BioPAX pathway converted from "Immune System" in the Reactome database. Immune System Signaling in Immune system Immune System signaling 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> Adaptive Immune System 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> TCR signaling 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> Downstream TCR signaling 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> LEFT-TO-RIGHT 3.1.3.67 PTEN dephosphorylates PIP3 PI(3,4,5)P3 is dephosphorylated to PI (4,5)P2 by PTEN at the plasma membrane 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> PIP3 PI(3,4,5)P3 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate Phosphatidylinositol-3,4,5-trisphosphate Reactome DB_ID: 179838 plasma membrane GENE ONTOLOGY GO:0005886 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate [ChEBI:16618] 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate PIP3 ChEBI CHEBI:16618 Reactome Database ID Release 78 179838 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=179838 Reactome R-ALL-179838 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-179838.3 Reactome http://www.reactome.org COMPOUND C05981 additional information MI MI:0361 H2O water Reactome DB_ID: 29356 cytosol GENE ONTOLOGY GO:0005829 water [ChEBI:15377] water ChEBI CHEBI:15377 Reactome Database ID Release 78 29356 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29356 Reactome R-ALL-29356 5 Reactome stable identifier. Use this 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-29356.5 COMPOUND C00001 PIP2 PI(4,5)P2 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate Phosphatidylinositol-4,5-bisphosphate 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate Reactome DB_ID: 179856 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate [ChEBI:18348] 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate PIP2 ChEBI CHEBI:18348 Reactome Database ID Release 78 179856 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=179856 Reactome R-ALL-179856 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-179856.3 COMPOUND C04637 Pi Orthophosphate hydrogenphosphate Phosphate Inorganic Phosphate Reactome DB_ID: 29372 hydrogenphosphate [ChEBI:43474] hydrogenphosphate hydrogen phosphate phosphate [PO3(OH)](2-) INORGANIC PHOSPHATE GROUP HYDROGENPHOSPHATE ION HPO4(2-) [P(OH)O3](2-) ChEBI CHEBI:43474 Reactome Database ID Release 78 29372 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29372 Reactome R-ALL-29372 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-29372.4 COMPOUND C00009 ACTIVATION TEP1 PTEN P53916 Reactome DB_ID: 10757636 UniProt:P53916 TEP1 Saccharomyces cerevisiae NCBI Taxonomy 4932 UniProt P53916 2 EQUAL 403 EQUAL Reactome Database ID Release 78 10757636 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757636 Reactome R-SCE-199420 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-SCE-199420.1 GENE ONTOLOGY GO:0016314 gene ontology term for cellular function MI MI:0355 Same Catalyst Activity Reactome Database ID Release 78 10757637 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757637 Reactome Database ID Release 78 10757639 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757639 Reactome R-SCE-199456 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-SCE-199456.1 GENE ONTOLOGY GO:0051898 gene ontology term for cellular process MI MI:0359 At the plasma membrane, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase aka phosphatase and tensin homolog (PTEN) dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) (Maehama & Dixon 1998, Myers et al. 1998, Das et al. 2003). The PI3K network is negatively regulated by phospholipid phosphatases that dephosphorylate PIP3, thus hampering AKT activation (Myers et al. 1998). The tumour suppressor PTEN is the primary phospholipid phosphatase.<br>Early studies indicated that magnesium ion, Mg2+, was needed for the catalytic activity of PTEN isolated from bovine thymus (Kabuyama et al. 1996). Subsequent studies have shown that PTEN was catalytically active in buffers free of magnesium and magnesium was not detected as part of the PTEN crystal (Lee et al. 1999). 10555148 Pubmed 1999 Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association Lee, Jie-Oh Yang, Haijuan Georgescu, Maria-Magdalena Di Cristofano, Antonio Maehama, Tomohiko Shi, Y Dixon, Jack Pandolfi, Pier Pavletich, Nikola Cell 99:323-34 12808147 Pubmed 2003 Membrane-binding and activation mechanism of PTEN Das, S Dixon, JE Cho, W Proc Natl Acad Sci U S A 100:7491-6 9811831 Pubmed 1998 The lipid phosphatase activity of PTEN is critical for its tumor supressor function Myers, MP Pass, I Batty, IH van der Kaay, J Stolarov, JP Hemmings, BA Downes, CP Tonks, NK Wigler, Michael H Proc Natl Acad Sci U S A 95:13513-8 8681945 Pubmed 1996 Purification and characterization of the phosphatidylinositol-3,4,5-trisphosphate phosphatase in bovine thymus Kabuyama, Y Nakatsu, N Homma, Y Fukui, Y Eur. J. Biochem. 238:350-6 9593664 Pubmed 1998 The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate Maehama, T Dixon, JE J Biol Chem 273:13375-8 inferred from electronic annotation EVIDENCE CODE ECO:0000203 LEFT-TO-RIGHT Translocation of PDK1 to Plasma membrane 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> PKH2 PDPK1 Q12236 Reactome DB_ID: 10757982 UniProt:Q12236 PKH2 UniProt Q12236 1 EQUAL 556 EQUAL Reactome Database ID Release 78 10757982 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757982 Reactome R-SCE-202210 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-SCE-202210.1 Converted from EntitySet in Reactome PIP3, PI(3,4)P2 Reactome DB_ID: 202277 PI(3,4)P2 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphates 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate Reactome DB_ID: 202247 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate [ChEBI:16152] 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate ChEBI CHEBI:16152 Reactome Database ID Release 78 202247 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=202247 Reactome R-ALL-202247 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-202247.3 Reactome Database ID Release 78 202277 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=202277 Reactome R-ALL-202277 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-202277.1 PDK1:PIP2,PIP3 Reactome DB_ID: 10757984 PKH2 PDPK1 Q12236 Reactome DB_ID: 10754835 1 EQUAL 556 EQUAL Reactome Database ID Release 78 10754835 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10754835 Reactome R-SCE-61459 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-SCE-61459.1 1 1 Reactome Database ID Release 78 10757984 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757984 Reactome R-SCE-202311 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-SCE-202311.1 Reactome Database ID Release 78 10757986 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757986 Reactome R-SCE-202164 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-SCE-202164.1 PI3K activation results in recruitment of the serine/threonine kinase PDK1, (3-phosphoinositide-dependent kinase 1) to the plasma membrane where PDK1 subsequently phosphorylates and activates AKT. PDK1 with its PH domain binds to either PIP3 or PIP2 and is translocated to the plasma membrane. PDK1 seems to exist in an active, phosphorylated configuration under basal conditions (Vanhaesebroeck & Alessi 2000). 10698680 Pubmed 2000 The PI3K-PDK1 connection: more than just a road to PKB Vanhaesebroeck, B Alessi, DR Biochem J 346:561-76 LEFT-TO-RIGHT Translocation of PKC theta to plasma membrane 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> PKC1 PRKCQ P24583 Reactome DB_ID: 10757886 UniProt:P24583 PKC1 UniProt P24583 1 EQUAL 706 EQUAL Reactome Database ID Release 78 10757886 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757886 Reactome R-SCE-58216 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-SCE-58216.1 DAG DAGs diacylglycerols diglyceride Reactome DB_ID: 112275 diglyceride [ChEBI:18035] diglyceride ChEBI CHEBI:18035 Reactome Database ID Release 78 112275 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112275 Reactome R-ALL-112275 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-112275.3 COMPOUND C00165 PKC-theta (open): DAG Reactome DB_ID: 10758005 PKC1 PRKCQ P24583 Reactome DB_ID: 10758003 1 EQUAL 706 EQUAL Reactome Database ID Release 78 10758003 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10758003 Reactome R-SCE-202346 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-SCE-202346.1 1 1 Reactome Database ID Release 78 10758005 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10758005 Reactome R-SCE-202187 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-SCE-202187.1 Reactome Database ID Release 78 10758007 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10758007 Reactome R-SCE-202328 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-SCE-202328.1 DAG along with intracellular calcium signals cooperatively to activate PKCs, which then trigger other pathways such as the NF-kB pathway, ultimately leading to mast cell (MC) degranulation and cytokine production (Wu 2011). PKC theta is a member of the Ca++ independent and DAG dependent, novel PKC subfamily expressed mainly in T cells. It contains, N-term C2 like domain, a pseudosubstrate (PS), DAG binding (C1) domain and a C-term kinase domain. The PS sequence resembles an ideal substrate with the exception that it contains an alanine residue instead of a substrate serine residue, is bound to the kinase domain in the resting state. As a result, PKC theta is maintained in a closed inactive state, which is inaccessible to cellular substrates.<br>MCs express several Protein kinase C (PKC) isozymes and these kinases are involved in both the activation and termination of the degranulation process. PKC-delta is a negative regulator of FCERI mediated mast cell degranulation, whereas PKC-theta facilitates in degranulation (Leitges et al. 2002, Liu et al. 2001). In response to FCERI activation PKC-theta translocates to membrane by binding to DAG with its C1 domain. PKC-theta exists in two conformations closed/inactive and open/active state. In resting state, PKC-theta is autoinhibited where the pseudosubstrate sequence in the N-terminal regulatory region of PKC-theta forms intramolecular interaction with the substrate-binding region in the catalytic domain. This prevents the catalytic domain gaining access to substrates. The allosteric change of PKC-theta from closed to open state involves two important mechanisms: DAG binding to the C1 domains and autophosphorylation of T538 on the activation loop. Interaction with DAG induces conformational change resulting in the exposure of the activation loop of PKC-theta (Wang et al. 2012, Melowic et al. 2007). 17548359 Pubmed 2007 Mechanism of diacylglycerol-induced membrane targeting and activation of protein kinase Ctheta Melowic, Heather R Stahelin, Robert V Blatner, Nichole R Tian, Wen Hayashi, Keitaro Altman, Amnon Cho, Wonhwa J. Biol. Chem. 282:21467-76 11358993 Pubmed 2001 Protein kinase C theta is expressed in mast cells and is functionally involved in Fcepsilon receptor I signaling Liu, Y Graham, C Parravicini, V Brown, M J Rivera, J Shaw, S J. Leukoc. Biol. 69:831-40 12473184 Pubmed 2002 Protein kinase C-theta (PKC theta): a key enzyme in T cell life and death Altman, A Villalba, M J Biochem (Tokyo) 132:841-6 16978534 Pubmed 2006 Selective function of PKC-theta in T cells Manicassamy, S Gupta, S Sun, Z Cell Mol Immunol 3:263-70 LEFT-TO-RIGHT 2.7.11 Phosphorylation of PKC theta 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> ATP Adenosine 5'-triphosphate ATP(4-) Reactome DB_ID: 113592 ATP(4-) [ChEBI:30616] ATP(4-) ATP atp Adenosine 5'-triphosphate ChEBI CHEBI:30616 Reactome Database ID Release 78 113592 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113592 Reactome R-ALL-113592 5 Reactome stable identifier. Use this 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-113592.5 COMPOUND C00002 3 p-Y90-PKC-theta:DAG Reactome DB_ID: 10757991 1 P24583 phospho-PKC1 p-Y90-PRKCQ Reactome DB_ID: 10757989 90 EQUAL O4'-phospho-L-tyrosine MOD MOD:00048 1 EQUAL 706 EQUAL Reactome Database ID Release 78 10757989 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757989 Reactome R-SCE-202395 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-SCE-202395.1 1 Reactome Database ID Release 78 10757991 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757991 Reactome R-SCE-202300 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-SCE-202300.1 ADP Adenosine 5'-diphosphate ADP(3-) Reactome DB_ID: 29370 ADP(3-) [ChEBI:456216] ADP(3-) ADP 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP trianion ChEBI CHEBI:456216 Reactome Database ID Release 78 29370 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29370 Reactome R-ALL-29370 5 Reactome stable identifier. Use this 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-29370.5 COMPOUND C00008 3 Active PKC theta bound to DAG Reactome DB_ID: 10757998 1 P24583 phospho-PKC1 p-Y90,T538,S676,S695-PRKCQ Reactome DB_ID: 10757996 538 EQUAL O-phospho-L-threonine MOD MOD:00047 676 EQUAL O-phospho-L-serine MOD MOD:00046 695 EQUAL 1 EQUAL 706 EQUAL Reactome Database ID Release 78 10757996 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757996 Reactome R-SCE-202152 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-SCE-202152.1 1 Reactome Database ID Release 78 10757998 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757998 Reactome R-SCE-202442 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-SCE-202442.1 ACTIVATION GENE ONTOLOGY GO:0004674 Reactome Database ID Release 78 10757999 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757999 Reactome Database ID Release 78 10758001 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10758001 Reactome R-SCE-202222 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-SCE-202222.1 Raft localized PKC theta is further phosphorylated and activated by PDK1. The threonine residue (T538) in the kinase domain is the potential target of PDK1. Phosphorylation of this site is critical for the PKC theta kinase activity, and its ability to activate NF-kB pathway. PKC theta is later trans-autophopshorylated on putative phosphorylation sites (S676, S695) for the fine-tuning of its kinase activity. Reactome Database ID Release 78 10780294 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10780294 Reactome R-SCE-202424 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-SCE-202424.1 Changes in gene expression are required for the T cell to gain full proliferative competence and to produce effector cytokines. Three transcription factors in particular have been found to play a key role in TCR-stimulated changes in gene expression, namely NFkappaB, NFAT and AP-1. A key step in NFkappaB activation is the stimulation and translocation of PRKCQ. The critical element that effects PRKCQ activation is PI3K. PI3K translocates to the plasma membrane by interacting with phospho-tyrosines on CD28 via its two SH2 domains located in p85 subunit (step 24). The p110 subunit of PI3K phosphorylates the inositol ring of PIP2 to generate PIP3 (steps 25). The reverse dephosphorylation process from PIP3 to PIP2 is catalysed by PTEN (step 27). PIP3 may also be dephosphorylated by the phosphatase SHIP to generate PI-3,4-P2 (step 26). PIP3 and PI-3,4-P2 acts as binding sites to the PH domain of PDK1 (step 28) and AKT (step 29). PKB is activated in response to PI3K stimulation by PDK1 (step 30). PDK1 has an essential role in regulating the activation of PRKCQ and recruitment of CBM complex to the immune synapse. PRKCQ is a member of novel class (DAG dependent, Ca++ independent) of PKC and the only member known to translocate to this synapse. Prior to TCR stimulation PRKCQ exists in an inactive closed conformation. TCR signals stimulate PRKCQ (step 31) and release DAG molecules. Subsequently, DAG binds to PRKCQ via the C1 domain and undergoes phosphorylation on tyrosine 90 by LCK to attain an open conformation (step 32). PRKCQ is further phosphorylated by PDK1 on threonine 538 (step 33). This step is critical for PKC activity. CARMA1 translocates to the plasma membrane following the interaction of its SH3 domain with the 'PxxP' motif on PDK1 (step 34). CARMA1 is phosphorylated by PKC-theta on residue S552 (step 35), leading to the oligomerization of CARMA1. This complex acts as a scaffold, recruiting BCL10 to the synapse by interacting with their CARD domains (step 36). BCL10 undergoes phosphorylation mediated by the enzyme RIP2 (step 37). Activated BCL10 then mediates the ubiquitination of IKBKG by recruiting MALT1 and TRAF6. MALT1 binds to BCL10 with its Ig-like domains and undergoes oligomerization (step 38). TRAF6 binds to the oligomerized MALT1 and also undergoes oligomerization (step 39). Oligomerized TRAF6 acts as a ubiquitin-protein ligase, catalyzing auto-K63-linked polyubiquitination (step 40). This K-63 ubiquitinated TRAF6 activates MAP3K7 kinase bound to TAB2 (step 41) and also ubiquitinates IKBKG in the IKK complex (step 44). MAP3K7 undergoes autophosphorylation on residues T184 and T187 and gets activated (step 42). Activated MAP3K7 kinase phosphorylates IKBKB on residues S177 and S181 in the activation loop and activates the IKK kinase activity (step 43). IKBKB phosphorylates the NFKBIA bound to the NFkappaB heterodimer, on residues S19 and S23 (step 45) and directs NFKBIA to 26S proteasome degradation (step 47). The NFkappaB heterodimer with a free NTS sequence finally migrates to the nucleus to regulate gene transcription (step 46). 