JAK3_RAT
ID JAK3_RAT Reviewed; 1100 AA.
AC Q63272; F1LR79;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2021, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Tyrosine-protein kinase JAK3 {ECO:0000305};
DE EC=2.7.10.2;
DE AltName: Full=Janus kinase 3;
DE Short=JAK-3;
GN Name=Jak3 {ECO:0000312|RGD:2940};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spleen;
RX PubMed=8143863; DOI=10.1016/0014-5793(94)80485-0;
RA Takahashi T., Shirasawa T.;
RT "Molecular cloning of rat JAK3, a novel member of the JAK family of protein
RT tyrosine kinases.";
RL FEBS Lett. 342:124-128(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Non-receptor tyrosine kinase involved in various processes
CC such as cell growth, development, or differentiation. Mediates
CC essential signaling events in both innate and adaptive immunity and
CC plays a crucial role in hematopoiesis during T-cells development. In
CC the cytoplasm, plays a pivotal role in signal transduction via its
CC association with type I receptors sharing the common subunit gamma such
CC as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to
CC cell surface receptors, phosphorylates specific tyrosine residues on
CC the cytoplasmic tails of the receptor, creating docking sites for STATs
CC proteins. Subsequently, phosphorylates the STATs proteins once they are
CC recruited to the receptor. Phosphorylated STATs then form homodimer or
CC heterodimers and translocate to the nucleus to activate gene
CC transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3
CC molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits
CC inducing the tyrosine phosphorylation of both receptor subunits on
CC their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited,
CC phosphorylated and activated by JAK1 and JAK3. Once activated,
CC dimerized STAT5 translocates to the nucleus and promotes the
CC transcription of specific target genes in a cytokine-specific fashion
CC (By similarity). {ECO:0000250}.
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 -!- SUBUNIT: Interacts with STAM2 and MYO18A. Interacts with SHB (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endomembrane system {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: In contrast with the ubiquitous expression of the
CC other JAKs, JAK3 is predominantly expressed in hematopoietic tissues.
CC -!- DOMAIN: Possesses two phosphotransferase domains. The second one
CC contains the catalytic domain, while the presence of a pseudokinase
CC domain is required for suppression of basal activity of JAK3.
CC -!- PTM: Autophosphorylated, leading to regulate its activity. IL2 promotes
CC phosphorylation on tyrosine residues, including autophosphorylation on
CC Tyr-781 (By similarity). Dephosphorylation of Tyr-976 and Tyr-977 by
CC PTPN2 negatively regulates cytokine-mediated signaling (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. JAK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA05868.1; Type=Frameshift; Evidence={ECO:0000305};
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; D28508; BAA05868.1; ALT_FRAME; mRNA.
DR EMBL; AABR07024869; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474031; EDL90763.1; -; Genomic_DNA.
DR EMBL; CH474031; EDL90761.1; -; Genomic_DNA.
DR EMBL; CH474031; EDL90762.1; -; Genomic_DNA.
DR PIR; S43677; S43677.
DR RefSeq; NP_036987.2; NM_012855.2.
DR RefSeq; XP_008769286.1; XM_008771064.2.
DR AlphaFoldDB; Q63272; -.
DR SMR; Q63272; -.
DR STRING; 10116.ENSRNOP00000025312; -.
DR BindingDB; Q63272; -.
DR ChEMBL; CHEMBL4295857; -.
DR iPTMnet; Q63272; -.
DR PhosphoSitePlus; Q63272; -.
DR PaxDb; Q63272; -.
DR PRIDE; Q63272; -.
DR GeneID; 25326; -.
DR KEGG; rno:25326; -.
DR UCSC; RGD:2940; rat.
DR CTD; 3718; -.
DR RGD; 2940; Jak3.
DR VEuPathDB; HostDB:ENSRNOG00000018669; -.
DR eggNOG; KOG0197; Eukaryota.
DR InParanoid; Q63272; -.
DR OMA; TEDLKCW; -.
DR OrthoDB; 58906at2759; -.
DR BRENDA; 2.7.10.2; 5301.
DR Reactome; R-RNO-1266695; Interleukin-7 signaling.
DR Reactome; R-RNO-201556; Signaling by ALK.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-RNO-8854691; Interleukin-20 family signaling.
DR Reactome; R-RNO-8983432; Interleukin-15 signaling.
DR Reactome; R-RNO-8985947; Interleukin-9 signaling.
DR Reactome; R-RNO-9020558; Interleukin-2 signaling.
DR Reactome; R-RNO-9020958; Interleukin-21 signaling.
DR Reactome; R-RNO-912526; Interleukin receptor SHC signaling.
DR PRO; PR:Q63272; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Proteomes; UP000234681; Chromosome 16.
DR Bgee; ENSRNOG00000018669; Expressed in thymus and 19 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
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: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:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:RGD.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISO:RGD.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0030183; P:B cell differentiation; ISS:BHF-UCL.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISO:RGD.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:RGD.
DR GO; GO:0007167; P:enzyme-linked receptor protein signaling pathway; ISS:BHF-UCL.
DR GO; GO:0030218; P:erythrocyte differentiation; IBA:GO_Central.
DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0035771; P:interleukin-4-mediated signaling pathway; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:BHF-UCL.
DR GO; GO:0002731; P:negative regulation of dendritic cell cytokine production; ISS:BHF-UCL.
