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Details on Person UniProt:Q62120 Jak2
| Class:Id | ReferenceGeneProduct:93491 |
|---|---|
| _chainChangeLog | chain:1-1129 added on Sat February 7 2015;chain:1-1129 for 93491 removed on Wed February 17 2021;chain:1-1132 for 93491 added on Wed February 17 2021 |
| _displayName | UniProt:Q62120 Jak2 |
| _timestamp | 2025-02-21 19:28:58 |
| chain | chain:1-1132 |
| checksum | 7BA35989B880D0A6 |
| comment | FUNCTION Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin receptor (MPL/TPOR); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. 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, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin. Up-regulates the potassium voltage-gated channel activity of KCNA3 (By similarity).CATALYTIC ACTIVITY L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)COFACTOR Mn(2+) was used in the in vitro kinase assay but Mg(2+) is likely to be the in vivo cofactor.ACTIVITY REGULATION Regulated by autophosphorylation, can both activate or decrease activity (PubMed:20304997, PubMed:21726629, PubMed:8343951). Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008 (By similarity).SUBUNIT Interacts with IL23R, SKB1 and STAM2 (By similarity). Interacts with EPOR (PubMed:11779507, PubMed:8343951). Interacts with LYN (PubMed:9573010). Interacts with SIRPA (PubMed:10842184). Interacts with SH2B1 (PubMed:16824542, PubMed:17565041). Interacts with TEC (PubMed:9473212). Interacts with IFNGR2 (via intracellular domain) (By similarity). Interacts with LEPR (Isoform B) (PubMed:11923481). Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner. Interacts with STRA6 (By similarity). Interacts with ASB2; the interaction targets JAK2 for Notch-induced proteasomal degradation (By similarity). Interacts with MPL/TPOR (By similarity).INTERACTION Ubiquitously expressed throughout most tissues.DOMAIN Possesses 2 protein kinase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for protein kinase 1.PTM Autophosphorylated, leading to regulate its activity. Leptin promotes phosphorylation on tyrosine residues, including phosphorylation on Tyr-813 (PubMed:16824542, PubMed:17565041). Autophosphorylation on Tyr-119 in response to EPO down-regulates its kinase activity (PubMed:17024180). Autophosphorylation on Tyr-868, Tyr-966 and Tyr-972 in response to growth hormone (GH) are required for maximal kinase activity (PubMed:20304997). Also phosphorylated by TEC (PubMed:9473212). Phosphorylated on tyrosine residues in response to interferon gamma signaling (By similarity). Phosphorylated on tyrosine residues in response to a signaling cascade that is activated by increased cellular retinol (PubMed:21368206).PTM Undergoes Notch-induced ubiquitination and subsequent proteasomal degradation which is mediated by ASB1 or ASB2, the substrate-recognition components of probable ECS E3 ubiquitin-protein ligase complexes.DISRUPTION PHENOTYPE Embryos are anemic and die around day 12.5 post-coitum (dpc). Primitive erythrocytes are found, but definitive erythropoiesis is absent. Fetal liver myeloid progenitors, although present based on the expression of lineage specific markers, fail to respond to erythropoietin (Epo), thrombopoietin (Thpo), interleukin-3 (Il3), or granulocyte and macrophage colony-stimulating factor 1 (Csf1 and Csf2). Fetal liver BFU-E and CFU-E colonies are completely absent. However, multilineage hematopoietic stem cells (CD34(low), c-kit(pos)) can be found, and B-lymphopoiesis appears intact.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily. |
| description | recommendedName: fullName evidence="25"Tyrosine-protein kinase JAK2 ecNumber evidence="14 17"2.7.10.2 alternativeName: Janus kinase 2 shortName: JAK-2 |
| geneName | Jak2 |
| identifier | Q62120 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Adaptive immunity ATP-binding Chromatin regulator Cytoplasm Immunity Innate immunity Kinase Magnesium Membrane Metal-binding Nucleotide-binding Nucleus Phosphoprotein Reference proteome Repeat SH2 domain Transferase Tyrosine-protein kinase Ubl conjugation |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:3132113] Weiser, JD [InstanceEdit:3445779] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:8869714] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9627708] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9715482] Weiser, JD [InstanceEdit:9730071] Weiser, JD [InstanceEdit:9767224] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | Jak2 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | JAK2_MOUSE G5E852 Q62124 Q7TQD0 |
| sequenceLength | 1132 |
| species | [Species:48892] Mus musculus |
| (referenceEntity) | [EntityWithAccessionedSequence:205743] Jak2 [cytosol] [Mus musculus] [EntityWithAccessionedSequence:205921] Jak2 [plasma membrane] [Mus musculus] [EntityWithAccessionedSequence:997296] p-Y1007-Jak2 [cytosol] [Mus musculus] [EntityWithAccessionedSequence:2586515] p-12Y-Jak2 [cytosol] [Mus musculus] [EntityWithAccessionedSequence:8950633] p-Jak2 [cytosol] [Mus musculus] |
| (referenceSequence) | [ModifiedResidue:997291] O4'-phospho-L-tyrosine at 1007 [ModifiedResidue:2586510] O4'-phospho-L-tyrosine at 868 [ModifiedResidue:2586519] O4'-phospho-L-tyrosine at 966 [ModifiedResidue:2586524] O4'-phospho-L-tyrosine at 972 [ModifiedResidue:2586539] O4'-phospho-L-tyrosine at 1008 [ModifiedResidue:2671845] O4'-phospho-L-tyrosine at 813 [ModifiedResidue:8950231] phosphorylated residue at unknown position [ModifiedResidue:8951292] O-phospho-L-serine at 523 [ModifiedResidue:9006286] O4'-phospho-L-tyrosine at 119 [ModifiedResidue:9006290] O4'-phospho-L-tyrosine at 570 |
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No pathways have been reviewed or authored by UniProt:Q62120 Jak2 (93491)
