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Q62689

- JAK2_RAT

UniProt

Q62689 - JAK2_RAT

Protein

Tyrosine-protein kinase JAK2

Gene

Jak2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 135 (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, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. 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, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin By similarity.By similarity

    Catalytic activityi

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

    Enzyme regulationi

    Regulated by autophosphorylation, can both activate or decrease activity. Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008 By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei882 – 8821ATPPROSITE-ProRule annotation
    Active sitei976 – 9761Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi855 – 8639ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. acetylcholine receptor binding Source: RGD
    2. ATP binding Source: UniProtKB-KW
    3. growth hormone receptor binding Source: BHF-UCL
    4. heme binding Source: UniProtKB
    5. histone binding Source: UniProtKB
    6. histone kinase activity (H3-Y41 specific) Source: UniProtKB
    7. insulin receptor substrate binding Source: RGD
    8. non-membrane spanning protein tyrosine kinase activity Source: Reactome
    9. peptide hormone receptor binding Source: RGD
    10. phosphatidylinositol 3-kinase binding Source: RGD
    11. protein binding Source: IntAct
    12. protein C-terminus binding Source: RGD
    13. protein tyrosine kinase activity Source: UniProtKB
    14. type 1 angiotensin receptor binding Source: RGD

    GO - Biological processi

    1. activation of JAK2 kinase activity Source: UniProtKB
    2. activation of MAPKK activity Source: RGD
    3. axon regeneration Source: RGD
    4. cytokine-mediated signaling pathway Source: UniProtKB
    5. erythrocyte differentiation Source: UniProtKB
    6. extrinsic apoptotic signaling pathway Source: Ensembl
    7. G-protein coupled receptor signaling pathway Source: RGD
    8. histone H3-Y41 phosphorylation Source: UniProtKB
    9. hormone-mediated signaling pathway Source: RGD
    10. host programmed cell death induced by symbiont Source: Ensembl
    11. interferon-gamma-mediated signaling pathway Source: BHF-UCL
    12. interleukin-12-mediated signaling pathway Source: Ensembl
    13. intrinsic apoptotic signaling pathway in response to oxidative stress Source: RGD
    14. JAK-STAT cascade Source: RGD
    15. JAK-STAT cascade involved in growth hormone signaling pathway Source: UniProtKB
    16. mammary gland epithelium development Source: Ensembl
    17. mineralocorticoid receptor signaling pathway Source: RGD
    18. negative regulation of cell-cell adhesion Source: RGD
    19. negative regulation of cell proliferation Source: Ensembl
    20. negative regulation of DNA binding Source: Ensembl
    21. negative regulation of heart contraction Source: RGD
    22. negative regulation of neuron apoptotic process Source: RGD
    23. platelet-derived growth factor receptor signaling pathway Source: RGD
    24. positive regulation of apoptotic process Source: RGD
    25. positive regulation of apoptotic signaling pathway Source: Ensembl
    26. positive regulation of cell activation Source: RGD
    27. positive regulation of cell differentiation Source: RGD
    28. positive regulation of cell migration Source: RGD
    29. positive regulation of cell proliferation Source: RGD
    30. positive regulation of cell-substrate adhesion Source: Ensembl
    31. positive regulation of cytosolic calcium ion concentration Source: RGD
    32. positive regulation of DNA binding Source: RGD
    33. positive regulation of inflammatory response Source: RGD
    34. positive regulation of insulin secretion Source: RGD
    35. positive regulation of interleukin-1 beta production Source: RGD
    36. positive regulation of nitric oxide biosynthetic process Source: RGD
    37. positive regulation of nitric-oxide synthase biosynthetic process Source: BHF-UCL
    38. positive regulation of phosphoprotein phosphatase activity Source: RGD
    39. positive regulation of protein import into nucleus, translocation Source: RGD
    40. positive regulation of sequence-specific DNA binding transcription factor activity Source: RGD
    41. positive regulation of tyrosine phosphorylation of Stat3 protein Source: UniProtKB
    42. protein autophosphorylation Source: UniProtKB
    43. response to antibiotic Source: Ensembl
    44. response to hydroperoxide Source: RGD
    45. response to oxidative stress Source: RGD
    46. signal transduction Source: UniProtKB
    47. STAT protein import into nucleus Source: Ensembl
    48. tumor necrosis factor-mediated signaling pathway Source: Ensembl
    49. tyrosine phosphorylation of Stat1 protein Source: RGD
    50. tyrosine phosphorylation of Stat3 protein Source: RGD
    51. tyrosine phosphorylation of Stat5 protein Source: RGD

    Keywords - Molecular functioni

    Chromatin regulator, 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.
    ReactomeiREACT_195025. Signaling by SCF-KIT.
    REACT_195204. Signaling by Leptin.
    REACT_196232. Factors involved in megakaryocyte development and platelet production.
    REACT_196425. Growth hormone receptor signaling.
    REACT_196446. Interferon gamma signaling.
    REACT_196448. Regulation of IFNG signaling.
    REACT_199232. Prolactin receptor signaling.
    REACT_199244. Interleukin-6 signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein kinase JAK2 (EC:2.7.10.2)
    Alternative name(s):
    Janus kinase 2
    Short name:
    JAK-2
    Gene namesi
    Name:Jak2
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 1

    Organism-specific databases

    RGDi2939. Jak2.