DR GO; GO:0045221; P:negative regulation of FasL production; ISS:BHF-UCL.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; ISS:BHF-UCL.
DR GO; GO:0032695; P:negative regulation of interleukin-12 production; ISS:BHF-UCL.
DR GO; GO:0050868; P:negative regulation of T cell activation; ISS:BHF-UCL.
DR GO; GO:0045626; P:negative regulation of T-helper 1 cell differentiation; ISS:BHF-UCL.
DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; ISS:BHF-UCL.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IMP:RGD.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IMP:RGD.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:RGD.
DR GO; GO:2000670; P:positive regulation of dendritic cell apoptotic process; ISO:RGD.
DR GO; GO:2001241; P:positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IMP:RGD.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
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:0070232; P:regulation of T cell apoptotic process; ISS:BHF-UCL.
DR GO; GO:0070670; P:response to interleukin-4; ISO:RGD.
DR GO; GO:0043029; P:T cell homeostasis; ISS:BHF-UCL.
DR GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IBA:GO_Central.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR019749; Band_41_domain.
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; IPR011993; PH-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; IPR020775; Tyr_kinase_non-rcpt_Jak3.
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; PR01826; JANUSKINASE3.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00295; B41; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00219; TyrKc; 2.
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.
PE 2: Evidence at transcript level;
KW Adaptive immunity; ATP-binding; Cytoplasm; Immunity; Innate immunity;
KW Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Repeat; SH2 domain; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..1100
FT /note="Tyrosine-protein kinase JAK3"
FT /id="PRO_0000088117"
FT DOMAIN 24..353
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT DOMAIN 372..472
FT /note="SH2; atypical"
FT DOMAIN 517..777
FT /note="Protein kinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 818..1091
FT /note="Protein kinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..223
FT /note="cytokine/interferon/growth hormone receptors"
FT /evidence="ECO:0000250"
FT ACT_SITE 945
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 824..832
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 851
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 17
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62137"
FT MOD_RES 781
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P52333"
FT MOD_RES 900
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P52333"
FT MOD_RES 935
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P52333"
FT MOD_RES 976
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P52333"
FT MOD_RES 977
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P52333"
FT CONFLICT 893
FT /note="S -> E (in Ref. 1; BAA05868)"
FT /evidence="ECO:0000305"
FT CONFLICT 981
FT /note="E -> V (in Ref. 1; BAA05868)"
FT /evidence="ECO:0000305"
FT CONFLICT 1034
FT /note="M -> I (in Ref. 1; BAA05868)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1100 AA; 122726 MW; F7FEBF8D91061C8A CRC64;
MAPPSEETPL ISQRSCSLSS SEAGALHVLL PPRGPGPPQR LSFSFGDYLA EDLCVRAAKA
CGILPVYHSL FALATEDLSC WFPPSHIFSI EDVDTQVLVY RLRFYFPGWF GLETCHRFGL
HKDLTSAILD VHVLEHLFAQ HRSDLVSGRL PVGLSLKDQG EFLSLAVLDL AQMARKQAQR
PGELLKSVSY KACLPPSLRD LIQGQSFVTR RRIRRTVVQA LRRVVACQAD RYALMAKYIL
DLERLHPAAT TESFLVGLPG AQEEPGCLRV TGDNGIAWSS KDQELFQTFC DFPEIVDVSI
KQAPRVGPAG EHRLVTITRM DGHILEAEFP GLPEALSFVA LVDGYFRLIC DSRHFFCKEV
APPRLLEEEA ELCHGPITLD FAIHKLKAAG SLPGSYILRR SPQDYDSFLL TACVQTPLGP
DYKGCLIRQD PSGAFSLVGL SQLHRSLQEL LTACWHSGLQ VDGTALNLTS CCVPRPKEKS
NLIVVRRGRN PTPAPGHSPS CCALTKLSFH TIPADSLEWH ENLGHGSFTK IFHGHRREVV
DGETHDTEVL LKVMDSRHQN CMESFLEAAS LMSQVSYPHL VLLHGVCMAG DSIMVQEFVY
LGAIDTYLRK RGHLVPASWK LQVTKQLAYA LNYLEDKGLP HGNVSARKVL LAREGVDGNP
PFIKLSDPGV SPTVLSLEML TDRIPWVAPE CLQEAGTLNL EADKWGFGAT TWEVFSGAPM
HITSLEPAKK LKFYEDRGQL PALKWTELEG LIAQCMAYDP GRRPSFRAIL RDLNGLITSD
YELLSDPTPG IPNPRDELCG GAQLYACQDP AIFEERHLKY ISLLGKGNFG SVELCRYDPL
GDNTGPLVAV KQLQHSGPEQ QRDFQREIQI LKALHCDFIV KYRGVSYGPG RQSLRLVMEY
LPSGCLRDFL QRHRARLHND RLLLFAWQIC KGMEYLGARR CVHRDLAARN ILVESEAHVK
IADFGLAKLL PLGKDYYVVR EPGQSPIFWY APESLSDNIF SRQSDVWSFG VVLYELFTYS
DKSCSPSTEF LRMMGPEREG SPLCHLLELL AEGRRLPPPS TCPTEVQELM QLCWSPNPQD
RPAFDTLSPQ LDALWRGSPG
