BioPAX pathway converted from "IL15:IL15RA binds IL2RB:JAK1 and IL2RG:JAK3" in the Reactome database.IL15:IL15RA binds IL2RB:JAK1 and IL2RG:JAK3IL15:IL15RA binds IL2RB:JAK1 and IL2RG:JAK3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 97437021plasma membraneGO0005886IL2RB:JAK1 [plasma membrane]IL2RB:JAK1Reactome DB_ID: 97434191cytosolGO0005829UniProt:P52332 Jak1Jak1Jak1FUNCTION Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor as well as interleukin (IL)-10 receptor.SUBUNIT Interacts with IL31RA. Interacts with IFNAR2. Interacts with IFNGR1. Interacts with JAKMIP1. Interacts with SHB. Interacts (via N-terminus) with IL2RB and IL10RA (via its cytoplasmic domain) (By similarity). Interacts with FER (PubMed:12738762).DOMAIN The FERM domain mediates interaction with JAKMIP1.DOMAIN Possesses two phosphotransferase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for domain 1.PTM Ubiquitinated by RNF125; leading to its degradation by the proteasome.PTM Autophosphorylated. Phosphorylated on tyrosine residues in response to interferon gamma signaling. Dephosphorylation of Tyr-1034 and Tyr-1034 by PTPN2 negatively regulates cytokine-mediated signaling.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.Reactomehttp://www.reactome.orgMus musculusNCBI Taxonomy10090UniProtP52332Chain Coordinates1EQUAL1154EQUALReactome DB_ID: 97437001UniProt:P16297 Il2rbIl2rbIl2rbFUNCTION Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2. Probably in association with IL15RA, involved in the stimulation of neutrophil phagocytosis by IL15 (By similarity).SUBUNIT Non-covalent dimer of an alpha and a beta subunit. IL2R exists in 3 different forms: a high affinity dimer, an intermediate affinity monomer (beta subunit), and a low affinity monomer (alpha subunit). The high and intermediate affinity forms also associate with a gamma subunit. Interacts with SHB upon interleukin stimulation (By similarity).DOMAIN The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.DOMAIN The box 1 motif is required for JAK interaction and/or activation.SIMILARITY Belongs to the type I cytokine receptor family. Type 4 subfamily.UniProtP1629727EQUAL551EQUALReactome Database ID Release 759743702Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9743702ReactomeR-MMU-4519051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-451905.1Reactome DB_ID: 97436971IL15:IL15RA [plasma membrane]IL15:IL15RAReactome DB_ID: 89831791extracellular regionGO0005576UniProt:P48346 Il15Il15Il15FUNCTION Cytokine that stimulates the proliferation of T-lymphocytes. Stimulation by IL-15 requires interaction of IL-15 with components of IL-2R, including IL-2R beta and probably IL-2R gamma but not IL-2R alpha (By similarity). In neutrophils, stimulates phagocytosis probably by signaling through the IL15 receptor, composed of the subunits IL15RA, IL2RB and IL2RG, which results in kinase SYK activation (By similarity).SIMILARITY Belongs to the IL-15/IL-21 family.UniProtP4834649EQUAL162EQUALReactome DB_ID: 97436951UniProt:Q60819 Il15raIl15raIl15raFUNCTION High-affinity receptor for interleukin-15 (PubMed:17947230). Can signal both in cis and trans where IL15R from one subset of cells presents IL15 to neighboring IL2RG-expressing cells (PubMed:17947230). In neutrophils, binds and activates kinase SYK in response to IL15 stimulation (By similarity). In neutrophils, required for IL15-induced phagocytosis in a SYK-dependent manner (By similarity).SUBUNIT The interleukin-15 receptor IL15R is a heterotrimer of IL15RA, IL2RB and IL2RG. IL15RA also self-associates (By similarity). Interacts with SYK (By similarity).TISSUE SPECIFICITY Widely expressed.PTM N-glycosylated and O-glycosylated.PTM A soluble form (sIL-15RA) arises from proteolytic shedding of the membrane-anchored receptor (By similarity). It also binds IL15 and thus interferes with IL15 binding to the membrane receptor (By similarity).CAUTION It was shown that proteolytic