15084594 Pubmed 2004 T cell receptor signaling: beyond complex complexes Huang, Y Wange, RL J Biol Chem 279:28827-30 Reactome Database ID Release 78 10780296 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10780296 Reactome R-SCE-202403 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-SCE-202403.1 GENE ONTOLOGY GO:0050852 The TCR is a multisubunit complex that consists of clonotypic alpha/beta chains noncovalently associated with the invariant CD3 delta/epsilon/gamma and TCR zeta chains. T cell activation by antigen presenting cells (APCs) results in the activation of protein tyrosine kinases (PTKs) that associate with CD3 and TCR zeta subunits and the co-receptor CD4. Members of the Src kinases (Lck), Syk kinases (ZAP-70), Tec (Itk) and Csk families of nonreceptor PTKs play a crucial role in T cell activation. Activation of PTKs following TCR engagement results in the recruitment and tyrosine phosphorylation of enzymes such as phospholipase C gamma1 and Vav as well as critical adaptor proteins such as LAT, SLP-76 and Gads. These proximal activation leads to reorganization of the cytoskeleton as well as transcription activation of multiple genes leading to T lymphocyte proliferation, differentiation and/or effector function. 9989491 Pubmed 1999 Adaptors and molecular scaffolds in immune cell signaling Rudd, CE Cell 96:5-8 10375551 Pubmed 1999 T cell antigen-receptor signal transduction van Leeuwen, JE Samelson, LE Curr Opin Immunol 11:242-8 12876557 Pubmed 2003 Unifying concepts in CD28, ICOS and CTLA4 co-receptor signalling Rudd, CE Schneider, H Nat Rev Immunol 3:544-56 Costimulation by the CD28 family 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> CD28 co-stimulation 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> CD28 dependent PI3K/Akt signaling 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> LEFT-TO-RIGHT PIP3 recruits PDPK1 to the membrane 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> PDPK1:PIP3 Reactome DB_ID: 10754837 1 1 Reactome Database ID Release 78 10754837 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10754837 Reactome R-SCE-109697 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-SCE-109697.1 Reactome Database ID Release 78 10764592 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10764592 Reactome R-SCE-2316429 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-SCE-2316429.1 PIP3 generated by PI3K recruits phosphatidylinositide-dependent protein kinase 1 (PDPK1 i.e. PDK1) to the membrane, through its PH (pleckstrin-homology) domain. PDPK1 binds PIP3 with high affinity, and also shows low affinity for PIP2 (Currie et al. 1999). 9895304 Pubmed 1999 Role of phosphatidylinositol 3,4,5-trisphosphate in regulating the activity and localization of 3-phosphoinositide-dependent protein kinase-1 Currie, RA Walker, KS Gray, A Deak, M Casamayor, A Downes, CP Cohen, P Alessi, DR Lucocq, J Biochem J 337:575-83 LEFT-TO-RIGHT PIP3 recruits AKT to the membrane 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> Converted from EntitySet in Reactome AKT Reactome DB_ID: 10759400 Converted from EntitySet in Reactome Homologues of AKT1 Reactome DB_ID: 10759392 SCH9 AKT1 P11792 Reactome DB_ID: 10759388 UniProt:P11792 SCH9 UniProt P11792 1 EQUAL 480 EQUAL Reactome Database ID Release 78 10759388 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759388 Reactome R-SCE-58252 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-SCE-58252.1 YPK1 AKT1 P12688 Reactome DB_ID: 10759390 UniProt:P12688 YPK1 UniProt P12688 1 EQUAL 480 EQUAL Reactome Database ID Release 78 10759390 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759390 Reactome R-SCE-58252-2 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-SCE-58252-2.1 Reactome Database ID Release 78 10759392 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759392 Reactome R-SCE-58252-3 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-SCE-58252-3.1 Converted from EntitySet in Reactome Homologues of AKT3 Reactome DB_ID: 10759398 SCH9 AKT3 P11792 Reactome DB_ID: 10759394 1 EQUAL 479 EQUAL Reactome Database ID Release 78 10759394 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759394 Reactome R-SCE-2976007 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-SCE-2976007.1 YPK1 AKT3 P12688 Reactome DB_ID: 10759396 1 EQUAL 479 EQUAL Reactome Database ID Release 78 10759396 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759396 Reactome R-SCE-2976007-2 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-SCE-2976007-2.1 Reactome Database ID Release 78 10759398 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759398 Reactome R-SCE-2976007-3 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-SCE-2976007-3.1 Converted from EntitySet in Reactome Homologues of AKT2 Reactome DB_ID: 10754851 SCH9 AKT2 P11792 Reactome DB_ID: 10754844 1 EQUAL 481 EQUAL Reactome Database ID Release 78 10754844 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10754844 Reactome R-SCE-49859 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-SCE-49859.1 YPK1 AKT2 P12688 Reactome DB_ID: 10754849 1 EQUAL 481 EQUAL Reactome Database ID Release 78 10754849 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10754849 Reactome R-SCE-49859-2 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-SCE-49859-2.1 Reactome Database ID Release 78 10754851 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10754851 Reactome R-SCE-49859-3 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-SCE-49859-3.1 Reactome Database ID Release 78 10759400 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759400 Reactome R-SCE-202088 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-SCE-202088.1 AKT:PIP3 Reactome DB_ID: 10757502 1 Converted from EntitySet in Reactome AKT Reactome DB_ID: 10757500 Converted from EntitySet in Reactome Homologues of AKT1 Reactome DB_ID: 10757486 SCH9 AKT1 P11792 Reactome DB_ID: 10757482 1 EQUAL 480 EQUAL Reactome Database ID Release 78 10757482 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757482 Reactome R-SCE-199416 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-SCE-199416.1 YPK1 AKT1 P12688 Reactome DB_ID: 10757484 1 EQUAL 480 EQUAL Reactome Database ID Release 78 10757484 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757484 Reactome R-SCE-199416-2 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-SCE-199416-2.1 Reactome Database ID Release 78 10757486 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757486 Reactome R-SCE-199416-3 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-SCE-199416-3.1 Converted from EntitySet in Reactome Homologues of AKT2 Reactome DB_ID: 10757492 SCH9 AKT2 P11792 Reactome DB_ID: 10757488 1 EQUAL 481 EQUAL Reactome Database ID Release 78 10757488 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757488 Reactome R-SCE-202053 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-SCE-202053.1 YPK1 AKT2 P12688 Reactome DB_ID: 10757490 1 EQUAL 481 EQUAL Reactome Database ID Release 78 10757490 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757490 Reactome R-SCE-202053-2 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-SCE-202053-2.1 Reactome Database ID Release 78 10757492 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757492 Reactome R-SCE-202053-3 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-SCE-202053-3.1 Converted from EntitySet in Reactome Homologues of AKT3 Reactome DB_ID: 10757498 SCH9 AKT3 P11792 Reactome DB_ID: 10757494 1 EQUAL 479 EQUAL Reactome Database ID Release 78 10757494 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757494 Reactome R-SCE-2976006 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-SCE-2976006.1 YPK1 AKT3 P12688 Reactome DB_ID: 10757496 1 EQUAL 479 EQUAL Reactome Database ID Release 78 10757496 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757496 Reactome R-SCE-2976006-2 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-SCE-2976006-2.1 Reactome Database ID Release 78 10757498 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757498 Reactome R-SCE-2976006-3 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-SCE-2976006-3.1 Reactome Database ID Release 78 10757500 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757500 Reactome R-SCE-202052 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-SCE-202052.1 1 Reactome Database ID Release 78 10757502 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757502 Reactome R-SCE-2317329 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-SCE-2317329.1 Reactome Database ID Release 78 10764596 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10764596 Reactome R-SCE-2317332 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-SCE-2317332.1 GENE ONTOLOGY GO:0032148 PIP3 generated by PI3K recruits AKT (also known as protein kinase B) to the membrane, through its PH (pleckstrin-homology) domains. The binding of PIP3 to the PH domain of AKT is the rate-limiting step in AKT activation (Scheid et al. 2002). In mammals there are three AKT isoforms (AKT1-3) encoded by three separate genes. The three isoforms share a high degree of amino acid identity and have indistinguishable substrate specificity in vitro. However, isoform-preferred substrates in vivo cannot be ruled out. The relative expression of the three isoforms differs in different mammalian tissues: AKT1 is the predominant isoform in the majority of tissues, AKT2 is the predominant isoform in insulin-responsive tissues, and AKT3 is the predominant isoform in brain and testes. All 3 isoforms are expressed in human and mouse platelets (Yin et al. 2008; O'Brien et al. 2008). Note: all data in the pathway refer to AKT1, which is the most studied. 12167717 Pubmed 2002 Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B Scheid, MP Marignani, PA Woodgett, JR Mol Cell Biol 22:6247-60 2008 The role of Akt3 in Platelet Activation O'Brien, K Stojanovic, A Hay, N Du, X Arteriosclerosis, Thrombosis, and Vascular Biology 28:e162 17914025 Pubmed 2008 The role of Akt in the signaling pathway of the glycoprotein Ib-IX induced platelet activation Yin, H Stojanovic, A Hay, N Du, X Blood 111:658-65 LEFT-TO-RIGHT 2.7.11 TORC2 (mTOR) phosphorylates AKT at S473 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> p-S-AKT:PIP3 Reactome DB_ID: 10757405 Converted from EntitySet in Reactome p-S-AKT Reactome DB_ID: 10757403 Converted from EntitySet in Reactome Homologues of p-S473-AKT1 Reactome DB_ID: 10757387 P11792 phospho-SCH9 p-S473-AKT1 Reactome DB_ID: 10757382 473 EQUAL 1 EQUAL 480 EQUAL Reactome Database ID Release 78 10757382 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757382 Reactome R-SCE-377265 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-SCE-377265.1 P12688 phospho-YPK1 p-S473-AKT1 Reactome DB_ID: 10757385 473 EQUAL 1 EQUAL 480 EQUAL Reactome Database ID Release 78 10757385 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757385 Reactome R-SCE-377265-2 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-SCE-377265-2.1 Reactome Database ID Release 78 10757387 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757387 Reactome R-SCE-377265-3 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-SCE-377265-3.1 Converted from EntitySet in Reactome Homologues of p-S474-AKT2 Reactome DB_ID: 10757393 P11792 phospho-SCH9 p-S474-AKT2 Reactome DB_ID: 10757389 474 EQUAL 1 EQUAL 481 EQUAL Reactome Database ID Release 78 10757389 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757389 Reactome R-SCE-2317312 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-SCE-2317312.1 P12688 phospho-YPK1 p-S474-AKT2 Reactome DB_ID: 10757391 474 EQUAL 1 EQUAL 481 EQUAL Reactome Database ID Release 78 10757391 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757391 Reactome R-SCE-2317312-2 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-SCE-2317312-2.1 Reactome Database ID Release 78 10757393 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757393 Reactome R-SCE-2317312-3 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-SCE-2317312-3.1 Converted from EntitySet in Reactome Homologues of p-S472-AKT3 Reactome DB_ID: 10757401 P11792 phospho-SCH9 p-S472-AKT3 Reactome DB_ID: 10757396 472 EQUAL 1 EQUAL 479 EQUAL Reactome Database ID Release 78 10757396 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757396 Reactome R-SCE-3009363 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-SCE-3009363.1 P12688 phospho-YPK1 p-S472-AKT3 Reactome DB_ID: 10757399 472 EQUAL 1 EQUAL 479 EQUAL Reactome Database ID Release 78 10757399 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757399 Reactome R-SCE-3009363-2 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-SCE-3009363-2.1 Reactome Database ID Release 78 10757401 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757401 Reactome R-SCE-3009363-3 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-SCE-3009363-3.1 Reactome Database ID Release 78 10757403 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757403 Reactome R-SCE-2317317 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-SCE-2317317.1 1 1 Reactome Database ID Release 78 10757405 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757405 Reactome R-SCE-2317310 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-SCE-2317310.1 ACTIVATION activeUnit: #Protein39 TORC2 complex Reactome DB_ID: 10757536 Converted from EntitySet in Reactome Homologues of PRR5 Reactome DB_ID: 10757534 BIT2 PRR5 P38346 Reactome DB_ID: 10757527 UniProt:P38346 BIT2 UniProt P38346 1 EQUAL 388 EQUAL Reactome Database ID Release 78 10757527 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757527 Reactome R-SCE-6795323 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-SCE-6795323.1 PRR5 BIT61 P47041 Reactome DB_ID: 10757532 UniProt:P47041 BIT61 UniProt P47041 1 EQUAL 388 EQUAL Reactome Database ID Release 78 10757532 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757532 Reactome R-SCE-6795323-2 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-SCE-6795323-2.1 Reactome Database ID Release 78 10757534 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757534 Reactome R-SCE-6795323-3 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-SCE-6795323-3.1 1 AVO1 MAPKAP1 Q08236 Reactome DB_ID: 10757522 UniProt:Q08236 AVO1 UniProt Q08236 2 EQUAL 522 EQUAL Reactome Database ID Release 78 10757522 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757522 Reactome R-SCE-3006620 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-SCE-3006620.1 1 TOR2 MTOR P32600 Reactome DB_ID: 10757517 UniProt:P32600 TOR2 UniProt P32600 1 EQUAL 2549 EQUAL Reactome Database ID Release 78 10757517 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757517 Reactome R-SCE-165662 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-SCE-165662.1 1 LST8 MLST8 P41318 Reactome DB_ID: 10757512 UniProt:P41318 LST8 UniProt P41318 1 EQUAL 326 EQUAL Reactome Database ID Release 78 10757512 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757512 Reactome R-SCE-165676 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-SCE-165676.1 1 TSC11 RICTOR P40061 Reactome DB_ID: 10757507 UniProt:P40061 TSC11 UniProt P40061 1 EQUAL 1708 EQUAL Reactome Database ID Release 78 10757507 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757507 Reactome R-SCE-198632 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-SCE-198632.1 1 Reactome Database ID Release 78 10757536 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757536 Reactome R-SCE-198626 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-SCE-198626.1 Reactome Database ID Release 78 10757537 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757537 Reactome Database ID Release 78 10757539 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757539 Reactome R-SCE-198640 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-SCE-198640.1 Under conditions of growth and mitogen stimulation S473 phosphorylation of AKT is carried out by mTOR (mammalian Target of Rapamycin). This kinase is found in two structurally and functionally distinct protein complexes, named TOR complex 1 (TORC1) and TOR complex 2 (TORC2). It is TORC2 complex, which is composed of mTOR, RICTOR, SIN1 (also named MAPKAP1) and LST8, that phosphorylates AKT at S473 (Sarbassov et al., 2005). This complex also regulates actin cytoskeletal reorganization (Jacinto et al., 2004; Sarbassov et al., 2004). TORC1, on the other hand, is a major regulator of ribosomal biogenesis and protein synthesis (Hay and Sonenberg, 2004). TORC1 regulates these processes largely by the phosphorylation/inactivation of the repressors of mRNA translation 4E binding proteins (4E BPs) and by the phosphorylation/activation of ribosomal S6 kinase (S6K1). TORC1 is also the principal regulator of autophagy. In other physiological conditions, other kinases may be responsible for AKT S473 phosphorylation.