ID   JAK3_MOUSE              Reviewed;        1100 AA.
AC   Q62137; A2RRI3; Q0D2M8; Q61746; Q61747; Q8BTY6; Q8BYU2;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   21-AUG-2007, sequence version 2.
DT   08-NOV-2023, entry version 214.
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|MGI:MGI:99928};
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] (ISOFORM 2).
RX   PubMed=7518579;
RA   Rane S.G., Reddy E.P.;
RT   "JAK3: a novel JAK kinase associated with terminal differentiation of
RT   hematopoietic cells.";
RL   Oncogene 9:2415-2423(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND MUTAGENESIS
RP   OF LEU-853.
RC   TISSUE=Thymus;
RX   PubMed=8605329;
RA   Gurniak C.B., Berg L.J.;
RT   "Murine JAK3 is preferentially expressed in hematopoietic tissues and
RT   lymphocyte precursor cells.";
RL   Blood 87:3151-3160(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   STRAIN=BALB/cJ;
RX   PubMed=8022486; DOI=10.1038/370153a0;
RA   Witthuhn B.A., Silvennoinen O., Miura O., Lai K.S., Cwik C., Liu E.T.,
RA   Ihle J.N.;
RT   "Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and
RT   4 in lymphoid and myeloid cells.";
RL   Nature 370:153-157(1994).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=C57BL/6J, and NOD; TISSUE=Heart, Spleen, and Thymus;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=FVB/N; TISSUE=Mammary tumor;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=7481767; DOI=10.1126/science.270.5237.794;
RA   Thomis D.C., Gurniak C.B., Tivol E., Sharpe A.H., Berg L.J.;
RT   "Defects in B lymphocyte maturation and T lymphocyte activation in mice
RT   lacking Jak3.";
RL   Science 270:794-797(1995).
RN   [7]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=7481769; DOI=10.1126/science.270.5237.800;
RA   Nosaka T., van Deursen J.M., Tripp R.A., Thierfelder W.E., Witthuhn B.A.,
RA   McMickle A.P., Doherty P.C., Grosveld G.C., Ihle J.N.;
RT   "Defective lymphoid development in mice lacking Jak3.";
RL   Science 270:800-802(1995).
RN   [8]
RP   FUNCTION.
RX   PubMed=9016869; DOI=10.1084/jem.185.2.197;
RA   Thomis D.C., Berg L.J.;
RT   "Peripheral expression of Jak3 is required to maintain T lymphocyte
RT   function.";
RL   J. Exp. Med. 185:197-206(1997).
RN   [9]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=9620658; DOI=10.1002/jlb.63.6.669;
RA   Baird A.M., Thomis D.C., Berg L.J.;
RT   "T cell development and activation in Jak3-deficient mice.";
RL   J. Leukoc. Biol. 63:669-677(1998).
RN   [10]
RP   INTERACTION WITH MYO18A.
RX   PubMed=10733938; DOI=10.1006/bbrc.2000.2413;
RA   Ji H., Zhai Q., Zhu J., Yan M., Sun L., Liu X., Zheng Z.;
RT   "A novel protein MAJN binds to Jak3 and inhibits apoptosis induced by IL-2
RT   deprival.";
RL   Biochem. Biophys. Res. Commun. 270:267-271(2000).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Spleen;
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: 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       {ECO:0000269|PubMed:9016869}.
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   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q62137-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q62137-2; Sequence=VSP_027575, VSP_027576;
CC   -!- TISSUE SPECIFICITY: In contrast with the ubiquitous expression of the
CC       other JAKs, JAK3 is predominantly expressed in hematopoietic tissues.
CC       {ECO:0000269|PubMed:8605329}.
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   -!- DISRUPTION PHENOTYPE: Mice show a severe block in B-cell development at
CC       the pre-B stage in the bone marrow. Additionally, they possesses small
CC       thymuses revealing a defect in T-cell development. The distribution of
CC       developmental subsets is relatively normal, suggesting a block in the
CC       expansion of early T-cell progenitors. Peripheral T-cells are present
CC       at normal or increased numbers but are functionally incompetent.
CC       {ECO:0000269|PubMed:7481767, ECO:0000269|PubMed:7481769,
CC       ECO:0000269|PubMed:9620658}.
