotonin [ChEBI:28790] serotonin ChEBI CHEBI:28790 Reactome Database ID Release 78 114523 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=114523 Reactome R-ALL-114523 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-114523.3 COMPOUND C00780 additional information MI MI:0361 1 Reactome Database ID Release 78 390955 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390955 Reactome R-HSA-390955 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390955.4 HRH4:Hist Reactome DB_ID: 390876 HRH4 Histamine H4 receptor RecName: Full=Histamine H4 receptor; Short=HH4R; AltName: Full=G-protein coupled receptor 105; AltName: Full=GPRv53; AltName: Full=SP9144; AltName: Full=AXOR35; AltName: Full=Pfi-013;<br>GN Name=HRH4; Synonyms=GPCR105;<br>OS Homo sapiens HRH4_HUMAN Reactome DB_ID: 390910 UniProt:Q9H3N8 HRH4 HRH4 GPCR105 FUNCTION The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist).TISSUE SPECIFICITY Expressed primarily in the bone marrow and eosinophils. Shows preferential distribution in cells of immunological relevance such as T-cells, dendritic cells, monocytes, mast cells, neutrophils. Also expressed in a wide variety of peripheral tissues, including the heart, kidney, liver, lung, pancreas, skeletal muscle, prostate, small intestine, spleen, testis, colon, fetal liver and lymph node.INDUCTION Expression is either up-regulated or down-regulated upon activation of the lymphoid tissues and this regulation may depend on the presence of IL10/interleukin-10 or IL13/interleukin-13.MISCELLANEOUS Does not bind diphenhydramine, loratadine, ranitidine, cimetidine and chlorpheniramine. Shows modest affinity for dimaprit, impromidine, clobenpropit, thioperamide, burimamide clozapine, immepip and imetit. The order of inhibitory activity was imetit &gt; clobenpropit &gt; burimamide &gt; thioperamide. Clobenpropit behaves as a partial agonist, dimaprit and impromidine show some agonist activity while clozapine behaves as a full agonist. Thioperamide shows inverse agonism (enhances cAMP activity). The order of inhibitory activity of histamine derivatives was Histamine &gt; N-alpha-methylhistamine &gt; R(-)-alpha-methylhistamine &gt; S(+)-alpha-methylhistamine. Both N-alpha-methylhistamine &gt; R(-)-alpha-methylhistamine behave as full agonists.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q9H3N8 1 EQUAL 390 EQUAL Reactome Database ID Release 78 390910 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390910 Reactome R-HSA-390910 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390910.1 1 Hist histamine Reactome DB_ID: 390899 histamine [ChEBI:18295] histamine ChEBI CHEBI:18295 Reactome Database ID Release 78 390899 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390899 Reactome R-ALL-390899 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-390899.3 COMPOUND C00388 1 Reactome Database ID Release 78 390876 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390876 Reactome R-HSA-390876 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390876.3 DRD3,4:DA Reactome DB_ID: 390849 Converted from EntitySet in Reactome DRD3,4 Reactome DB_ID: 390818 DRD3 Dopamine receptor 3 DRD3_HUMAN RecName: Full=D Reactome DB_ID: 390834 UniProt:P35462 DRD3 DRD3 FUNCTION Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.SUBUNIT Interacts with CLIC6 (By similarity). Interacts with GRK4 (PubMed:19520868). Interacts with PALM (PubMed:16386234). Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA (PubMed:26460884).TISSUE SPECIFICITY Brain.PTM Phosphorylated by GRK4 (GRK4-alpha and GRK4-gamma).PTM Palmitoylated.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P35462 1 EQUAL 400 EQUAL Reactome Database ID Release 78 390834 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390834 Reactome R-HSA-390834 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390834.1 DRD4 Dopamine receptor 4 RecName: Full=D DRD4_HUMAN Reactome DB_ID: 390809 UniProt:P21917 DRD4 DRD4 FUNCTION Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Activated by dopamine, but also by epinephrine and norepinephrine, and by numerous synthetic agonists and drugs (PubMed:9003072, PubMed:16423344, PubMed:27659709, PubMed:29051383). Agonist binding triggers signaling via G proteins that inhibit adenylyl cyclase (PubMed:7512953, PubMed:7643093, PubMed:16423344, PubMed:27659709, PubMed:29051383). Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).ACTIVITY REGULATION Signaling in response to agonists such as dopamine, epinephrine and norepinephrine is modulated by Na(+); lower Na(+) levels result in higher receptor activity (in vitro).SUBUNIT Forms homo- and heterooligomers with DRD2. D4.7 allele exhibits higher affinity for homodimers compared to DRD2 heterodimers, while alleles D42. and 4.4 have similar affinities for both. The interaction with DRD2 may modulate agonist-induced downstream signaling (PubMed:21184734). Interacts with CLIC6 (By similarity). Interacts with GPRASP1 (PubMed:12142540). May interact with ADORA2A (PubMed:20836733). Interacts with KLHL12 (PubMed:18303015).TISSUE SPECIFICITY Highly expressed in retina. Detected at much lower levels in brain, in amygdala, thalamus, hypothalamus, cerebellum and pituitary.PTM Polyubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex: polyubiquitination does not lead to degradation of DRD4 protein.PTM Palmitoylated. Palmitoylation of the C-terminal Cys is important for normal expression at the cell membrane.POLYMORPHISM The number of repeats of 16 amino acids in the third cytoplasmic loop is highly polymorphic and varies among different alleles. Alleles corresponding in size to a 2 (D4.2), 3 (D4.3), 4 (D4.4), 5 (D4.5), 6 (D4.6), 7 (D4.7) and 9 (D4.9) repeats have been described. The sequence shown is that of allele D4.4. The polymorphic repeat sequence has little influence on DRD4-binding profiles and might not be essential for G protein interaction.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P21917 1 EQUAL 467 EQUAL Reactome Database ID Release 78 390809 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390809 Reactome R-HSA-390809 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390809.1 Reactome Database ID Release 78 390818 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390818 Reactome R-HSA-390818 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390818.3 1 DA dopamine Reactome DB_ID: 380873 dopamine [ChEBI:18243] dopamine ChEBI CHEBI:18243 Reactome Database ID Release 78 380873 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380873 Reactome R-ALL-380873 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-380873.3 COMPOUND C03758 1 Reactome Database ID Release 78 390849 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390849 Reactome R-HSA-390849 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390849.3 ADRA2A,B,C:ADR,NAd Alpha-2 adrenoceptor:Catecholamine Reactome DB_ID: 390700 Converted from EntitySet in Reactome ADR, NAd Catecholamine adrenaline or noradrenaline Reactome DB_ID: 390627 ADR Adrenaline (R)-adrenaline Epinephrine Reactome DB_ID: 390625 (R)-adrenaline [ChEBI:28918] (R)-adrenaline ChEBI CHEBI:28918 Reactome Database ID Release 78 390625 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390625 Reactome R-ALL-390625 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-390625.3 COMPOUND C00788 NAd Noradrenaline (R)-noradrenaline Norepinephrine Reactome DB_ID: 374935 (R)-noradrenaline [ChEBI:18357] (R)-noradrenaline ChEBI CHEBI:18357 Reactome Database ID Release 78 374935 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374935 Reactome R-ALL-374935 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-374935.3 COMPOUND C00547 Reactome Database ID Release 78 390627 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390627 Reactome R-ALL-390627 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-390627.2 1 Converted from EntitySet in Reactome ADRA2A,B,C Alpha-2 adrenoceptor Reactome DB_ID: 390664 ADRA2A Alpha-2A adrenoceptor RecName: Full=Alpha-2A adrenergic receptor; AltName: Full=Alpha-2A adrenoreceptor; AltName: Full=Alpha-2A adrenoceptor; Short=Alpha-2AAR; AltName: Full=Alpha-2 adrenergic receptor subtype C10;<br>GN Name=ADRA2A; Synonyms=ADRA2R, ADRAR;<br>OS Homo sapiens ADA2A_HUMAN Reactome DB_ID: 390655 UniProt:P08913 ADRA2A ADRA2A ADRA2R ADRAR FUNCTION Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline &gt; clonidine &gt; epinephrine &gt; norepinephrine &gt; phenylephrine &gt; dopamine &gt; p-synephrine &gt; p-tyramine &gt; serotonin = p-octopamine. For antagonists, the rank order is yohimbine &gt; phentolamine = mianserine &gt; chlorpromazine = spiperone = prazosin &gt; propanolol &gt; alprenolol = pindolol.SIMILARITY Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2A sub-subfamily.CAUTION It is uncertain whether Met-1 or Met-16 is the initiator. UniProt P08913 1 EQUAL 450 EQUAL Reactome Database ID Release 78 390655 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390655 Reactome R-HSA-390655 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390655.1 ADRA2B Alpha-2B adrenoceptor RecName: Full=Alpha-2B adrenergic receptor; AltName: Full=Alpha-2B adrenoreceptor; AltName: Full=Alpha-2B adrenoceptor; AltName: Full=Alpha-2 adrenergic receptor subtype C2;<br>GN Name=ADRA2B; Synonyms=ADRA2L1, ADRA2RL1;<br>OS Homo sapiens ADA2B_HUMAN Reactome DB_ID: 390659 UniProt:P18089 ADRA2B ADRA2B ADRA2L1 ADRA2RL1 FUNCTION Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine &gt; norepinephrine &gt; epinephrine = oxymetazoline &gt; dopamine &gt; p-tyramine = phenylephrine &gt; serotonin &gt; p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine &gt; chlorpromazine &gt; phentolamine &gt; mianserine &gt; spiperone &gt; prazosin &gt; alprenolol &gt; propanolol &gt; pindolol.SUBUNIT Interacts with RAB26 (PubMed:23105096). Interacts with PPP1R9B (PubMed:24114805). Interacts with GGA1, GGA2 and GGA3 (PubMed:27901063, PubMed:26811329).POLYMORPHISM A rare polymorphic frameshift in position 451 produces a protein of 545 residues.SIMILARITY Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2B sub-subfamily. UniProt P18089 1 EQUAL 450 EQUAL Reactome Database ID Release 78 390659 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390659 Reactome R-HSA-390659 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390659.1 ADRA2C Alpha-2C adrenoceptor RecName: Full=Alpha-2C adrenergic receptor; AltName: Full=Alpha-2C adrenoreceptor; AltName: Full=Alpha-2C adrenoceptor; AltName: Full=Alpha-2 adrenergic receptor subtype C4;<br>GN Name=ADRA2C; Synonyms=ADRA2L2, ADRA2RL2;<br>OS Homo sapiens ADA2C_HUMAN Reactome DB_ID: 390662 UniProt:P18825 ADRA2C ADRA2C ADRA2L2 ADRA2RL2 FUNCTION Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.POLYMORPHISM The Del322-325 variant has a significant loss of function. It is approximately 10 times more frequent in African-Americans compared with Caucasians (allele frequencies 0.381 versus 0.040).SIMILARITY Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2C sub-subfamily. UniProt P18825 1 EQUAL 462 EQUAL Reactome Database ID Release 78 390662 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390662 Reactome R-HSA-390662 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390662.1 Reactome Database ID Release 78 390664 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390664 Reactome R-HSA-390664 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390664.3 1 Reactome Database ID Release 78 390700 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390700 Reactome R-HSA-390700 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390700.3 CHRM2,CHRM4:AcCho M2/M4:acetylcholine Reactome DB_ID: 390685 Converted from EntitySet in Reactome CHRM2,CHRM4 M2/M4 receptors Reactome DB_ID: 390686 M2 CHRM2 RecName: Full=Muscarinic acetylcholine receptor M2;<br>GN Name=CHRM2;<br>OS Homo sapiens ACM2_HUMAN Reactome DB_ID: 390654 UniProt:P08172 CHRM2 CHRM2 FUNCTION The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.SUBUNIT Interacts with ARRB1 and ARRB2. Interacts with RACK1; the interaction regulates CHRM2 internalization.INDUCTION Up-regulated in response to enterovirus 71 (EV71) infection.PTM Phosphorylated in response to agonist treatment.POLYMORPHISM Genetic variations in CHRM2 can influence susceptibility to alcoholism [MIM:103780].SIMILARITY Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM2 sub-subfamily. UniProt P08172 1 EQUAL 466 EQUAL Reactome Database ID Release 78 390654 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390654 Reactome R-HSA-390654 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390654.1 M4 CHRM4 RecName: Full=Muscarinic acetylcholine receptor M4;<br>GN Name=CHRM4;<br>OS Homo sapiens ACM4_HUMAN Reactome DB_ID: 390693 UniProt:P08173 CHRM4 CHRM4 FUNCTION The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.SIMILARITY Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM4 sub-subfamily. UniProt P08173 1 EQUAL 479 EQUAL Reactome Database ID Release 78 390693 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390693 Reactome R-HSA-390693 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390693.1 Reactome Database ID Release 78 390686 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390686 Reactome R-HSA-390686 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390686.2 1 AcCho O-acetylcholine acetylcholine Reactome DB_ID: 372533 acetylcholine [ChEBI:15355] acetylcholine ChEBI CHEBI:15355 Reactome Database ID Release 78 372533 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=372533 Reactome R-ALL-372533 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-372533.3 1 Reactome Database ID Release 78 390685 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390685 Reactome R-HSA-390685 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390685.2 P2RY4:UTP Reactome DB_ID: 417869 P2RY4 P2Y purinoceptor 4 P2RY4_HUMAN Reactome DB_ID: 417861 UniProt:P51582 P2RY4 P2RY4 NRU FUNCTION Receptor for UTP and UDP coupled to G-proteins that activate a phosphatidylinositol-calcium second messenger system. Not activated by ATP or ADP.TISSUE SPECIFICITY Pancreas.PTM Phosphorylation of Ser-333 and Ser-334 is a key step in agonist-dependent desensitization and loss of surface P2RY4. This phosphorylation does not involve PKC, nor other calcium activated kinases.