<br> Phosphorylation of AKT on S473 by TORC2 complex is a prerequisite for AKT phosphorylation on T308 by PDPK1 (Scheid et al. 2002, Sarabassov et al. 2005). 15718470 Pubmed 2005 Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex Sarbassov, DD Guertin, DA Ali, SM Sabatini, DM Science 307:1098-101 19303758 Pubmed 2009 PIKKing on PKB: regulation of PKB activity by phosphorylation Bozulic, L Hemmings, BA Curr Opin Cell Biol 21:256-61 15314020 Pubmed 2004 Upstream and downstream of mTOR Hay, N Sonenberg, Nahum Genes Dev 18:1926-45 15268862 Pubmed 2004 Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton Sarbassov, DD Ali, SM Kim, DH Guertin, DA Latek, RR Erdjument-Bromage, H Tempst, P Sabatini, DM Curr Biol 14:1296-302 15467718 Pubmed 2004 Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive Jacinto, E Loewith, R Schmidt, A Lin, S Ruegg, MA Hall, A Hall, MN Nat Cell Biol 6:1122-8 LEFT-TO-RIGHT AKT binds PDPK1 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> p-S-AKT:PDPK1:PIP3 Reactome DB_ID: 10757407 1 1 Reactome Database ID Release 78 10757407 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757407 Reactome R-SCE-2317313 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-SCE-2317313.1 Reactome Database ID Release 78 10764594 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10764594 Reactome R-SCE-2317314 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-SCE-2317314.1 Once phosphorylated on serine residue S473, AKT bound to PIP3 forms a complex with PIP3-bound PDPK1 i.e. PDK1 (Scheid et al. 2002, Sarabassov et al. 2005) LEFT-TO-RIGHT 2.7.11 PDPK1 phosphorylates AKT at T308 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> Converted from EntitySet in Reactome Active AKT p-T,p-S-AKT Reactome DB_ID: 10757425 Converted from EntitySet in Reactome Homologues of p-T308,S473-AKT1 Reactome DB_ID: 10757415 P11792 phospho-SCH9 p-T308,S473-AKT1 Reactome DB_ID: 10757410 308 EQUAL 1 EQUAL 480 EQUAL Reactome Database ID Release 78 10757410 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757410 Reactome R-SCE-198356 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-SCE-198356.1 P12688 phospho-YPK1 p-T308,S473-AKT1 Reactome DB_ID: 10757413 308 EQUAL 1 EQUAL 480 EQUAL Reactome Database ID Release 78 10757413 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757413 Reactome R-SCE-198356-2 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-SCE-198356-2.1 Reactome Database ID Release 78 10757415 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757415 Reactome R-SCE-198356-3 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-SCE-198356-3.1 Converted from EntitySet in Reactome Homologues of p-T309,S474-AKT2 Reactome DB_ID: 10754863 P11792 phospho-SCH9 p-T309,S474-AKT2 Reactome DB_ID: 10754857 309 EQUAL 1 EQUAL 481 EQUAL Reactome Database ID Release 78 10754857 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10754857 Reactome R-SCE-166800 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-SCE-166800.1 P12688 phospho-YPK1 p-T309,S474-AKT2 Reactome DB_ID: 10754861 309 EQUAL 1 EQUAL 481 EQUAL Reactome Database ID Release 78 10754861 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10754861 Reactome R-SCE-166800-2 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-SCE-166800-2.1 Reactome Database ID Release 78 10754863 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10754863 Reactome R-SCE-166800-3 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-SCE-166800-3.1 Converted from EntitySet in Reactome Homologues of p-T305,S472-AKT3 Reactome DB_ID: 10757423 P11792 phospho-SCH9 p-T305,S472-AKT3 Reactome DB_ID: 10757418 305 EQUAL 1 EQUAL 479 EQUAL Reactome Database ID Release 78 10757418 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757418 Reactome R-SCE-3009367 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-SCE-3009367.1 P12688 phospho-YPK1 p-T305,S472-AKT3 Reactome DB_ID: 10757421 305 EQUAL 1 EQUAL 479 EQUAL Reactome Database ID Release 78 10757421 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757421 Reactome R-SCE-3009367-2 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-SCE-3009367-2.1 Reactome Database ID Release 78 10757423 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757423 Reactome R-SCE-3009367-3 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-SCE-3009367-3.1 Reactome Database ID Release 78 10757425 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757425 Reactome R-SCE-202074 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-SCE-202074.1 ACTIVATION activeUnit: #Protein3 Reactome Database ID Release 78 10757426 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757426 Reactome Database ID Release 78 10757428 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757428 Reactome R-SCE-198270 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-SCE-198270.1 Once AKT is localized at the plasma membrane, it is phosphorylated at two critical residues for its full activation. These residues are a threonine (T308 in AKT1) in the activation loop within the catalytic domain, and a serine (S473 in AKT1), in a hydrophobic motif (HM) within the carboxy terminal, non-catalytic region. PDPK1 (PDK1) is the activation loop kinase; this kinase can also directly phosphorylate p70S6K. The HM kinase, previously termed PDK2, has been identified as the mammalian TOR (Target Of Rapamycin; Sarbassov et al., 2005) but several other kinases are also able to phosphorylate AKT at S473. Phosphorylation of AKT at S473 by TORC2 complex is a prerequisite for PDPK1-mediated phosphorylation of AKT threonine T308 (Scheid et al. 2002, Sarabassov et al. 2005). 7637810 Pubmed 1995 Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction Burgering, BM Coffer, PJ Nature 376:599-602 9736715 Pubmed 1998 Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase Delcommenne, M Tan, C Gray, V Rue, L Woodgett, J Dedhar, S Proc Natl Acad Sci U S A 95:11211-6 LEFT-TO-RIGHT 2.7.11 AKT interacts and phosphorylates Cot 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> Converted from EntitySet in Reactome Homologues of MAP3K8 Reactome DB_ID: 10759275 SSK22 MAP3K8 P25390 Reactome DB_ID: 10759268 UniProt:P25390 SSK22 UniProt P25390 1 EQUAL 467 EQUAL Reactome Database ID Release 78 10759268 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759268 Reactome R-SCE-389388 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-SCE-389388.1 SSK2 MAP3K8 P53599 Reactome DB_ID: 10759273 UniProt:P53599 SSK2 UniProt P53599 1 EQUAL 467 EQUAL Reactome Database ID Release 78 10759273 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759273 Reactome R-SCE-389388-2 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-SCE-389388-2.1 Reactome Database ID Release 78 10759275 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759275 Reactome R-SCE-389388-3 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-SCE-389388-3.1 Converted from EntitySet in Reactome Homologues of p-S400-MAP3K8 Reactome DB_ID: 10759283 P25390 phospho-SSK22 p-S400-MAP3K8 Reactome DB_ID: 10759278 400 EQUAL 1 EQUAL 467 EQUAL Reactome Database ID Release 78 10759278 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759278 Reactome R-SCE-389738 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-SCE-389738.1 P53599 phospho-SSK2 p-S400-MAP3K8 Reactome DB_ID: 10759281 400 EQUAL 1 EQUAL 467 EQUAL Reactome Database ID Release 78 10759281 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759281 Reactome R-SCE-389738-2 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-SCE-389738-2.1 Reactome Database ID Release 78 10759283 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759283 Reactome R-SCE-389738-3 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-SCE-389738-3.1 ACTIVATION activeUnit: #PhysicalEntity4 Reactome Database ID Release 78 10757478 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10757478 Reactome Database ID Release 78 10759285 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759285 Reactome R-SCE-389756 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-SCE-389756.1 Cot/Tpl 2 is a serine/threonine kinase of the mitogen activated protein kinase kinase kinase (MAP3K) family. Cot is observed as one of the downstream effectors of Akt. Based on in-vitro kinase assays and following overexpression in cell lines its been showed that AKT can phosphorylate Cot under non-physiological conditions. Akt and Cot physically interact through the amino terminus of Cot, and this interaction results in the phosphorylation of Cot on serine 400. Cot was shown to activate the IkB kinase (IKK) complex, possibly acting through NF kB inducing kinase (NIK). 12138205 Pubmed 2002 Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription Kane, LP Mollenauer, MN Xu, Z Turck, CW Weiss, A Mol Cell Biol 22:5962-74 LEFT-TO-RIGHT 2.7.11.25 p-S400-Cot phosphorylates NIK 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> SSK22 MAP3K14 P25390 Reactome DB_ID: 10759458 1 EQUAL 947 EQUAL Reactome Database ID Release 78 10759458 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759458 Reactome R-SCE-168189 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-SCE-168189.1 P25390 phospho-SSK22 p-MAP3K14 Reactome DB_ID: 10759461 phosphorylated residue MOD MOD:00696 1 EQUAL 947 EQUAL Reactome Database ID Release 78 10759461 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759461 Reactome R-SCE-168187 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-SCE-168187.1 ACTIVATION activeUnit: #Protein51 GENE ONTOLOGY GO:0004709 Reactome Database ID Release 78 10759462 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759462 Reactome Database ID Release 78 10759464 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759464 Reactome R-SCE-392530 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-SCE-392530.1 Cot functions upstream of NIK in the CD28-costimulation signaling pathway leading to activation of NF-kB. Cot binds avidly to NIK and induces NIK phosphorylation in vivo. 18439422 Pubmed 2008 NIK and Cot cooperate to trigger NF-kappaB p65 phosphorylation Wittwer, T Schmitz, ML Biochem Biophys Res Commun 371:294-7 Reactome Database ID Release 78 10780254 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10780254 Reactome R-SCE-389357 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-SCE-389357.1 PI3Ks can be activated by a number of different receptors, including the TcR (T cell receptor), co-stimulatory receptors (CD28), cytokine receptors and chemokine receptors. However, the specific roles of PI3Ks downstream of these receptors vary. CD28 contains the YMNM consensus PI3K-binding motif, and PI3K recruitment by CD28 contributes to or complements TCR-dependent PI3K signaling. Activation of PI3K promotes PIP3 production at the plasma membrane and several potential target molecules for this phospholipid have been implicated in PI3K pathways downstream of the TcR and CD28. Of these targets, at least Vav and Akt have been implicated in CD28 costimulation of T cell activation. AKT/PKB connects PI3K to signaling pathways that promote cytokine transcription, survival, cell-cycle entry and growth. 12670391 Pubmed 2003 The PI-3 kinase/Akt pathway and T cell activation: pleiotropic pathways downstream of PIP3 Kane, LP Weiss, A Immunol Rev 192:7-20 15046602 Pubmed 2004 Phosphoinositide 3-kinase in T cell activation and survival Okkenhaug, K Bilancio, A Emery, JL Vanhaesebroeck, B Biochem Soc Trans 32:332-5 CD28 dependent Vav1 pathway 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> LEFT-TO-RIGHT Activation of PAKs by RAC1 and CDC42 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> Converted from EntitySet in Reactome PAK1,2,3 dimer Reactome DB_ID: 10759314 PAK1 dimer Reactome DB_ID: 10759292 PAK1 STE20 Q03497 Reactome DB_ID: 10759290 UniProt:Q03497 STE20 UniProt Q03497 1 EQUAL 545 EQUAL Reactome Database ID Release 78 10759290 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759290 Reactome R-SCE-162629 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-SCE-162629.1 2 Reactome Database ID Release 78 10759292 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759292 Reactome R-SCE-445002 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-SCE-445002.1 PAK2 dimer Reactome DB_ID: 10759308 Converted from EntitySet in Reactome Homologues of PAK2 Reactome DB_ID: 10759306 CLA4 PAK2 P48562 Reactome DB_ID: 10759297 UniProt:P48562 CLA4 UniProt P48562 2 EQUAL 524 EQUAL Reactome Database ID Release 78 10759297 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759297 Reactome R-SCE-211604 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-SCE-211604.1 PAK2 STE20 Q03497 Reactome DB_ID: 10759299 2 EQUAL 524 EQUAL Reactome Database ID Release 78 10759299 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759299 Reactome R-SCE-211604-2 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-SCE-211604-2.1 SKM1 PAK2 Q12469 Reactome DB_ID: 10759304 UniProt:Q12469 SKM1 UniProt Q12469 2 EQUAL 524 EQUAL Reactome Database ID Release 78 10759304 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759304 Reactome R-SCE-211604-3 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-SCE-211604-3.1 Reactome Database ID Release 78 10759306 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759306 Reactome R-SCE-211604-4 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-SCE-211604-4.1 2 Reactome Database ID Release 78 10759308 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759308 Reactome R-SCE-2685645 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-SCE-2685645.1 PAK3 dimer Reactome DB_ID: 10759312 PAK3 STE20 Q03497 Reactome DB_ID: 10759310 1 EQUAL 559 EQUAL Reactome Database ID Release 78 10759310 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759310 Reactome R-SCE-428457 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-SCE-428457.1 2 Reactome Database ID Release 78 10759312 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759312 Reactome R-SCE-5669154 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-SCE-5669154.1 Reactome Database ID Release 78 10759314 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759314 Reactome R-SCE-399856 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-SCE-399856.1 CDC42:GTP Reactome DB_ID: 10759214 GTP Guanosine 5'-triphosphate GTP)(4-) Reactome DB_ID: 29438 GTP(4-) [ChEBI:37565] GTP(4-) GTP gtp guanosine 5'-triphosphate(4-) ChEBI CHEBI:37565 Reactome Database ID Release 78 29438 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29438 Reactome R-ALL-29438 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-29438.4 COMPOUND C00044 1 CDC42 CDC42 P19073 Reactome DB_ID: 10759212 UniProt:P19073 CDC42 UniProt P19073 1 EQUAL 188 EQUAL Reactome Database ID Release 78 10759212 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759212 Reactome R-SCE-449545 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-SCE-449545.1 1 Reactome Database ID Release 78 10759214 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759214 Reactome R-SCE-182921 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-SCE-182921.1 Converted from EntitySet in Reactome PAK1,2,3 Reactome DB_ID: 10759316 Reactome Database ID Release 78 10759316 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759316 Reactome R-SCE-390765 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-SCE-390765.1 PAK1,2,3:CDC42:GTP, RAC1:GTP Reactome DB_ID: 10759318 1 1 Reactome Database ID Release 78 10759318 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759318 Reactome R-SCE-389782 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-SCE-389782.1 Reactome Database ID Release 78 10759320 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10759320 Reactome R-SCE-389788 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-SCE-389788.1 Inactive p21-associated kinases (PAKs), PAK1, PAK2 and PAK3, form homodimers that are autoinhibited through in trans interaction between the inhibitory N-terminus of one PAK molecule and the catalytic domain of the other PAK molecule. All PAK isoforms are direct effectors of RAC1 and CDC42 GTPases. RAC1 and CDC42 bind to a highly conserved motif in the amino terminus of PAK known as p21-binding domain (PBD) or Cdc42/Rac interactive binding (CRIB) domain. This binding induces a conformational change that disrupts PAK homodimers and relieves autoinhibition of the catalytic carboxyl terminal domain, thereby inducing autophosphorylation at several sites and enabling the phosphorylation of exogenous substrates (Manser et al. 1994, Manser et al. 1995, Zhang et al. 1998, Lei et al. 2000, Parrini et al. 2002; reviewed by Daniels and Bokoch 1999, Szczepanowska 2009). 