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=AAA21415.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=AAA21565.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; L33768; AAA21415.1; ALT_FRAME; mRNA.
DR   EMBL; L40172; AAC42085.1; -; mRNA.
DR   EMBL; L32955; AAA21565.1; ALT_FRAME; mRNA.
DR   EMBL; AK038268; BAC29956.1; -; mRNA.
DR   EMBL; AK142178; BAE24964.1; -; mRNA.
DR   EMBL; AK156646; BAE33790.1; -; mRNA.
DR   EMBL; AK164520; BAE37819.1; -; mRNA.
DR   EMBL; AK088365; BAC40305.1; -; mRNA.
DR   EMBL; BC105577; AAI05578.1; -; mRNA.
DR   EMBL; BC131646; AAI31647.1; -; mRNA.
DR   EMBL; BC131647; AAI31648.1; -; mRNA.
DR   CCDS; CCDS22403.1; -. [Q62137-1]
DR   PIR; I58401; I58401.
DR   PIR; S48053; S48053.
DR   RefSeq; NP_001177759.1; NM_001190830.1.
DR   RefSeq; NP_034719.2; NM_010589.6.
DR   AlphaFoldDB; Q62137; -.
DR   SMR; Q62137; -.
DR   BioGRID; 200858; 5.
DR   IntAct; Q62137; 2.
DR   MINT; Q62137; -.
DR   STRING; 10090.ENSMUSP00000060073; -.
DR   BindingDB; Q62137; -.
DR   ChEMBL; CHEMBL5250; -.
DR   DrugCentral; Q62137; -.
DR   iPTMnet; Q62137; -.
DR   PhosphoSitePlus; Q62137; -.
DR   EPD; Q62137; -.
DR   jPOST; Q62137; -.
DR   MaxQB; Q62137; -.
DR   PaxDb; 10090-ENSMUSP00000060073; -.
DR   ProteomicsDB; 269117; -. [Q62137-1]
DR   ProteomicsDB; 269118; -. [Q62137-2]
DR   DNASU; 16453; -.
DR   GeneID; 16453; -.
DR   KEGG; mmu:16453; -.
DR   UCSC; uc009mel.2; mouse. [Q62137-1]
DR   AGR; MGI:99928; -.
DR   CTD; 3718; -.
DR   MGI; MGI:99928; Jak3.
DR   eggNOG; KOG0197; Eukaryota.
DR   InParanoid; Q62137; -.
DR   OrthoDB; 1614410at2759; -.
DR   PhylomeDB; Q62137; -.
DR   TreeFam; TF327041; -.
DR   BRENDA; 2.7.10.2; 3474.
DR   Reactome; R-MMU-1266695; Interleukin-7 signaling.
DR   Reactome; R-MMU-201556; Signaling by ALK.
DR   Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-MMU-6785807; Interleukin-4 and Interleukin-13 signaling.
DR   Reactome; R-MMU-8854691; Interleukin-20 family signaling.
DR   Reactome; R-MMU-8983432; Interleukin-15 signaling.
DR   Reactome; R-MMU-8985947; Interleukin-9 signaling.
DR   Reactome; R-MMU-9020558; Interleukin-2 signaling.
DR   Reactome; R-MMU-9020958; Interleukin-21 signaling.
DR   Reactome; R-MMU-912526; Interleukin receptor SHC signaling.
DR   BioGRID-ORCS; 16453; 5 hits in 84 CRISPR screens.
DR   ChiTaRS; Jak3; mouse.
DR   PRO; PR:Q62137; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q62137; Protein.
DR   GO; GO:0005737; C:cytoplasm; ISS:BHF-UCL.
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:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISO:MGI.
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: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:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR   GO; GO:0030183; P:B cell differentiation; IMP:BHF-UCL.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0071345; P:cellular response to cytokine stimulus; IMP: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:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0035723; P:interleukin-15-mediated signaling pathway; ISO:MGI.
DR   GO; GO:0038110; P:interleukin-2-mediated signaling pathway; ISO:MGI.
DR   GO; GO:0035771; P:interleukin-4-mediated signaling pathway; ISO:MGI.