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P51582 1 EQUAL 365 EQUAL Reactome Database ID Release 78 417861 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=417861 Reactome R-HSA-417861 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-417861.1 1 UTP uridine 5'-triphosphate Uridine triphosphate Reactome DB_ID: 417877 UTP(4-) [ChEBI:46398] UTP(4-) UTP utp uridine 5'-triphosphate(4-) URIDINE 5'-TRIPHOSPHATE ChEBI CHEBI:46398 Reactome Database ID Release 78 417877 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=417877 Reactome R-ALL-417877 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-417877.3 COMPOUND C00075 1 Reactome Database ID Release 78 417869 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=417869 Reactome R-HSA-417869 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-417869.1 P2RY12:ADP Reactome DB_ID: 417834 P2RY12 P2Y purinoceptor 12 P2Y12_HUMAN Reactome DB_ID: 391959 UniProt:Q9H244 P2RY12 P2RY12 HORK3 FUNCTION Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation.TISSUE SPECIFICITY Highly expressed in the platelets, lower levels in the brain. Lowest levels in the lung, appendix, pituitary and adrenal gland. Expressed in the spinal cord and in the fetal brain.DOMAIN The transmembrane domain is composed of seven transmembrane helices; most of these are not strictly perpendicular to the plane of the membrane, but are tilted and/or kinked. Agonist binding promotes a conformation change in the extracellular loops that leads to an inward movement of the transmembrane helices. Antagonists such as AZD1283 can bind to an overlapping site, but block the inward movement of the transmembrane helices (PubMed:24670650, PubMed:24784220).SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q9H244 1 EQUAL 342 EQUAL Reactome Database ID Release 78 391959 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=391959 Reactome R-HSA-391959 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-391959.1 1 ADP Adenosine 5'-diphosphate ADP(3-) Reactome DB_ID: 114564 ADP(3-) [ChEBI:456216] ADP(3-) ADP 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP trianion ChEBI CHEBI:456216 Reactome Database ID Release 78 114564 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=114564 Reactome R-ALL-114564 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-114564.4 COMPOUND C00008 1 Reactome Database ID Release 78 417834 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=417834 Reactome R-HSA-417834 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-417834.3 P2RY13:ADP Reactome DB_ID: 417853 P2RY13 P2Y purinoceptor 13 P2Y13_HUMAN Reactome DB_ID: 417871 UniProt:Q9BPV8 P2RY13 P2RY13 GPR86 GPR94 FKSG77 FUNCTION Receptor for ADP. Coupled to G(i)-proteins. May play a role in hematopoiesis and the immune system.TISSUE SPECIFICITY Strong expression in spleen and adult brain. Lower expression in placenta, lung, liver, spinal cord, thymus, small intestine, uterus, stomach, testis, fetal brain, and adrenal gland. Not detected in pancreas, heart, kidney, skeletal muscle, ovary or fetal aorta. Clearly detected in lymph node and bone marrow, weakly detected in peripheral blood mononuclear cells (PBMC) and in peripheral blood leukocytes (PBL), but not detected in polymorphonuclear cells (PMN). In the brain, detected in all brain regions examined.MISCELLANEOUS Stimulation by ADP in stably transfected CHO cells resulted in inhibition of adenylyl cyclase and the phosphorylation of the MAP kinases MAPK3 and MAPK1 in a pertussis toxin-sensitive way. Inhibition of adenylyl cyclase and phosphorylation of the MAP kinases are transduction mechanisms that involve G(i) proteins.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q9BPV8 1 EQUAL 354 EQUAL Reactome Database ID Release 78 417871 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=417871 Reactome R-HSA-417871 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-417871.1 1 1 Reactome Database ID Release 78 417853 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=417853 Reactome R-HSA-417853 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-417853.1 P2RY14:UDP-Glc Reactome DB_ID: 417863 P2RY14 P2Y purinoceptor 14 P2Y14_HUMAN Reactome DB_ID: 417835 UniProt:Q15391 P2RY14 P2RY14 GPR105 KIAA0001 FUNCTION Receptor for UDP-glucose and other UDP-sugar coupled to G-proteins. Not activated by ATP, ADP, UTP or ATP.TISSUE SPECIFICITY Highest expression in the placenta, adipose tissue, stomach and intestine, intermediate levels in the brain, spleen, lung and heart, lowest levels in the kidney.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q15391 1 EQUAL 338 EQUAL Reactome Database ID Release 78 417835 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=417835 Reactome R-HSA-417835 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-417835.1 1 UDP-Glc UDP-glucose UDP-D-glucose UDPglucose Reactome DB_ID: 417855 UDP-D-glucose [ChEBI:18066] UDP-D-glucose ChEBI CHEBI:18066 Reactome Database ID Release 78 417855 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=417855 Reactome R-ALL-417855 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-417855.3 COMPOUND C00029 1 Reactome Database ID Release 78 417863 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=417863 Reactome R-HSA-417863 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-417863.2 ADORA1,3:Ade-Rib A1/A3 receptor:Adenosine Reactome DB_ID: 418897 Ade-Rib adenosine Reactome DB_ID: 83908 adenosine [ChEBI:16335] adenosine ChEBI CHEBI:16335 Reactome Database ID Release 78 83908 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83908 Reactome R-ALL-83908 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-83908.3 COMPOUND C00212 1 Converted from EntitySet in Reactome ADORA1,3 A1/A3 receptors Reactome DB_ID: 418922 ADORA3 Adenosine receptor A3 AA3R_HUMAN Reactome DB_ID: 5693919 UniProt:P0DMS8 ADORA3 ADORA3 TISSUE SPECIFICITY Expressed in the lung and bone. Expressed at lower levels in osteosarcoma tissues (at protein level).SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P0DMS8 1 EQUAL 318 EQUAL Reactome Database ID Release 78 5693919 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5693919 Reactome R-HSA-5693919 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5693919.1 ADORA1 Adenosine receptor A1 AA1R_HUMAN Reactome DB_ID: 418941 UniProt:P30542 ADORA1 ADORA1 FUNCTION Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P30542 1 EQUAL 326 EQUAL Reactome Database ID Release 78 418941 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=418941 Reactome R-HSA-418941 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-418941.1 Reactome Database ID Release 78 418922 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=418922 Reactome R-HSA-418922 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-418922.1 1 Reactome Database ID Release 78 418897 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=418897 Reactome R-HSA-418897 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-418897.2 CNRs:Cannabinoids Reactome DB_ID: 419404 Converted from EntitySet in Reactome CNRs Cannabinoid receptors Reactome DB_ID: 419398 CNR1 Cannabinoid receptor 1 CNR1_HUMAN Reactome DB_ID: 419411 UniProt:P21554 CNR1 CNR1 CNR FUNCTION G-protein coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids, such as delta(9)-tetrahydrocannabinol (THC) (PubMed:15620723, PubMed:27768894, PubMed:27851727). Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Signaling typically involves reduction in cyclic AMP (PubMed:1718258, PubMed:21895628, PubMed:27768894). In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. Increases respiration at low doses, while decreases respiration at high doses. At high doses, CNR1 signal transduction involves G-protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP concentration, inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system, including NDUFS2. In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression. In response to cannabinoids, drives the release of orexigenic beta-endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-MSH, from hypothalamic POMC neurons, hence promoting food intake. In the hippocampus, regulates cellular respiration and energy production in response to cannabinoids. Involved in cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), a process in which depolarization of CA1 postsynaptic pyramidal neurons mobilizes eCBs, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission. Also reduces excitatory synaptic transmission (By similarity). In superior cervical ganglions and cerebral vascular smooth muscle cells, inhibits voltage-gated Ca(2+) channels in a constitutive, as well as agonist-dependent manner (PubMed:17895407). In cerebral vascular smooth muscle cells, cannabinoid-induced inhibition of voltage-gated Ca(2+) channels leads to vasodilation and decreased vascular tone (By similarity). Induces leptin production in adipocytes and reduces LRP2-mediated leptin clearance in the kidney, hence participating in hyperleptinemia. In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes (By similarity). In the liver, activation by endocannabinoids leads to increased de novo lipogenesis and reduced fatty acid catabolism, associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes. May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake. Peripherally modulates energy metabolism (By similarity). In high carbohydrate diet-induced obesity, may decrease the expression of mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as well as that of selected glucose/ pyruvate metabolic enzymes, hence affecting energy expenditure through mitochondrial metabolism (By similarity). In response to cannabinoid anandamide, elicits a proinflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion (By similarity). In macrophages infiltrating pancreatic islets, this process may participate in the progression of type-2 diabetes and associated loss of pancreatic beta-cells (PubMed:23955712).SUBUNIT Interacts (via C-terminus) with CNRIP1; this interaction attenuates constitutive, but not agonist-dependent, inhibition of voltage-gated Ca(2+) channels in neurons (PubMed:17895407). Associates with G protein alpha subunits, including G(i) alpha-1/GNAI1, G(i) alpha-3/GNAI3 and G(o) alpha/GNAO1; palmitoylation is important for interaction with GNAI3 and GNAO1 (PubMed:12237474).TISSUE SPECIFICITY Widely expressed, with highest levels in fetal and adult brain. Expression levels of isoform 2 and isoform 3 are much lower than those of isoform 1.INDUCTION Up-regulated by endocannabinoid anandamide.PTM Palmitoylation at Cys-415 is important for recruitment at plasma membrane and lipid rafts and association with G protein alpha subunits.MISCELLANEOUS High-fat diet also increases the hepatic levels of CNR1 ligand anandamide, but not that of 2-arachidonoylglycerol.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P21554 1 EQUAL 472 EQUAL Reactome Database ID Release 78 419411 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419411 Reactome R-HSA-419411 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419411.1 CNR2 Cannabinoid receptor 2 CNR2_HUMAN Reactome DB_ID: 419372 UniProt:P34972 CNR2 CNR2 CB2A CB2B FUNCTION Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.TISSUE SPECIFICITY Preferentially expressed in cells of the immune system with higher expression in B-cells and NK cells (at protein level). Expressed in skin in suprabasal layers and hair follicles (at protein level). Highly expressed in tonsil and to a lower extent in spleen, peripheral blood mononuclear cells, and thymus. PubMed:14657172 could not detect expression in normal brain. Expressed in brain by perivascular microglial cells and dorsal root ganglion sensory neurons (at protein level). Two isoforms are produced by alternative promoter usage and differ only in the 5' UTR: isoform CB2A is observed predominantly in testis with some expression in brain, while isoform CB2B is predominant in spleen and leukocytes.INDUCTION In macrophages, down-regulated by endocannabinoid anandamide/AEA.PTM Constitutively phosphorylated on Ser-352; phosphorylation increases cell internalization and desensitizes the receptor.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P34972 1 EQUAL 360 EQUAL Reactome Database ID Release 78 419372 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419372 Reactome R-HSA-419372 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419372.1 CB3 GPR55 Probable G-protein coupled receptor 55 GPR55_HUMAN Reactome DB_ID: 444504 UniProt:Q9Y2T6 GPR55 GPR55 FUNCTION May be involved in hyperalgesia associated with inflammatory and neuropathic pain (By similarity). Receptor for L-alpha-lysophosphatidylinositol (LPI). LPI induces Ca(2+) release from intracellular stores via the heterotrimeric G protein GNA13 and RHOA. Putative cannabinoid receptor. May play a role in bone physiology by regulating osteoclast number and function.TISSUE SPECIFICITY Expressed in the caudate nucleus and putamen, but not detected in the hippocampus, thalamus, pons cerebellum, frontal cortex of the brain or in the liver. Expressed in osteoclasts and osteoblasts.MISCELLANEOUS The classification of this protein as a cannabinoid receptor remains a contentious issue due to conflicting pharmacological results.