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Q63272

- JAK3_RAT

UniProt

Q63272 - JAK3_RAT

Protein

Tyrosine-protein kinase JAK3

Gene

Jak3

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 1 (01 Nov 1997)
      Previous versions | rss
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    Functioni

    Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion By similarity.By similarity

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei851 – 8511ATPPROSITE-ProRule annotation
    Active sitei945 – 9451Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi824 – 8329ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
    3. protein tyrosine kinase activity Source: RGD
    4. transcription factor binding Source: RGD

    GO - Biological processi

    1. B cell differentiation Source: BHF-UCL
    2. cytokine-mediated signaling pathway Source: RGD
    3. enzyme linked receptor protein signaling pathway Source: BHF-UCL
    4. innate immune response Source: UniProtKB-KW
    5. intracellular signal transduction Source: BHF-UCL
    6. negative regulation of dendritic cell cytokine production Source: BHF-UCL
    7. negative regulation of FasL biosynthetic process Source: BHF-UCL
    8. negative regulation of interleukin-10 production Source: BHF-UCL
    9. negative regulation of interleukin-12 production Source: BHF-UCL
    10. negative regulation of T cell activation Source: BHF-UCL
    11. negative regulation of T-helper 1 cell differentiation Source: BHF-UCL
    12. negative regulation of thymocyte apoptotic process Source: BHF-UCL
    13. peptidyl-tyrosine phosphorylation Source: BHF-UCL
    14. positive regulation of activated T cell proliferation Source: RGD
    15. positive regulation of calcium ion transport Source: RGD
    16. positive regulation of cytosolic calcium ion concentration Source: RGD
    17. positive regulation of immune response Source: RGD
    18. positive regulation of T cell proliferation Source: BHF-UCL
    19. protein autophosphorylation Source: RGD
    20. regulation of T cell apoptotic process Source: BHF-UCL
    21. T cell homeostasis Source: BHF-UCL
    22. tyrosine phosphorylation of Stat5 protein Source: RGD

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Adaptive immunity, Immunity, Innate immunity

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.2. 5301.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein kinase JAK3 (EC:2.7.10.2)
    Alternative name(s):
    Janus kinase 3
    Short name:
    JAK-3
    Gene namesi
    Name:Jak3
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi2940. Jak3.

    Subcellular locationi

    Endomembrane system By similarity; Peripheral membrane protein By similarity. Cytoplasm By similarity

    GO - Cellular componenti

    1. cytoplasm Source: RGD
    2. cytoskeleton Source: InterPro
    3. endomembrane system Source: UniProtKB-SubCell
    4. membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Cytoplasm, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11001100Tyrosine-protein kinase JAK3PRO_0000088117Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei781 – 7811Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei900 – 9001PhosphotyrosineBy similarity
    Modified residuei935 – 9351PhosphotyrosineBy similarity
    Modified residuei976 – 9761Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei977 – 9771Phosphotyrosine; by autocatalysisBy similarity

    Post-translational modificationi

    Autophosphorylated, leading to regulate its activity. IL2 promotes phosphorylation on tyrosine residues, including autophosphorylation on Tyr-781 By similarity. Dephosphorylation of Tyr-976 and Tyr-977 by PTPN2 negatively regulates cytokine-mediated signaling By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiQ63272.

    PTM databases

    PhosphoSiteiQ63272.

    Expressioni

    Tissue specificityi

    In contrast with the ubiquitous expression of the other JAKs, JAK3 is predominantly expressed in hematopoietic tissues.

    Gene expression databases

    GenevestigatoriQ63272.

    Interactioni

    Subunit structurei

    Interacts with STAM2 and MYO18A. Interacts with SHB By similarity.By similarity

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000032301.

    Structurei

    3D structure databases

    ProteinModelPortaliQ63272.
    SMRiQ63272. Positions 810-1098.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini24 – 353330FERMPROSITE-ProRule annotationAdd
    BLAST
    Domaini372 – 472101SH2; atypicalAdd
    BLAST
    Domaini517 – 777261Protein kinase 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini818 – 1091274Protein kinase 2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 223223cytokine/interferon/growth hormone receptorsBy similarityAdd
    BLAST

    Domaini

    Possesses two phosphotransferase domains. The second one contains the catalytic domain, while the presence of a pseudokinase domain is required for suppression of basal activity of JAK3.

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.PROSITE-ProRule annotation
    Contains 1 FERM domain.PROSITE-ProRule annotation
    Contains 2 protein kinase domains.PROSITE-ProRule annotation
    Contains 1 SH2 domain.Curated

    Keywords - Domaini

    Repeat, SH2 domain

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000049158.
    HOVERGENiHBG006195.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR019749. Band_41_domain.
    IPR000299. FERM_domain.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR016251. Tyr_kinase_non-rcpt_Jak/Tyk2.
    IPR020775. Tyr_kinase_non-rcpt_Jak3.
    [Graphical view]
    PfamiPF07714. Pkinase_Tyr. 2 hits.
    [Graphical view]
    PIRSFiPIRSF000636. TyrPK_Jak. 1 hit.
    PRINTSiPR01823. JANUSKINASE.
    PR01826. JANUSKINASE3.
    PR00109. TYRKINASE.
    SMARTiSM00295. B41. 1 hit.
    SM00252. SH2. 1 hit.
    SM00219. TyrKc. 2 hits.
    [Graphical view]
    SUPFAMiSSF55550. SSF55550. 2 hits.
    SSF56112. SSF56112. 2 hits.
    PROSITEiPS50057. FERM_3. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 2 hits.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q63272-1 [UniParc]FASTAAdd to Basket