    Subcellular locationi

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

    GO - Cellular componenti

    1. caveola Source: Ensembl
    2. cytoplasm Source: RGD
    3. cytoskeleton Source: InterPro
    4. cytosol Source: RGD
    5. endomembrane system Source: UniProtKB-SubCell
    6. nuclear matrix Source: RGD
    7. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11321132Tyrosine-protein kinase JAK2PRO_0000088114Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei119 – 1191Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei372 – 3721PhosphotyrosineBy similarity
    Modified residuei373 – 3731PhosphotyrosineBy similarity
    Modified residuei523 – 5231PhosphoserineBy similarity
    Modified residuei813 – 8131PhosphotyrosineBy similarity
    Modified residuei868 – 8681Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei966 – 9661Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei972 – 9721Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1007 – 10071Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1008 – 10081Phosphotyrosine; by autocatalysisBy similarity

    Post-translational modificationi

    Autophosphorylated, leading to regulate its activity. Leptin promotes phosphorylation on tyrosine residues, including phosphorylation on Tyr-813. Autophosphorylation on Tyr-119 in response to EPO down-regulates its kinase activity. Autophosphorylation on Tyr-868, Tyr-966 and Tyr-972 in response to growth hormone (GH) are required for maximal kinase activity. Also phosphorylated by TEC By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiQ62689.

    PTM databases

    PhosphoSiteiQ62689.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed throughout most tissues.1 Publication

    Gene expression databases

    GenevestigatoriQ62689.

    Interactioni

    Subunit structurei

    Interacts with EPOR, SIRPA and SH2B1. Interacts with IL23R, LYN, SKB1, STAM2 and TEC By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    InsrP151272EBI-8656708,EBI-7472166
    Ptpn11P414993EBI-8656708,EBI-7180604

    Protein-protein interaction databases

    BioGridi246670. 10 interactions.
    DIPiDIP-491N.
    IntActiQ62689. 3 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliQ62689.
    SMRiQ62689. Positions 840-1132.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini37 – 380344FERMPROSITE-ProRule annotationAdd
    BLAST
    Domaini401 – 48282SH2; atypicalPROSITE-ProRule annotationAdd
    BLAST
    Domaini545 – 809265Protein kinase 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini849 – 1126278Protein kinase 2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 239239Interaction with cytokine/interferon/growth hormone receptorsBy similarityAdd
    BLAST

    Domaini

    The N-terminal domain of JAKs mediates their interaction with cytokine/interferon/growth hormone receptors. Possesses 2 protein kinase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for protein kinase 1 By similarity.By similarity

    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.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, SH2 domain

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00710000106680.
    HOGENOMiHOG000049158.
    HOVERGENiHBG006195.
    InParanoidiQ62689.
    KOiK04447.
    OMAiCHGPISM.
    OrthoDBiEOG7BW0HM.
    PhylomeDBiQ62689.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR019749. Band_41_domain.
    IPR019748. FERM_central.
    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.
    IPR020693. Tyr_kinase_non-rcpt_Jak2.
    [Graphical view]
    PfamiPF07714. Pkinase_Tyr. 2 hits.
    PF00017. SH2. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000636. TyrPK_Jak. 1 hit.
    PRINTSiPR01823. JANUSKINASE.
    PR01825. JANUSKINASE2.
    PR00109. TYRKINASE.
    SMARTiSM00295. B41. 1 hit.
    SM00252. SH2. 1 hit.
    SM00219. TyrKc. 2 hits.
    [Graphical view]
    SUPFAMiSSF47031. SSF47031. 1 hit.
    SSF55550. 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.
    PS50001. SH2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q62689-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGMACLTMTE MEGTSTSPAH QNGDIPGNAN SVKQTEPVLQ VYLYHSLGQA     50
    EGDYLKFPNG EYVAEEICVA ASKACGITPV YHNMFALMSE TERIWYPPNH 100
    VFHIDESTRH NILYRIRFYF PHWYCSGSNR TYRYGVSRGA EAPLLDDFVM 150
    SYLFAQWRHD FVHGWIKVPV THETQEECLG MAVLDMMRIA KEKDQTPLAV 200
    YNSISYKTFL PKCVRAKIQD YHILTRKRIR YRFRRFIQQF SQCKATARNL 250
    KLKYLINLET LQSAFYTEQF EVKESARGPS GEEIFATIII TGNGGIQWSR 300
    GKHKESETLT EQDLQLYCDF PDIIDVSIKQ ANQECSTESR VVTVHKQDGK 350
    VLEIELSSLK EALSFVSLID GYYRLTADAH HYLCKEVAPP AVLENIHSNC 400
    HGPISMDFAI SKLKKAGNQT GLYVLRCSPK DFNKYFLTFA VERENVIEYK 450
    HCLITKNENG EYNLSGTKRN FSSLKDLLNC YQMETVRSDS IIFQFTKCCP 500
    PKPKDKSNLL VFRTNGVSDV QLSPTLQRHN NVNQMVFHKI RNEDLIFNES 550
    LGQGTFTKIF KGVRREVGDY GQLHETEVLL KVLDKAHRNY SESFFEAASM 600
    MSQLSHKHLV LNYGVCVCGE ENILVQEFVK FGSLDTYLKK NKNSINILWK 650
    LGVAKQLAWA MHFLEEKSLI HGNVCAKNIL LIREEDRKTG NPPFIKLSDP 700
    GISITVLPKD ILQERIPWVP PECIENPKNL TLATDKWSFG TTLWEICSGG 750
    DKPLSALDSQ RKLQFYEDKH QLPAPKWTEL ANLINTCMDY EPDFRPAFRA 800
    VIRDLNSLFT PDYELLTEND MLPNMRIGAL GFSGAFEDRD PTQFEERHLK 850
    FLQQLGKGNF GSVEMCRYDP LQDNTGEVVA VKKLQHSTEE HLRDFEREIE 900
    ILKSLQHDNI VKYKGVCYSA GRRNLRLIME YLPYGSLRDY LQKHKERIDH 950
    KKLLQYTSQI CKGMEYLGTK RYIHRDLATR NILVENENRV KIGDFGLTKV 1000
    LPQDKEYYKV KEPGESPIFW YAPESLTESK FSVASDVWSF GVVLYELFTY 1050
    IEKSKSPPVE FMRMIGNDKQ GQMIVFHLIE LLKNNGRLPR PEGCPDEIYV 1100
    IMTECWNNNV NQRPSFRDLS LRVDQIRDSM AA 1132
    Length:1,132
    Mass (Da):130,585
    Last modified:November 1, 1997 - v1
    Checksum:iC3AEDF2FECE8B95A
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U13396 mRNA. Translation: AAA79911.1.
    PIRiJC4127.
    RefSeqiNP_113702.1. NM_031514.1.
    XP_006231257.1. XM_006231195.1.
    UniGeneiRn.18909.