DR   GO; GO:0038113; P:interleukin-9-mediated signaling pathway; ISO:MGI.
DR   GO; GO:0035556; P:intracellular signal transduction; IDA:MGI.
DR   GO; GO:0048535; P:lymph node development; TAS:MGI.
DR   GO; GO:0002731; P:negative regulation of dendritic cell cytokine production; IMP:BHF-UCL.
DR   GO; GO:0045221; P:negative regulation of FasL production; IMP:BHF-UCL.
DR   GO; GO:0032693; P:negative regulation of interleukin-10 production; IMP:BHF-UCL.
DR   GO; GO:0032695; P:negative regulation of interleukin-12 production; IMP:BHF-UCL.
DR   GO; GO:0050868; P:negative regulation of T cell activation; IMP:BHF-UCL.
DR   GO; GO:0045626; P:negative regulation of T-helper 1 cell differentiation; IMP:BHF-UCL.
DR   GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; IMP:BHF-UCL.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISS:BHF-UCL.
DR   GO; GO:0051928; P:positive regulation of calcium ion transport; ISS:BHF-UCL.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:BHF-UCL.
DR   GO; GO:2000670; P:positive regulation of dendritic cell apoptotic process; IMP:BHF-UCL.
DR   GO; GO:2001241; P:positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; IMP:BHF-UCL.
DR   GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISO:MGI.
DR   GO; GO:0042102; P:positive regulation of T cell proliferation; ISS:BHF-UCL.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI.
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; IMP:BHF-UCL.
DR   GO; GO:0070672; P:response to interleukin-15; TAS:BHF-UCL.
DR   GO; GO:0070669; P:response to interleukin-2; TAS:BHF-UCL.
DR   GO; GO:0070670; P:response to interleukin-4; ISS:BHF-UCL.
DR   GO; GO:0071104; P:response to interleukin-9; TAS:BHF-UCL.
DR   GO; GO:0043029; P:T cell homeostasis; IMP:BHF-UCL.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; IMP:MGI.
DR   CDD; cd13334; FERM_C_JAK3; 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; 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   PANTHER; PTHR45807; TYROSINE-PROTEIN KINASE HOPSCOTCH; 1.
DR   PANTHER; PTHR45807:SF3; TYROSINE-PROTEIN KINASE JAK3; 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; PR01826; JANUSKINASE3.
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; 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.
PE   1: Evidence at protein level;
KW   Adaptive immunity; Alternative splicing; ATP-binding; Cytoplasm; Immunity;
KW   Innate immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein;
KW   Reference proteome; Repeat; SH2 domain; Transferase;
KW   Tyrosine-protein kinase.
FT   CHAIN           1..1100
FT                   /note="Tyrosine-protein kinase JAK3"
FT                   /id="PRO_0000088116"
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..1100
FT                   /note="Protein kinase 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1..223
FT                   /note="Interaction with cytokine/interferon/growth hormone
FT                   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:0007744|PubMed:21183079"
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   VAR_SEQ         284
FT                   /note="E -> EVLGLGLRSGVRGEAWRLVKKPVRTIRKVASPGRADCTTGQGGGVNL
FT                   KVGPGMELPQGLTWGVTRRVRLDRGRGRTEGDSMDWISGHDPTRPVFSPLTSSPPPHKW
FT                   RWEGGRRGGCAGSRSVIPWLLSLFLFFFFNGFARQGFSYSSGCPGTHFVRPGWPRTQKS
FT                   ACLCLSSAVIKGRVPLRRYCLSFLPQ (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:7518579"
FT                   /id="VSP_027575"
FT   VAR_SEQ         379
FT                   /note="L -> LGASWGQQWGWGWAARTVLGWTWLLSWPRL (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:7518579"
FT                   /id="VSP_027576"
FT   MUTAGEN         853
FT                   /note="L->R: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:8605329"
FT   CONFLICT        62
FT                   /note="G -> A (in Ref. 1; AAA21415 and 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        277
FT                   /note="S -> P (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        281..283
FT                   /note="GDQ -> ND (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        301
