ID JAK2_CHICK Reviewed; 1129 AA. AC Q75R65; DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 24-JAN-2024, entry version 133. DE RecName: Full=Tyrosine-protein kinase JAK2 {ECO:0000250|UniProtKB:O60674}; DE EC=2.7.10.2 {ECO:0000250|UniProtKB:O60674}; DE AltName: Full=Janus kinase 2; DE Short=JAK-2; GN Name=JAK2 {ECO:0000250|UniProtKB:O60674}; OS Gallus gallus (Chicken). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae; OC Phasianinae; Gallus. OX NCBI_TaxID=9031; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=White leghorn; TISSUE=Spleen; RA Sayed A.A., Horiuchi H., Furusawa S., Matsuda H.; RT "molecular cloning and characterization of chicken tyrosine kinase JAK-2."; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Non-receptor tyrosine kinase involved in various processes CC such as cell growth, development, differentiation or histone CC modifications. Mediates essential signaling events in both innate and CC adaptive immunity. In the cytoplasm, plays a pivotal role in signal CC transduction via its association with cytokine receptors. Following CC ligand-binding to cell surface receptors, phosphorylates specific CC tyrosine residues on the cytoplasmic tails of the receptor, creating CC docking sites for STATs proteins. Subsequently, phosphorylates the CC STATs proteins once they are recruited to the receptor. Phosphorylated CC STATs then form homodimer or heterodimers and translocate to the CC nucleus to activate gene transcription. For example, cell stimulation CC with erythropoietin (EPO) during erythropoiesis leads to JAK2 CC autophosphorylation, activation, and its association with CC erythropoietin receptor (EPOR) that becomes phosphorylated in its CC cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, CC phosphorylated and activated by JAK2. Once activated, dimerized STAT5 CC translocates into the nucleus and promotes the transcription of several CC essential genes involved in the modulation of erythropoiesis. Part of a CC signaling cascade that is activated by increased cellular retinol and CC that leads to the activation of STAT5 (STAT5A or STAT5B). In the CC nucleus, plays a key role in chromatin by specifically mediating CC phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag CC that promotes exclusion of CBX5 (HP1 alpha) from chromatin. CC {ECO:0000250|UniProtKB:O60674}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028}; CC -!- ACTIVITY REGULATION: Regulated by autophosphorylation, can both CC activate or decrease activity. Heme regulates its activity by enhancing CC the phosphorylation on Tyr-1004 and Tyr-1005. CC {ECO:0000250|UniProtKB:O60674, ECO:0000250|UniProtKB:Q62120}. CC -!- SUBCELLULAR LOCATION: Endomembrane system {ECO:0000250}; Peripheral CC membrane protein {ECO:0000250}. Nucleus {ECO:0000250}. CC -!- DOMAIN: Possesses 2 protein kinase domains. The second one probably CC contains the catalytic domain, while the presence of slight differences CC suggest a different role for protein kinase 1 (By similarity). CC {ECO:0000250}. CC -!- PTM: Autophosphorylated, leading to regulate its activity. CC {ECO:0000250|UniProtKB:O60674, ECO:0000250|UniProtKB:Q62120}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. JAK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB159042; BAD07298.1; -; mRNA. DR AlphaFoldDB; Q75R65; -. DR SMR; Q75R65; -. DR STRING; 9031.ENSGALP00000074116; -. DR PaxDb; 9031-ENSGALP00000037587; -. DR VEuPathDB; HostDB:geneid_374199; -. DR eggNOG; KOG0197; Eukaryota. DR InParanoid; Q75R65; -. DR PhylomeDB; Q75R65; -. DR Proteomes; UP000000539; Unassembled WGS sequence. DR GO; GO:0005856; C:cytoskeleton; IEA:InterPro. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005131; F:growth hormone receptor binding; IBA:GO_Central. DR GO; GO:0020037; F:heme binding; ISS:UniProtKB. DR GO; GO:0042393; F:histone binding; ISS:UniProtKB. DR GO; GO:0035401; F:histone H3Y41 kinase activity; ISS:UniProtKB. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central. DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB. DR GO; GO:0042976; P:activation of Janus kinase activity; ISS:UniProtKB. