BioPAX pathway converted from "DAP12 interacts with NKG2C" in the Reactome database.DAP12 interacts with NKG2C

DAP12 interacts with NKG2C

This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>

Reactome DB_ID: 9729725

plasma membraneGO0005886CD94:NKG2C:HLA-E [plasma membrane]

CD94:NKG2C:HLA-E

Reactome DB_ID: 9729723

CD94:NKG2C [plasma membrane]

CD94:NKG2C

Converted from EntitySet in Reactome

Reactome DB_ID: 9729721

Homologues of KLRC2 [plasma membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityKlrc2 [plasma membrane]Klrc3 [plasma membrane]Klrc1 [plasma membrane]

Reactomehttp://www.reactome.orgMus musculus

NCBI Taxonomy10090UniProtQ9WTJ9UniProtQ9QXN7UniProtQ9Z202

Reactome DB_ID: 9726551

UniProt:O54707Klrd1

UniProtO54707

Chain Coordinates

EQUAL

179

EQUAL

Reactome Database ID Release 759729723Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9729723ReactomeR-MMU-2326783

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2326783.1

Reactome DB_ID: 9726543

HLA-E [plasma membrane]

HLA-E

Converted from EntitySet in Reactome

Reactome DB_ID: 9725994

Homologues of HLA class I histocompatibility antigen, E alpha chain precursor [plasma membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityH2-M5 [plasma membrane]Gm8909 [plasma membrane]H2-K1 [plasma membrane]H2-M2 [plasma membrane]H2-Q4 [plasma membrane]H2-M10.1 [plasma membrane]H2-Q10 [plasma membrane]Gm7030 [plasma membrane]H2-M10.2 [plasma membrane]H2-T3 [plasma membrane]H2-M10.6 [plasma membrane]H2-T10 [plasma membrane]H2-Q1 [plasma membrane]H2-M10.4 [plasma membrane]Gm11127 [plasma membrane]H2-M10.3 [plasma membrane]H2-M3 [plasma membrane]H2-M1 [plasma membrane]H2-Q7 [plasma membrane]H2-Bl [plasma membrane]H2-M11 [plasma membrane]H2-T23 [plasma membrane]H2-M10.5 [plasma membrane]H2-D1 [plasma membrane]H2-Q2 [plasma membrane]H2-M9 [plasma membrane]H2-Q6 [plasma membrane]H2-T22 [plasma membrane]

UniProtA7VMS3UniProtG3UXE9UniProtP01901UniProtQ6W9L1UniProtQ8HWB2UniProtO19443UniProtP01898UniProtQ0WXH6UniProtQ85ZW9UniProtP14432UniProtQ85ZW5UniProtF6T1I5UniProtO19441UniProtQ85ZW8UniProtA7VMS2UniProtQ85ZW6UniProtQ31093UniProtF7CXU4UniProtP14429UniProtV9GXR0UniProtF6U8V3UniProtP06339UniProtQ85ZW7UniProtP14427UniProtQ4KN81UniProtO19442UniProtP79568UniProtQ31615

Reactome DB_ID: 9725886

UniProt:P01887 B2m

B2m

B2mFUNCTION Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.SUBUNIT Heterodimer of an alpha chain and a beta chain. Beta-2-microglobulin is the beta-chain of major histocompatibility complex class I molecules. Forms a heterotrimer with MR1 and a metabolite antigen.POLYMORPHISM The following alleles of B2M are known: A, B, W2, W3, W4 and W5 (C). The sequence shown is that of allele B.SIMILARITY Belongs to the beta-2-microglobulin family.