FT                   /note="K -> N (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        362
FT                   /note="P -> A (in Ref. 1; AAA21415)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        371..372
FT                   /note="EL -> DV (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        390
FT                   /note="G -> A (in Ref. 1; AAA21415)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        454
FT                   /note="Missing (in Ref. 4; BAC40305)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        467
FT                   /note="N -> Y (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        490
FT                   /note="T -> N (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        518..519
FT                   /note="EW -> G (in Ref. 1; AAA21415)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        535
FT                   /note="R -> S (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        699
FT                   /note="C -> G (in Ref. 4;
FT                   BAC40305/BAC29956/BAE24964/BAE33790/BAE37819)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        716..717
FT                   /note="SG -> QR (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        800
FT                   /note="G -> VA (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        826
FT                   /note="K -> N (in Ref. 5; AAI31647)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        841
FT                   /note="Missing (in Ref. 1; AAA21415)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        857
FT                   /note="G -> V (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        909
FT                   /note="F -> L (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        915..916
FT                   /note="AR -> G (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        916
FT                   /note="R -> A (in Ref. 1; AAA21415)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1032
FT                   /note="R -> S (in Ref. 4;
FT                   BAC40305/BAC29956/BAE24964/BAE33790/BAE37819)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1074
FT                   /note="W -> V (in Ref. 1; AAA21415)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1077
FT                   /note="S -> E (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1085
FT                   /note="G -> A (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1093
FT                   /note="A -> G (in Ref. 1; AAA21415)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1093
FT                   /note="A -> P (in Ref. 2; AAA21565)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1100 AA;  122641 MW;  979A120861ED37C1 CRC64;
     MAPPSEETPL IPQRSCSLSS SEAGALHVLL PPRGPGPPQR LSFSFGDYLA EDLCVRAAKA
     CGILPVYHSL FALATEDFSC WFPPSHIFCI EDVDTQVLVY RLRFYFPDWF GLETCHRFGL
     RKDLTSAILD LHVLEHLFAQ HRSDLVSGRL PVGLSMKEQG EFLSLAVLDL AQMAREQAQR
     PGELLKTVSY KACLPPSLRD VIQGQNFVTR RRIRRTVVLA LRRVVACQAD RYALMAKYIL
     DLERLHPAAT TETFRVGLPG AQEEPGLLRV AGDNGISWSS GDQELFQTFC DFPEIVDVSI
     KQAPRVGPAG EHRLVTVTRM DGHILEAEFP GLPEALSFVA LVDGYFRLIC DSRHYFCKEV
     APPRLLEEEA ELCHGPITLD FAIHKLKAAG SLPGTYILRR SPQDYDSFLL TACVQTPLGP
     DYKGCLIRQD PSGAFSLVGL SQPHRSLREL LAACWNSGLR VDGAALNLTS CCAPRPKEKS
     NLIVVRRGCT PAPAPGCSPS CCALTQLSFH TIPTDSLEWH ENLGHGSFTK IFRGRRREVV
     DGETHDSEVL LKVMDSRHRN CMESFLEAAS LMSQVSYPHL VLLHGVCMAG DSIMVQEFVY
     LGAIDMYLRK RGHLVSASWK LQVTKQLAYA LNYLEDKGLP HGNVSARKVL LAREGGDGNP
     PFIKLSDPGV SPTVLSLEML TDRIPWVAPE CLQEAQTLCL EADKWGFGAT TWEVFSGGPA
     HITSLEPAKK LKFYEDQGQL PALKWTELAG LITQCMAYDP GRRPSFRAIL RDLNGLITSD
     YELLSDPTPG IPSPRDELCG GAQLYACQDP AIFEERHLKY ISLLGKGNFG SVELCRYDPL
     GDNTGPLVAV KQLQHSGPDQ QRDFQREIQI LKALHSDFIV KYRGVSYGPG RQSLRLVMEY
     LPSGCLRDFL QRHRARLHTD RLLLFAWQIC KGMEYLGARR CVHRDLAARN ILVESEAHVK
     IADFGLAKLL PLGKDYYVVR EPGQSPIFWY APESLSDNIF SRQSDVWSFG VVLYELFTYC
     DKSCSPSAEF LRMMGPEREG PPLCRLLELL AEGRRLPPPP TCPTEVQELM QLCWAPSPHD
     RPAFGTLSPQ LDALWRGRPG
//