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    MAPPSEETPL ISQRSCSLSS SEAGALHVLL PPRGPGPPQR LSFSFGDYLA     50
    EDLCVRAAKA CGILPVYHSL FALATEDLSC WFPPSHIFSI EDVDTQVLVY 100
    RLRFYFPGWF GLETCHRFGL HKDLTSAILD VHVLEHLFAQ HRSDLVSGRL 150
    PVGLSLKDQG EFLSLAVLDL AQMARKQAQR PGELLKSVSY KACLPPSLRD 200
    LIQGQSFVTR RRIRRTVVQA LAPCSSLPSR PYALMAKYIL DLERLHPAAT 250
    TESFLVGLPG AQEEPGCLRV TGDNGIAWSS KDQELFQTFC DFPEIVDVSI 300
    KQAPRVGPAG EHRLVTITRM DGHILEAEFP GLPEALSFVA LVDGYFRLIC 350
    DSRHFFCKEV APPRLLEEEA ELCHGPITLD FAIHKLKAAG SLPGSYILRR 400
    SPQDYDSFLL TACVQTPLGP DYKGCLIRQD PSGAFSLVGL SQLHRSLQEL 450
    LTACWHSGLQ VDGTALNLTS CCVPRPKEKS NLIVVRRGRN PTPAPGHSPS 500
    CCALTKLSFH TIPADSLEWH ENLGHGSFTK IFHGHRREVV DGETHDTEVL 550
    LKVMDSRHQN CMESFLEAAS LMSQVSYPHL VLLHGVCMAG DSIMVQEFVY 600
    LGAIDTYLRK RGHLVPASWK LQVTKQLAYA LNYLEDKGLP HGNVSARKVL 650
    LAREGVDGNP PFIKLSDPGV SPTVLSLEML TDRIPWVAPE CLQEAGTLNL 700
    EADKWGFGAT TWEVFSGAPM HITSLEPAKK LKFYEDRGQL PALKWTELEG 750
    LIAQCMAYDP GRRPSFRAIL RDLNGLITSD YELLSDPTPG IPNPRDELCG 800
    GAQLYACQDP AIFEERHLKY ISLLGKGNFG SVELCRYDPL GDNTGPLVAV 850
    KQLQHSGPEQ QRDFQREIQI LKALHCDFIV KYRGVSYGPG RQELRLVMEY 900
    LPSGCLRDFL QRHRARLHND RLLLFAWQIC KGMEYLGARR CVHRDLAARN 950
    ILVESEAHVK IADFGLAKLL PLGKDYYVVR VPGQSPIFWY APESLSDNIF 1000
    SRQSDVWSFG VVLYELFTYS DKSCSPSTEF LRMIGPEREG SPLCHLLELL 1050
    AEGRRLPPPS TCPTEVQELM QLCWSPNPQD RPAFDTLSPQ LDALWRGSPG 1100
    Length:1,100
    Mass (Da):122,561
    Last modified:November 1, 1997 - v1
    Checksum:i1D59CA05F4DD7EE2
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D28508 mRNA. Translation: BAA05868.1.
    PIRiS43677.
    UniGeneiRn.11159.

    Genome annotation databases

    UCSCiRGD:2940. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D28508 mRNA. Translation: BAA05868.1 .
    PIRi S43677.
    UniGenei Rn.11159.

    3D structure databases

    ProteinModelPortali Q63272.
    SMRi Q63272. Positions 810-1098.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000032301.

    PTM databases

    PhosphoSitei Q63272.

    Proteomic databases

    PRIDEi Q63272.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    UCSCi RGD:2940. rat.

    Organism-specific databases

    RGDi 2940. Jak3.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000049158.
    HOVERGENi HBG006195.

    Enzyme and pathway databases

    BRENDAi 2.7.10.2. 5301.

    Miscellaneous databases

    NextBioi 13955491.
    PROi Q63272.

    Gene expression databases

    Genevestigatori Q63272.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR019749. Band_41_domain.
    IPR000299. FERM_domain.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR016251. Tyr_kinase_non-rcpt_Jak/Tyk2.
    IPR020775. Tyr_kinase_non-rcpt_Jak3.
    [Graphical view ]
    Pfami PF07714. Pkinase_Tyr. 2 hits.
    [Graphical view ]
    PIRSFi PIRSF000636. TyrPK_Jak. 1 hit.
    PRINTSi PR01823. JANUSKINASE.
    PR01826. JANUSKINASE3.
    PR00109. TYRKINASE.
    SMARTi SM00295. B41. 1 hit.
    SM00252. SH2. 1 hit.
    SM00219. TyrKc. 2 hits.
    [Graphical view ]
    SUPFAMi SSF55550. SSF55550. 2 hits.
    SSF56112. SSF56112. 2 hits.
    PROSITEi PS50057. FERM_3. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 2 hits.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning of rat JAK3, a novel member of the JAK family of protein tyrosine kinases."
      Takahashi T., Shirasawa T.
      FEBS Lett. 342:124-128(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Spleen.

    Entry informationi

    Entry nameiJAK3_RAT
    AccessioniPrimary (citable) accession number: Q63272
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: November 1, 1997
    Last modified: October 1, 2014
    This is version 124 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3