JAK2_CHICK
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 03-AUG-2022, entry version 126.
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}.
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DR EMBL; AB159042; BAD07298.1; -; mRNA.
DR AlphaFoldDB; Q75R65; -.
DR SMR; Q75R65; -.
DR STRING; 9031.ENSGALP00000037587; -.
DR PaxDb; Q75R65; -.
DR VEuPathDB; HostDB:geneid_374199; -.
DR eggNOG; KOG0197; Eukaryota.
DR InParanoid; Q75R65; -.
DR PhylomeDB; Q75R65; -.
DR Proteomes; UP000000539; Unplaced.
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:0005126; F:cytokine receptor binding; IBA:GO_Central.
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 kinase activity (H3-Y41 specific); 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:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
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 GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IBA:GO_Central.
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; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
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 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; SSF47031; SSF47031; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 2.
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