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q9Y2T6 1 EQUAL 319 EQUAL Reactome Database ID Release 78 444504 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444504 Reactome R-HSA-444504 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444504.1 Reactome Database ID Release 78 419398 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419398 Reactome R-HSA-419398 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419398.2 1 Converted from EntitySet in Reactome Cannabinoids Reactome DB_ID: 444560 AEA anandamide Reactome DB_ID: 444510 anandamide [ChEBI:2700] anandamide ChEBI CHEBI:2700 Reactome Database ID Release 78 444510 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444510 Reactome R-ALL-444510 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-444510.3 2AG 2-AG 2-arachidonoylglycerol Reactome DB_ID: 419405 2-arachidonoylglycerol [ChEBI:52392] 2-arachidonoylglycerol ChEBI CHEBI:52392 Reactome Database ID Release 78 419405 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419405 Reactome R-ALL-419405 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-419405.3 COMPOUND C13856 Reactome Database ID Release 78 444560 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444560 Reactome R-ALL-444560 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-444560.1 1 Reactome Database ID Release 78 419404 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419404 Reactome R-HSA-419404 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419404.3 CASR:Ca2+ Reactome DB_ID: 420743 Ca2+ Calcium calcium(2+) Reactome DB_ID: 74112 calcium(2+) [ChEBI:29108] calcium(2+) ChEBI CHEBI:29108 Reactome Database ID Release 78 74112 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=74112 Reactome R-ALL-74112 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-74112.4 COMPOUND C00076 1 CASR Extracellular calcium-sensing receptor CASR_HUMAN Reactome DB_ID: 420719 UniProt:P41180 CASR CASR GPRC2A PCAR1 FUNCTION G-protein-coupled receptor that senses changes in the extracellular concentration of calcium ions and plays a key role in maintaining calcium homeostasis (PubMed:7759551, PubMed:8702647, PubMed:8636323, PubMed:8878438, PubMed:17555508, PubMed:19789209, PubMed:21566075, PubMed:22114145, PubMed:23966241, PubMed:25292184, PubMed:25104082, PubMed:26386835, PubMed:25766501, PubMed:22789683). Senses fluctuations in the circulating calcium concentration and modulates the production of parathyroid hormone (PTH) in parathyroid glands (By similarity). The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system (PubMed:7759551). The G-protein-coupled receptor activity is activated by a co-agonist mechanism: aromatic amino acids, such as Trp or Phe, act concertedly with divalent cations, such as calcium or magnesium, to achieve full receptor activation (PubMed:27434672, PubMed:27386547).ACTIVITY REGULATION In resting state, adopts an open conformation, anion-binding promoting the inactive configuration (PubMed:27434672). Upon aromatic amino acid-binding, the groove in the extracellular venus flytrap module is closed, thereby inducing the formation of a novel homodimer interface between subunits (PubMed:27434672, PubMed:27386547). Calcium ions stabilize the active state by enhancing homodimer interactions between membrane-proximal domains to fully activate the receptor (PubMed:27434672, PubMed:27386547). Activated by AMG 416, a D-amino acid-containing peptide agonist that is being evaluated for the treatment of secondary hyperparathyroidism in chronic kidney disease patients receiving hemodialysis (PubMed:26290606). AMG 416 agonist acts by forming a disulfide bond with Cys-482 (PubMed:26290606).SUBUNIT Homodimer; disulfide-linked (PubMed:27434672, PubMed:27386547, PubMed:16740594). Interacts with VCP and RNF19A (PubMed:16513638). Interacts with ARRB1 (By similarity).TISSUE SPECIFICITY Expressed in the temporal lobe, frontal lobe, parietal lobe, hippocampus, and cerebellum. Also found in kidney, lung, liver, heart, skeletal muscle, placenta.DOMAIN The extracellular regions of the homodimer interact in a side-by-side fashion while facing opposite directions (PubMed:27434672, PubMed:27386547). Each extracellular region consists of three domains, LB1 (ligand-binding 1), LB2 and CR (cysteine-rich) (PubMed:17360426). The two lobe-shaped domains LB1 and LB2 form a venus flytrap module (PubMed:27434672, PubMed:27386547). In the inactive configuration, the venus flytrap modules of both protomers are in the open conformation associated with the resting state (open-open) and the interdomain cleft is empty (PubMed:27434672). In addition, each protomer contains three anions, which reinforce the inactive conformation, and one calcium ion (PubMed:27434672). In the active configuration, both protomers of extracellular regions have the closed conformation associated with agonist-binding (closed-closed) (PubMed:27434672, PubMed:27386547). The ligand-binding cleft of each protomer is solely occupied by an aromatic amino-acid (PubMed:27434672, PubMed:27386547). Calcium is bound at four novel sites, including one at the homodimer interface (PubMed:27434672, PubMed:27386547). Agonist-binding induces large conformational changes within the extracellular region homodimer: first, the venus flytrap module of each protomer undergoes domain closure (PubMed:27434672, PubMed:27386547). Second, the LB2 regions of the two protomers approach each other, resulting in an expansion of the homodimer interactions involving LB2 domains (PubMed:27434672, PubMed:27386547). Third, the CR regions of the two subunits interact to form a large homodimer interface that is unique to the active state (PubMed:27434672, PubMed:27386547). The CR regions are brought into close contact by the motion involving LB2 since the two domains are rigidly associated within each subunit (PubMed:27434672, PubMed:27386547).PTM N-glycosylated.PTM Ubiquitinated by RNF19A; which induces proteasomal degradation.SIMILARITY Belongs to the G-protein coupled receptor 3 family. UniProt P41180 20 EQUAL 1078 EQUAL Reactome Database ID Release 78 420719 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=420719 Reactome R-HSA-420719 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-420719.1 1 Reactome Database ID Release 78 420743 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=420743 Reactome R-HSA-420743 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-420743.2 GALR1-3:GAL Galanin:Galanin receptor Reactome DB_ID: 389042 GAL Galanin RecName: Full=Galanin; Contains: RecName: Full=Galanin; Contains: RecName: Full=Galanin message-associated peptide; Short=GMAP; Flags: Precursor;<br>GN Name=GAL; Synonyms=GAL1, GALN, GLNN;<br>OS Homo sapiens GALA_HUMAN Reactome DB_ID: 389038 UniProt:P22466 GAL GAL GAL1 GALN GLNN FUNCTION Endocrine hormone of the central and peripheral nervous systems that binds and activates the G protein-coupled receptors GALR1, GALR2, and GALR3. This small neuropeptide may regulate diverse physiologic functions including contraction of smooth muscle of the gastrointestinal and genitourinary tract, growth hormone and insulin release and adrenal secretion.SIMILARITY Belongs to the galanin family. UniProt P22466 33 EQUAL 62 EQUAL Reactome Database ID Release 78 389038 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389038 Reactome R-HSA-389038 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-389038.1 1 Converted from EntitySet in Reactome GALR1-3 Galanin receptor Reactome DB_ID: 389011 GALR1 RecName: Full=Galanin receptor type 1; AltName: Full=GAL1-R; AltName: Full=GALR1;<br>GN Name=GALR1; Synonyms=GALNR, GALNR1;<br>OS Homo sapiens GALR1_HUMAN Reactome DB_ID: 388967 UniProt:P47211 GALR1 GALR1 GALNR GALNR1 FUNCTION Receptor for the hormone galanin. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity.PTM Palmitoylated on at least one of the three cysteine residues present in the C-terminal part.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P47211 1 EQUAL 349 EQUAL Reactome Database ID Release 78 388967 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=388967 Reactome R-HSA-388967 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-388967.1 GALR2 RecName: Full=Galanin receptor type 2; AltName: Full=GAL2-R; AltName: Full=GALR2;<br>GN Name=GALR2; Synonyms=GALNR2;<br>OS Homo sapiens GALR2_HUMAN Reactome DB_ID: 388949 UniProt:O43603 GALR2 GALR2 GALNR2 FUNCTION Receptor for the hormone galanin and GALP. Receptor for the hormone spexin-1 (PubMed:24517231). The activity of this receptor is mediated by G proteins that activate the phospholipase C/protein kinase C pathway (via G(q)) and that inhibit adenylyl cyclase (via G(i)).TISSUE SPECIFICITY Expressed abundantly within the central nervous system in both hypothalamus and hippocampus. In peripheral tissues, the strongest expression was observed in heart, kidney, liver, and small intestine.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt O43603 1 EQUAL 387 EQUAL Reactome Database ID Release 78 388949 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=388949 Reactome R-HSA-388949 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-388949.1 GALR3 RecName: Full=Galanin receptor type 3; AltName: Full=GAL3-R; AltName: Full=GALR3;<br>GN Name=GALR3; Synonyms=GALNR3;<br>OS Homo sapiens GALR3_HUMAN Reactome DB_ID: 389033 UniProt:O60755 GALR3 GALR3 GALNR3 FUNCTION Receptor for the hormone galanin (PubMed:25691535). Receptor for the hormone spexin-1 (PubMed:24517231).SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt O60755 1 EQUAL 368 EQUAL Reactome Database ID Release 78 389033 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389033 Reactome R-HSA-389033 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-389033.1 Reactome Database ID Release 78 389011 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389011 Reactome R-HSA-389011 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-389011.2 1 Reactome Database ID Release 78 389042 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389042 Reactome R-HSA-389042 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-389042.2 GPR17:Cysteinyl leukotrienes Reactome DB_ID: 416381 Converted from EntitySet in Reactome LTC4,LTD4,LTE4 Cysteinyl leukotrienes Reactome DB_ID: 416372 LTC4 leukotriene C4 Reactome DB_ID: 266013 leukotriene C4 [ChEBI:16978] leukotriene C4 ChEBI CHEBI:16978 Reactome Database ID Release 78 266013 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=266013 Reactome R-ALL-266013 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-266013.3 COMPOUND C02166 LTD4 leukotriene D4 Reactome DB_ID: 266074 leukotriene D4 [ChEBI:28666] leukotriene D4 ChEBI CHEBI:28666 Reactome Database ID Release 78 266074 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=266074 Reactome R-ALL-266074 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-266074.3 COMPOUND C05951 LTE4 leukotriene E4 Reactome DB_ID: 266033 leukotriene E4 [ChEBI:15650] leukotriene E4 ChEBI CHEBI:15650 Reactome Database ID Release 78 266033 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=266033 Reactome R-ALL-266033 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-266033.3 COMPOUND C05952 Reactome Database ID Release 78 416372 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=416372 Reactome R-ALL-416372 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-416372.2 1 GPR17 Uracil nucleotide/cysteinyl leukotriene receptor GPR17_HUMAN Reactome DB_ID: 416429 UniProt:Q13304 GPR17 GPR17 FUNCTION Dual specificity receptor for uracil nucleotides and cysteinyl leukotrienes (CysLTs). Signals through G(i) and inhibition of adenylyl cyclase. May mediate brain damage by nucleotides and CysLTs following ischemia.TISSUE SPECIFICITY Expressed in brain, kidney, heart and umbilical vein endothelial cells. Highest level in brain.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q13304 1 EQUAL 367 EQUAL Reactome Database ID Release 78 416429 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=416429 Reactome R-HSA-416429 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-416429.1 1 Reactome Database ID Release 78 416381 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=416381 Reactome R-HSA-416381 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-416381.2 PTGDR2:PGD2 DP2 receptor:PGD2 Reactome DB_ID: 416875 GPR44 PTGDR2 DP2 receptor CRTH2 receptor Putative G-protein coupled receptor 44 GPR44_HUMAN Reactome DB_ID: 416895 UniProt:Q9Y5Y4 PTGDR2 PTGDR2 CRTH2 DL1R GPR44 FUNCTION Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, GRK2, GPRK5/GRK5 and GRK6. Receptor activation is responsible, at least in part, in immune regulation and allergic/inflammation responses.TISSUE SPECIFICITY Widespread expression. High expression in stomach, small intestine, heart and thymus. Intermediate expression in colon, spinal cord and peripheral blood and low expression in brain, skeletal muscle and spleen. Expressed also on Th2- and Tc2- type cells, eosinophils and basophils.DOMAIN The 330-DSEL-333 motif is involved in the recycling of PTGDR2 to the cell surface after agonist-induced internalization. This motif seems to be required for GRK2 and GPRK5/GRK5 to promote agonist-induced internalization. Thr-347 is a major site for PKC-induced internalization of the receptor.PTM Phosphorylated.