cleavage of Il15ra involves ADAM17/TACE; this publication has later been retracted.UniProtQ6081931EQUAL267EQUALReactome Database ID Release 759743697Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9743697ReactomeR-MMU-89831241Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8983124.1Reactome DB_ID: 97437111IL2RG:JAK3 [plasma membrane]IL2RG:JAK3Reactome DB_ID: 97437061UniProt:A2AGH5Gm20489UniProtA2AGH523EQUAL369EQUALReactome DB_ID: 97437091UniProt:Q62137 Jak3Jak3Jak3FUNCTION Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion.SUBUNIT Interacts with STAM2 and MYO18A. Interacts with SHB (By similarity).TISSUE SPECIFICITY In contrast with the ubiquitous expression of the other JAKs, JAK3 is predominantly expressed in hematopoietic tissues.DOMAIN Possesses two phosphotransferase domains. The second one contains the catalytic domain, while the presence of a pseudokinase domain is required for suppression of basal activity of JAK3.PTM Autophosphorylated, leading to regulate its activity. IL2 promotes phosphorylation on tyrosine residues, including autophosphorylation on Tyr-781 (By similarity). Dephosphorylation of Tyr-976 and Tyr-977 by PTPN2 negatively regulates cytokine-mediated signaling (By similarity).DISRUPTION PHENOTYPE Mice show a severe block in B-cell development at the pre-B stage in the bone marrow. Additionally, they possesses small thymuses revealing a defect in T-cell development. The distribution of developmental subsets is relatively normal, suggesting a block in the expansion of early T-cell progenitors. Peripheral T-cells are present at normal or increased numbers but are functionally incompetent.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.UniProtQ621371EQUAL1124EQUALReactome Database ID Release 759743711Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9743711ReactomeR-MMU-4519111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-451911.1Reactome DB_ID: 97437131IL15RA:IL15:IL2RB:JAK1:IL2RG:JAK3 [plasma membrane]IL15RA:IL15:IL2RB:JAK1:IL2RG:JAK3Reactome DB_ID: 97437021Reactome DB_ID: 97436971Reactome DB_ID: 97437111Reactome Database ID Release 759743713Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9743713ReactomeR-MMU-4491201Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-449120.1Reactome Database ID Release 759743715Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9743715ReactomeR-MMU-4491151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-449115.1The Interleukin-15 (IL15) / Interleukin-15 receptor subunit alpha (IL15RA, IL15Rα) complex binds Interleukin-2 receptor subunit beta (IL2RB, IL2Rβ), which is associated with Tyrosine-protein kinase JAK1 (JAK1) and Cytokine receptor common subunit gamma (IL2RG, IL2Rγ), which is associated with Tyrosine-protein kinase JAK3 (JAK3) (Johnston et al. 1995). The heterodimer of IL2RB and IL2RG can bind IL15 with low affinity but high affinity binding requires a third component, IL15RA (Giri et al. 1994, 1995, Anderson et al. 1995). This is a Black Box Event because it is not clear whether the beta and gamma subunits pre-associate before binding IL15:IL15RA.7641685Pubmed1995Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptorGiri, JGKumaki, SAhdieh, MFriend, DJLoomis, AShanebeck, KDuBose, RCosman, DPark, LSAnderson, DMEMBO J 14:3654-638530383Pubmed1995Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genesAnderson, DMKumaki, SAhdieh, MBertles, JTometsko, MLoomis, AGiri, JCopeland, NGGilbert, DJJenkins, NAJ Biol Chem 270:29862-98026467Pubmed1994Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15Giri, J GAhdieh, MEisenman, JShanebeck, KGrabstein, KKumaki, SNamen, APark, L SCosman, DAnderson, DEMBO J. 13:2822-307568001Pubmed1995Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukins 2 and 15Johnston, JABacon, CMFinbloom, DSRees, RCKaplan, DShibuya, KOrtaldo, JRGupta, SChen, YQGiri, JDProc Natl Acad Sci U S A 92:8705-9inferred by electronic annotationIEAGOIEA