UniProtP01887

EQUAL

119

EQUAL

Reactome Database ID Release 759726543Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9726543ReactomeR-MMU-198912

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-198912.1Reactome Database ID Release 759729725Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9729725ReactomeR-MMU-2326867

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2326867.1

Reactome DB_ID: 2326847

Dap12 dimer [plasma membrane]

Dap12 dimer

Reactome DB_ID: 2326825

UniProt:O54885 Tyrobp

Tyrobp

TyrobpKarapDap12FUNCTION Adapter protein which non-covalently associates with activating receptors found on the surface of a variety of immune cells to mediate signaling and cell activation following ligand binding by the receptors (PubMed:15471863, PubMed:9647200). TYROBP is tyrosine-phosphorylated in the ITAM domain following ligand binding by the associated receptors which leads to activation of additional tyrosine kinases and subsequent cell activation (PubMed:15728241). Also has an inhibitory role in some cells (PubMed:21727189). Non-covalently associates with activating receptors of the CD300 family to mediate cell activation (By similarity). Also mediates cell activation through association with activating receptors of the CD200R family (PubMed:15471863). Required for neutrophil activation mediated by integrin (PubMed:17086186). Required for the activation of myeloid cells mediated by the CLEC5A/MDL1 receptor (By similarity). Associates with natural killer (NK) cell receptors such as the KLRD1/KLRC2 heterodimer to mediate NK cell activation (By similarity). Also associates non-covalently with the NK cell receptors KLRA4/LY49D and KLRA8/LY49H which leads to NK cell activation (PubMed:9647200). Associates with TREM1 to mediate activation of neutrophils and monocytes (By similarity). Associates with TREM2 on monocyte-derived dendritic cells to mediate up-regulation of chemokine receptor CCR7 and dendritic cell maturation and survival (By similarity). Association with TREM2 mediates cytokine-induced formation of multinucleated giant cells which are formed by the fusion of macrophages (PubMed:18957693). Stabilizes the TREM2 C-terminal fragment (TREM2-CTF) which is produced by TREM2 ectodomain shedding (By similarity). In microglia, required with TREM2 for phagocytosis of apoptotic neurons (PubMed:15728241). Required with ITGAM/CD11B in microglia to control production of microglial superoxide ions which promote the neuronal apoptosis that occurs during brain development (PubMed:18685038). Promotes proinflammatory responses in microglia following nerve injury which accelerates degeneration of injured neurons (PubMed:25690660). Positively regulates the expression of the IRAK3/IRAK-M kinase and IL10 production by liver dendritic cells and inhibits their T cell allostimulatory ability (PubMed:21257958). Negatively regulates B cell proliferation (PubMed:21727189). Required for CSF1-mediated osteoclast cytoskeletal organization (PubMed:18691974). Positively regulates multinucleation during osteoclast development (PubMed:12569157, PubMed:14969392).SUBUNIT Homodimer; disulfide-linked (By similarity). Homotrimer; disulfide-linked (By similarity). Homotetramer; disulfide-linked (By similarity). Homotrimers and homotetramers form when low levels of partner receptors are available and are competitive with assembly with interacting receptors (By similarity). They may represent alternative oligomerization states or may be intermediates in the receptor assembly process (By similarity). Binding of a metal cation aids in homooligomerization through coordination of the metal ion by the subunits of the oligomer (By similarity). Interacts with TREM1 (By similarity). Interacts with TREM2 (PubMed:29518356). Interacts with TREM3 (PubMed:11754004). Interacts with CLECSF5 (PubMed:10449773). Interacts with CD300LB and CD300C2 (PubMed:12874256, PubMed:12893283, PubMed:17202337, PubMed:17928527). Interacts with CD300E (By similarity). Interacts (via ITAM domain) with SYK (via SH2 domains); activates SYK mediating neutrophil and macrophage integrin-mediated activation (PubMed:17086186). Interacts (via transmembrane domain) with KLRK1 isoform 2 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface expression and NK cell-mediated cytotoxicity (PubMed:12426564, PubMed:12426565, PubMed:15294961). Interacts with KLRC2 (By similarity). Interacts with CD300H (By similarity). Interacts with KLRD1 (By similarity). Interacts with KLRA4 and KLRA8 (PubMed:9647200).TISSUE SPECIFICITY Expressed on microglia (at protein level) (PubMed:12569157, PubMed:18685038). Expressed on oligodendrocytes (at protein level) (PubMed:12569157). Expressed on macrophages and osteoclasts (PubMed:14969392). Expressed on dendritic cells in liver, spleen, kidney and lung with highest levels in liver dendritic cells (PubMed:21257958).INDUCTION Induced in microglia following nerve injury (at protein level) (PubMed:25690660). Induced in liver dendritic cells by physiological concentrations of lipopolysaccharide (PubMed:21257958).PTM Tyrosine phosphorylated (PubMed:11754004, PubMed:12426565, PubMed:15728241, PubMed:17086186, PubMed:18691974, PubMed:9490415, PubMed:9852069). Following ligand binding by associated receptors, tyrosine phosphorylated in the ITAM domain which leads to activation of additional tyrosine kinases and subsequent cell activation (By similarity).DISRUPTION PHENOTYPE Increased bone mass and failure to generate multinuclear osteoclasts in vitro (PubMed:12569157, PubMed:14969392). Thalamic hypomyelination, synaptic degeneration, reduced startle response and aberrant electrophysiological profiles (PubMed:12569157). Enhanced proliferation of B cells (PubMed:21727189). Reduced number of microglia at sites of nerve injury and high rate of neuronal survival (PubMed:25690660). Impaired macrophage fusion (PubMed:18957693). Defective osteoclast cytoskeletal organization and function (PubMed:18691974).SIMILARITY Belongs to the TYROBP family.