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q9Y5Y4 1 EQUAL 395 EQUAL Reactome Database ID Release 78 416895 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=416895 Reactome R-HSA-416895 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-416895.1 1 PGD2 prostaglandin D2 Reactome DB_ID: 416911 prostaglandin D2 [ChEBI:15555] prostaglandin D2 ChEBI CHEBI:15555 Reactome Database ID Release 78 416911 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=416911 Reactome R-ALL-416911 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-416911.3 COMPOUND C00696 1 Reactome Database ID Release 78 416875 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=416875 Reactome R-HSA-416875 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-416875.2 LPAR1,2,3,5:LPA LPA-binding EDG receptors: LPA Reactome DB_ID: 419353 Converted from EntitySet in Reactome LPAR1,2,3,5 LPA-binding EDG receptors Reactome DB_ID: 419369 LPAR1 Lysophosphatidic acid receptor 1 LPAR1_HUMAN Reactome DB_ID: 419354 UniProt:Q92633 LPAR1 LPAR1 EDG2 LPA1 FUNCTION Receptor for lysophosphatidic acid (LPA) (PubMed:9070858, PubMed:19306925, PubMed:25025571, PubMed:26091040). Plays a role in the reorganization of the actin cytoskeleton, cell migration, differentiation and proliferation, and thereby contributes to the responses to tissue damage and infectious agents. Activates downstream signaling cascades via the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Signaling inhibits adenylyl cyclase activity and decreases cellular cAMP levels (PubMed:26091040). Signaling triggers an increase of cytoplasmic Ca(2+) levels (PubMed:19656035, PubMed:19733258, PubMed:26091040). Activates RALA; this leads to the activation of phospholipase C (PLC) and the formation of inositol 1,4,5-trisphosphate (PubMed:19306925). Signaling mediates activation of down-stream MAP kinases (By similarity). Contributes to the regulation of cell shape. Promotes Rho-dependent reorganization of the actin cytoskeleton in neuronal cells and neurite retraction (PubMed:26091040). Promotes the activation of Rho and the formation of actin stress fibers (PubMed:26091040). Promotes formation of lamellipodia at the leading edge of migrating cells via activation of RAC1 (By similarity). Through its function as lysophosphatidic acid receptor, plays a role in chemotaxis and cell migration, including responses to injury and wounding (PubMed:18066075, PubMed:19656035, PubMed:19733258). Plays a role in triggering inflammation in response to bacterial lipopolysaccharide (LPS) via its interaction with CD14. Promotes cell proliferation in response to lysophosphatidic acid. Required for normal skeleton development. May play a role in osteoblast differentiation. Required for normal brain development. Required for normal proliferation, survival and maturation of newly formed neurons in the adult dentate gyrus. Plays a role in pain perception and in the initiation of neuropathic pain (By similarity).SUBUNIT Interacts with RALA and GRK2 (PubMed:19306925). Interacts with GNAQ and GNA13. Interacts with CD14; the interaction is enhanced by exposure to bacterial lipopolysaccharide (LPS) (By similarity).TISSUE SPECIFICITY Expressed in many adult organs, including brain, heart, colon, small intestine, placenta, prostate, ovary, pancreas, testes, spleen, skeletal muscle, and kidney. Little or no expression in liver, lung, thymus, or peripheral blood leukocytes (PubMed:9070858). Detected in lung fibroblasts from bronchoalveolar fluid from patients with idiopathic pulmonary fibrosis (PubMed:18066075). Detected in bone marrow-derived mesenchymal stem cells (PubMed:19733258).PTM N-glycosylated.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q92633 1 EQUAL 364 EQUAL Reactome Database ID Release 78 419354 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419354 Reactome R-HSA-419354 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419354.1 LPAR2 Lysophosphatidic acid receptor 2 LPAR2_HUMAN Reactome DB_ID: 419393 UniProt:Q9HBW0 LPAR2 LPAR2 EDG4 LPA2 FUNCTION Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. Seems to be coupled to the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Plays a key role in phospholipase C-beta (PLC-beta) signaling pathway. Stimulates phospholipase C (PLC) activity in a manner that is independent of RALA activation.SUBUNIT Interacts with SLC9A3R2/NHERF2, MAGI3 and PLCB3. Interacts with RALA and GRK2.TISSUE SPECIFICITY Expressed most abundantly in testes and peripheral blood leukocytes with less expression in pancreas, spleen, thymus and prostate. Little or no expression in heart, brain, placenta, lung, liver, skeletal muscle, kidney, ovary, small intestine, or colon.MISCELLANEOUS PubMed:9525886 cDNA clone has a guanine nucleotide deletion that causes a frameshift near its C-terminal coding region. This likely reflects a somatic mutation in the ovary tumor cells from which the cDNA was isolated and may have altered the function of the encoded receptor, and contributed to transformation of the original ovary cells that formed a tumor.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q9HBW0 1 EQUAL 351 EQUAL Reactome Database ID Release 78 419393 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419393 Reactome R-HSA-419393 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419393.1 LPAR3 Lysophosphatidic acid receptor 3 LPAR3_HUMAN Reactome DB_ID: 419379 UniProt:Q9UBY5 LPAR3 LPAR3 EDG7 LPA3 FUNCTION Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. May play a role in the development of ovarian cancer. Seems to be coupled to the G(i)/G(o) and G(q) families of heteromeric G proteins.TISSUE SPECIFICITY Most abundantly expressed in prostate, testes, pancreas, and heart, with moderate levels in lung and ovary. No detectable expression in brain, placenta, liver, skeletal muscle, kidney, spleen, thymus, small intestine, colon, or peripheral blood leukocytes.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q9UBY5 1 EQUAL 353 EQUAL Reactome Database ID Release 78 419379 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419379 Reactome R-HSA-419379 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419379.1 LPAR5 Lysophosphatidic acid receptor 5 LPAR5_HUMAN Reactome DB_ID: 3249414 UniProt:Q9H1C0 LPAR5 LPAR5 GPR92 GPR93 FUNCTION Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities.TISSUE SPECIFICITY Not expressed in frontal cortex, basal forebrain, caudate putamen, thalamus, or hippocampus.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q9H1C0 1 EQUAL 372 EQUAL Reactome Database ID Release 78 3249414 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3249414 Reactome R-HSA-3249414 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3249414.1 Reactome Database ID Release 78 419369 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419369 Reactome R-HSA-419369 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419369.2 1 LPA Lysophosphatidic acid 1-octadec-9-enoylglycero-3-phosphate Reactome DB_ID: 417891 1-octadec-9-enoylglycero-3-phosphate [ChEBI:52288] 1-octadec-9-enoylglycero-3-phosphate ChEBI CHEBI:52288 Reactome Database ID Release 78 417891 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=417891 Reactome R-ALL-417891 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-417891.3 1 Reactome Database ID Release 78 419353 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419353 Reactome R-HSA-419353 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419353.2 Melatonin receptors:melatonin Reactome DB_ID: 419365 Converted from EntitySet in Reactome Melatonin receptors Reactome DB_ID: 419423 MTNR1A Melatonin receptor type 1A MTR1A_HUMAN Reactome DB_ID: 419316 UniProt:P48039 MTNR1A MTNR1A FUNCTION High affinity receptor for melatonin. Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity.TISSUE SPECIFICITY Expressed in hypophyseal pars tuberalis and hypothalamic suprachiasmatic nuclei (SCN). Hippocampus.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P48039 1 EQUAL 350 EQUAL Reactome Database ID Release 78 419316 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419316 Reactome R-HSA-419316 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419316.1 MTNR1B Melatonin receptor type 1B MTR1B_HUMAN Reactome DB_ID: 419349 UniProt:P49286 MTNR1B MTNR1B FUNCTION High affinity receptor for melatonin. Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity.SUBUNIT Interacts with GPR61, GPR62 and GPR135 (PubMed:28827538).TISSUE SPECIFICITY Expressed in retina and less in brain and hippocampus.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P49286 1 EQUAL 362 EQUAL Reactome Database ID Release 78 419349 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419349 Reactome R-HSA-419349 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419349.1 Reactome Database ID Release 78 419423 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419423 Reactome R-HSA-419423 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419423.1 1 MLT melatonin Reactome DB_ID: 419339 melatonin [ChEBI:16796] melatonin ChEBI CHEBI:16796 Reactome Database ID Release 78 419339 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419339 Reactome R-ALL-419339 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-419339.3 COMPOUND C01598 1 Reactome Database ID Release 78 419365 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419365 Reactome R-HSA-419365 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419365.1 NPY peptides:NPY receptors Neuropeptide Y receptors:NPY receptor ligands Reactome DB_ID: 388866 Converted from EntitySet in Reactome Neuropeptide Y receptors Reactome DB_ID: 388858 NPY1R RecName: Full=Neuropeptide Y receptor type 1; AltName: Full=NPY1-R;<br>GN Name=NPY1R; Synonyms=NPYR, NPYY1;<br>OS Homo sapiens NPY1R_HUMAN Reactome DB_ID: 388896 UniProt:P25929 NPY1R NPY1R NPYR NPYY1 FUNCTION Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is NPY &gt; [Pro-34] PYY, PYY and [Leu-31, Pro-34] NPY &gt; NPY (2-36) &gt; [Ile-31, Gln-34] PP and PYY (3-36) &gt; PP &gt; NPY free acid.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P25929 1 EQUAL 384 EQUAL Reactome Database ID Release 78 388896 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=388896 Reactome R-HSA-388896 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-388896.1 NPY2R RecName: Full=Neuropeptide Y receptor type 2; Short=NPY2-R; AltName: Full=NPY-Y2 receptor; Short=Y2 receptor;<br>GN Name=NPY2R;<br>OS Homo sapiens NPY2R_HUMAN Reactome DB_ID: 388905 UniProt:P49146 NPY2R NPY2R FUNCTION Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is PYY &gt; NPY &gt; PYY (3-36) &gt; NPY (2-36) &gt; [Ile-31, Gln-34] PP &gt; [Leu-31, Pro-34] NPY &gt; PP, [Pro-34] PYY and NPY free acid.TISSUE SPECIFICITY High levels in amygdala, corpus callosum, hippocampus and subthalamic nucleus. Also detectable in caudate nucleus, hypothalamus and substantia nigra.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P49146 1 EQUAL 381 EQUAL Reactome Database ID Release 78 388905 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=388905 Reactome R-HSA-388905 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-388905.1 PPYR1 NYP4R RecName: Full=Neuropeptide Y receptor type 4; Short=NPY4-R; AltName: Full=Pancreatic polypeptide receptor 1; Short=PP1;<br>GN Name=PPYR1; Synonyms=NPY4R;<br>OS Homo sapiens NPY4R_HUMAN Reactome DB_ID: 388868 UniProt:P50391 NPY4R NPY4R PPYR1 FUNCTION Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is PP, PP (2-36) and [Ile-31, Gln-34] PP &gt; [Pro-34] PYY &gt; PYY and [Leu-31, Pro-34] NPY &gt; NPY &gt; PYY (3-36) and NPY (2-36) &gt; PP (13-36) &gt; PP (31-36) &gt; NPY free acid.TISSUE SPECIFICITY Highest levels found in brain, coronary artery and ileum. Low levels in pancreas and kidney. Detected in colon and small intestine.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P50391 1 EQUAL 375 EQUAL Reactome Database ID Release 78 388868 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=388868 Reactome R-HSA-388868 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-388868.1 NPY5R RecName: Full=Neuropeptide Y receptor type 5; Short=NPY5-R; AltName: Full=NPY-Y5 receptor; Short=Y5 receptor; AltName: Full=NPYY5;<br>GN Name=NPY5R; Synonyms=NPYR5;<br>OS Homo sapiens NPY5R_HUMAN Reactome DB_ID: 388854 UniProt:Q15761 NPY5R NPY5R NPYR5 FUNCTION Receptor for neuropeptide Y and peptide YY. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity. Seems to be associated with food intake. Could be involved in feeding disorders.TISSUE SPECIFICITY Brain; hypothalamus.