    Genome annotation databases

    EnsembliENSRNOT00000021217; ENSRNOP00000021218; ENSRNOG00000015547.
    GeneIDi24514.
    KEGGirno:24514.
    UCSCiRGD:2939. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U13396 mRNA. Translation: AAA79911.1 .
    PIRi JC4127.
    RefSeqi NP_113702.1. NM_031514.1.
    XP_006231257.1. XM_006231195.1.
    UniGenei Rn.18909.

    3D structure databases

    ProteinModelPortali Q62689.
    SMRi Q62689. Positions 840-1132.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 246670. 10 interactions.
    DIPi DIP-491N.
    IntActi Q62689. 3 interactions.

    Chemistry

    ChEMBLi CHEMBL1075225.

    PTM databases

    PhosphoSitei Q62689.

    Proteomic databases

    PRIDEi Q62689.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000021217 ; ENSRNOP00000021218 ; ENSRNOG00000015547 .
    GeneIDi 24514.
    KEGGi rno:24514.
    UCSCi RGD:2939. rat.

    Organism-specific databases

    CTDi 3717.
    RGDi 2939. Jak2.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00710000106680.
    HOGENOMi HOG000049158.
    HOVERGENi HBG006195.
    InParanoidi Q62689.
    KOi K04447.
    OMAi CHGPISM.
    OrthoDBi EOG7BW0HM.
    PhylomeDBi Q62689.

    Enzyme and pathway databases

    BRENDAi 2.7.10.2. 5301.
    Reactomei REACT_195025. Signaling by SCF-KIT.
    REACT_195204. Signaling by Leptin.
    REACT_196232. Factors involved in megakaryocyte development and platelet production.
    REACT_196425. Growth hormone receptor signaling.
    REACT_196446. Interferon gamma signaling.
    REACT_196448. Regulation of IFNG signaling.
    REACT_199232. Prolactin receptor signaling.
    REACT_199244. Interleukin-6 signaling.

    Miscellaneous databases

    NextBioi 603541.
    PROi Q62689.

    Gene expression databases

    Genevestigatori Q62689.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR019749. Band_41_domain.
    IPR019748. FERM_central.
    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.
    IPR020693. Tyr_kinase_non-rcpt_Jak2.
    [Graphical view ]
    Pfami PF07714. Pkinase_Tyr. 2 hits.
    PF00017. SH2. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000636. TyrPK_Jak. 1 hit.
    PRINTSi PR01823. JANUSKINASE.
    PR01825. JANUSKINASE2.
    PR00109. TYRKINASE.
    SMARTi SM00295. B41. 1 hit.
    SM00252. SH2. 1 hit.
    SM00219. TyrKc. 2 hits.
    [Graphical view ]
    SUPFAMi SSF47031. SSF47031. 1 hit.
    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.
    PS50001. SH2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning of the gene encoding rat JAK2, a protein tyrosine kinase."
      Duhe R.J., Rui H., Greenwood J.D., Garvey K., Farrar W.L.
      Gene 158:281-285(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiJAK2_RAT
    AccessioniPrimary (citable) accession number: Q62689
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: November 1, 1997
    Last modified: October 1, 2014
    This is version 135 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