9535855 Pubmed 1998 Interaction of Rac1 with GTPase-activating proteins and putative effectors. A comparison with Cdc42 and RhoA Zhang, B Chernoff, J Zheng, Y J. Biol. Chem. 273:8776-82 19513348 Pubmed 2009 Involvement of Rac/Cdc42/PAK pathway in cytoskeletal rearrangements Szczepanowska, J Acta Biochim Pol 56:225-34 10470034 Pubmed 1999 p21-activated protein kinase: a crucial component of morphological signaling? Daniels, RH Bokoch, GM Trends Biochem Sci 24:350-5 10975528 Pubmed 2000 Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch Lei, M Lu, W Meng, W Parrini, M C Eck, M J Mayer, B J Harrison, S C Cell 102:387-97 11804587 Pubmed 2002 Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1 Parrini, MC Lei, M Harrison, SC Mayer, BJ Mol Cell 9:73-83 8107774 Pubmed 1994 A brain serine/threonine protein kinase activated by Cdc42 and Rac1 Manser, E Leung, T Salihuddin, H Zhao, ZS Lim, L Nature 367:40-6 7559638 Pubmed 1995 Molecular cloning of a new member of the p21-Cdc42/Rac-activated kinase (PAK) family Manser, E Chong, C Zhao, Z S Leung, T Michael, G Hall, C Lim, L J. Biol. Chem. 270:25070-8 Reactome Database ID Release 78 10780424 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10780424 Reactome R-SCE-389359 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-SCE-389359.1 CD28 binds to several intracellular proteins including PI3 kinase, Grb-2, Gads and ITK. Grb-2 specifically co-operates with Vav-1 in the up-regulation of NFAT/AP-1 transcription. CD28 costimulation resulted in a prolonged and sustained phosphorylation and membrane localization of Vav1 in comparison to T-cell receptor activation alone. Tyrosine-phosphorylated Vav1 is an early point of integration between the signaling routes triggered by the T-cell receptor and CD28.<br>Vav1 transduces TCR and co-stimulatory signals to multiple biochemical pathways and several cytoskeleton-dependent processes. The products of Vav1 activation, Rac1 and Cdc42, in turn activate the mitogen-activated protein kinases JNK and p38. Vav1 is also required for TCR-induced calcium flux, activation of the ERK MAP kinase pathway, activation of the NF-kB transcription factor, inside-out activation of the integrin LFA-1, TCR clustering, and polarisation of the T cell. 15886116 Pubmed 2005 Vav-family proteins in T-cell signalling Tybulewicz, VL Curr Opin Immunol 17:267-74 12670394 Pubmed 2003 Vav1: a key signal transducer downstream of the TCR Tybulewicz, VL Ardouin, L Prisco, A Reynolds, LF Immunol Rev 192:42-52 10849438 Pubmed 2000 Tyrosine-phosphorylated Vav1 as a point of integration for T-cell receptor- and CD28-mediated activation of JNK, p38, and interleukin-2 transcription Hehner, SP Hofmann, TG Dienz, O Droge, W Schmitz, ML J Biol Chem 275:18160-71 Reactome Database ID Release 78 10780256 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10780256 Reactome R-SCE-389356 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-SCE-389356.1 GENE ONTOLOGY GO:0031295 In naive T cells, CD28 costimulation enhances cell cycle entry, potently stimulates expression of both the mitogenic lymphokine interleukin-2 (IL-2) and its receptor, and stimulates the activation of an antiapoptotic program. CD28 engages with one or both members of the B7 receptor family, B7.1 and B7.2. Upon ligand binding the tyrosines and proline-rich motifs present in the cytoplasmic tail of CD28 are phosphorylated by Lck or Fyn. Upon phosphorylation CD28 recruits and induces phosphorylation and activation of a more restricted set of intracellular signaling components that, together with those mobilized by the TCR, contribute to convert membrane-based biochemical and biophysical changes into gene activation events. Proteins like PI3K, Vav-1, Tec and Itk kinases, AKT, and the Dok-1 adaptor have been identified as elements of the CD28 signaling pathway by biochemical or genetic approaches or both. 12165654 Pubmed 2002 CD28 costimulation: a source of Vav-1 for TCR signaling with the help of SLP-76? Michel, F Acuto, O Sci STKE 2002:PE35 8609386 Pubmed 1996 Interactions of CD80 and CD86 with CD28 and CTLA4 Ellis, JH Burden, MN Vinogradov, DV Linge, C Crowe, JS J Immunol 156:2700-9 8649453 Pubmed 1996 Differential recognition by CD28 of its cognate counter receptors CD80 (B7.1) and B70 (B7.2): analysis by site directed mutagenesis Truneh, A Reddy, M Ryan, P Lyn, SD Eichman, C Couez, D Hurle, MR Sekaly, RP Olive, D Sweet, R Mol Immunol 33:321-34 Reactome Database ID Release 78 10780258 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10780258 Reactome R-SCE-388841 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-SCE-388841.1 Optimal activation of T-lymphocytes requires at least two signals. A primary one is delivered by the T-cell receptor (TCR) complex after antigen recognition and additional costimulatory signals are delivered by the engagement of costimulatory receptors such as CD28. The best-characterized costimulatory pathways are mediated by a set of cosignaling molecules belonging to the CD28 superfamily, including CD28, CTLA4, ICOS, PD1 and BTLA receptors. These proteins deliver both positive and negative second signals to T-cells by interacting with B7 family ligands expressed on antigen presenting cells. Different subsets of T-cells have very different requirements for costimulation. CD28 family mediated costimulation is not required for all T-cell responses in vivo, and alternative costimulatory pathways also exist. Different receptors of the CD28 family and their ligands have different regulation of expression. CD28 is constitutively expressed on naive T cells whereas CTLA4 expression is dependent on CD28/B7 engagement and the other receptor members ICOS, PD1 and BTLA are induced after initial T-cell stimulation. <br>The positive signals induced by CD28 and ICOS molecules are counterbalanced by other members of the CD28 family, including cytotoxic T-lymphocyte associated antigen (CTLA)4, programmed cell death (PD)1, and B and T lymphocyte attenuator (BTLA), which dampen immune responses. The balance of stimulatory and inhibitory signals is crucial to maximize protective immune responses while maintaining immunological tolerance and preventing autoimmunity. <br>The costimulatory receptors CD28, CTLA4, ICOS and PD1 are composed of single extracellular IgV-like domains, whereas BTLA has one IgC-like domain. Receptors CTLA4, CD28 and ICOS are covalent homodimers, due to an interchain disulphide linkage. The costimulatory ligands B71, B72, B7H2, B7H1 and B7DC, have a membrane proximal IgC-like domain and a membrane distal IgV-like domain that is responsible for receptor binding and dimerization. CD28 and CTLA4 have no known intrinsic enzymatic activity. Instead, engagement by their physiologic ligands B71 and B72 leads to the physical recruitment and activation of downstream T-cell effector molecules. 14647476 Pubmed 2003 CD28-mediated co-stimulation: a quantitative support for TCR signalling Acuto, O Michel, F Nat Rev Immunol 3:939-51 11905831 Pubmed 2001 T-cell regulation by CD28 and CTLA-4 Alegre, ML Frauwirth, KA Thompson, CB Nat Rev Immunol 1:220-8 10374692 Pubmed 1999 CD28/CTLA-4 and CD80/CD86 families: signaling and function Slavik, JM Hutchcroft, JE Bierer, BE Immunol Res 19:1-24 B Cell Activation Signaling by the B Cell Receptor (BCR) 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> Downstream signaling events of B Cell Receptor (BCR) 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> Activation of NF-kappaB in B cells 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> LEFT-TO-RIGHT Protein Kinase C beta (PKC-beta, PRKCB) is activated PRKCB (Protein kinase C beta, PKC-beta) binds diacylglycerol and phosphatidylserine 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> Ca2+ Calcium calcium(2+) Reactome DB_ID: 74016 calcium(2+) [ChEBI:29108] calcium(2+) ChEBI CHEBI:29108 Reactome Database ID Release 78 74016 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=74016 Reactome R-ALL-74016 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-74016.3 COMPOUND C00076 3 PKC1 PRKCB P24583 Reactome DB_ID: 10755564 2 EQUAL 671 EQUAL Reactome Database ID Release 78 10755564 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10755564 Reactome R-SCE-58198 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-SCE-58198.1 DAG 1,2-Diacylglycerol 1,2-diacyl-sn-glycerol Reactome DB_ID: 114519 1,2-diacyl-sn-glycerol [ChEBI:17815] 1,2-diacyl-sn-glycerol ChEBI CHEBI:17815 Reactome Database ID Release 78 114519 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=114519 Reactome R-ALL-114519 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-114519.4 PS Phosphatidylserine phosphatidyl-L-serine 1,2-Diacyl-sn-glycerol 3-phospho-L-serine 3-O-sn-Phosphatidyl-L-serine O3-Phosphatidyl-L-serine Reactome DB_ID: 33625 phosphatidyl-L-serine [ChEBI:18303] phosphatidyl-L-serine phosphatidyl-L-serines ChEBI CHEBI:18303 Reactome Database ID Release 78 33625 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=33625 Reactome R-ALL-33625 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-33625.4 Activated PKC beta Reactome DB_ID: 10755574 Ca2+ Calcium calcium(2+) Reactome DB_ID: 140648 Reactome Database ID Release 78 140648 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=140648 Reactome R-ALL-140648 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-140648.4 COMPOUND C00076 3 1 1 PKC1 PRKCB P24583 Reactome DB_ID: 10755572 2 EQUAL 671 EQUAL Reactome Database ID Release 78 10755572 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10755572 Reactome R-SCE-156467 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-SCE-156467.1 1 Reactome Database ID Release 78 10755574 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10755574 Reactome R-SCE-139829 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-SCE-139829.1 Reactome Database ID Release 78 10762902 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762902 Reactome R-SCE-1168373 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-SCE-1168373.1 Human Protein kinase C beta (PKC-beta) is activated by calcium ions, diacylglycerol, and binds phosphatidylserine (Kochs et al. 1991). Experiments in mice have shown that knocking out PKC-beta causes severe defects in B cells, leading to the conclusion that PKC-beta is the predominant signaling PKC in these cells (Leitges et al. 1996, Su et al. 2002, Saijo et al. 2002). 8387275 Pubmed 1993 Activation of purified human protein kinase C alpha and beta I isoenzymes in vitro by Ca2+, phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate Kochs, G Hummel, R Fiebich, B Sarre, TF Marmé, D Hug, H Biochem J 291:627-33 12070292 Pubmed 2002 Protein kinase C beta controls nuclear factor kappaB activation in B cells through selective regulation of the IkappaB kinase alpha Saijo, K Mecklenbräuker, I Santana, A Leitger, M Schmedt, C Tarakhovsky, A J Exp Med 195:1647-52 12118249 Pubmed 2002 PKC-beta controls I kappa B kinase lipid raft recruitment and activation in response to BCR signaling Su, TT Guo, B Kawakami, Y Sommer, K Chae, K Humphries, LA Kato, RM Kang, S Patrone, L Wall, R Teitell, M Leitges, M Kawakami, T Rawlings, DJ Nat Immunol 3:780-6 8670417 Pubmed 1996 Immunodeficiency in protein kinase cbeta-deficient mice Leitges, M Schmedt, C Guinamard, R Davoust, J Schaal, S Stabel, S Tarakhovsky, A Science 273:788-91 Reactome Database ID Release 78 10780624 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10780624 Reactome R-SCE-1169091 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-SCE-1169091.1 DAG and calcium activate protein kinase C beta (PKC-beta, Kochs et al. 1991) which phosphorylates CARMA1 and other proteins (Sommer et al. 2005). Phosphorylated CARMA1 recruits BCL10 and MALT1 to form the CBM complex (Sommer et al. 2005, Tanner et al. 2007) which, in turn, recruits the kinase TAK1 and the IKK complex (Sommer et al. 2005, Shinohara et al. 2005 using chicken cells). TAK1 phosphorylates the IKK-beta subunit, activating it (Wang et al. 2001). The IKK complex then phosphorylates IkB complexed with NF-kappaB dimers in the cytosol (Zandi et al. 1998, Burke et al. 1999, Heilker et al. 1999), resulting in the degradation of IkB (Miyamoto et al. 1994, Traenckner et al. 1994, Alkalay et al. 1995, DiDonato et al. 1995, Li et al. 1995, Lin et al. 1995, Scherer et al. 1995, Chen et al. 1995). NF-kappaB dimers are thereby released and are translocated to the nucleus where they activate transcription (Baeuerle and Baltimore 1988, Blank et al. 1991, Ghosh et al. 2008, Fagerlund et al. 2008). 16356855 Pubmed 2005 Phosphorylation of the CARMA1 linker controls NF-kappaB activation Sommer, K Guo, B Pomerantz, JL Bandaranayake, AD Moreno-Garcia, ME Ovechkina, YL Rawlings, DJ Immunity 23:561-74 16301747 Pubmed 2005 PKC beta regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1 Shinohara, H Yasuda, T Aiba, Y Sanjo, H Hamadate, M Watarai, H Sakurai, H Kurosaki, T J Exp Med 202:1423-31 7479976 Pubmed 1995 Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination Scherer, DC Brockman, JA Chen, Z Maniatis, T Ballard, DW Proc Natl Acad Sci U S A 92:11259-63 7831327 Pubmed 1995 Activation of NF-kappa B requires proteolysis of the inhibitor I kappa B-alpha: signal-induced phosphorylation of I kappa B-alpha alone does not release active NF-kappa B Lin, YC Brown, K Siebenlist, U Proc Natl Acad Sci U S A 92:552-6 18462924 Pubmed 2008 NF-kappaB p52, RelB and c-Rel are transported into the nucleus via a subset of importin alpha molecules Fagerlund, R Melén, K Cao, X Julkunen, I Cell Signal 20:1442-51 10593898 Pubmed 1999 Peptides corresponding to the N and C termini of IkappaB-alpha, -beta, and -epsilon as probes of the two catalytic subunits of IkappaB kinase, IKK-1 and IKK-2 Burke, JR Wood, MK Ryseck, RP Walther, S Meyers, CA J Biol Chem 274:36146-52 7862124 Pubmed 1995 Phosphorylation of I kappa B alpha precedes but is not sufficient for its dissociation from NF-kappa B DiDonato, JA Mercurio, F Karin, M Mol Cell Biol 15:1302-11 1756723 Pubmed 1991 Cytoplasmic retention, DNA binding and processing of the NF-kappa B p50 precursor are controlled by a small region in its C-terminus Blank, V Kourilsky, P Israel, A EMBO J 10:4159-67 9721103 Pubmed 1998 Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: discrimination between free and NF-kappaB-bound substrate Zandi, E Chen, Y Karin, M Science 281:1360-3 7957109 Pubmed 1994 A proteasome inhibitor prevents activation of NF-kappa B and stabilizes a newly phosphorylated form of I kappa B-alpha that is still bound to NF-kappa B Traenckner, EB Wilk, S Baeuerle, PA EMBO J 13:5433-41 7479848 Pubmed 1995 Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin-proteasome pathway Alkalay, I Yaron, A Hatzubai, A Orian, A Ciechanover, A Ben-Neriah, Y Proc Natl Acad Sci U S A 92:10599-603 19066035 Pubmed 2008 Analysis of nucleocytoplasmic shuttling of NF kappa B proteins in human leukocytes Ghosh, CC Vu, HY Mujo, T Vancurova, I Methods Mol Biol 457:279-92 3129195 Pubmed 1988 Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor Baeuerle, PA Baltimore, D Cell 53:211-7 7575604 Pubmed 1995 Inactivation of NF-kappa B inhibitor I kappa B alpha: ubiquitin-dependent proteolysis and its degradation product Li, CC Dai, RM Longo, DL Biochem Biophys Res Commun 215:292-301 7628694 Pubmed 1995 Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway Chen, Z Hagler, J Palombella, VJ Melandri, F Scherer, D Ballard, D Maniatis, T Genes Dev 9:1586-97 17428801 Pubmed 2007 CARMA1 coiled-coil domain is involved in the oligomerization and subcellular localization of CARMA1 and is required for T cell receptor-induced NF-kappaB activation Tanner, MJ Hanel, W Gaffen, SL Lin, X J Biol Chem 282:17141-7 11460167 Pubmed 2001 TAK1 is a ubiquitin-dependent kinase of MKK and IKK Wang, C Deng, L Hong, M Akkaraju, GR Inoue, J Chen, ZJ Nature 412:346-51 7809113 Pubmed 1994 Tumor necrosis factor alpha-induced phosphorylation of I kappa B alpha is a signal for its degradation but not dissociation from NF-kappa B Miyamoto, S Maki, M Schmitt, MJ Hatanaka, M Verma, IM Proc Natl Acad Sci U S A 91:12740-4 9914500 Pubmed 1999 All three IkappaB isoforms and most Rel family members are stably associated with the IkappaB kinase 1/2 complex Heilker, R Freuler, F Pulfer, R di Padova, F Eder, J Eur J Biochem 259:253-61 Calcineurin activates NFAT 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> LEFT-TO-RIGHT FKBP1A binds tacrolimus 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> FPR1 FKBP1A P20081 Reactome DB_ID: 10779347 UniProt:P20081 FPR1 UniProt P20081 2 EQUAL 108 EQUAL Reactome Database ID Release 78 10779347 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10779347 Reactome R-SCE-2026007 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-SCE-2026007.1 FK506 tacrolimus fujimycin Prograf&reg; Protopic&reg; Reactome DB_ID: 9678991 tacrolimus [Guide to Pharmacology:6784] tacrolimus FK506 fujimycin Prograf&reg; Protopic&reg; Guide to Pharmacology 6784 Reactome Database ID Release 78 9678991 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9678991 Reactome R-ALL-9678991 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-9678991.1 FKBP1A:tacrolimus Reactome DB_ID: 10779364 1 1 Reactome Database ID Release 78 10779364 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10779364 Reactome R-SCE-2026019 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-SCE-2026019.1 Reactome Database ID Release 78 10779366 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10779366 Reactome R-SCE-9690461 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-SCE-9690461.1 Tacrolimus (also FK-506 or Fujimycin) is a macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Tacrolimus is an immunosuppressive drug whose main use is after organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It reduces peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP1A, creating a new complex. This complex inhibits calcineurin (Bierer et al. 1991) which inhibits T-lymphocyte signal transduction and IL-2 transcription (Kino et al. 1987, Ding et al. 2019). 