Protein: Non-receptor tyrosine-protein kinase TYK2 (EC 2.7.10.2) (Q9R117)
Organism: Mus musculus (Mouse)
Function: Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity. Plays both structural and catalytic roles in numerous interleukins and interferons (IFN-alpha/beta) signaling (By similarity). Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6. The heterodimeric cytokine receptor complexes are composed of (1) a TYK2-associated receptor chain (IFNAR1, IL12RB1, IL10RB or IL13RA1), and (2) a second receptor chain associated either with JAK1 or JAK2 (By similarity). In response to cytokine-binding to receptors, phosphorylates and activates receptors (IFNAR1, IL12RB1, IL10RB or IL13RA1), creating docking sites for STAT members (By similarity). In turn, recruited STATs are phosphorylated by TYK2 (or JAK1/JAK2 on the second receptor chain), form homo- and heterodimers, translocate to the nucleus, and regulate cytokine/growth factor responsive genes (By similarity). Negatively regulates STAT3 activity by promototing phosphorylation at a specific tyrosine that differs from the site used for signaling (By similarity).
Sequence: MVGTMPLCGRRAILEDSKADGTEAQPLVPTGCLMVLLHWPGPEGGEPWVTFSQTSLTAEEVCIHIAHKVGITPPCLNLFALYNAQAKVWLPPNHILDTSQDMNLYFRMRFYFRNWHGMNPQEPAVYRCGFPGAETSSDRAEQGVQLLDSASFEYLFEQGKHEFMNDVVSLRDLSSEEEIHHFKNESLGMAFLHLCHLALSRGVPLEEMAREISFKNCIPHSFRQHIRQHNVLTRLRLHRVFRRFLRAFRPGHLSQQVVMVKYLATLERLAPRFGSERIPVCHLEVLAQPERDPCYIQNSGQTAGDPGPELPSGPPTHEVLVTGTGGIQWHPLQTQESERGNSRGNPHGSRSGKKPKAPKAGEHLTESPQEPPWTYFCDFQDISHVVLKERRVHIHLQDNKCLLLCLCSQAEALSFVALVDGYFRLTADSSHYLCHEVAPPRLVTSIQNGIHGPLMDPFVQAKLWPEDGLYLIQWSTSHLHRLILTVAHRNPAFSNGPRGLRLRKFPITQQPGAFVLDGWGRSFASLGDLRLALQGCSLRAGDDCFPLHHCCLPRPREISNLVIMRGSRAHTRPLNLSQLSFHRVHQDEITQLSHLGQGTRTNVYEGLLRVGGPDEGKVDNGCPPEPGGTSGQQLRVVLKVLDPSHHDIALAFYETASLMSQVSHMHLAFLHGVCVRGSENIIVTEFVEHGPLDVWLRRQRGQVPMTWKMVVAQQLASALSYLEDKNLVHGNVCGRNILLARLGLEEGTNPFIKLSDPGVGQGALSREERVERIPWTAPECLSGGTSSLGTATDMWGFGATLLEICFDGEAPLQGRGPSEKERFYTKKHQLPEPSSPELATLTRQCLTYEPAQRPSFRTILRDLTRLQPQNLVGTSAVNSDSPASDPTVFHKRYLKKIRDLGEGHFGKVSLYCYDPTNDGTGEMVAVKALKEGCGPQLRSGWQREIEILRTLYHEHIVKYKGCCEDQGEKSVQLVMEYVPLGSLRDYLPRHCVGLAQLLLFAQQICEGMAYLHAQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVPEGHEYYRVREDGDSPVFWYAPECLKECKFYYASDVWSFGVTLYELLTYCDSNQSPHMKFTELIGHTQGQMTVLRLTELLERGERLPRPDRCPCEIYHLMKNCWETEASFRPTFQNLVPILQTAQEKYQGQVPSVFSVC
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [575-1170]
- IPR041381: JAK1-3/TYK2, pleckstrin homology-like domain (domain) [290-431]
- IPR035963: FERM superfamily, second domain (homologous_superfamily) [145-269]
- IPR016045: Tyrosine-protein kinase, non-receptor, TYK2, N-terminal (domain) [172-526]
- IPR000299: FERM domain (domain) [33-430]
- IPR041046: JAK, FERM F2 lobe domain (domain) [145-269]
- IPR036860: SH2 domain superfamily (homologous_superfamily) [447-608]
- IPR016251: Tyrosine-protein kinase, non-receptor Jak/Tyk2 (family) [4-1175]
- IPR001245: Serine-threonine/tyrosine-protein kinase, catalytic domain (domain) [590-1164]
- IPR017441: Protein kinase, ATP binding site (binding_site) [900-927]
- IPR000719: Protein kinase domain (domain) [589-1166]
- IPR008266: Tyrosine-protein kinase, active site (active_site) [1016-1028]
- IPR041155: FERM F1 lobe ubiquitin-like domain (domain) [33-127]
- IPR020635: Tyrosine-protein kinase, catalytic domain (domain) [589-1166]
- IPR000980: SH2 domain (domain) [448-553]
- IPR051286: Janus Kinase (JAK) (family) [16-1173]
- IPR019749: Band 4.1 domain (domain) [29-278]
Interaction partners: - Suppressor of cytokine signaling 3
- Interleukin-12 receptor subunit beta-1
- Suppressor of cytokine signaling 1
- Interferon alpha/beta receptor 1
- Interleukin-10 receptor subunit beta
- Interleukin-13 receptor subunit alpha-1
- Tyrosine-protein kinase JAK2
- Interleukin-10 receptor subunit alpha
- Signal transducer and activator of transcription
- Signal transducer and activator of transcription 2
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0005102 (signaling receptor binding), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0004672 (protein kinase activity), GO:0070851 (growth factor receptor binding), GO:0016301 (kinase activity), GO:0016773 (phosphotransferase activity, alcohol group as acceptor), GO:0005126 (cytokine receptor binding), GO:0004713 (protein tyrosine kinase activity), GO:0004715 (non-membrane spanning protein tyrosine kinase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0002376 (immune system process), GO:0023052 (signaling), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0009605 (response to external stimulus), GO:0023056 (positive regulation of signaling), GO:0042221 (response to chemical), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0006955 (immune response), GO:0051240 (positive regulation of multicellular organismal process), GO:0002684 (positive regulation of immune system process), GO:0006807 (nitrogen compound metabolic process), GO:0002682 (regulation of immune system process), GO:0051239 (regulation of multicellular organismal process), GO:0071704 (organic substance metabolic process), GO:0044237 (cellular metabolic process), GO:0009607 (response to biotic stimulus), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0006950 (response to stress), GO:0051707 (response to other organism), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0009967 (positive regulation of signal transduction), GO:1901564 (organonitrogen compound metabolic process), GO:0043207 (response to external biotic stimulus), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0019538 (protein metabolic process), GO:0030155 (regulation of cell adhesion), GO:0009966 (regulation of signal transduction), GO:0006952 (defense response), GO:0060255 (regulation of macromolecule metabolic process), GO:0002694 (regulation of leukocyte activation), GO:0045785 (positive regulation of cell adhesion), GO:0001817 (regulation of cytokine production), GO:0043170 (macromolecule metabolic process), GO:0010033 (response to organic substance), GO:0045087 (innate immune response), GO:0009891 (positive regulation of biosynthetic process), GO:0050867 (positive regulation of cell activation), GO:0098542 (defense response to other organism), GO:0006793 (phosphorus metabolic process), GO:0002696 (positive regulation of leukocyte activation), GO:0042127 (regulation of cell population proliferation), GO:0010646 (regulation of cell communication), GO:0031325 (positive regulation of cellular metabolic process), GO:0070887 (cellular response to chemical stimulus), GO:0007166 (cell surface receptor signaling pathway), GO:0010647 (positive regulation of cell communication), GO:0031323 (regulation of cellular metabolic process), GO:0001819 (positive regulation of cytokine production), GO:0050865 (regulation of cell activation), GO:0008284 (positive regulation of cell population proliferation), GO:0034097 (response to cytokine), GO:0022409 (positive regulation of cell-cell adhesion), GO:0071310 (cellular response to organic substance), GO:0022407 (regulation of cell-cell adhesion), GO:0097696 (receptor signaling pathway via STAT), GO:0032649 (regulation of type II interferon production), GO:0010628 (positive regulation of gene expression), GO:0051249 (regulation of lymphocyte activation), GO:0006796 (phosphate-containing compound metabolic process), GO:1904894 (positive regulation of receptor signaling pathway via STAT), GO:0032729 (positive regulation of type II interferon production), GO:0070663 (regulation of leukocyte proliferation), GO:1904892 (regulation of receptor signaling pathway via STAT), GO:0010468 (regulation of gene expression), GO:0036211 (protein modification process), GO:0043412 (macromolecule modification), GO:0051251 (positive regulation of lymphocyte activation), GO:0034341 (response to type II interferon), GO:0070665 (positive regulation of leukocyte proliferation), GO:0034340 (response to type I interferon), GO:0019221 (cytokine-mediated signaling pathway), GO:0046427 (positive regulation of receptor signaling pathway via JAK-STAT), GO:0050670 (regulation of lymphocyte proliferation), GO:0050870 (positive regulation of T cell activation), GO:0050863 (regulation of T cell activation), GO:0071357 (cellular response to type I interferon), GO:0032944 (regulation of mononuclear cell proliferation), GO:0046425 (regulation of receptor signaling pathway via JAK-STAT), GO:0006468 (protein phosphorylation), GO:0050671 (positive regulation of lymphocyte proliferation), GO:0071345 (cellular response to cytokine stimulus), GO:0016310 (phosphorylation), GO:0032816 (positive regulation of natural killer cell activation), GO:0032946 (positive regulation of mononuclear cell proliferation), GO:0032814 (regulation of natural killer cell activation), GO:0140888 (interferon-mediated signaling pathway), GO:1903037 (regulation of leukocyte cell-cell adhesion), GO:1903039 (positive regulation of leukocyte cell-cell adhesion), GO:0071346 (cellular response to type II interferon), GO:0007259 (receptor signaling pathway via JAK-STAT), GO:0042102 (positive regulation of T cell proliferation), GO:0046635 (positive regulation of alpha-beta T cell activation), GO:0046634 (regulation of alpha-beta T cell activation), GO:0060337 (type I interferon-mediated signaling pathway), GO:0042129 (regulation of T cell proliferation), GO:0046640 (regulation of alpha-beta T cell proliferation), GO:0046641 (positive regulation of alpha-beta T cell proliferation)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0071944 (cell periphery), GO:0012505 (endomembrane system), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0043231 (intracellular membrane-bounded organelle), GO:0031982 (vesicle), GO:0097708 (intracellular vesicle), GO:0005634 (nucleus)