BioPAX pathway converted from "Phosphorylated STAT5 is released" in the Reactome database.Phosphorylated STAT5 is releasedPhosphorylated STAT5 is releasedDeletion mutants have demonstrated that STAT dimerization can occur independently of the binding of 2 STAT molecules by a dimeric receptor. Although this does not exclude the possibility that STATs may dimerize while still associated with the receptor complex, dimerization is believe to occur following the release of phosphorylated monomers (e.g. Turkson & Jove 2000).Authored: Ray, KP, 2010-05-17Reviewed: Villarino, A, 2011-02-11Reviewed: Dooms, H, 2011-03-17Edited: Jupe, S, 2010-08-06Reactome DB_ID: 5079431plasma membraneGO0005886IL2:IL2R trimer p-(Y338,Y392, Y510) beta subunit:p-JAK1:JAK3:p-STAT5 [plasma membrane]IL2:IL2R trimer p-(Y338,Y392, Y510) beta subunit:p-JAK1:JAK3:p-STAT5Reactome DB_ID: 4521191IL2:IL2R trimer p-(Y338,392,510) beta subunit:p-JAK1:JAK3 [plasma membrane]IL2:IL2R trimer p-(Y338,392,510) beta subunit:p-JAK1:JAK3Reactome DB_ID: 4519111IL2RG:JAK3 [plasma membrane]IL2RG:JAK3Reactome DB_ID: 4518931cytosolGO0005829UniProt:P52333 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 (By similarity). Interacts with SHB.TISSUE SPECIFICITY In NK cells and an NK-like cell line but not in resting T-cells or in other tissues. The S-form is more commonly seen in hematopoietic lines, whereas the B-form is detected in cells both of hematopoietic and epithelial origins.DOMAIN Possesses two phosphotransferase domains. The second one probably contains the catalytic domain (By similarity), while the presence of slight differences suggest a different role for domain 1.PTM Tyrosine phosphorylated in response to IL-2 and IL-4. Dephosphorylation of Tyr-980 and Tyr-981 by PTPN2 negatively regulates cytokine-mediated signaling (Probable).SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.Reactomehttp://www.reactome.orgHomo sapiensNCBI Taxonomy9606UniProtP52333Chain Coordinates1EQUAL1124EQUALReactome DB_ID: 4491391UniProt:P31785 IL2RGIL2RGIL2RGFUNCTION Common subunit for the receptors for a variety of interleukins. Probably in association with IL15RA, involved in the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770).SUBUNIT The gamma subunit is common to the IL2, IL4, IL7, IL15, IL21 and probably also the IL13 receptors. Interacts with SHB upon interleukin stimulation.SUBUNIT (Microbial infection) Interacts with HTLV-1 accessory protein p12I.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 5 subfamily.UniProtP3178523EQUAL369EQUALReactome Database ID Release 75451911Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=451911ReactomeR-HSA-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-HSA-451911.1Reactome DB_ID: 4470991extracellular regionGO0005576UniProt:P60568 IL2IL2IL2FUNCTION Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells.DISEASE A chromosomal aberration involving IL2 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with involves TNFRSF17.PHARMACEUTICAL Available under the name Proleukin (Chiron). Used in patients with renal cell carcinoma or metastatic melanoma.SIMILARITY Belongs to the IL-2 family.UniProtP6056821EQUAL153EQUALReactome DB_ID: 4519211UniProt:P23458 JAK1JAK1JAK1BJAK1AJAK1FUNCTION Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:7615558). Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529) as well as interleukin (IL)-10 receptor (PubMed:12133952).SUBUNIT Interacts with IL31RA (PubMed:15194700). Interacts with IFNAR2 (PubMed:7759950). Interacts with IFNGR1 (PubMed:7615558). Interacts with JAKMIP1 (PubMed:15277531). Interacts with SHB (PubMed:12200137). Interacts (via N-terminus) with IL2RB and IL10RA (via its cytoplasmic domain) (PubMed:12133952). Interacts with FER (By similarity).TISSUE SPECIFICITY Expressed at higher levels in primary colon tumors than in normal colon tissue. The expression level in metastatic colon tumors is comparable to the expression level in normal colon tissue.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.DOMAIN The FERM domain mediates interaction with JAKMIP1.PTM Autophosphorylated (PubMed:7615558). Phosphorylated on tyrosine residues in response to interferon gamma signaling (PubMed:7615558). Dephosphorylation of Tyr-1034 and Tyr-1035 by PTPN2 negatively regulates cytokine-mediated signaling (PubMed:11909529).PTM Ubiquitinated by RNF125; leading to its degradation by the proteasome.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.UniProtP23458O4'-phospho-L-tyrosine at unknown positionO4'-phospho-L-tyrosine [MOD:00048]1EQUAL1154EQUALReactome DB_ID: 4500461UniProt:P01589 IL2RAIL2RAIL2RAFUNCTION Receptor for interleukin-2. The receptor is involved in the regulation of immune tolerance by controlling regulatory T cells (TREGs) activity. TREGs suppress the activation and expansion of autoreactive T-cells.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.UniProtP0158922EQUAL272EQUALReactome DB_ID: 4520931UniProt:P14784 IL2RBIL2RBIL15RBIL2RBFUNCTION 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 (PubMed:15123770, PubMed:31040185).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.SUBUNIT (Microbial infection) Interacts with HTLV-1 accessory protein p12I.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.UniProtP14784O4'-phospho-L-tyrosine at 364364EQUALO4'-phospho-L-tyrosine at 418418EQUALO4'-phospho-L-tyrosine at 536536EQUAL27EQUAL551EQUALReactome Database ID Release 75452119Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=452119ReactomeR-HSA-4521191Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-452119.1Converted from EntitySet in ReactomeReactome DB_ID: 5079291p-STAT5A, p-STAT5B [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityp-Y699-STAT5B [cytosol]p-Y694-STAT5A [cytosol]UniProtP51692UniProtP42229Reactome Database ID Release 75507943Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=507943ReactomeR-HSA-5079431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-507943.1Reactome DB_ID: 4521191Converted from EntitySet in ReactomeReactome DB_ID: 5079291Reactome Database ID Release 75919404Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=919404ReactomeR-HSA-9194043Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-919404.39030599Pubmed1997A single STAT recruitment module in a chimeric cytokine receptor complex is sufficient for STAT activationBehrmann, IJanzen, CGerhartz, CSchmitz-Van de Leur, HHermanns, HHeesel, BGraeve, LHorn, FTavernier, JHeinrich, PCJ Biol Chem 272:5269-7411426647Pubmed2000STAT proteins: novel molecular targets for cancer drug discoveryTurkson, JJove, ROncogene 19:6613-26