2445721 Pubmed 1987 FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics Kino, T Hatanaka, H Hashimoto, M Nishiyama, M Goto, T Okuhara, M Kohsaka, M Aoki, H Imanaka, H J. Antibiot. 40:1249-55 1715244 Pubmed 1991 Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes Liu, J Farmer, J D Lane, WS Friedman, J Weissman, I Schreiber, S L Cell 66:807-15 30294901 Pubmed 2019 Rapamycin and FK506 derivative TH2849 could ameliorate neurodegenerative diseases through autophagy with low immunosuppressive effect Ding, Li Nan, Wen-Hao Zhu, Xian-Bing Li, Xiao-Ming Zhou, Li-Yan Chen, Hou-Jie Yu, Lu Ullah Khan, Fahim Zhong, Han-Bing Shi, Xiao-Jun CNS Neurosci Ther 25:452-464 Reactome Database ID Release 78 10781230 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10781230 Reactome R-SCE-2025928 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-SCE-2025928.1 Signaling by the B cell receptor and the T cell receptor stimulate transcription by NFAT factors via calcium (reviewed in Gwack et al. 2007). Cytosolic calcium from intracellular stores and extracellular sources binds calmodulin and activates the protein phosphatase calcineurin. Activated calcineurin dephosphorylates NFATs in the cytosol, exposing nuclear localization sequences on the NFATs and causing the NFATs to be imported into the nucleus where they regulate transcription of target genes in complexes with other transcription factors such as AP-1 and JUN. Calcineurin in the target of the immunosuppressive drugs cyclosporin A and FK-506 (reviewed in Lee and Park 2006). 17572487 Pubmed 2007 Signalling to transcription: store-operated Ca2+ entry and NFAT activation in lymphocytes Gwack, Y Feske, S Srikanth, S Hogan, PG Rao, A Cell Calcium 42:145-56 16951543 Pubmed 2006 Regulation of NFAT activation: a potential therapeutic target for immunosuppression Lee, M Park, J Mol Cells 22:1-7 Reactome Database ID Release 78 10780626 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10780626 Reactome R-SCE-1168372 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-SCE-1168372.1 Second messengers (calcium, diacylglycerol, inositol 1,4,5-trisphosphate, and phosphatidyinositol 3,4,5-trisphosphate) trigger signaling pathways: NF-kappaB is activated via protein kinase C beta, RAS via RasGRP proteins, NF-AT via calcineurin, and AKT via PDK1 (reviewed in Shinohara and Kurosaki 2009, Stone 2006). 19909372 Pubmed 2009 Comprehending the complex connection between PKCbeta, TAK1, and IKK in BCR signaling Shinohara, H Kurosaki, T Immunol Rev 232:300-18 17052215 Pubmed 2006 Regulation of Ras in lymphocytes: get a GRP Stone, JC Biochem Soc Trans 34:858-61 Reactome Database ID Release 78 10780628 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10780628 Reactome R-SCE-983705 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-SCE-983705.1 Mature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, Fu et al. 1975, Kunkel et al. 1975, Van Noesel et al. 1992, Sanchez et al. 1993, reviewed in Brezski and Monroe 2008). Binding of antigen to the immunoglobulin activates phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic tails of Ig-alpha and Ig-beta by Src family tyrosine kinases, including LYN, FYN, and BLK (Nel et al. 1984, Yamanashi et al. 1991, Flaswinkel and Reth 1994, Saouaf et al. 1994, Hata et al. 1994, Saouaf et al. 1995, reviewed in Gauld and Cambier 2004, reviewed in Harwood and Batista 2010).<br>The protein kinase SYK binds the phosphorylated immunoreceptor tyrosine-activated motifs (ITAMs) on the cytoplasmic tails of Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) (Wienands et al. 1995, Rowley et al. 1995, Tsang et al. 2008). The binding causes the activation and autophosphorylation of SYK (Law et al. 1994, Baldock et al. 2000, Irish et al. 2006, Tsang et al. 2008, reviewed in Bradshaw 2010).<br>Activated SYK and other kinases phosphorylate BLNK (SLP-65), BCAP, and CD19 which serve as scaffolds for the assembly of large complexes, the signalosomes, by recruiting phosphoinositol 3-kinase (PI3K), phospholipase C gamma (predominantly PLC-gamma2 in B cells, Coggeshall et al. 1992), NCK, BAM32, BTK, VAV1, and SHC. The effectors are phosphorylated by SYK and other kinases.<br>PLC-gamma associated with BLNK hydrolyzes phosphatidylinositol-4,5-bisphosphate to yield inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (Carter et al. 1991, Kim et al. 2004). IP3 binds receptors on the endoplasmic reticulum and causes release of calcium ions from the ER into the cytosol. The depletion of calcium from the ER in turn activates STIM1 to interact with ORAI and TRPC1 channels in the plasma membrane, resulting in an influx of extracellular calcium ions (Muik et al. 2008, Luik et al. 2008, Park et al. 2009, Mori et al. 2002). PI3K associated with BCAP and CD19 phosphorylates phosphatidylinositol 4,5-bisphosphate to yield phosphatidyinositol 3,4,5-trisphosphate.<br>Second messengers (calcium, diacylglycerol, inositol 1,4,5-trisphosphate, and phosphatidylinositol 3,4,5-trisphosphate) trigger signaling pathways: NF-kappaB is activated via protein kinase C beta, RAS is activated via RasGRP proteins, NF-AT is activated via calcineurin, and AKT (PKB) is activated via PDK1 (reviewed in Shinohara and Kurosaki 2009, Stone 2006). 20192804 Pubmed 2010 Early events in B cell activation Harwood, NE Batista, FD Annu Rev Immunol 28:185-210 7688784 Pubmed 1993 Signal transduction by immunoglobulin is mediated through Ig alpha and Ig beta Sanchez, M Misulovin, Z Burkhardt, AL Mahajan, S Costa, T Franke, R Bolen, JB Nussenzweig, M J Exp Med 178:1049-55 15489917 Pubmed 2004 Src-family kinases in B-cell development and signaling Gauld, SB Cambier, JC Oncogene 23:8001-6 2011584 Pubmed 1991 Tyrosine phosphorylation of phospholipase C induced by membrane immunoglobulin in B lymphocytes Carter, RH Park, DJ Rhee, SG Fearon, DT Proc Natl Acad Sci U S A 88:2745-9 7927516 Pubmed 1994 Tyrosine phosphorylation of MB-1, B29, and HS1 proteins in human B cells following receptor crosslinking Hata, D Nakamura, T Kawakami, T Kawakami, Y Herren, B Mayumi, M Immunol Lett 40:65-71 15509800 Pubmed 2004 Mechanism of B-cell receptor-induced phosphorylation and activation of phospholipase C-gamma2 Kim, YJ Sekiya, F Poulin, B Bae, YS Rhee, SG Mol Cell Biol 24:9986-99 7538118 Pubmed 1995 Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig alpha/Ig beta immunoreceptor tyrosine activation motif binding and autophosphorylation Rowley, RB Burkhardt, AL Chao, HG Matsueda, GR Bolen, JB J Biol Chem 270:11590-4 20206686 Pubmed 2010 The Src, Syk, and Tec family kinases: distinct types of molecular switches Bradshaw, JM Cell Signal 22:1175-84 1376928 Pubmed 1992 Predominant expression and activation-induced tyrosine phosphorylation of phospholipase C-gamma 2 in B lymphocytes Coggeshall, KM McHugh, JC Altman, A Proc Natl Acad Sci U S A 89:5660-4 16849466 Pubmed 2006 Kinetics of B cell receptor signaling in human B cell subsets mapped by phosphospecific flow cytometry Irish, JM Czerwinski, DK Nolan, GP Levy, R J Immunol 177:1581-9 8580068 Pubmed 1995 Tyrosine-phosphorylated forms of Ig beta, CD22, TCR zeta and HOSS are major ligands for tandem SH2 domains of Syk Wienands, J Freuler, F Baumann, G Int Immunol 7:1701-8 11901194 Pubmed 2002 Transient receptor potential 1 regulates capacitative Ca(2+) entry and Ca(2+) release from endoplasmic reticulum in B lymphocytes Mori, Y Wakamori, M Miyakawa, T Hermosura, M Hara, Y Nishida, M Hirose, K Mizushima, A Kurosaki, M Mori, E Gotoh, K Okada, T Fleig, A Penner, R Iino, M Kurosaki, T J Exp Med 195:673-81 18818202 Pubmed 2008 Molecular mechanism of the Syk activation switch Tsang, E Giannetti, AM Shaw, D Dinh, M Tse, JK Gandhi, S Ho, H Wang, S Papp, E Bradshaw, JM J Biol Chem 283:32650-9 18187424 Pubmed 2008 Dynamic coupling of the putative coiled-coil domain of ORAI1 with STIM1 mediates ORAI1 channel activation Muik, M Frischauf, I Derler, I Fahrner, M Bergsmann, J Eder, P Schindl, R Hesch, C Polzinger, B Fritsch, R Kahr, H Madl, J Gruber, H Groschner, K Romanin, C J Biol Chem 283:8014-22 19249086 Pubmed 2009 STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1 Park, CY Hoover, PJ Mullins, FM Bachhawat, P Covington, ED Raunser, S Walz, T Garcia, KC Dolmetsch, RE Lewis, RS Cell 136:876-90 803528 Pubmed 1975 Similar idiotypic specificity for the membrane IgD and IgM of human B lymphocytes Fu, SM Winchester, RJ Kunkel, HG J Immunol 114:250-2 10648173 Pubmed 2000 Purification and characterization of human Syk produced using a baculovirus expression system Baldock, D Graham, B Akhlaq, M Graff, P Jones, CE Menear, K Protein Expr Purif 18:86-94 8306975 Pubmed 1994 Dual role of the tyrosine activation motif of the Ig-alpha protein during signal transduction via the B cell antigen receptor Flaswinkel, H Reth, M EMBO J 13:83-9 19065780 Pubmed 2008 B-cell receptor Brezski, RJ Monroe, JG Adv Exp Med Biol 640:12-21 6335036 Pubmed 1984 Enhanced tyrosine phosphorylation in B lymphocytes upon complexing of membrane immunoglobulin Nel, AE Landreth, GE Goldschmidt-Clermont, PJ Tung, HE Galbraith, RM Biochem Biophys Res Commun 125:859-66 7592958 Pubmed 1995 Reconstitution of the B cell antigen receptor signaling components in COS cells Saouaf, SJ Kut, SA Fargnoli, J Rowley, RB Bolen, JB Mahajan, S J Biol Chem 270:27072-8 1375264 Pubmed 1992 Comparison of human B cell antigen receptor complexes: membrane-expressed forms of immunoglobulin (Ig)M, IgD, and IgG are associated with structurally related heterodimers Van Noesel, CJ Brouns, GS van Schijndel, GM Bende, RJ Mason, DY Borst, J van Lier, RA J Exp Med 175:1511-9 1081164 Pubmed 1975 Surface markers of human lymphocytes Kunkel, HG Johns Hopkins Med J 137:216-23 7524079 Pubmed 1994 Temporal differences in the activation of three classes of non-transmembrane protein tyrosine kinases following B-cell antigen receptor surface engagement Saouaf, SJ Mahajan, S Rowley, RB Kut, SA Fargnoli, J Burkhardt, AL Tsukada, S Witte, ON Bolen, JB Proc Natl Acad Sci U S A 91:9524-8 18596693 Pubmed 2008 Oligomerization of STIM1 couples ER calcium depletion to CRAC channel activation Luik, RM Wang, B Prakriya, M Wu, MM Lewis, RS Nature 454:538-42 8163536 Pubmed 1994 Molecular cloning of human Syk. A B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex Law, CL Sidorenko, SP Chandran, KA Draves, KE Chan, AC Weiss, A Edelhoff, S Disteche, CM Clark, EA J Biol Chem 269:12310-9 4589993 Pubmed 1974 Occurrence of surface IgM, IgD, and free light chains of human lymphocytes Fu, SM Winchester, RJ Kunkel, HG J Exp Med 139:451-6 1702903 Pubmed 1991 Association of B cell antigen receptor with protein tyrosine kinase Lyn Yamanashi, Y Kakiuchi, T Mizuguchi, J Yamamoto, T Toyoshima, K Science 251:192-4 Class I MHC mediated antigen processing & presentation 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> Antigen processing: Ubiquitination & Proteasome degradation 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> LEFT-TO-RIGHT 6.3.2.19 E1 mediated ubiquitin activation 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> Converted from EntitySet in Reactome Ub ubiquitin Reactome DB_ID: 10750954 Converted from EntitySet in Reactome Homologues of RPS27A(1-76) Reactome DB_ID: 10750888 RPS31 Ubiquitin-40S ribosomal protein S31 component recommendedName: Ubiquitin /component component recommendedName: fullName evidence="9"40S ribosomal protein S31 RS31_YEAST Reactome DB_ID: 9633126 UniProt:P05759 RPS31 RPS31 RPS37 UBI3 YLR167W L9470.14 SUBUNIT Component of the small ribosomal subunit (SSU). Mature yeast ribosomes consist of a small (40S) and a large (60S) subunit. The 40S small subunit contains 1 molecule of ribosomal RNA (18S rRNA) and 33 different proteins (encoded by 57 genes). The large 60S subunit contains 3 rRNA molecules (25S, 5.8S and 5S rRNA) and 46 different proteins (encoded by 81 genes) (PubMed:9559554, PubMed:22096102).MISCELLANEOUS Ubiquitin is encoded by several different genes. UBI1 and UBI2 genes code for a single copy of ubiquitin fused to the ribosomal proteins eL40. UBI3 is a polyprotein with one copy of ubiquitin fused to ribosomal protein eS31. UBI4 is a polyprotein containing 5 exact head to tail repeats of ubiquitin.SIMILARITY In the N-terminal section; belongs to the ubiquitin family.SIMILARITY In the C-terminal section; belongs to the eukaryotic ribosomal protein eS31 family. UniProt P05759 1 EQUAL 76 EQUAL Reactome Database ID Release 78 9633126 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9633126 Reactome R-SCE-9633126 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-SCE-9633126.1 RPL40A Ubiquitin-60S ribosomal protein L40 component recommendedName: Ubiquitin /component component recommendedName: fullName evidence="10"60S ribosomal protein L40-A RL40A_YEAST Reactome DB_ID: 9633110 UniProt:P0CH08 RPL40A RPL40A UBI1 YIL148W SUBUNIT Component of the large ribosomal subunit (LSU). Mature yeast ribosomes consist of a small (40S) and a large (60S) subunit. The 40S small subunit contains 1 molecule of ribosomal RNA (18S rRNA) and 33 different proteins (encoded by 57 genes). The large 60S subunit contains 3 rRNA molecules (25S, 5.8S and 5S rRNA) and 46 different proteins (encoded by 81 genes) (PubMed:9559554, PubMed:22096102).MISCELLANEOUS Ubiquitin is encoded by several different genes. UBI1 and UBI2 genes code for a single copy of ubiquitin fused to the ribosomal proteins eL40. UBI3 is a polyprotein with one copy of ubiquitin fused to ribosomal protein eS31. UBI4 is a polyprotein containing 5 exact head to tail repeats of ubiquitin.MISCELLANEOUS The 60S ribosomal protein L40 is present with 40000 molecules/cell in log phase SD medium.SIMILARITY In the N-terminal section; belongs to the ubiquitin family.SIMILARITY In the C-terminal section; belongs to the eukaryotic ribosomal protein eL40 family. UniProt P0CH08 1 EQUAL 76 EQUAL Reactome Database ID Release 78 9633110 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9633110 Reactome R-SCE-9633110 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-SCE-9633110.1 RPL40B Ubiquitin-60S ribosomal protein L40 component recommendedName: Ubiquitin /component component recommendedName: fullName evidence="9"60S ribosomal protein L40-B RL40B_YEAST Reactome DB_ID: 9633176 UniProt:P0CH09 RPL40B RPL40B UBI2 YKR094C SUBUNIT Component of the large ribosomal subunit (LSU). Mature yeast ribosomes consist of a small (40S) and a large (60S) subunit. The 40S small subunit contains 1 molecule of ribosomal RNA (18S rRNA) and 33 different proteins (encoded by 57 genes). The large 60S subunit contains 3 rRNA molecules (25S, 5.8S and 5S rRNA) and 46 different proteins (encoded by 81 genes) (PubMed:9559554, PubMed:22096102).MISCELLANEOUS Ubiquitin is encoded by several different genes. UBI1 and UBI2 genes code for a single copy of ubiquitin fused to the ribosomal proteins eL40. UBI3 is a polyprotein with one copy of ubiquitin fused to ribosomal protein eS31. UBI4 is a polyprotein containing 5 exact head to tail repeats of ubiquitin.MISCELLANEOUS The 60S ribosomal protein L40 is present with 40000 molecules/cell in log phase SD medium.SIMILARITY In the N-terminal section; belongs to the ubiquitin family.SIMILARITY In the C-terminal section; belongs to the eukaryotic ribosomal protein eL40 family. UniProt P0CH09 1 EQUAL 76 EQUAL Reactome Database ID Release 78 9633176 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9633176 Reactome R-SCE-9633176 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-SCE-9633176.1 Reactome Database ID Release 78 10750888 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750888 Reactome R-SCE-939205 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-SCE-939205.1 Converted from EntitySet in Reactome Homologues of UBB(77-152) Reactome DB_ID: 10750896 RPS31 UBB(77-152) P05759 Reactome DB_ID: 10750890 77 EQUAL 152 EQUAL Reactome Database ID Release 78 10750890 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750890 Reactome R-SCE-939213 