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISS:UniProtKB. DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB. DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; ISS:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:UniProt. DR GO; GO:0043687; P:post-translational protein modification; ISS:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB. DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IBA:GO_Central. DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central. DR GO; GO:0007165; P:signal transduction; ISS:UniProtKB. DR CDD; cd14473; FERM_B-lobe; 1. DR CDD; cd13333; FERM_C_JAK2; 1. DR CDD; cd05078; PTK_Jak2_rpt1; 1. DR CDD; cd14205; PTKc_Jak2_rpt2; 1. DR CDD; cd10379; SH2_Jak2; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 2. DR InterPro; IPR019749; Band_41_domain. DR InterPro; IPR035963; FERM_2. DR InterPro; IPR019748; FERM_central. DR InterPro; IPR000299; FERM_domain. DR InterPro; IPR041155; FERM_F1. DR InterPro; IPR041046; FERM_F2. DR InterPro; IPR041381; JAK1-3/TYK2_PHL_dom. DR InterPro; IPR037838; JAK2_FERM_C-lobe. DR InterPro; IPR035860; JAK2_SH2. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR035588; PTK_Jak2_rpt1. DR InterPro; IPR035589; PTKc_Jak2_rpt2. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR016251; Tyr_kinase_non-rcpt_Jak/Tyk2. DR InterPro; IPR020693; Tyr_kinase_non-rcpt_Jak2. DR PANTHER; PTHR45807; TYROSINE-PROTEIN KINASE HOPSCOTCH; 1. DR PANTHER; PTHR45807:SF1; TYROSINE-PROTEIN KINASE JAK2; 1. DR Pfam; PF18379; FERM_F1; 1. DR Pfam; PF18377; FERM_F2; 1. DR Pfam; PF17887; Jak1_Phl; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 2. DR PIRSF; PIRSF000636; TyrPK_Jak; 1. DR PRINTS; PR01823; JANUSKINASE. DR PRINTS; PR01825; JANUSKINASE2. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00295; B41; 1. DR SMART; SM00252; SH2; 1. DR SMART; SM00219; TyrKc; 2. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 2. DR SUPFAM; SSF47031; Second domain of FERM; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR PROSITE; PS50057; FERM_3; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 2. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50001; SH2; 1. PE 2: Evidence at transcript level; KW ATP-binding; Chromatin regulator; Kinase; Membrane; Nucleotide-binding; KW Nucleus; Phosphoprotein; Reference proteome; Repeat; SH2 domain; KW Transferase; Tyrosine-protein kinase. FT CHAIN 1..1129 FT /note="Tyrosine-protein kinase JAK2" FT /id="PRO_0000324095" FT DOMAIN 35..378 FT /note="FERM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084" FT DOMAIN 399..480 FT /note="SH2; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 542..806 FT /note="Protein kinase 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 846..1118 FT /note="Protein kinase 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT ACT_SITE 973 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 852..860 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 879 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 117 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 865 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 963 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 969 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 1004 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:O60674" FT MOD_RES 1005 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:O60674" SQ SEQUENCE 1129 AA; 129847 MW; 1631EE82D331B9BE CRC64; MACLTMANIE GSATATVHQN GDILGNTSAP KQTEPLLQVY LYYSPGKTGG DYLQFPAGEY VAEEICIVAC KACGIMPVYH NMFALMSETE RVWYPPNHIF HVDEATRLKL LYRIRFYFPH WYCNGTSRAC RYGIIRGSES PVLDDLVMSY LFAQWRKDFL DGWIQMPVTH ETQEECLGMA VLDMMRVAKE KDQTPLAVYN SVSYKMFLPK CVRAKIQEYH ILTRKRIRYR FRKFIQQFGQ CKATARNLKL KYLINLETLQ SAFYSEVFEV KEPGGDPSGE ESFATIVITG NGGIQCSRGK LKNCETLAEQ DLQTYCDFPD IIDVSIKQAS QEGSSERRIV TIHKQDSKNL EAEFQSLREA LSFVSLIDGY YRLTADAHHY LCKEVAPPSV LENIQSNCHG PIFMDFAINK LKKAGNQTGF YVLRCSPKDF KKYFLTFAIE RENATDYKHC LITKNENGEY NLSGTKRSFG NLKDLLTCYQ TETVRSDSII FQFIKCCPPK PKDKSNLLVF RSNSVSDVPS SPTLQRHNVS QMVFHKIRNE DLIFEESLGQ GTFTKIFKGI RKEVGDYGQL HQTEVLLKVL DKVHRNYSES FFEAASMMSQ LSYKHLVLNY GVCVCGEENI LVQEYVKFGS LDTYLKKNKN VINILWKLEV AKQLALAMHF LEDKGLVHGN VCAKNILLIR EEDRKSGNLP FIKLSDPGIS ITVLPRDILL ERIPWVPPEC IENPRQLSLA TDKWSFGTTL WEICSGGDKP LSALDSSRKL QFYEDRHQLP APNWTELANL INNCMDYEPD FRPSFRAIIR DLNSLFTPDY ELLTENDMLP NIRTGALGFS GAFEDRDPTQ FEERHLKFLQ QLGKGNFGSV EMCRYDPLQD NTGEVVAVKK LQHSTEEHLR DFEREIEILK SLQHDNIVKY KGVCYSAGRR NLRLIMEYLP YGSLRDYLQK HKERLDHKKL LLYASQICKG MEYLGTKRYV HRDLATRNIL VENENRVKIG DFGLTKVLPQ DKEYYKVKEP GESPIFWYAP ESLTESKFSV ASDVWSFGVV LYELFTYIEK SKSPPAEFMR MIGNDKQGQM IVFHLIELLK NNGRLPRPDG CPDEIYAIMK ECWNNNVAQR PTFRDLAQRV DQIRDNMGG //