JAK1_MOUSE
ID JAK1_MOUSE Reviewed; 1153 AA.
AC P52332; Q62126;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Tyrosine-protein kinase JAK1;
DE EC=2.7.10.2;
DE AltName: Full=Janus kinase 1;
DE Short=JAK-1;
GN Name=Jak1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8331382; DOI=10.1523/jneurosci.13-07-03006.1993;
RA Yang X., Chung D., Cepko C.L.;
RT "Molecular cloning of the murine JAK1 protein tyrosine kinase and its
RT expression in the mouse central nervous system.";
RL J. Neurosci. 13:3006-3017(1993).
RN [2]
RP PROTEIN SEQUENCE OF 718-723, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 999-1069.
RX PubMed=2482828; DOI=10.1016/0378-1119(89)90465-4;
RA Wilks A.F., Kurban R.R., Hovens C.M., Ralph S.J.;
RT "The application of the polymerase chain reaction to cloning members of the
RT protein tyrosine kinase family.";
RL Gene 85:67-74(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 999-1069.
RX PubMed=2466296; DOI=10.1073/pnas.86.5.1603;
RA Wilks A.F.;
RT "Two putative protein-tyrosine kinases identified by application of the
RT polymerase chain reaction.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:1603-1607(1989).
RN [5]
RP INTERACTION WITH FER.
RX PubMed=12738762; DOI=10.1210/me.2002-0328;
RA Taler M., Shpungin S., Salem Y., Malovani H., Pasder O., Nir U.;
RT "Fer is a downstream effector of insulin and mediates the activation of
RT signal transducer and activator of transcription 3 in myogenic cells.";
RL Mol. Endocrinol. 17:1580-1592(2003).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Tyrosine kinase of the non-receptor type, involved in the
CC IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin
CC (IL)-2 receptor as well as interleukin (IL)-10 receptor. Directly
CC phosphorylates STAT but also activates STAT signaling through the
CC transactivation of other JAK kinases associated with signaling
CC receptors. {ECO:0000250|UniProtKB:P23458}.
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:0000250|UniProtKB:P23458, ECO:0000255|PROSITE-
CC ProRule:PRU10028};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P23458};
CC Note=Mn(2+) was used in the in vitro kinase assay but Mg(2+) is likely
CC to be the in vivo cofactor. {ECO:0000250|UniProtKB:P23458};
CC -!- SUBUNIT: Interacts with IL31RA. Interacts with IFNAR2. Interacts with
CC IFNGR1. Interacts with JAKMIP1. Interacts with SHB. Interacts (via N-
CC terminus) with IL2RB and IL10RA (via its cytoplasmic domain) (By
CC similarity). Interacts with FER (PubMed:12738762).
CC {ECO:0000250|UniProtKB:P23458, ECO:0000269|PubMed:12738762}.
CC -!- SUBCELLULAR LOCATION: Endomembrane system; Peripheral membrane protein.
CC Note=Wholly intracellular, possibly membrane associated.
CC -!- DOMAIN: The FERM domain mediates interaction with JAKMIP1.
CC {ECO:0000250}.
CC -!- DOMAIN: The protein kinase 1 domain is also called the pseudokinase
CC domain and has a regulatory role through the transactivation of other
CC JAK kinases associated with signaling receptors.
CC {ECO:0000250|UniProtKB:P23458}.
CC -!- DOMAIN: The protein kinase 2 domain is the catalytically active domain.
CC {ECO:0000250|UniProtKB:P23458}.
CC -!- PTM: Ubiquitinated by RNF125; leading to its degradation by the
CC proteasome. {ECO:0000250|UniProtKB:P23458}.
CC -!- PTM: Autophosphorylated. Phosphorylated on tyrosine residues in
CC response to interferon gamma signaling. Dephosphorylation of Tyr-1034
CC and Tyr-1034 by PTPN2 negatively regulates cytokine-mediated signaling.
CC {ECO:0000250|UniProtKB:P23458}.