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-SCE-939213.1 RPL40A UBB(77-152) P0CH08 Reactome DB_ID: 10750892 77 EQUAL 152 EQUAL Reactome Database ID Release 78 10750892 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750892 Reactome R-SCE-939213-2 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-SCE-939213-2.1 RPL40B UBB(77-152) P0CH09 Reactome DB_ID: 10750894 77 EQUAL 152 EQUAL Reactome Database ID Release 78 10750894 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750894 Reactome R-SCE-939213-3 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-SCE-939213-3.1 Reactome Database ID Release 78 10750896 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750896 Reactome R-SCE-939213-4 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-SCE-939213-4.1 Converted from EntitySet in Reactome Homologues of UBB(153-228) Reactome DB_ID: 10750904 RPS31 UBB(153-228) P05759 Reactome DB_ID: 10750898 153 EQUAL 228 EQUAL Reactome Database ID Release 78 10750898 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750898 Reactome R-SCE-939230 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-SCE-939230.1 RPL40A UBB(153-228) P0CH08 Reactome DB_ID: 10750900 153 EQUAL 228 EQUAL Reactome Database ID Release 78 10750900 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750900 Reactome R-SCE-939230-2 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-SCE-939230-2.1 RPL40B UBB(153-228) P0CH09 Reactome DB_ID: 10750902 153 EQUAL 228 EQUAL Reactome Database ID Release 78 10750902 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750902 Reactome R-SCE-939230-3 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-SCE-939230-3.1 Reactome Database ID Release 78 10750904 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750904 Reactome R-SCE-939230-4 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-SCE-939230-4.1 Converted from EntitySet in Reactome Homologues of UBC(229-304) Reactome DB_ID: 10750912 RPS31 UBC(229-304) P05759 Reactome DB_ID: 10750906 229 EQUAL 304 EQUAL Reactome Database ID Release 78 10750906 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750906 Reactome R-SCE-939192 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-SCE-939192.1 RPL40A UBC(229-304) P0CH08 Reactome DB_ID: 10750908 229 EQUAL 304 EQUAL Reactome Database ID Release 78 10750908 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750908 Reactome R-SCE-939192-2 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-SCE-939192-2.1 RPL40B UBC(229-304) P0CH09 Reactome DB_ID: 10750910 229 EQUAL 304 EQUAL Reactome Database ID Release 78 10750910 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750910 Reactome R-SCE-939192-3 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-SCE-939192-3.1 Reactome Database ID Release 78 10750912 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750912 Reactome R-SCE-939192-4 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-SCE-939192-4.1 Converted from EntitySet in Reactome Homologues of UBC(305-380) Reactome DB_ID: 10750920 RPS31 UBC(305-380) P05759 Reactome DB_ID: 10750914 305 EQUAL 380 EQUAL Reactome Database ID Release 78 10750914 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750914 Reactome R-SCE-939232 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-SCE-939232.1 RPL40A UBC(305-380) P0CH08 Reactome DB_ID: 10750916 305 EQUAL 380 EQUAL Reactome Database ID Release 78 10750916 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750916 Reactome R-SCE-939232-2 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-SCE-939232-2.1 RPL40B UBC(305-380) P0CH09 Reactome DB_ID: 10750918 305 EQUAL 380 EQUAL Reactome Database ID Release 78 10750918 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750918 Reactome R-SCE-939232-3 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-SCE-939232-3.1 Reactome Database ID Release 78 10750920 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750920 Reactome R-SCE-939232-4 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-SCE-939232-4.1 Converted from EntitySet in Reactome Homologues of UBC(381-456) Reactome DB_ID: 10750928 RPS31 UBC(381-456) P05759 Reactome DB_ID: 10750922 381 EQUAL 456 EQUAL Reactome Database ID Release 78 10750922 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750922 Reactome R-SCE-939191 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-SCE-939191.1 RPL40A UBC(381-456) P0CH08 Reactome DB_ID: 10750924 381 EQUAL 456 EQUAL Reactome Database ID Release 78 10750924 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750924 Reactome R-SCE-939191-2 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-SCE-939191-2.1 RPL40B UBC(381-456) P0CH09 Reactome DB_ID: 10750926 381 EQUAL 456 EQUAL Reactome Database ID Release 78 10750926 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750926 Reactome R-SCE-939191-3 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-SCE-939191-3.1 Reactome Database ID Release 78 10750928 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750928 Reactome R-SCE-939191-4 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-SCE-939191-4.1 Converted from EntitySet in Reactome Homologues of UBC(457-532) Reactome DB_ID: 10750936 RPS31 UBC(457-532) P05759 Reactome DB_ID: 10750930 457 EQUAL 532 EQUAL Reactome Database ID Release 78 10750930 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750930 Reactome R-SCE-939184 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-SCE-939184.1 RPL40A UBC(457-532) P0CH08 Reactome DB_ID: 10750932 457 EQUAL 532 EQUAL Reactome Database ID Release 78 10750932 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750932 Reactome R-SCE-939184-2 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-SCE-939184-2.1 RPL40B UBC(457-532) P0CH09 Reactome DB_ID: 10750934 457 EQUAL 532 EQUAL Reactome Database ID Release 78 10750934 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750934 Reactome R-SCE-939184-3 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-SCE-939184-3.1 Reactome Database ID Release 78 10750936 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750936 Reactome R-SCE-939184-4 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-SCE-939184-4.1 Converted from EntitySet in Reactome Homologues of UBC(533-608) Reactome DB_ID: 10750944 RPS31 UBC(533-608) P05759 Reactome DB_ID: 10750938 533 EQUAL 608 EQUAL Reactome Database ID Release 78 10750938 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750938 Reactome R-SCE-939239 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-SCE-939239.1 RPL40A UBC(533-608) P0CH08 Reactome DB_ID: 10750940 533 EQUAL 608 EQUAL Reactome Database ID Release 78 10750940 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750940 Reactome R-SCE-939239-2 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-SCE-939239-2.1 RPL40B UBC(533-608) P0CH09 Reactome DB_ID: 10750942 533 EQUAL 608 EQUAL Reactome Database ID Release 78 10750942 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750942 Reactome R-SCE-939239-3 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-SCE-939239-3.1 Reactome Database ID Release 78 10750944 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750944 Reactome R-SCE-939239-4 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-SCE-939239-4.1 Converted from EntitySet in Reactome Homologues of UBC(609-684) Reactome DB_ID: 10750952 RPS31 UBC(609-684) P05759 Reactome DB_ID: 10750946 609 EQUAL 684 EQUAL Reactome Database ID Release 78 10750946 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750946 Reactome R-SCE-939165 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-SCE-939165.1 RPL40A UBC(609-684) P0CH08 Reactome DB_ID: 10750948 609 EQUAL 684 EQUAL Reactome Database ID Release 78 10750948 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750948 Reactome R-SCE-939165-2 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-SCE-939165-2.1 RPL40B UBC(609-684) P0CH09 Reactome DB_ID: 10750950 609 EQUAL 684 EQUAL Reactome Database ID Release 78 10750950 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750950 Reactome R-SCE-939165-3 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-SCE-939165-3.1 Reactome Database ID Release 78 10750952 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750952 Reactome R-SCE-939165-4 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-SCE-939165-4.1 Reactome Database ID Release 78 10750954 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750954 Reactome R-SCE-113595 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-SCE-113595.1 Mg2+ Magnesium magnesium(2+) Mg++ Reactome DB_ID: 29926 magnesium(2+) [ChEBI:18420] magnesium(2+) ChEBI CHEBI:18420 Reactome Database ID Release 78 29926 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29926 Reactome R-ALL-29926 5 Reactome stable identifier. Use this 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-29926.5 COMPOUND C00305 Converted from EntitySet in Reactome Activating enzymes E1 Ubiquitin activating E1 enzymes Reactome DB_ID: 10762717 UBA1 UBA1 P22515 Reactome DB_ID: 10762705 UniProt:P22515 UBA1 UniProt P22515 41 EQUAL 1058 EQUAL Reactome Database ID Release 78 10762705 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762705 Reactome R-SCE-947698 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-SCE-947698.1 UBA3 UBA3 Q99344 Reactome DB_ID: 10762710 UniProt:Q99344 UBA3 UniProt Q99344 1 EQUAL 463 EQUAL Reactome Database ID Release 78 10762710 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762710 Reactome R-SCE-947632 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-SCE-947632.1 ATG7 ATG7 P38862 Reactome DB_ID: 10762715 UniProt:P38862 ATG7 UniProt P38862 2 EQUAL 703 EQUAL Reactome Database ID Release 78 10762715 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762715 Reactome R-SCE-947867 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-SCE-947867.1 Reactome Database ID Release 78 10762717 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762717 Reactome R-SCE-947695 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-SCE-947695.1 PPi pyrophosphate diphosphoric acid pyrophosphoric acid diphosphate Reactome DB_ID: 111294 diphosphate(3-) [ChEBI:33019] diphosphate(3-) ChEBI CHEBI:33019 Reactome Database ID Release 78 111294 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111294 Reactome R-ALL-111294 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-111294.4 COMPOUND C00013 E1 bound ubiquitin Reactome DB_ID: 10762719 1 1 Reactome Database ID Release 78 10762719 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762719 Reactome R-SCE-976164 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-SCE-976164.1 AMP adenosine 5'-monophosphate adenosine 5'-monophosphate(2-) Adenylic acid Adenylate 5'-AMP 5'-Adenylic acid 5'-Adenosine monophosphate Reactome DB_ID: 76577 adenosine 5'-monophosphate(2-) [ChEBI:456215] adenosine 5'-monophosphate(2-) AMP Adenosine-5-monophosphate(2-) AMP dianion 5'-O-phosphonatoadenosine Adenosine-5-monophosphate dianion AMP(2-) ChEBI CHEBI:456215 Reactome Database ID Release 78 76577 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=76577 Reactome R-ALL-76577 5 Reactome stable identifier. Use this 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-76577.5 COMPOUND C00020 ACTIVATION GENE ONTOLOGY GO:0004842 Reactome Database ID Release 78 10762723 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762723 Reactome Database ID Release 78 10762725 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762725 Reactome R-SCE-983153 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-SCE-983153.1 Ubiquitin is activated in an ATP-dependent manner, catalyzed by E1 ubiquitin-activating enzymes. In the first step of ubiquitin activation, the E1 enzyme binds ATP, Mg+2 and ubiquitin, and catalyses ubiquitin C-terminal acyl-adenylation (Ubiquitin-AMP). In the second step, the catalytic cystine in the E1 attacks the ubiquitin-adenylate (Ub-AMP) to form the activated ubiquitin-E1 thioester-bonded complex and an AMP leaving group. The intermediate reaction involving the formation of the ubiquitin-AMP complex is not represented here. 16595681 Pubmed 2006 Pleiotropic effects of ATP.Mg2+ binding in the catalytic cycle of ubiquitin-activating enzyme Tokgöz, Z Bohnsack, RN Haas, AL J Biol Chem 281:14729-37 19352404 Pubmed 2009 Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways Schulman, BA Harper, JW Nat Rev Mol Cell Biol 10:319-31 18662542 Pubmed 2008 Structural insights into E1-catalyzed ubiquitin activation and transfer to conjugating enzymes Lee, I Schindelin, H Cell 134:268-78 LEFT-TO-RIGHT Transfer of ubiquitin from E1 to E2 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> Converted from EntitySet in Reactome E2 Ubiquitin-conjugating enzyme Reactome DB_ID: 10762676 RAD6 UBE2A P06104 Reactome DB_ID: 10762592 UniProt:P06104 RAD6 UniProt P06104 1 EQUAL 152 EQUAL Reactome Database ID Release 78 10762592 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762592 Reactome R-SCE-947617 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-SCE-947617.1 UBC11 UBE2C P52492 Reactome DB_ID: 10762597 UniProt:P52492 UBC11 UniProt P52492 2 EQUAL 179 EQUAL Reactome Database ID Release 78 10762597 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762597 Reactome R-SCE-174244 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-SCE-174244.1 Converted from EntitySet in Reactome Homologues of UBE2D1 Reactome DB_ID: 10762609 UBC4 UBE2D1 P15731 Reactome DB_ID: 10762602 UniProt:P15731 UBC4 UniProt P15731 1 EQUAL 147 EQUAL Reactome Database ID Release 78 10762602 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762602 Reactome R-SCE-174236 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-SCE-174236.1 UBC5 UBE2D1 P15732 Reactome DB_ID: 10762607 UniProt:P15732 UBC5 UniProt P15732 1 EQUAL 147 EQUAL Reactome Database ID Release 78 10762607 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762607 Reactome R-SCE-174236-2 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-SCE-174236-2.1 Reactome Database ID Release 78 10762609 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762609 Reactome R-SCE-174236-3 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-SCE-174236-3.1 CDC34 UBE2G1 P14682 Reactome DB_ID: 10762614 UniProt:P14682 CDC34 UniProt P14682 2 EQUAL 170 EQUAL Reactome Database ID Release 78 10762614 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762614 Reactome R-SCE-947627 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-SCE-947627.1 UBC7 UBE2G2 Q02159 Reactome DB_ID: 10762619 UniProt:Q02159 UBC7 UniProt Q02159 1 EQUAL 165 EQUAL Reactome Database ID Release 78 10762619 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762619 Reactome R-SCE-947640 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-SCE-947640.1 UBC8 UBE2H P28263 Reactome DB_ID: 10762624 UniProt:P28263 UBC8 UniProt P28263 1 EQUAL 183 EQUAL Reactome Database ID Release 78 10762624 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762624 Reactome R-SCE-947638 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-SCE-947638.1 UBC6 UBE2J2 P33296 Reactome DB_ID: 10762629 UniProt:P33296 UBC6 UniProt P33296 1 EQUAL 259 EQUAL Reactome Database ID Release 78 10762629 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762629 Reactome R-SCE-947637 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-SCE-947637.1 UBC1 UBE2K P21734 Reactome DB_ID: 10762634 UniProt:P21734 UBC1 UniProt P21734 2 EQUAL 200 EQUAL Reactome Database ID Release 78 10762634 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762634 Reactome R-SCE-934631 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-SCE-934631.1 Converted from EntitySet in Reactome Homologues of UBE2L3 Reactome DB_ID: 10762640 UBC4 UBE2L3 P15731 Reactome DB_ID: 10762636 1 EQUAL 154 EQUAL Reactome Database ID Release 78 10762636 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762636 Reactome R-SCE-947631 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-SCE-947631.1 UBC5 UBE2L3 P15732 Reactome DB_ID: 10762638 1 EQUAL 154 EQUAL Reactome Database ID Release 78 10762638 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762638 Reactome R-SCE-947631-2 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-SCE-947631-2.1 Reactome Database ID Release 78 10762640 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762640 Reactome R-SCE-947631-3 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-SCE-947631-3.1 Converted from EntitySet in Reactome Homologues of UBE2L6 Reactome DB_ID: 10762646 UBC4 UBE2L6 P15731 Reactome DB_ID: 10762642 1 EQUAL 153 EQUAL Reactome Database ID Release 78 10762642 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762642 Reactome R-SCE-936014 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-SCE-936014.1 UBC5 UBE2L6 P15732 Reactome DB_ID: 10762644 1 EQUAL 153 EQUAL Reactome Database ID Release 78 10762644 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762644 Reactome R-SCE-936014-2 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-SCE-936014-2.1 Reactome Database ID Release 78 10762646 