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q15761 1 EQUAL 445 EQUAL Reactome Database ID Release 78 388854 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=388854 Reactome R-HSA-388854 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-388854.1 Reactome Database ID Release 78 388858 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=388858 Reactome R-HSA-388858 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-388858.1 1 Converted from EntitySet in Reactome NPY receptor ligands Reactome DB_ID: 388902 NPY Neuropeptide Y NPY(29-64) RecName: Full=Neuropeptide Y; Contains: RecName: Full=Neuropeptide Y; AltName: Full=Neuropeptide tyrosine; Short=NPY; Contains: RecName: Full=C-flanking peptide of NPY; Short=CPON; Flags: Precursor;<br>GN Name=NPY;<br>OS Homo sapiens NPY_HUMAN Reactome DB_ID: 388906 UniProt:P01303 NPY NPY FUNCTION NPY is implicated in the control of feeding and in secretion of gonadotrophin-release hormone.TISSUE SPECIFICITY One of the most abundant peptides in the nervous system. Also found in some chromaffin cells of the adrenal medulla.PTM The neuropeptide Y form is cleaved at Pro-30 by the prolyl endopeptidase FAP (seprase) activity (in vitro).SIMILARITY Belongs to the NPY family. UniProt P01303 29 EQUAL 64 EQUAL Reactome Database ID Release 78 388906 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=388906 Reactome R-HSA-388906 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-388906.2 PPY PPY(30-65) Pancreatic peptide RecName: Full=Pancreatic prohormone; AltName: Full=Pancreatic polypeptide; Short=PP; AltName: INN=Obinepitide; Contains: RecName: Full=Pancreatic hormone; Short=PH; Contains: RecName: Full=Pancreatic icosapeptide; Short=PI; Flags: Precursor;<br>GN Name=PPY; Synonyms=PNP;<br>OS Homo sapiens PAHO_HUMAN Reactome DB_ID: 388882 UniProt:P01298 PPY PPY PNP FUNCTION Pancreatic hormone is synthesized in pancreatic islets of Langerhans and acts as a regulator of pancreatic and gastrointestinal functions.FUNCTION The physiological role for the icosapeptide has not yet been elucidated.PHARMACEUTICAL Obinepitide is under clinical trial by 7TM Pharma to be used for the treatment of obesity. Obinepitide is derived from pancreatic hormone by having Gln-63.SIMILARITY Belongs to the NPY family. UniProt P01298 30 EQUAL 65 EQUAL Reactome Database ID Release 78 388882 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=388882 Reactome R-HSA-388882 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-388882.1 PYY PYY(29-64) Peptide YY RecName: Full=Peptide YY; Short=PYY; AltName: Full=PYY-I; AltName: Full=Peptide tyrosine tyrosine; Contains: RecName: Full=Peptide YY PYY_HUMAN Reactome DB_ID: 388878 UniProt:P10082 PYY PYY FUNCTION This gut peptide inhibits exocrine pancreatic secretion, has a vasoconstrictory action and inhibitis jejunal and colonic mobility.PTM The peptide YY form is cleaved at Pro-30 by the prolyl endopeptidase FAP (seprase) activity (in vitro) to generate peptide YY(3-36).SIMILARITY Belongs to the NPY family. UniProt P10082 29 EQUAL 64 EQUAL Reactome Database ID Release 78 388878 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=388878 Reactome R-HSA-388878 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-388878.1 Reactome Database ID Release 78 388902 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=388902 Reactome R-HSA-388902 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-388902.2 1 Reactome Database ID Release 78 388866 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=388866 Reactome R-HSA-388866 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-388866.2 OXER1:5-oxoETE OXE receptor:5-oxo-ETE Reactome DB_ID: 416461 OXER1 Oxoeicosanoid receptor 1 OXER1_HUMAN Reactome DB_ID: 416425 UniProt:Q8TDS5 OXER1 OXER1 GPR170 TG1019 FUNCTION Receptor for eicosanoids and polyunsaturated fatty acids such as 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-OXO-ETE), 5(S)-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5(S)-HPETE) and arachidonic acid. Seems to be coupled to the G(i)/G(o), families of heteromeric G proteins.TISSUE SPECIFICITY Expressed in various tissues except brain. Expression is more intense in liver, kidney, peripheral leukocyte, lung, and spleen than in other tissues. Highly expressed in eosinophils, neutrophils, and lung macrophages.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q8TDS5 1 EQUAL 423 EQUAL Reactome Database ID Release 78 416425 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=416425 Reactome R-HSA-416425 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-416425.1 1 5-oxoETE 5-oxo-ETE Reactome DB_ID: 416428 5-oxo-ETE [ChEBI:52449] 5-oxo-ETE ChEBI CHEBI:52449 Reactome Database ID Release 78 416428 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=416428 Reactome R-ALL-416428 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-416428.3 1 Reactome Database ID Release 78 416461 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=416461 Reactome R-HSA-416461 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-416461.2 PTGER3:PGE2 EP3 receptor:PGE2 Reactome DB_ID: 391924 PTGER3 EP3 receptor RecName: Full=Prostaglandin E2 receptor EP3 subtype; Short=PGE receptor, EP3 subtype; Short=PGE2-R; AltName: Full=Prostanoid EP3 receptor;<br>GN Name=PTGER3;<br>OS Homo sapiens PE2R3_HUMAN Reactome DB_ID: 391828 UniProt:P43115 PTGER3 PTGER3 FUNCTION Receptor for prostaglandin E2 (PGE2) (PubMed:8307176, PubMed:7883006, PubMed:8117308, PubMed:8135729, PubMed:7981210). The activity of this receptor can couple to both the inhibition of adenylate cyclase mediated by G(i) proteins, and to an elevation of intracellular calcium (PubMed:7883006, PubMed:8117308, PubMed:8135729, PubMed:7981210). Required for normal development of fever in response to pyrinogens, including IL1B, prostaglandin E2 and bacterial lipopolysaccharide (LPS). Required for normal potentiation of platelet aggregation by prostaglandin E2, and thus plays a role in the regulation of blood coagulation. Required for increased HCO3(-) secretion in the duodenum in response to mucosal acidification, and thereby contributes to the protection of the mucosa against acid-induced ulceration. Not required for normal kidney function, normal urine volume and osmolality (By similarity).SUBUNIT Interacts (via C-terminus) with MKLN1.TISSUE SPECIFICITY Detected in kidney (PubMed:8117308, PubMed:8135729). Expressed in small intestine, heart, pancreas, gastric fundic mucosa, mammary artery and pulmonary vessels.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P43115 1 EQUAL 390 EQUAL Reactome Database ID Release 78 391828 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=391828 Reactome R-HSA-391828 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-391828.1 1 PGE2 prostaglandin E2 Reactome DB_ID: 391930 prostaglandin E2 [ChEBI:15551] prostaglandin E2 ChEBI CHEBI:15551 Reactome Database ID Release 78 391930 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=391930 Reactome R-ALL-391930 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-391930.3 1 Reactome Database ID Release 78 391924 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=391924 Reactome R-HSA-391924 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-391924.2 S1PR2-5:S1P S1P-binding EDG receptors: S1P Reactome DB_ID: 419346 S1P SPGP sphingosine 1-phosphate Sphingosine-1-phosphate Reactome DB_ID: 419305 sphingosine 1-phosphate [ChEBI:37550] sphingosine 1-phosphate ChEBI CHEBI:37550 Reactome Database ID Release 78 419305 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419305 Reactome R-ALL-419305 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-419305.4 1 Converted from EntitySet in Reactome S1PR2-5 S1P-binding EDG receptors Reactome DB_ID: 419401 S1PR2 Sphingosine 1-phosphate receptor 2 S1PR2_HUMAN Reactome DB_ID: 419419 UniProt:O95136 S1PR2 S1PR2 EDG5 FUNCTION Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P) (PubMed:10617617). S1P is a bioactive lysophospholipid that elicits diverse physiological effects on most types of cells and tissues (PubMed:10617617). When expressed in rat HTC4 hepatoma cells, is capable of mediating S1P-induced cell proliferation and suppression of apoptosis (PubMed:10617617). Receptor for the chemokine-like protein FAM19A5 (PubMed:29453251). Mediates the inhibitory effect of FAM19A5 on vascular smooth muscle cell proliferation and migration (By similarity).SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt O95136 1 EQUAL 353 EQUAL Reactome Database ID Release 78 419419 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419419 Reactome R-HSA-419419 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419419.1 S1PR3 Sphingosine 1-phosphate receptor 3 S1PR3_HUMAN Reactome DB_ID: 419396 UniProt:Q99500 S1PR3 S1PR3 EDG3 FUNCTION Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. When expressed in rat HTC4 hepatoma cells, is capable of mediating S1P-induced cell proliferation and suppression of apoptosis.TISSUE SPECIFICITY Expressed in all tissues, but most abundantly in heart, placenta, kidney, and liver.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q99500 1 EQUAL 378 EQUAL Reactome Database ID Release 78 419396 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419396 Reactome R-HSA-419396 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419396.1 S1PR4 Sphingosine 1-phosphate receptor 4 S1PR4_HUMAN Reactome DB_ID: 419347 UniProt:O95977 S1PR4 S1PR4 EDG6 FUNCTION Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. May be involved in cell migration processes that are specific for lymphocytes.TISSUE SPECIFICITY Specifically expressed in fetal and adult lymphoid and hematopoietic tissue as well as in lung. Considerable level of expression in adult and fetal spleen as well as adult peripheral leukocytes and lung. Lower expression in adult thymus, lymph node, bone marrow, and appendix as well as in fetal liver, thymus, and lung.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt O95977 1 EQUAL 384 EQUAL Reactome Database ID Release 78 419347 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419347 Reactome R-HSA-419347 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419347.1 S1PR5 Sphingosine 1-phosphate receptor 5 S1PR5_HUMAN Reactome DB_ID: 419420 UniProt:Q9H228 S1PR5 S1PR5 EDG8 FUNCTION Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. Is coupled to both the G(i/0)alpha and G(12) subclass of heteromeric G-proteins (By similarity). May play a regulatory role in the transformation of radial glial cells into astrocytes and may affect proliferative activity of these cells.TISSUE SPECIFICITY Widely expressed in the brain, most prominently in the corpus callosum, which is predominantly white matter. Detected in spleen, peripheral blood leukocytes, placenta, lung, aorta and fetal spleen. Low-level signal detected in many tissue extracts. Overexpressed in leukemic large granular lymphocytes. Isoform 1 is predominantly expressed in peripheral tissues. Isoform 2 is expressed in brain, spleen and peripheral blood leukocytes.DEVELOPMENTAL STAGE At 24 weeks of gestation, fragments of radial glial fibers are positive within the cortical plate and subplate of allocortical areas. These positive fragments often appear enlarged as varicosities and some of them terminate at blood vessels. Between 28 and 30 weeks of gestation, all iso- and allocortical areas contain immunolabeled radial glial fibers revealing curvature next to sulci. After 32 weeks of gestation, radial glial fibers gradually disappear; instead positive transitional stages between radial glia and astrocytes were found.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q9H228 1 EQUAL 398 EQUAL Reactome Database ID Release 78 419420 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419420 Reactome R-HSA-419420 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419420.1 Reactome Database ID Release 78 419401 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419401 Reactome R-HSA-419401 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419401.3 1 Reactome Database ID Release 78 419346 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=419346 Reactome R-HSA-419346 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-419346.3 FPR2:FPR2 ligands FPRL1:FPRL1 ligands Reactome DB_ID: 416459 FPR2 FPRL1 LXA4 receptor N-formyl peptide receptor 2 FPR2_HUMAN Reactome DB_ID: 416408 UniProt:P25090 FPR2 FPR2 FPRH1 FPRL1 LXA4R FUNCTION Low affinity receptor for N-formyl-methionyl peptides, which are powerful neutrophil chemotactic factors (PubMed:1374236). Binding of FMLP to the receptor causes activation of neutrophils (PubMed:1374236). This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system (PubMed:1374236). The activation of LXA4R could result in an anti-inflammatory outcome counteracting the actions of proinflammatory signals such as LTB4 (leukotriene B4) (PubMed:9547339). Receptor for the chemokine-like protein FAM19A5, mediating FAM19A5-stimulated macrophage chemotaxis and the inhibitory effect on TNFSF11/RANKL-induced osteoclast differentiation (By similarity).SUBUNIT Interacts with Amyloid-beta protein 42, product of APP; the interaction takes place at the cell surface and the complex is then rapidly internalized.SUBUNIT (Microbial infection) Interacts with Staphylococcus aureus protein SSL13; this interaction leads to the activation of neutrophils.TISSUE SPECIFICITY Expressed abundantly in the lung and neutrophils. Also found in the spleen and testis.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P25090 1 EQUAL 351 EQUAL Reactome Database ID Release 78 416408 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=416408 Reactome R-HSA-416408 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-416408.1 1 Converted from EntitySet in Reactome FPR2 ligands FPRL1 ligands Reactome DB_ID: 444472 LXA4 lipoxin A4 Reactome DB_ID: 416384 lipoxin A4 [ChEBI:6498] lipoxin A4 ChEBI CHEBI:6498 Reactome Database ID Release 78 416384 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=416384 Reactome R-ALL-416384 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-416384.3 ANXA1 Annexin A1 ANXA1_HUMAN Reactome DB_ID: 444539 UniProt:P04083 ANXA1 ANXA1 ANX1 LPC1 FUNCTION Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (By similarity). Promotes resolution of inflammation and wound healing (PubMed:25664854). Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades (PubMed:15187149, PubMed:25664854). Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors (PubMed:15187149). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells (PubMed:17008549). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration (PubMed:15187149). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity).SUBUNIT Homodimer; non-covalently linked (By similarity). Homodimer; linked by transglutamylation (PubMed:2532504). Homodimers linked by transglutamylation are observed in placenta, but not in other tissues (PubMed:2532504). Interacts with S100A11 (PubMed:8557678, PubMed:10673436). Heterotetramer, formed by two molecules each of S100A11 and ANXA1 (PubMed:10673436). Interacts with DYSF (By similarity). Interacts with EGFR (By similarity).TISSUE SPECIFICITY Detected in resting neutrophils (PubMed:10772777). Detected in peripheral blood T-cells (PubMed:17008549). Detected in extracellular vesicles in blood serum from patients with inflammatory bowel disease, but not in serum from healthy donors (PubMed:25664854). Detected in placenta (at protein level) (PubMed:2532504). Detected in liver.DOMAIN The full-length protein can bind eight Ca(2+) ions via the annexin repeats. Calcium binding causes a major conformation change that modifies dimer contacts and leads to surface exposure of the N-terminal phosphorylation sites; in the absence of Ca(2+), these sites are buried in the interior of the protein core. The N-terminal region becomes disordered in response to calcium-binding.DOMAIN The N-terminal 26 amino acids are sufficient for its extracellular functions in the regulation of inflammation and wound healing (PubMed:25664854). Acylated peptides that contain the first 26 amino acids of the mature protein can activate signaling via the formyl peptide receptors (PubMed:15187149, PubMed:25664854).PTM Phosphorylated by protein kinase C, EGFR and TRPM7 (PubMed:2457390, PubMed:15485879). Phosphorylated in response to EGF treatment (PubMed:2532504).PTM Sumoylated.PHARMACEUTICAL Peptides based on the N-terminal sequence might be used for the treatment of inflammation, e.g. in chronic bowel diseases and in rheumatoid arthritis.MISCELLANEOUS Was originally identified as calcium and phospholipid binding protein that displays Ca(2+)-dependent binding to phospholipid membranes and can promote membrane aggregation in vitro. Was initially identified as inhibitor of phospholipase A2 activity (in vitro) (PubMed:2936963, PubMed:8425544). Inhibition of phospholipase activity is mediated via its phospholipid binding activity that limits the access of phospholipase to its substrates.SIMILARITY Belongs to the annexin family. UniProt P04083 2 EQUAL 346 EQUAL Reactome Database ID Release 78 444539 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444539 Reactome R-HSA-444539 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444539.1 CCL23-2 sCKbeta8-1 CCL23 isoform 2 Reactome DB_ID: 444564 UniProt:P55773-2 CCL23 CCL23 MIP3 MPIF1 SCYA23 FUNCTION Shows chemotactic activity for monocytes, resting T-lymphocytes, and neutrophils, but not for activated lymphocytes. Inhibits proliferation of myeloid progenitor cells in colony formation assays. This protein can bind heparin. Binds CCR1. CCL23(19-99), CCL23(22-99), CCL23(27-99), CCL23(30-99) are more potent chemoattractants than the small-inducible cytokine A23.TISSUE SPECIFICITY High levels in adult lung, liver, skeletal muscle and pancreas. Moderate levels in fetal liver, adult bone marrow and placenta. The short form is the major species and the longer form was detected only in very low abundance. CCL23(19-99), CCL23(22-99), CCL23(27-99), CCL23(30-99) are found in high levels in synovial fluids from rheumatoid patients.SIMILARITY Belongs to the intercrine beta (chemokine CC) family. UniProt Isoform P55773-2 46 EQUAL 137 EQUAL Reactome Database ID Release 78 444564 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444564 Reactome R-HSA-444564 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444564.1 HN MT-RNR2 Humanin HUNIN_HUMAN Reactome DB_ID: 444568 UniProt:Q8IVG9 MT-RNR2 MT-RNR2 HN FUNCTION Plays a role as a neuroprotective factor. Protects against death induced by multiple different familial Alzheimer disease genes and amyloid-beta proteins in Alzheimer disease. Suppresses apoptosis by binding to BAX and preventing the translocation of BAX from the cytosol to mitochondria. Binds to IGFBP3 and specifically blocks IGFBP3-induced cell death Induces chemotaxis of mononuclear phagocytes via FPR2. Reduces the aggregation and fibrillary formation by suppressing the effect of APP on mononuclear phagocytes and acts by competitively inhibiting the access of FPRL1 to APP.SUBUNIT Interacts with BAX, IGFBP3 and TRIM11.TISSUE SPECIFICITY Expressed in the heart, skeletal muscles, kidney and liver. Lesser but significant expression is observed in the brain and the gastrointestinal tract. Expressed in the AD brain, where it is found in some of the large intact neurons of the occipital lobes and small and round reactive glial cells in the hippocampus.INDUCTION Release is regulated by intracellular mechanism. The intracellular level is regulated by TRIM11 through proteasome-mediated degradation.DOMAIN Largely unstructured in aqueous solution.SIMILARITY Belongs to the humanin family.CAUTION The humanin peptide described here has been shown to be biologically active but is the product of a mitochondrial gene, MT-RNR2 (PubMed:12009529). If translation of the mRNA occurs in the mitochondrion rather than in the cytoplasm, then the usage of the mitochondrial genetic code would lead to the production of a shorter peptide lacking the last three C-terminal residues. The mechanisms allowing the production and the secretion of humanin remaining unclear, the possibility exist that the physiologically active humanin peptide is encoded by one of the related genes present in the nuclear genome (PubMed:19477263). UniProt Q8IVG9 1 EQUAL 24 EQUAL Reactome Database ID Release 78 444568 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444568 Reactome R-HSA-444568 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444568.1 APP APP(672-713) Beta-amyloid protein 42 Amyloid beta A4 protein A4_HUMAN Reactome DB_ID: 879340 UniProt:P05067 APP APP A4 AD1 FUNCTION Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis (PubMed:25122912). Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapes in axons (PubMed:17062754, PubMed:23011729). Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.FUNCTION Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Amyloid-beta protein 42 is a more effective reductant than amyloid-beta protein 40. Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. APP42-beta may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.FUNCTION Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.FUNCTION The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.FUNCTION N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).SUBUNIT Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, MAPK8IP1, SHC1 and, NUMB and DAB1 (By similarity). Binding to DAB1 inhibits its serine phosphorylation (By similarity). Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Also interacts with GPCR-like protein BPP, APPBP1, IB1, KNS2 (via its TPR domains), APPBP2 (via BaSS) and DDB1. In vitro, it binds MAPT via the MT-binding domains (By similarity). Associates with microtubules in the presence of ATP and in a kinesin-dependent manner (By similarity). Interacts, through a C-terminal domain, with GNAO1. Amyloid-beta protein 42 binds CHRNA7 in hippocampal neurons. Amyloid-beta associates with HADH2. Soluble APP binds, via its N-terminal head, to FBLN1. Interacts with CPEB1 and AGER (By similarity). Interacts with ANKS1B and TNFRSF21. Interacts with ITM2B. Interacts with ITM2C. Interacts with IDE. Can form homodimers; dimerization is enhanced in the presence of Cu(2+) ions (PubMed:25122912). Can form homodimers; this is promoted by heparin binding. Amyloid-beta protein 40 interacts with S100A9. CTF-alpha product of APP interacts with GSAP. Isoform APP695 interacts with SORL1 (via N-terminal ectodomain); this interaction retains APP in the trans-Golgi network and reduces processing into soluble APP-alpha and amyloid-beta peptides (PubMed:16174740, PubMed:16407538, PubMed:17855360, PubMed:24523320). The C99 fragment also interacts with SORL1 (PubMed:16407538). Isoform APP751 interacts with SORL1 (PubMed:16174740). Isoform APP770 interacts with SORL1 (PubMed:16174740). Interacts with PLD3. Interacts with VDAC1 (PubMed:25168729). Interacts with NSG1; could regulate APP processing (By similarity). Amyloid-beta protein 42 interacts with FPR2 (PubMed:11689470). Interacts with SYT7 (By similarity). Interacts (via transmembrane region) with PSEN1; the interaction is direct (PubMed:30630874). Interacts with LRRK2 (PubMed:28720718). Interacts (via cytoplasmic domain) with KIF5B (PubMed:23011729).TISSUE SPECIFICITY Expressed in the brain and in cerebrospinal fluid (at protein level) (PubMed:2649245). Expressed in all fetal tissues examined with highest levels in brain, kidney, heart and spleen. Weak expression in liver. In adult brain, highest expression found in the frontal lobe of the cortex and in the anterior perisylvian cortex-opercular gyri. Moderate expression in the cerebellar cortex, the posterior perisylvian cortex-opercular gyri and the temporal associated cortex. Weak expression found in the striate, extra-striate and motor cortices. Expressed in cerebrospinal fluid, and plasma. Isoform APP695 is the predominant form in neuronal tissue, isoform APP751 and isoform APP770 are widely expressed in non-neuronal cells. Isoform APP751 is the most abundant form in T-lymphocytes. Appican is expressed in astrocytes.INDUCTION Increased levels during neuronal differentiation.DOMAIN The transmembrane helix undergoes a conformation change and unravels partially when bound to PSEN1, facilitating cleavage by PSEN1.DOMAIN The basolateral sorting signal (BaSS) is required for sorting of membrane proteins to the basolateral surface of epithelial cells.DOMAIN The GFLD subdomain binds Cu(2+) ions; this promotes homodimerization.DOMAIN The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain. However, additional amino acids either N- or C-terminal to the NPXY motif are often required for complete interaction. The PID domain-containing proteins which bind APP require the YENPTY motif for full interaction. These interactions are independent of phosphorylation on the terminal tyrosine residue. The YENPXY site is also involved in clathrin-mediated endocytosis.DOMAIN The C-terminal region can bind zinc ions; this favors dimerization and formation of higher oligomers.DOMAIN The OX-2 motif shows some similarity to a region in the N-terminus of CD200/MOX2.PTM Proteolytically processed under normal cellular conditions. Cleavage either by alpha-secretase, beta-secretase or theta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, and the retention of corresponding membrane-anchored C-terminal fragments, C80, C83 and C99. Subsequent processing of C80 and C83 by gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid-beta proteins, amyloid-beta protein 40 and amyloid-beta protein 42, major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). PSEN1 cleavage is more efficient with C83 than with C99 as substrate (in vitro) (PubMed:30630874). Many other minor amyloid-beta peptides, amyloid-beta 1-X peptides, are found in cerebral spinal fluid (CSF) including the amyloid-beta X-15 peptides, produced from the cleavage by alpha-secretase and all terminating at Gln-686.PTM Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either CASP6, CASP8 or CASP9 results in the production of the neurotoxic C31 peptide and the increased production of amyloid-beta peptides.PTM N-glycosylated (PubMed:2900137). N- and O-glycosylated (PubMed:2649245). O-glycosylation on Ser and Thr residues with core 1 or possibly core 8 glycans. Partial tyrosine glycosylation (Tyr-681) is found on some minor, short amyloid-beta peptides (amyloid-beta 1-15, 1-16, 1-17, 1-18, 1-19 and 1-20) but not found on amyloid-beta protein 38, amyloid-beta protein 40 nor on amyloid-beta protein 42. Modification on a tyrosine is unusual and is more prevelant in AD patients. Glycans had Neu5AcHex(Neu5Ac)HexNAc-O-Tyr, Neu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr and O-AcNeu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr structures, where O-Ac is O-acetylation of Neu5Ac. Neu5AcNeu5Ac is most likely Neu5Ac 2,8Neu5Ac linked. O-glycosylations in the vicinity of the cleavage sites may influence the proteolytic processing. Appicans are L-APP isoforms with O-linked chondroitin sulfate.PTM Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific (PubMed:10341243). Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins (PubMed:10341243). Phosphorylated on Thr-743 in neuronal cells by Cdc5 kinase and Mapk10, in dividing cells by Cdc2 kinase in a cell-cycle dependent manner with maximal levels at the G2/M phase and, in vitro, by GSK-3-beta (PubMed:8131745, PubMed:11146006). The Thr-743 phosphorylated form causes a conformational change which reduces binding of Fe65 family members (PubMed:11517218). In dopaminergic (DA) neurons, phosphorylation on Thr-743 by LRKK2 promotes the production and the nuclear translocation of the APP intracellular domain (AICD) which induces DA neuron apoptosis (PubMed:28720718). Phosphorylation on Tyr-757 is required for SHC binding (PubMed:11877420). Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound APP. This phosphorylation is inhibited by heparin (PubMed:8999878).PTM Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond. In vitro, the APP-Cu(+) complex in the presence of hydrogen peroxide results in an increased production of amyloid-beta-containing peptides.PTM Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP).PTM Amyloid-beta peptides are degraded by IDE.PTM Sulfated on tyrosine residues.MISCELLANEOUS Chelation of metal ions, notably copper, iron and zinc, can induce histidine-bridging between amyloid-beta molecules resulting in amyloid-beta-metal aggregates. The affinity for copper is much higher than for other transient metals and is increased under acidic conditions. Extracellular zinc-binding increases binding of heparin to APP and inhibits collagen-binding.SIMILARITY Belongs to the APP family. UniProt P05067 672 EQUAL 713 EQUAL Reactome Database ID Release 78 879340 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=879340 Reactome R-HSA-879340 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-879340.1 SAA1 SAA1(19-122) Serum amyloid A protein 1 alpha Serum amyloid A-1 protein SAA1_HUMAN Reactome DB_ID: 2457833 UniProt:P0DJI8 SAA1 SAA1 FUNCTION Major acute phase protein.SUBUNIT Homohexamer; dimer of trimers. Can form amyloid fibrils after partial proteolysis; the native, undenatured protein does not form amyloid fibrils (in vitro). Apolipoprotein of the HDL complex. Binds to heparin.TISSUE SPECIFICITY Expressed by the liver; secreted in plasma (at protein level).INDUCTION Upon cytokine stimulation.PTM This protein is the precursor of amyloid protein A, which is formed by the removal of approximately 24 residues from the C-terminal end.POLYMORPHISM At least 5 different SAA1 alleles have been described: SAA1.1 (SAA1alpha), SAA1.2 (SAA1beta), SAA1.3 (SAA1gamma), SAA1.4 (SAA1delta), SAA1.5 (also named SAA1beta but which differs from SAA1.2). We use here the revised nomenclature described in PubMed:10211414. The sequence shown is that of SAA1.1.DISEASE Reactive, secondary amyloidosis is characterized by the extracellular accumulation in various tissues of the SAA1 protein. These deposits are highly insoluble and resistant to proteolysis; they disrupt tissue structure and compromise function.DISEASE Elevated serum SAA1 protein levels may be associated with lung cancer.SIMILARITY Belongs to the SAA family. UniProt P0DJI8 19 EQUAL 122 EQUAL Reactome Database ID Release 78 2457833 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2457833 Reactome R-HSA-2457833 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2457833.1 Reactome Database ID Release 78 444472 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444472 Reactome R-HSA-444472 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444472.2 1 Reactome Database ID Release 78 416459 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=416459 Reactome R-HSA-416459 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-416459.2 FPR1:FMLP FPR:fMet-Leu-Phe Reactome DB_ID: 444509 FPR FPR1 Formyl peptide receptor fMet-Leu-Phe receptor FPR1_HUMAN Reactome DB_ID: 375450 UniProt:P21462 FPR1 FPR1 FUNCTION High affinity receptor for N-formyl-methionyl peptides (fMLP), which are powerful neutrophil chemotactic factors (PubMed:2161213, PubMed:2176894, PubMed:10514456, PubMed:15153520). Binding of fMLP to the receptor stimulates intracellular calcium mobilization and superoxide anion release (PubMed:2161213, PubMed:1712023, PubMed:15153520). This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system (PubMed:1712023, PubMed:10514456). Receptor for TAFA4, mediates its effects on chemoattracting macrophages, promoting phagocytosis and increasing ROS release (PubMed:25109685).SUBUNIT Interacts with S.aureus chemotaxis inhibitory protein (CHIPS); the interaction blocks the receptor and may thus inhibit the immune response.TISSUE SPECIFICITY Neutrophils.PTM Phosphorylated; which is necessary for desensitization.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P21462 1 EQUAL 350 EQUAL Reactome Database ID Release 78 375450 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=375450 Reactome R-HSA-375450 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-375450.1 1 FMLP fMet-Leu-Phe N-formyl-L-methionyl-L-leucyl-L-phenylalanine fMLP Reactome DB_ID: 444519 N-formyl-L-methionyl-L-leucyl-L-phenylalanine [ChEBI:53490] N-formyl-L-methionyl-L-leucyl-L-phenylalanine ChEBI CHEBI:53490 Reactome Database ID Release 78 444519 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444519 Reactome R-ALL-444519 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-444519.3 1 Reactome Database ID Release 78 444509 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444509 Reactome R-HSA-444509 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444509.2 FPR3:FPR3 ligands FPRL2:FPRL2 ligands Reactome DB_ID: 444553 FPR3 FPRL2 N-formyl peptide receptor 3 FPR3_HUMAN Reactome DB_ID: 444569 UniProt:P25089 FPR3 FPR3 FPRH1 FPRL2 FUNCTION Low affinity receptor for N-formyl-methionyl peptides, which are powerful neutrophils chemotactic factors. Binding of FMLP to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt P25089 1 EQUAL 353 EQUAL Reactome Database ID Release 78 444569 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444569 Reactome R-HSA-444569 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444569.1 1 Converted from EntitySet in Reactome FPR3 ligands FPRL2 ligands Reactome DB_ID: 444545 F2L HEBP1(1-21) Heme-binding protein 1 HEBP1 HEBP1_HUMAN Reactome DB_ID: 444480 UniProt:Q9NRV9 HEBP1 HEBP1 HBP FUNCTION May bind free porphyrinogens that may be present in the cell and thus facilitate removal of these potentially toxic compound. Binds with a high affinity to one molecule of heme or porphyrins. It binds metalloporphyrins, free porphyrins and N-methylprotoporphyrin with similar affinities.SUBUNIT Monomer.DOMAIN Forms a distorted beta-barrel structure, with two helices that are packed against the outer surface of the barrel. Porphyrins are expected to bind to a hydrophobic patch on the outer surface of the beta-barrel structure (By similarity).SIMILARITY Belongs to the HEBP family. UniProt Q9NRV9 1 EQUAL 21 EQUAL Reactome Database ID Release 78 444480 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444480 Reactome R-HSA-444480 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444480.1 Reactome Database ID Release 78 444545 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444545 Reactome R-HSA-444545 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444545.2 1 Reactome Database ID Release 78 444553 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444553 Reactome R-HSA-444553 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444553.2 RXFP3:Relaxin-3 Relaxin-3 receptor 1:Relaxin-3 Reactome DB_ID: 444847 RXFP3 Relaxin-3 receptor 1 RL3R1_HUMAN SALPR Reactome DB_ID: 444841 UniProt:Q9NSD7 RXFP3 RXFP3 GPCR135 RLN3R1 SALPR FUNCTION Receptor for RNL3/relaxin-3. Binding of the ligand inhibit cAMP accumulation.TISSUE SPECIFICITY Expressed predominantly in brain regions. Highest expression in substantia nigra and pituitary, followed by hippocampus, spinal cord, amygdala, caudate nucleus and corpus callosum, quite low level in cerebellum. In peripheral tissues, relatively high levels in adrenal glands, low levels in pancreas, salivary gland, placenta, mammary gland and testis.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q9NSD7 1 EQUAL 469 EQUAL Reactome Database ID Release 78 444841 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444841 Reactome R-HSA-444841 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444841.1 1 Relaxin-3 Reactome DB_ID: 444822 RLN3 RLN3(119-142) Relaxin-3 A chain REL3_HUMAN Reactome DB_ID: 444820 UniProt:Q8WXF3 RLN3 RLN3 INSL7 RXN3 ZINS4 UNQ6188/PRO20213 FUNCTION May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4.SUBUNIT Heterodimer of a B chain and an A chain linked by two disulfide bonds.SIMILARITY Belongs to the insulin family. UniProt Q8WXF3 119 EQUAL 142 EQUAL Reactome Database ID Release 78 444820 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444820 Reactome R-HSA-444820 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444820.1 1 RLN3 RLN3(26-52) Relaxin-3 B chain REL3_HUMAN Reactome DB_ID: 444849 26 EQUAL 52 EQUAL Reactome Database ID Release 78 444849 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444849 Reactome R-HSA-444849 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444849.1 1 Reactome Database ID Release 78 444822 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444822 Reactome R-HSA-444822 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444822.1 1 Reactome Database ID Release 78 444847 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444847 Reactome R-HSA-444847 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444847.2 RXFP4:RXFP4 ligands Relaxin-3 receptor 2:relaxin-3 receptor 2 ligands Reactome DB_ID: 444907 Converted from EntitySet in Reactome RXFP4 ligands Relaxin-3 receptor 2 ligands Reactome DB_ID: 444889 Insulin-like peptide 5 Reactome DB_ID: 444898 INSL5 INSL5(115-135) Insulin-like peptide 5 A chain Insulin-like peptide INSL5 INSL5_HUMAN Reactome DB_ID: 444867 UniProt:Q9Y5Q6 INSL5 INSL5 UNQ156/PRO182 FUNCTION May have a role in gut contractility or in thymic development and regulation. Activates RXFP4 with high potency and appears to be the endogenous ligand for this receptor.SUBUNIT Heterodimer of a B chain and an A chain linked by two disulfide bonds.TISSUE SPECIFICITY Highly expressed in rectum with lower levels in uterus and ascending and descending colon.SIMILARITY Belongs to the insulin family. UniProt Q9Y5Q6 115 EQUAL 135 EQUAL Reactome Database ID Release 78 444867 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444867 Reactome R-HSA-444867 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444867.1 1 INSL5 INSL5(23-48) Insulin-like peptide 5 B chain Insulin-like peptide INSL5 INSL5_HUMAN Reactome DB_ID: 444855 23 EQUAL 48 EQUAL Reactome Database ID Release 78 444855 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444855 Reactome R-HSA-444855 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444855.1 1 Reactome Database ID Release 78 444898 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444898 Reactome R-HSA-444898 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444898.1 Reactome Database ID Release 78 444889 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444889 Reactome R-HSA-444889 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444889.2 1 RXFP4 Relaxin-3 receptor 2 RL3R2_HUMAN GPR100 Reactome DB_ID: 444826 UniProt:Q8TDU9 RXFP4 RXFP4 GPCR142 GPR100 RLN3R2 FUNCTION High affinity receptor for INSL5. Also acts as receptor for RLN3/relaxin-3, as well as bradykinin and kallidin. Binding of the ligand inhibit cAMP accumulation.TISSUE SPECIFICITY Expressed in a broader range of tissues including brain, kidney, testis, thymus, placenta, prostate, salivary gland, thyroid and colon.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q8TDU9 1 EQUAL 374 EQUAL Reactome Database ID Release 78 444826 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444826 Reactome R-HSA-444826 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444826.1 1 Reactome Database ID Release 78 444907 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=444907 Reactome R-HSA-444907 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-444907.2 GPR18:NAGLY N-arachidonyl glycine receptor:NAGly Reactome DB_ID: 517528 NAGLY N-arachidonyl glycine N-arachidonoylglycine Reactome DB_ID: 517533 N-arachidonoylglycine [ChEBI:58961] N-arachidonoylglycine ChEBI CHEBI:58961 Reactome Database ID Release 78 517533 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=517533 Reactome R-ALL-517533 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-517533.3 1 GPR18 N-arachidonyl glycine receptor GPR18_HUMAN Reactome DB_ID: 517529 UniProt:Q14330 GPR18 GPR18 GPCRW FUNCTION Receptor for endocannabinoid N-arachidonyl glycine (NAGly) (PubMed:16844083, PubMed:24762058, PubMed:27572937). However, conflicting results about the role of NAGly as an agonist are reported (PubMed:27018161). Can also be activated by plant-derived and synthetic cannabinoid agonists (PubMed:24762058). The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase (PubMed:16844083). May contribute to regulation of the immune system. Is required for normal homeostasis of CD8+ subsets of intraepithelial lymphocytes (IELs) (CD8alphaalpha and CD8alphabeta IELs)in small intstine by supporting preferential migration of CD8alphaalpha T-cells to intraepithelial compartment over lamina propria compartment, and by mediating their reconstitution into small intestine after bone marrow transplant (By similarity). Plays a role in hypotensive responses, mediating reduction in intraocular and blood pressure (By similarity). Mediates NAGly-induced process of reorganization of actin filaments and induction of acrosomal exocytosis (PubMed:27572937).TISSUE SPECIFICITY Expressed in midpiece of spermatozoon (at protein level) (PubMed:27572937). Most abundant in testis and spleen (PubMed:16844083). Highly expressed in CD4 and CD8-positive T-cells as well as CD19-positive B-cells (PubMed:16844083).SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q14330 1 EQUAL 331 EQUAL Reactome Database ID Release 78 517529 