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; S63728; AAB27517.2; -; mRNA.
DR EMBL; M33425; AAA40016.1; -; mRNA.
DR AlphaFoldDB; P52332; -.
DR SMR; P52332; -.
DR CORUM; P52332; -.
DR DIP; DIP-41965N; -.
DR IntAct; P52332; 6.
DR MINT; P52332; -.
DR STRING; 10090.ENSMUSP00000099842; -.
DR BindingDB; P52332; -.
DR ChEMBL; CHEMBL2968; -.
DR GlyConnect; 2803; 1 N-Linked glycan (1 site).
DR GlyGen; P52332; 1 site, 1 N-linked glycan (1 site).
DR iPTMnet; P52332; -.
DR PhosphoSitePlus; P52332; -.
DR SwissPalm; P52332; -.
DR EPD; P52332; -.
DR jPOST; P52332; -.
DR MaxQB; P52332; -.
DR PaxDb; P52332; -.
DR PeptideAtlas; P52332; -.
DR PRIDE; P52332; -.
DR ProteomicsDB; 269115; -.
DR MGI; MGI:96628; Jak1.
DR eggNOG; KOG0197; Eukaryota.
DR InParanoid; P52332; -.
DR PhylomeDB; P52332; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-1059683; Interleukin-6 signaling.
DR Reactome; R-MMU-110056; MAPK3 (ERK1) activation.
DR Reactome; R-MMU-112411; MAPK1 (ERK2) activation.
DR Reactome; R-MMU-1169408; ISG15 antiviral mechanism.
DR Reactome; R-MMU-1266695; Interleukin-7 signaling.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-6783783; Interleukin-10 signaling.
DR Reactome; R-MMU-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-MMU-6788467; IL-6-type cytokine receptor ligand interactions.
DR Reactome; R-MMU-877300; Interferon gamma signaling.
DR Reactome; R-MMU-877312; Regulation of IFNG signaling.
DR Reactome; R-MMU-8854691; Interleukin-20 family signaling.
DR Reactome; R-MMU-8983432; Interleukin-15 signaling.
DR Reactome; R-MMU-8984722; Interleukin-35 Signalling.
DR Reactome; R-MMU-8985947; Interleukin-9 signaling.
DR Reactome; R-MMU-9020558; Interleukin-2 signaling.
DR Reactome; R-MMU-9020591; Interleukin-12 signaling.
DR Reactome; R-MMU-9020956; Interleukin-27 signaling.
DR Reactome; R-MMU-9020958; Interleukin-21 signaling.
DR Reactome; R-MMU-909733; Interferon alpha/beta signaling.
DR Reactome; R-MMU-912526; Interleukin receptor SHC signaling.
DR Reactome; R-MMU-912694; Regulation of IFNA/IFNB signaling.
DR Reactome; R-MMU-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-MMU-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR SABIO-RK; P52332; -.
DR ChiTaRS; Jak1; mouse.
DR PRO; PR:P52332; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P52332; protein.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031730; F:CCR5 chemokine receptor binding; ISO:MGI.
DR GO; GO:0005126; F:cytokine receptor binding; IBA:GO_Central.
DR GO; GO:0005131; F:growth hormone receptor binding; IPI:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0036016; P:cellular response to interleukin-3; IDA:MGI.
DR GO; GO:0098761; P:cellular response to interleukin-7; IDA:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:MGI.
DR GO; GO:0007167; P:enzyme-linked receptor protein signaling pathway; IDA:MGI.
DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; IBA:GO_Central.
DR GO; GO:0038110; P:interleukin-2-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0034112; P:positive regulation of homotypic cell-cell adhesion; ISO:MGI.
DR GO; GO:1904894; P:positive regulation of receptor signaling pathway via STAT; IMP:MGI.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISO:MGI.
DR GO; GO:0150105; P:protein localization to cell-cell junction; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; ISS:UniProtKB.
DR GO; GO:0046677; P:response to antibiotic; ISO:MGI.
DR GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IMP:MGI.