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762646 Reactome R-SCE-936014-3 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-SCE-936014-3.1 UBC12 UBE2M P52491 Reactome DB_ID: 10762651 UniProt:P52491 UBC12 UniProt P52491 1 EQUAL 183 EQUAL Reactome Database ID Release 78 10762651 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762651 Reactome R-SCE-947619 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-SCE-947619.1 UBC13 UBE2N P52490 Reactome DB_ID: 10758011 UniProt:P52490 UBC13 UBC13 YDR092W YD6652.04 FUNCTION Has a role in the DNA error-free postreplication repair (PRR) pathway. The UBC13/MMS2 heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Heterodimer with MMS2.MISCELLANEOUS Present with 8970 molecules/cell in log phase SD medium.SIMILARITY Belongs to the ubiquitin-conjugating enzyme family. UniProt P52490 1 EQUAL 152 EQUAL Reactome Database ID Release 78 10758011 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10758011 Reactome R-SCE-206072 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-SCE-206072.1 UBA1 UBA7 P22515 Reactome DB_ID: 10762656 1 EQUAL 1012 EQUAL Reactome Database ID Release 78 10762656 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762656 Reactome R-SCE-936550 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-SCE-936550.1 Converted from EntitySet in Reactome Homologues of UBE2Q1 Reactome DB_ID: 10762662 UBC4 UBE2Q1 P15731 Reactome DB_ID: 10762658 1 EQUAL 422 EQUAL Reactome Database ID Release 78 10762658 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762658 Reactome R-SCE-947629 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-SCE-947629.1 UBC5 UBE2Q1 P15732 Reactome DB_ID: 10762660 1 EQUAL 422 EQUAL Reactome Database ID Release 78 10762660 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762660 Reactome R-SCE-947629-2 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-SCE-947629-2.1 Reactome Database ID Release 78 10762662 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762662 Reactome R-SCE-947629-3 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-SCE-947629-3.1 Converted from EntitySet in Reactome Homologues of UBE2Q2 Reactome DB_ID: 10762668 UBC4 UBE2Q2 P15731 Reactome DB_ID: 10762664 1 EQUAL 375 EQUAL Reactome Database ID Release 78 10762664 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762664 Reactome R-SCE-947618 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-SCE-947618.1 UBC5 UBE2Q2 P15732 Reactome DB_ID: 10762666 1 EQUAL 375 EQUAL Reactome Database ID Release 78 10762666 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762666 Reactome R-SCE-947618-2 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-SCE-947618-2.1 Reactome Database ID Release 78 10762668 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762668 Reactome R-SCE-947618-3 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-SCE-947618-3.1 MMS2 UBE2V1 P53152 Reactome DB_ID: 10758015 UniProt:P53152 MMS2 MMS2 YGL087C FUNCTION Has a role in the DNA error-free postreplication repair (PRR) pathway. Lacks catalytic activity by itself. The UBC13/MMS2 heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'.SUBUNIT Heterodimer with UBC13.MISCELLANEOUS Present with 2760 molecules/cell in log phase SD medium.SIMILARITY Belongs to the ubiquitin-conjugating enzyme family. UniProt P53152 2 EQUAL 147 EQUAL Reactome Database ID Release 78 10758015 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10758015 Reactome R-SCE-205753 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-SCE-205753.1 Reactome Database ID Release 78 10762676 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762676 Reactome R-SCE-947628 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-SCE-947628.1 Ubiquitin:E2 conjugating enzymes Reactome DB_ID: 10762678 1 1 Reactome Database ID Release 78 10762678 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762678 Reactome R-SCE-976165 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-SCE-976165.1 ACTIVATION GENE ONTOLOGY GO:0043130 Reactome Database ID Release 78 10762720 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762720 Reactome Database ID Release 78 10762722 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762722 Reactome R-SCE-983152 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-SCE-983152.1 Activated ubiquitin is transferred from E1 to the active site cystine of ubiquitin conjugating enzymes (E2s) via a trans-esterification reaction. E2s catalyze covalent attachment of ubiquitin to target proteins. They all share an active-site ubiquitin-binding cysteine residue and are distinguished by the presence of a ubiquitin-conjugating catalytic (UBC) fold required for binding of distinct ubiquitin ligases or E3s. Once conjugated to ubiquitin, the E2 molecule binds one of several E3s (Glickman et al. 2002). 19940261 Pubmed 2010 The family of ubiquitin-conjugating enzymes (E2s): deciding between life and death of proteins van Wijk, SJ Timmers, HT FASEB J 24:981-93 11917093 Pubmed 2002 The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction Glickman, MH Ciechanover, A Physiol Rev 82:373-428 19452197 Pubmed 2009 What was the set of ubiquitin and ubiquitin-like conjugating enzymes in the eukaryote common ancestor? Michelle, C Vourc'h, P Mignon, L Andres, CR J Mol Evol 68:616-28 19851334 Pubmed 2009 Building ubiquitin chains: E2 enzymes at work Ye, Y Rape, M Nat Rev Mol Cell Biol 10:755-64 LEFT-TO-RIGHT Interaction of E3 with substrate and E2-Ub complex 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> Converted from EntitySet in Reactome E3 ligases in proteasomal degradation Reactome DB_ID: 10762587 CUL1 CDC53 Q12018 Reactome DB_ID: 10758370 UniProt:Q12018 CDC53 UniProt Q12018 1 EQUAL 776 EQUAL Reactome Database ID Release 78 10758370 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10758370 Reactome R-SCE-174230 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-SCE-174230.1 HEL1 RNF19B P36113 Reactome DB_ID: 10762351 UniProt:P36113 HEL1 UniProt P36113 1 EQUAL 732 EQUAL Reactome Database ID Release 78 10762351 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762351 Reactome R-SCE-975969 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-SCE-975969.1 RSP5 NEDD4L P39940 Reactome DB_ID: 10762356 UniProt:P39940 RSP5 UniProt P39940 1 EQUAL 975 EQUAL Reactome Database ID Release 78 10762356 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762356 Reactome R-SCE-976003 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-SCE-976003.1 UFD4 TRIP12 P33202 Reactome DB_ID: 10762361 UniProt:P33202 UFD4 UniProt P33202 2 EQUAL 1992 EQUAL Reactome Database ID Release 78 10762361 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762361 Reactome R-SCE-976046 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-SCE-976046.1 Converted from EntitySet in Reactome Homologues of UBR2 Reactome DB_ID: 10762373 UBR1 UBR2 P19812 Reactome DB_ID: 10762366 UniProt:P19812 UBR1 UniProt P19812 1 EQUAL 1755 EQUAL Reactome Database ID Release 78 10762366 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762366 Reactome R-SCE-976055 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-SCE-976055.1 UBR2 UBR2 Q07963 Reactome DB_ID: 10762371 UniProt:Q07963 UBR2 UniProt Q07963 1 EQUAL 1755 EQUAL Reactome Database ID Release 78 10762371 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762371 Reactome R-SCE-976055-2 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-SCE-976055-2.1 Reactome Database ID Release 78 10762373 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762373 Reactome R-SCE-976055-3 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-SCE-976055-3.1 TOM1 HUWE1 Q03280 Reactome DB_ID: 10762378 UniProt:Q03280 TOM1 UniProt Q03280 1 EQUAL 4374 EQUAL Reactome Database ID Release 78 10762378 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762378 Reactome R-SCE-975983 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-SCE-975983.1 SCF E3 ubiquitin ligase Reactome DB_ID: 10762415 1 SKP1 SKP1 P52286 Reactome DB_ID: 10758368 UniProt:P52286 SKP1 UniProt P52286 2 EQUAL 163 EQUAL Reactome Database ID Release 78 10758368 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10758368 Reactome R-SCE-174150 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-SCE-174150.1 1 Converted from EntitySet in Reactome F-box protein substrate recognition component of a SCF E3 ligase complex Reactome DB_ID: 10762413 Converted from EntitySet in Reactome Homologues of CCNF Reactome DB_ID: 10762396 CLN3 CCNF P13365 Reactome DB_ID: 10762382 UniProt:P13365 CLN3 UniProt P13365 1 EQUAL 786 EQUAL Reactome Database ID Release 78 10762382 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762382 Reactome R-SCE-8862602 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-SCE-8862602.1 CLN1 CCNF P20437 Reactome DB_ID: 10762384 UniProt:P20437 CLN1 UniProt P20437 1 EQUAL 786 EQUAL Reactome Database ID Release 78 10762384 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762384 Reactome R-SCE-8862602-2 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-SCE-8862602-2.1 CLN2 CCNF P20438 Reactome DB_ID: 10762386 UniProt:P20438 CLN2 UniProt P20438 1 EQUAL 786 EQUAL Reactome Database ID Release 78 10762386 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762386 Reactome R-SCE-8862602-3 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-SCE-8862602-3.1 CLB1 CCNF P24868 Reactome DB_ID: 10762388 UniProt:P24868 CLB1 UniProt P24868 1 EQUAL 786 EQUAL Reactome Database ID Release 78 10762388 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762388 Reactome R-SCE-8862602-4 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-SCE-8862602-4.1 CLB2 CCNF P24869 Reactome DB_ID: 10762390 UniProt:P24869 CLB2 UniProt P24869 1 EQUAL 786 EQUAL Reactome Database ID Release 78 10762390 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762390 Reactome R-SCE-8862602-5 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-SCE-8862602-5.1 CLB5 CCNF P30283 Reactome DB_ID: 10762392 UniProt:P30283 CLB5 UniProt P30283 1 EQUAL 786 EQUAL Reactome Database ID Release 78 10762392 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762392 Reactome R-SCE-8862602-6 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-SCE-8862602-6.1 CLB6 CCNF P32943 Reactome DB_ID: 10762394 UniProt:P32943 CLB6 UniProt P32943 1 EQUAL 786 EQUAL Reactome Database ID Release 78 10762394 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762394 Reactome R-SCE-8862602-7 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-SCE-8862602-7.1 Reactome Database ID Release 78 10762396 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762396 Reactome R-SCE-8862602-8 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-SCE-8862602-8.1 HRT3 FBXO9 Q12347 Reactome DB_ID: 10762401 UniProt:Q12347 HRT3 UniProt Q12347 1 EQUAL 447 EQUAL Reactome Database ID Release 78 10762401 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762401 Reactome R-SCE-8862608 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-SCE-8862608.1 UFO1 FBXW4 Q04511 Reactome DB_ID: 10762406 UniProt:Q04511 UFO1 UniProt Q04511 1 EQUAL 412 EQUAL Reactome Database ID Release 78 10762406 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762406 Reactome R-SCE-391305 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-SCE-391305.1 DOA1 FBXW7 P36037 Reactome DB_ID: 10762411 UniProt:P36037 DOA1 UniProt P36037 1 EQUAL 707 EQUAL Reactome Database ID Release 78 10762411 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762411 Reactome R-SCE-391304 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-SCE-391304.1 Reactome Database ID Release 78 10762413 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762413 Reactome R-SCE-976085 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-SCE-976085.1 1 HRT1 RBX1 Q08273 Reactome DB_ID: 10758372 UniProt:Q08273 HRT1 UniProt Q08273 2 EQUAL 108 EQUAL Reactome Database ID Release 78 10758372 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10758372 Reactome R-SCE-180582 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-SCE-180582.1 1 Reactome Database ID Release 78 10762415 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762415 Reactome R-SCE-976110 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-SCE-976110.1 MPE1 RBBP6 P35728 Reactome DB_ID: 10762420 UniProt:P35728 MPE1 UniProt P35728 1 EQUAL 1792 EQUAL Reactome Database ID Release 78 10762420 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762420 Reactome R-SCE-8850895 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-SCE-8850895.1 ITT1 RNF217 Q04638 Reactome DB_ID: 10762427 UniProt:Q04638 ITT1 UniProt Q04638 1 EQUAL 542 EQUAL Reactome Database ID Release 78 10762427 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762427 Reactome R-SCE-8850896 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-SCE-8850896.1 Converted from EntitySet in Reactome Homologues of MYLIP Reactome DB_ID: 10762433 CSS1 MYLIP P40442 Reactome DB_ID: 10762429 UniProt:P40442 CSS1 UniProt P40442 1 EQUAL 445 EQUAL Reactome Database ID Release 78 10762429 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762429 Reactome R-SCE-8850908 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-SCE-8850908.1 HPF1 MYLIP Q05164 Reactome DB_ID: 10762431 UniProt:Q05164 HPF1 UniProt Q05164 1 EQUAL 445 EQUAL Reactome Database ID Release 78 10762431 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762431 Reactome R-SCE-8850908-2 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-SCE-8850908-2.1 Reactome Database ID Release 78 10762433 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762433 Reactome R-SCE-8850908-3 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-SCE-8850908-3.1 UBR2 UBR1 Q07963 Reactome DB_ID: 10762441 2 EQUAL 1749 EQUAL Reactome Database ID Release 78 10762441 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762441 Reactome R-SCE-976040 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-SCE-976040.1 UFD2 UBE4A P54860 Reactome DB_ID: 10762448 UniProt:P54860 UFD2 UniProt P54860 1 EQUAL 1066 EQUAL Reactome Database ID Release 78 10762448 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762448 Reactome R-SCE-976022 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-SCE-976022.1 HUL5 UBE3B P53119 Reactome DB_ID: 10762453 UniProt:P53119 HUL5 UniProt P53119 1 EQUAL 1068 EQUAL Reactome Database ID Release 78 10762453 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762453 Reactome R-SCE-976043 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-SCE-976043.1 RBX1:CUL3:BTB Reactome DB_ID: 10762467 CUL3 CUL3 P53202 Reactome DB_ID: 10762465 UniProt:P53202 CUL3 UniProt P53202 1 EQUAL 768 EQUAL Reactome Database ID Release 78 10762465 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762465 Reactome R-SCE-975979 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-SCE-975979.1 1 ADR1 ZBTB16 P07248 Reactome DB_ID: 10762460 UniProt:P07248 ADR1 UniProt P07248 1 EQUAL 673 EQUAL Reactome Database ID Release 78 10762460 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762460 Reactome R-SCE-976047 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-SCE-976047.1 1 1 Reactome Database ID Release 78 10762467 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762467 Reactome R-SCE-976101 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-SCE-976101.1 RNF7 (RBX2):CUL5:EloB/C:ASB Reactome DB_ID: 10762505 ELC1 ELOC Q03071 Reactome DB_ID: 10762499 UniProt:Q03071 ELC1 UniProt Q03071 1 EQUAL 112 EQUAL Reactome Database ID Release 78 10762499 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762499 Reactome R-SCE-180535 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-SCE-180535.1 1 Ghost homologue of ELOB Reactome DB_ID: 10762501 Reactome Database ID Release 78 10762501 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762501 Reactome R-SCE-180551 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-SCE-180551.1 1 Converted from EntitySet in Reactome ASB family Reactome DB_ID: 10762495 Converted from EntitySet in Reactome Homologues of ASB15 Reactome DB_ID: 10762479 SPT23 ASB15 P35210 Reactome DB_ID: 10762472 UniProt:P35210 SPT23 UniProt P35210 1 EQUAL 588 EQUAL Reactome Database ID Release 78 10762472 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762472 Reactome R-SCE-975426 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-SCE-975426.1 MGA2 ASB15 P40578 Reactome DB_ID: 10762477 UniProt:P40578 MGA2 UniProt P40578 1 EQUAL 588 EQUAL Reactome Database ID Release 78 10762477 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762477 Reactome R-SCE-975426-2 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-SCE-975426-2.1 Reactome Database ID Release 78 10762479 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762479 Reactome R-SCE-975426-3 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-SCE-975426-3.1 SPT23 ASB16 P35210 Reactome DB_ID: 10762481 1 EQUAL 453 EQUAL Reactome Database ID Release 78 10762481 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762481 Reactome R-SCE-975416 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-SCE-975416.1 Converted