UniProtO54885

EQUAL

113

EQUAL

Reactome Database ID Release 752326847Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2326847ReactomeR-MMU-2326847

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2326847.1

Reactome DB_ID: 9770308

HLA-E:CD94:NKG2C:DAP12 [plasma membrane]

HLA-E:CD94:NKG2C:DAP12

Reactome DB_ID: 9729725

Reactome DB_ID: 2326847

Reactome Database ID Release 759770308Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9770308ReactomeR-MMU-2326822

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2326822.1Reactome Database ID Release 759770310Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9770310ReactomeR-MMU-2172126

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2172126.1NKG2C, a C-type lectin-like surface receptor, is a member of the NKG2 family and forms heterodimers with CD94 that is expressed on NK cells and a subset of T cells. The CD94/NKG2C killer lectin-like receptor (KLR) perform an important role in immunosurveillance by binding to HLA-E complexes that present peptides derived from the signal sequences of other HLA class I molecules (A, B, C, G), thereby monitoring MHC class I expression. It has been proposed that the activating receptor CD94/NKG2C may contribute with other NK stimulatory molecules (like NKp46, NKp44 and NKp30 and NKG2D) to trigger effector functions when the control exerted by inhibitory receptors is overcome (Guma et al. 2005). NKG2C/CD94 associates with the ITAM-containing adapter protein DAP12 and this leads to cell activation and cytotoxic function. The charged residues in the transmembrane domains of DAP12 and NKG2C are necessary for this interaction (Lanier et al. 1998). NK cells expressing the CD94/NKG2C receptor are preferentially expanded during cytomegalovirus infection in humans (Lopez-Verges et al. 2011)

9655483Pubmed1998Association of DAP12 with activating CD94/NKG2C NK cell receptorsLanier, L LCorliss, BWu, JPhillips, J HImmunity 8:693-70115940674Pubmed2005The CD94/NKG2C killer lectin-like receptor constitutes an alternative activation pathway for a subset of CD8+ T cellsGumá, MónicaBusch, Lisa KSalazar-Fontana, Laura IBellosillo, BMorte, CarlesGarcía, PilarLópez-Botet, MiguelEur. J. Immunol. 35:2071-8021825173Pubmed2011Expansion of a unique CD57?NKG2Chi natural killer cell subset during acute human cytomegalovirus infectionLopez-Vergès, SandraMilush, Jeffrey MSchwartz, Brian SPando, Marcelo JJarjoura, JessicaYork, Vanessa AHouchins, Jeffrey PMiller, SteveKang, Sang-MoNorris, Phillip JNixon, Douglas FLanier, Lewis LProc. Natl. Acad. Sci. U.S.A. 108:14725-32inferred by electronic annotationIEAGOIEA