DR CDD; cd14473; FERM_B-lobe; 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; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
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; IPR020776; Tyr_kinase_non-rcpt_Jak1.
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; PR01824; JANUSKINASE1.
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 1: Evidence at protein level;
KW Acetylation; ATP-binding; Direct protein sequencing; Kinase; Magnesium;
KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; SH2 domain; Transferase;
KW Tyrosine-protein kinase; Ubl conjugation.
FT CHAIN 1..1153
FT /note="Tyrosine-protein kinase JAK1"
FT /id="PRO_0000088109"
FT DOMAIN 34..420
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT DOMAIN 439..542
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 582..854
FT /note="Protein kinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 874..1152
FT /note="Protein kinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 1002
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 880..888
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 907
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P23458"
FT MOD_RES 3
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P23458"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23458"
FT MOD_RES 1033
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P23458"
FT MOD_RES 1034
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P23458"
FT CONFLICT 999
FT /note="V -> I (in Ref. 3 and 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 1068..1069
FT /note="VT -> IP (in Ref. 3 and 4)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1153 AA; 133367 MW; 0B9816AEA5B3868B CRC64;
MQYLNIKEDC NAMAFCAKMR SFKKTEVKQV VPEPGVEVTF YLLDREPLRL GSGEYTAEEL
CIRAAQECSI SPLCHNLFAL YDESTKLWYA PNRIITVDDK TSLRLHYRMR FYFTNWHGTN
DNEQSVWRHS PKKQKNGYEK KRVPEATPLL DASSLEYLFA QGQYDLIKCL APIRDPKTEQ
DGHDIENECL GMAVLAISHY AMMKKMQLPE LPKDISYKRY IPETLNKSIR QRNLLTRMRI
NNVFKDFLKE FNNKTICDSS VHDLKVKYLA TLETSTLTKH YGAEIFETSM LLISSENELS
RCHSNDSGNV LYEVMVTGNL GIQWRQKPNV VPVEKEKNKL KRKKLEYNKH KKDDERNKLR
EEWNNFSYFP EITHIVIKES VVSINKQDNK NMELKLSSRE EALSFVSLVD GYFRLTADAH
HYLCTDVAPP LIVHNIQNGC HGPICTEYAI NKLRQEGSEE GMYVLRWSCT DFDNILMTVT
CFEKSEVLGG QKQFKNFQIE VQKGRYSLHG SMDHFPSLRD LMNHLKKQIL RTDNISFVLK
RCCQPKPREI SNLLVATKKA QEWQPVYSMS QLSFDRILKK DIIQGEHLGR GTRTHIYSGT
LLDYKDEEGI AEEKKIKVIL KVLDPSHRDI SLAFFEAASM MRQVSHKHIV YLYGVCVRDV
ENIMVEEFVE GGPLDLFMHR KSDALTTPWK FKVAKQLASA LSYLEDKDLV HGNVCTKNLL
LAREGIDSDI GPFIKLSDPG IPVSVLTRQE CIERIPWIAP ECVEDSKNLS VAADKWSFGT
TLWEICYNGE IPLKDKTLIE KERFYESRCR PVTPSCKELA DLMTRCMNYD PNQRPFFRAI
MRDINKLEEQ NPDIVSEKQP TTEVDPTHFE KRFLKRIRDL GEGHFGKVEL CRYDPEGDNT
GEQVAVKSLK PESGGNHIAD LKKEIEILRN LYHENIVKYK GICMEDGGNG IKLIMEFLPS
GSLKEYLPKN KNKINLKQQL KYAIQICKGM DYLGSRQYVH RDLAARNVLV ESEHQVKIGD
FGLTKAIETD KEYYTVKDDR DSPVFWYAPE CLIQCKFYIA SDVWSFGVTL HELLTYCDSD
FSPMALFLKM IGPTHGQMTV TRLVKTLKEG KRLPCPPNCP DEVYQLMRKC WEFQPSNRTT
FQNLIEGFEA LLK