from EntitySet in Reactome Homologues of ASB18 Reactome DB_ID: 10762487 SPT23 ASB18 P35210 Reactome DB_ID: 10762483 1 EQUAL 466 EQUAL Reactome Database ID Release 78 10762483 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762483 Reactome R-SCE-975418 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-SCE-975418.1 MGA2 ASB18 P40578 Reactome DB_ID: 10762485 1 EQUAL 466 EQUAL Reactome Database ID Release 78 10762485 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762485 Reactome R-SCE-975418-2 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-SCE-975418-2.1 Reactome Database ID Release 78 10762487 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762487 Reactome R-SCE-975418-3 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-SCE-975418-3.1 Converted from EntitySet in Reactome Homologues of ASB7 Reactome DB_ID: 10762493 ASB7 SPT23 P35210 Reactome DB_ID: 10762489 1 EQUAL 318 EQUAL Reactome Database ID Release 78 10762489 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762489 Reactome R-SCE-975425 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-SCE-975425.1 MGA2 ASB7 P40578 Reactome DB_ID: 10762491 1 EQUAL 318 EQUAL Reactome Database ID Release 78 10762491 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762491 Reactome R-SCE-975425-2 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-SCE-975425-2.1 Reactome Database ID Release 78 10762493 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762493 Reactome R-SCE-975425-3 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-SCE-975425-3.1 Reactome Database ID Release 78 10762495 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762495 Reactome R-SCE-975431 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-SCE-975431.1 1 HRT1 RNF7 (RBX2) Q08273 Reactome DB_ID: 10762503 2 EQUAL 113 EQUAL Reactome Database ID Release 78 10762503 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762503 Reactome R-SCE-8863132 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-SCE-8863132.1 1 CUL5 CDC53 Q12018 Reactome DB_ID: 10762497 2 EQUAL 780 EQUAL Reactome Database ID Release 78 10762497 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762497 Reactome R-SCE-180528 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-SCE-180528.1 1 Reactome Database ID Release 78 10762505 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762505 Reactome R-SCE-976109 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-SCE-976109.1 APC/C E3 ligase complex Reactome DB_ID: 10762560 Ghost homologue of CDC26 Reactome DB_ID: 10762549 Reactome Database ID Release 78 10762549 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762549 Reactome R-SCE-174052 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-SCE-174052.1 1 APC4 ANAPC4 Q04601 Reactome DB_ID: 10762530 UniProt:Q04601 APC4 UniProt Q04601 1 EQUAL 808 EQUAL Reactome Database ID Release 78 10762530 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762530 Reactome R-SCE-174168 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-SCE-174168.1 1 Ghost homologue of ANAPC7 Reactome DB_ID: 10762542 Reactome Database ID Release 78 10762542 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762542 Reactome R-SCE-174242 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-SCE-174242.1 1 Converted from EntitySet in Reactome Cdc20/Cdh1 Reactome DB_ID: 10762556 CDC20 CDC20 P26309 Reactome DB_ID: 10755647 UniProt:P26309 CDC20 UniProt P26309 1 EQUAL 499 EQUAL Reactome Database ID Release 78 10755647 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10755647 Reactome R-SCE-141412 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-SCE-141412.1 CDH1 FZR1 P53197 Reactome DB_ID: 10756547 UniProt:P53197 CDH1 UniProt P53197 1 EQUAL 496 EQUAL Reactome Database ID Release 78 10756547 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10756547 Reactome R-SCE-174249 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-SCE-174249.1 Reactome Database ID Release 78 10762556 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762556 Reactome R-SCE-177320 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-SCE-177320.1 1 APC1 ANAPC1 P53886 Reactome DB_ID: 10762510 UniProt:P53886 APC1 UniProt P53886 1 EQUAL 1944 EQUAL Reactome Database ID Release 78 10762510 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762510 Reactome R-SCE-174189 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-SCE-174189.1 1 DOC1 ANAPC10 P53068 Reactome DB_ID: 10762515 UniProt:P53068 DOC1 UniProt P53068 1 EQUAL 185 EQUAL Reactome Database ID Release 78 10762515 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762515 Reactome R-SCE-174142 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-SCE-174142.1 1 CDC27 CDC27 P38042 Reactome DB_ID: 10762525 UniProt:P38042 CDC27 UniProt P38042 1 EQUAL 824 EQUAL Reactome Database ID Release 78 10762525 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762525 Reactome R-SCE-174073 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-SCE-174073.1 1 CDC23 CDC23 P16522 Reactome DB_ID: 10762547 UniProt:P16522 CDC23 UniProt P16522 1 EQUAL 597 EQUAL Reactome Database ID Release 78 10762547 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762547 Reactome R-SCE-174137 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-SCE-174137.1 1 Ghost homologue of ANAPC13 Reactome DB_ID: 10762558 Reactome Database ID Release 78 10762558 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762558 Reactome R-SCE-975982 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-SCE-975982.1 1 APC5 ANAPC5 Q08683 Reactome DB_ID: 10762535 UniProt:Q08683 APC5 UniProt Q08683 1 EQUAL 755 EQUAL Reactome Database ID Release 78 10762535 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762535 Reactome R-SCE-174211 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-SCE-174211.1 1 CDC16 CDC16 P09798 Reactome DB_ID: 10762540 UniProt:P09798 CDC16 UniProt P09798 1 EQUAL 620 EQUAL Reactome Database ID Release 78 10762540 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762540 Reactome R-SCE-174156 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-SCE-174156.1 1 APC11 ANAPC11 Q12157 Reactome DB_ID: 10762554 UniProt:Q12157 APC11 UniProt Q12157 1 EQUAL 84 EQUAL Reactome Database ID Release 78 10762554 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762554 Reactome R-SCE-174126 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-SCE-174126.1 1 APC2 ANAPC2 Q12440 Reactome DB_ID: 10762520 UniProt:Q12440 APC2 UniProt Q12440 1 EQUAL 822 EQUAL Reactome Database ID Release 78 10762520 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762520 Reactome R-SCE-174229 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-SCE-174229.1 1 Reactome Database ID Release 78 10762560 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762560 Reactome R-SCE-976123 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-SCE-976123.1 RKR1 LTN1 Q04781 Reactome DB_ID: 10762569 UniProt:Q04781 RKR1 UniProt Q04781 1 EQUAL 1766 EQUAL Reactome Database ID Release 78 10762569 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762569 Reactome R-SCE-5688967 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-SCE-5688967.1 RSA4 TRAF7 P25382 Reactome DB_ID: 10762574 UniProt:P25382 RSA4 UniProt P25382 1 EQUAL 670 EQUAL Reactome Database ID Release 78 10762574 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762574 Reactome R-SCE-5688973 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-SCE-5688973.1 UBE3D P47172 Reactome DB_ID: 10762585 UniProt:P47172 UniProt P47172 2 EQUAL 389 EQUAL Reactome Database ID Release 78 10762585 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762585 Reactome R-SCE-8851647 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-SCE-8851647.1 Reactome Database ID Release 78 10762587 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762587 Reactome R-SCE-976075 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-SCE-976075.1 antigenic substrate misfolded or infective protein Reactome DB_ID: 983035 Reactome Database ID Release 78 983035 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=983035 Reactome R-ALL-983035 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-983035.2 ChEBI 23367 Ag-substrate:E3:E2:Ub Reactome DB_ID: 10762680 1 1 1 Reactome Database ID Release 78 10762680 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762680 Reactome R-SCE-983126 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-SCE-983126.1 Reactome Database ID Release 78 10762730 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762730 Reactome R-SCE-983157 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-SCE-983157.1 Ubiquitin E3 ligases confer specificity to ubiquitination by recognizing target substrates and mediating transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to substrate (Raymond et al. 2009). E3 ligases includes a large, diverse set of proteins characterized by several defining motifs which include a HECT (homologous to E6-associated C-terminus), RING (Really Interesting New Gene) and U-box domains. The E3 ligases can be multisubunit complexes rather than a single polypeptide. Presently three different kinds of E3 complexes have been described called SCF, APC, and VHL. E3 ligases binds to both substrate and an E2 thioesterified with ubiquitin (E2-Ub). 12646216 Pubmed 2003 U-box proteins as a new family of ubiquitin ligases Hatakeyama, S Nakayama, KI Biochem Biophys Res Commun 302:635-45 16954532 Pubmed 2006 A novel family of membrane-bound E3 ubiquitin ligases Ohmura-Hoshino, M Goto, E Matsuki, Y Aoki, M Mito, M Uematsu, M Hotta, H Ishido, S J Biochem 140:147-54 19028597 Pubmed 2009 Maturation of human dendritic cells is accompanied by functional remodelling of the ubiquitin-proteasome system Ebstein, Frédéric Lange, Nicole Urban, Sabrina Seifert, Ulrike Krüger, Elke Kloetzel, Peter-Michael Int. J. Biochem. Cell Biol. 41:1205-15 19489725 Pubmed 2009 RING domain E3 ubiquitin ligases Deshaies, RJ Joazeiro, Claudio A Annu Rev Biochem 78:399-434 LEFT-TO-RIGHT 6.3.2.19 Transfer of Ub from E2 to substrate and release of E2 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> E3:Ub:substrate Reactome DB_ID: 10762684 1 Ub:substrate Reactome DB_ID: 10762682 1 1 Reactome Database ID Release 78 10762682 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762682 Reactome R-SCE-983130 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-SCE-983130.1 1 Reactome Database ID Release 78 10762684 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762684 Reactome R-SCE-983131 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-SCE-983131.1 ACTIVATION Reactome Database ID Release 78 10762685 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762685 Reactome Database ID Release 78 10762687 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762687 Reactome R-SCE-983140 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-SCE-983140.1 Interaction of E3 with both substrate and E2-Ub, brings them into proximity so that ubiquitin is transferred from E2 to the substrate. In most cases the transfer of ubiquitin is direct from E2 to substrate, but in a small subset of E3s, it occurs via a covalent E3-Ub thioester intermediate (Raymond et al. 2009). LEFT-TO-RIGHT 6.3.2.19 Polyubiquitination of substrate 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> 2 E3:K48-polyubiquitinated substrate Reactome DB_ID: 10762699 K48polyUb-antigenic substrate K48-polyubiquitinated substrate Reactome DB_ID: 983123 Reactome Database ID Release 78 983123 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=983123 Reactome R-ALL-983123 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-983123.2 ChEBI 23367 1 1 Reactome Database ID Release 78 10762699 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762699 Reactome R-SCE-983134 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-SCE-983134.1 2 ACTIVATION activeUnit: #PhysicalEntity8 Reactome Database ID Release 78 10762726 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762726 Reactome Database ID Release 78 10762728 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762728 Reactome R-SCE-983156 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-SCE-983156.1 Monoubiquitinated substrate acquires additional ubiquitin modifications in the form of multiple single attachments or a ubiquitin chain. Polyubiquitin chains added through K48 residue of ubiquitin typically targets the substrate for degradation (Raymond et al. 2009). 19874575 Pubmed 2009 Mechanisms of ubiquitin transfer by the anaphase-promoting complex Matyskiela, ME Rodrigo-Brenni, MC Morgan, DO J Biol 8:92 LEFT-TO-RIGHT Release of E3 from polyubiquitinated substrate 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 Database ID Release 78 10762701 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10762701 Reactome R-SCE-983147 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-SCE-983147.1 K48 polyubiquitinated substrate dissociates from E3 to become a substrate for a multicatalytic complex called the 26S proteasome. LEFT-TO-RIGHT Proteasomal cleavage of substrate 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> L-amino acid L-alpha-amino acid zwitterion Reactome DB_ID: 8942986 L-alpha-amino acid zwitterion [ChEBI:59869] L-alpha-amino acid zwitterion C2H4NO2R L-alpha-amino acid zwitterions [NH3+][C@@H]([*])C([O-])=O an L-amino acid ChEBI CHEBI:59869 Reactome Database ID Release 78 8942986 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8942986 Reactome R-ALL-8942986 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-8942986.3 oligopeptide oligopeptide fragment (8-16aa) Reactome DB_ID: 983032 oligopeptide [ChEBI:25676] oligopeptide Oligopeptid oligopeptido ChEBI CHEBI:25676 Reactome Database ID Release 78 983032 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=983032 Reactome R-ALL-983032 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-983032.4 oligopeptide precursor peptide fragment (>16 aa) Reactome DB_ID: 983036 Reactome Database ID Release 78 983036 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=983036 Reactome R-ALL-983036 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-983036.4 ACTIVATION 26S proteasome Reactome DB_ID: 10751145 PRE6 PSMA8 P40303 Reactome DB_ID: 10751139 UniProt:P40303 PRE6 UniProt P40303 1 EQUAL 256 EQUAL Reactome Database ID Release 78 10751139 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10751139 Reactome R-SCE-947610 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-SCE-947610.1 1 Ghost homologue of PSMD10 Reactome DB_ID: 10751072 Reactome Database ID Release 78 10751072 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10751072 Reactome R-SCE-68788 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-SCE-68788.1 1 Ghost homologue of PSME2 Reactome DB_ID: 10751128 Reactome Database ID Release 78 10751128 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10751128 Reactome R-SCE-68814 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-SCE-68814.1 1 PUP3 PSMB3 P25451 Reactome DB_ID: 10751014 UniProt:P25451 PUP3 UniProt P25451 2 EQUAL 205 EQUAL Reactome Database ID Release 78 10751014 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10751014 Reactome R-SCE-68747 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-SCE-68747.1 1 RPN9 PSMD13 Q04062 Reactome DB_ID: 10751087 UniProt:Q04062 RPN9 UniProt Q04062 1 EQUAL 376 EQUAL Reactome Database ID Release 78 10751087 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10751087 Reactome R-SCE-68794 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-SCE-68794.1 1 PRE8 PSMA2 P23639 Reactome DB_ID: 10750969 UniProt:P23639 PRE8 UniProt P23639 2 EQUAL 234 EQUAL Reactome Database ID Release 78 10750969 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750969 Reactome R-SCE-68726 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-SCE-68726.1 1 PRE5 PSMA1 P40302 Reactome DB_ID: 10750964 UniProt:P40302 PRE5 UniProt P40302 1 EQUAL 263 EQUAL Reactome Database ID Release 78 10750964 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750964 Reactome R-SCE-68724 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-SCE-68724.1 1 PUP2 PSMA5 P32379 Reactome DB_ID: 10750984 UniProt:P32379 PUP2 UniProt P32379 1 EQUAL 241 EQUAL Reactome Database ID Release 78 10750984 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750984 Reactome R-SCE-68732 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-SCE-68732.1 1 PRE1 PSMB2 P22141 Reactome DB_ID: 10751009 UniProt:P22141 PRE1 UniProt P22141 1 EQUAL 201 EQUAL Reactome Database ID Release 78 10751009 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10751009 Reactome R-SCE-68744 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-SCE-68744.1 1 PRE10 PSMA3 P21242 Reactome DB_ID: 10750974 UniProt:P21242 PRE10 UniProt P21242 2 EQUAL 255 EQUAL Reactome Database ID Release 78 10750974 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10750974 Reactome R-SCE-68728 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-SCE-68728.1 1 RPN1 PSMD2 P38764 Reactome DB_ID: 10751092 UniProt:P38764 RPN1