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=517529 Reactome R-HSA-517529 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-517529.1 1 Reactome Database ID Release 78 517528 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=517528 Reactome R-HSA-517528 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-517528.2 MCHR1,MCHR2:PMCH(147-165) MCH:Melanin-concentrating hormone receptors Reactome DB_ID: 947670 Converted from EntitySet in Reactome MCHR1,MCHR2 Melanin-concentrating hormone receptors Reactome DB_ID: 947667 MCHR1 Melanin-concentrating hormone receptor 1 MCHR1_HUMAN Reactome DB_ID: 947682 UniProt:Q99705 MCHR1 MCHR1 GPR24 SLC1 FUNCTION Receptor for melanin-concentrating hormone, coupled to both G proteins that inhibit adenylyl cyclase and G proteins that activate phosphoinositide hydrolysis.SUBUNIT Interacts with NCDN.TISSUE SPECIFICITY Highest level in brain, particularly in the frontal cortex and hypothalamus, lower levels in the liver and heart.SIMILARITY Belongs to the G-protein coupled receptor 1 family.CAUTION It is uncertain whether Met-1, Met-6 or Met-70 is the initiator. UniProt Q99705 1 EQUAL 422 EQUAL Reactome Database ID Release 78 947682 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=947682 Reactome R-HSA-947682 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-947682.1 MCHR2 Melanin-concentrating hormone receptor 2 MCHR2_HUMAN Reactome DB_ID: 947674 UniProt:Q969V1 MCHR2 MCHR2 GPR145 SLT FUNCTION Receptor for melanin-concentrating hormone, coupled to G proteins that activate phosphoinositide hydrolysis.TISSUE SPECIFICITY Specifically expressed in the brain, with highest levels in cerebral cortex, hippocampus and amygdala. No expression detected in the cerebellum, thalamus or hypothalamus.SIMILARITY Belongs to the G-protein coupled receptor 1 family. UniProt Q969V1 1 EQUAL 340 EQUAL Reactome Database ID Release 78 947674 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=947674 Reactome R-HSA-947674 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-947674.1 Reactome Database ID Release 78 947667 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=947667 Reactome R-HSA-947667 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-947667.2 1 MCH PMCH(147-165) Melanin-concentrating hormone MCH_HUMAN Reactome DB_ID: 947685 UniProt:P20382 PMCH PMCH MCH FUNCTION MCH may act as a neurotransmitter or neuromodulator in a broad array of neuronal functions directed toward the regulation of goal-directed behavior, such as food intake, and general arousal. May also have a role in spermatocyte differentiation.TISSUE SPECIFICITY Predominantly expressed in lateral hypothalamus, also detected in pallidum, neocortex and cerebellum. Also found in thymus, brown adipose tissue, duodenum and testis (spermatogonia, early spermatocytes and Sertoli cells). No expression in peripheral blood. In brain exclusively mature MCH and NEI peptides are present. In peripheral tissues a large product, encompassing the NEI and MCH domains of the precursor, is found predominantly.PTM Differentially processed in the brain and in peripheral organs producing two neuropeptides; NEI and MCH. A third peptide, NGE, may also be produced. Preferential processing in neurons by prohormone convertase 2 (PC2) generates NEI. MCH is generated in neurons of the lateral hypothalmic area by several prohormone convertases including PC1/3, PC2 and PC5/6.SIMILARITY Belongs to the melanin-concentrating hormone family. UniProt P20382 147 EQUAL 165 EQUAL Reactome Database ID Release 78 947685 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=947685 Reactome R-HSA-947685 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-947685.1 1 Reactome Database ID Release 78 947670 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=947670 Reactome R-HSA-947670 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-947670.2 NMUR2:NMS Neuromedin-S:Neuromedin-U receptor 2 Reactome DB_ID: 981831 NMS Neuromedin-S NMS_HUMAN Reactome DB_ID: 964796 UniProt:Q5H8A3 NMS NMS FUNCTION Implicated in the regulation of circadian rhythms through autocrine and/or paracrine actions.SIMILARITY Belongs to the NmU family. UniProt Q5H8A3 109 EQUAL 141 EQUAL Reactome Database ID Release 78 964796 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=964796 Reactome R-HSA-964796 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-964796.1 1 NMUR2 Neuromedin-U receptor 2 NMUR2_HUMAN Reactome DB_ID: 964816 UniProt:Q9GZQ4 NMUR2 NMUR2 NMU2R TGR1 FUNCTION Receptor for the neuromedin-U and neuromedin-S neuropeptides.TISSUE SPECIFICITY Predominantly expressed in the CNS, particularly in the medulla oblongata, pontine reticular formation, spinal cord, and thalamus. High level in testis whereas lower levels are present in a variety of peripheral tissues including the gastrointestinal tract, genitourinary tract, liver, pancreas, adrenal gland, thyroid gland, lung, trachea, spleen and thymus.SIMILARITY Belongs to the G-protein coupled receptor 1 family.CAUTION It is uncertain whether Met-1 or Met-4 is the initiator. UniProt Q9GZQ4 1 EQUAL 415 EQUAL Reactome Database ID Release 78 964816 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=964816 Reactome R-HSA-964816 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-964816.1 1 Reactome Database ID Release 78 981831 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=981831 Reactome R-HSA-981831 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-981831.2 NMUR1,NMUR2:NMU Neuromedin-U:Neuromedin receptors Reactome DB_ID: 964802 NMU Neuromedin-U-25 NMU_HUMAN Reactome DB_ID: 964817 UniProt:P48645 NMU NMU TISSUE SPECIFICITY Expressed throughout the enteric nervous system with highest levels being found in the jejunum.SIMILARITY Belongs to the NmU family. UniProt P48645 142 EQUAL 166 EQUAL Reactome Database ID Release 78 964817 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=964817 Reactome R-HSA-964817 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-964817.1 1 Converted from EntitySet in Reactome NMUR1,NMUR2 Neuromedin-U receptors Reactome DB_ID: 964805 NMUR1 Neuromedin-U receptor 1 NMUR1_HUMAN Reactome DB_ID: 964790 UniProt:Q9HB89 NMUR1 NMUR1 GPR66 FUNCTION Receptor for the neuromedin-U and neuromedin-S neuropeptides.TISSUE SPECIFICITY Expressed in greatest abundance in peripheral organs, particularly in elements of the gastrointestinal and urogenital systems with highest levels in testes. In central nervous system structures express levels are much lower than those seen in peripheral organs. Within the CNS, has been detected in highest abundance in the cerebellum, dorsal root ganglia, hippocampus, and spinal cord.SIMILARITY Belongs to the G-protein coupled receptor 1 family.CAUTION It is uncertain whether Met-1 or Met-24 is the initiator. UniProt Q9HB89 1 EQUAL 426 EQUAL Reactome Database ID Release 78 964790 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=964790 Reactome R-HSA-964790 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-964790.1 Reactome Database ID Release 78 964805 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=964805 Reactome R-HSA-964805 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-964805.2 1 Reactome Database ID Release 78 964802 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=964802 Reactome R-HSA-964802 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-964802.2 Group II and III metabotropic gutamate receptors:Glu Reactome DB_ID: 3222582 L-Glu L-Glutamate L-glutamate(1-) L-glutamic acid L-Glutaminic acid Reactome DB_ID: 210382 L-glutamate(1-) [ChEBI:29985] L-glutamate(1-) L-glutamic acid, ion(1-) [NH3+][C@@H](CCC([O-])=O)C([O-])=O WHUUTDBJXJRKMK-VKHMYHEASA-M C5H8NO4 146.12136 (2S)-2-ammoniopentanedioate hydrogen L-glutamate L-glutamate L-glutamic acid monoanion InChI=1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)/p-1/t3-/m0/s1 ChEBI CHEBI:29985 Reactome Database ID Release 78 210382 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=210382 Reactome R-ALL-210382 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-210382.4 COMPOUND C00025 1 Converted from EntitySet in Reactome GRM2,GRM3,GRM4,GRM6,GRM7,GRM8 Groups II and III Metabotropic glutamate receptors Reactome DB_ID: 420517 GRM2 Metabotropic glutamate receptor 2 GRM2_HUMAN Reactome DB_ID: 420468 UniProt:Q14416 GRM2 GRM2 GPRC1B MGLUR2 FUNCTION G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. May mediate suppression of neurotransmission or may be involved in synaptogenesis or synaptic stabilization.SUBUNIT Interacts with TAMALIN (By similarity). Interacts with HTR2A.TISSUE SPECIFICITY Detected in brain cortex (at protein level). Widely expressed in different regions of the adult brain as well as in fetal brain.SIMILARITY Belongs to the G-protein coupled receptor 3 family. UniProt Q14416 19 EQUAL 872 EQUAL Reactome Database ID Release 78 420468 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=420468 Reactome R-HSA-420468 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-420468.1 GRM3 Metabotropic glutamate receptor 3 GRM3_HUMAN Reactome DB_ID: 420509 UniProt:Q14832 GRM3 GRM3 GPRC1C MGLUR3 FUNCTION G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity.SUBUNIT Interacts with TAMALIN.TISSUE SPECIFICITY Detected in brain cortex, thalamus, subthalamic nucleus, substantia nigra, hypothalamus, hippocampus, corpus callosum, caudate nucleus and amygdala.SIMILARITY Belongs to the G-protein coupled receptor 3 family. UniProt Q14832 23 EQUAL 879 EQUAL Reactome Database ID Release 78 420509 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=420509 Reactome R-HSA-420509 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-420509.1 GRM4 Metabotropic glutamate receptor 4 GRM4_HUMAN Reactome DB_ID: 420528 UniProt:Q14833 GRM4 GRM4 GPRC1D MGLUR4 FUNCTION G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity.SUBUNIT Interacts with PICK1.TISSUE SPECIFICITY Strongly expressed in the cerebellum. Expressed at low levels in hippocampus, hypothalamus and thalamus. No expression detected in liver.SIMILARITY Belongs to the G-protein coupled receptor 3 family. UniProt Q14833 33 EQUAL 912 EQUAL Reactome Database ID Release 78 420528 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=420528 Reactome R-HSA-420528 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-420528.1 GRM6 Metabotropic glutamate receptor 6 GRM6_HUMAN Reactome DB_ID: 420574 UniProt:O15303 GRM6 GRM6 GPRC1F MGLUR6 FUNCTION G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity (By similarity). Signaling stimulates TRPM1 channel activity and Ca(2+) uptake. Required for normal vision.SUBUNIT Homodimer.TISSUE SPECIFICITY Detected in melanocytes.SIMILARITY Belongs to the G-protein coupled receptor 3 family. UniProt O15303 25 EQUAL 877 EQUAL Reactome Database ID Release 78 420574 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=420574 Reactome R-HSA-420574 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-420574.1 GRM7 Metabotropic glutamate receptor 7 GRM7_HUMAN Reactome DB_ID: 420536 UniProt:Q14831 GRM7 GRM7 GPRC1G MGLUR7 FUNCTION G-protein coupled receptor activated by glutamate that regulates axon outgrowth through the MAPK-cAMP-PKA signaling pathway during neuronal development (PubMed:33500274). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase that it inhibits (PubMed:9473604).SUBUNIT Homodimer (PubMed:33476302, PubMed:33500274). Interacts with PICK1.TISSUE SPECIFICITY Expressed in many areas of the brain, especially in the cerebral cortex, hippocampus, and cerebellum. Expression of GRM7 isoforms in non-neuronal tissues appears to be restricted to isoform 3 and isoform 4.PTM N-glycosylated.SIMILARITY Belongs to the G-protein coupled receptor 3 family. UniProt Q14831 35 EQUAL 915 EQUAL Reactome Database ID Release 78 420536 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=420536 Reactome R-HSA-420536 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-420536.1 GRM8 Metabotropic glutamate receptor 8 GRM8_HUMAN Reactome DB_ID: 420567 UniProt:O00222 GRM8 GRM8 GPRC1H MGLUR8 FUNCTION G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.SUBUNIT Interacts with PICK1.SIMILARITY Belongs to the G-protein coupled receptor 3 family. UniProt O00222 34 EQUAL 908 EQUAL Reactome Database ID Release 78 420567 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=420567 Reactome R-HSA-420567 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-420567.1 Reactome Database ID Release 78 420517 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=420517 Reactome R-HSA-420517 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-420517.2 1 Reactome Database ID Release 78 3222582 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3222582 Reactome R-HSA-3222582 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3222582.1 TAS2Rs:Bitter-tasting compounds Reactome DB_ID: 3299631 Converted from EntitySet in Reactome Bitter-tasting compounds Reactome DB_ID: 3296423 Absynthin absinthin Reactome DB_ID: 3296417 absinthin [ChEBI:2366] absinthin ChEBI CHEBI:2366 Reactome Database ID Release 78 3296417 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3296417 Reactome R-ALL-3296417 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-3296417.3 Aloin Barbaloin Reactome DB_ID: 3296433 aloin [ChEBI:73222] aloin ChEBI CHEBI:73222 Reactome Database ID Release 78 3296433 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3296433 Reactome R-ALL-3296433 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-3296433.2 AITC allyl isothiocyanate Reactome DB_ID: 3296410 allyl isothiocyanate [ChEBI:73224]