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Q5RB23

- JAK2_PONAB

UniProt

Q5RB23 - JAK2_PONAB

Protein

Tyrosine-protein kinase JAK2

Gene

JAK2

Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 80 (01 Oct 2014)
      Sequence version 1 (21 Dec 2004)
      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. ATP binding Source: UniProtKB-KW
    2. heme binding Source: UniProtKB
    3. histone binding Source: UniProtKB
    4. histone kinase activity (H3-Y41 specific) Source: UniProtKB
    5. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
    6. protein tyrosine kinase activity Source: UniProtKB

    GO - Biological processi

    1. activation of JAK2 kinase activity Source: UniProtKB
    2. cytokine-mediated signaling pathway Source: UniProtKB
    3. erythrocyte differentiation Source: UniProtKB
    4. histone H3-Y41 phosphorylation Source: UniProtKB
    5. innate immune response Source: UniProtKB-KW
    6. JAK-STAT cascade involved in growth hormone signaling pathway Source: UniProtKB
    7. positive regulation of tyrosine phosphorylation of Stat3 protein Source: UniProtKB
    8. protein autophosphorylation Source: UniProtKB
    9. signal transduction Source: UniProtKB

    Keywords - Molecular functioni

    Chromatin regulator, Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Adaptive immunity, Immunity, Innate immunity

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    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
    OrganismiPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
    Taxonomic identifieri9601 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo
    ProteomesiUP000001595: Unplaced

    Subcellular locationi

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

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11321132Tyrosine-protein kinase JAK2PRO_0000324094Add
    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

    Interactioni

    Subunit structurei

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

    Structurei

    3D structure databases

    ProteinModelPortaliQ5RB23.
    SMRiQ5RB23. 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

    HOGENOMiHOG000049158.
    HOVERGENiHBG006195.
    InParanoidiQ5RB23.
    KOiK04447.

    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.

    Q5RB23-1 [UniParc]FASTAAdd to Basket

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    MGMACLTMTE MEGTSTSSIY QNGDISGNAN SMKQIDPVLL VYLYHSLGKS     50
    EADYLTFPSG EYVAEEICIA ASKACGITPV YHNMFALMSE TERIWYPPNH 100
    VFHIDESTRH NVLYRIRFYF PRWYCSGSNR AYRHGISRGA EAPLLDDFVM 150
    SYLFAQWRHD FVHGWIKVPV THETQEECLG MAVLDMMRIA KENDQTPLAI 200
    YNSISYKTFL PKCIRAKIQD YHILTRKRIR YRFRRFIQQF SQCKATARNL 250
    KLKYLINLET LQSAFYTEKF EVKEPGSGPS GEEIFATIII TGNGGIQWSR 300
    GKHKESETLT EQDLQLYCDF PNIIDVSIKQ ANQEGSNESR VVTIHKQDGK 350
    NLEIELSSLR EALSFVSLID GYYRLTADAH HYLCKEVAPP TVLENIQSNC 400
    HGPISMDFAI SKLKKAGNQT GLYVLRCSPK DFNKYFLTFA VERENVIEYK 450
    HCLITKNENE EYNLSGTKKN FSSLKDLLNC YQMETVRSDN IIFQFTKCCP 500
    PKPKDKSNLL VFRTNGVSDV PTSPTLQRPT HMNQMVFHKI RNEDLIFNES 550
    LGQGTFTKIF KGVRREVGDY GQLHETEVLL KVLDKAHRNY SESFFEAASM 600
    MSKLSHKHLV LNYGVCVCGD ENILVQEFVK FGSLDTYLKK NKNCINILWK 650
    LEVAKQLAWA MHFLEENTLI HGNVCAKNIL LIREEDRKTG NPPFIKLSDP 700
    GISITVLPKD ILQERIPWVP PECIENPKNL NLATDKWSFG TTLWEICSGG 750
    DKPLSALDSQ RKLQFYEDRH QLPAPKWAEL ANLINNCMDY EPDFRPSFRA 800
    IIRDLNSLFT PDYELLTEND MLPNMRIGAL GFSGAFEDRD PTQFEERHLK 850
    FLQQLGKGNF GSVEMCRYDP LQDNTGEVVA VKKLQHSTEE HLRDFEREIE 900
    ILKSLQHDNI VKYKGVCYSA GRRNLKLIME YLPYGSLRDY LQKHKERIDH 950
    KKLLQYTSQI CKGMEYLGTK RYIHRDLATR NILVENENRV KIGDFGLTKV 1000
    LPQDKEYYKV KEPGESPIFW YAPESLTESK FSVASDVWSF GVVLYELFTY 1050
    IEKSKSPPAE FMRMIGNDKQ GQMIVFHLIE LLKNNGRLPR PDGCPDEIYM 1100
    IMTECWNNNV NQRPSFRDLA LRVDQIRDNM AG 1132
    Length:1,132
    Mass (Da):130,704
    Last modified:December 21, 2004 - v1
    Checksum:i25EA1ADCB4B2B918
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    CR858835 mRNA. Translation: CAH91037.1.
    RefSeqiNP_001125600.1. NM_001132128.1.
    UniGeneiPab.11396.

    Genome annotation databases

    GeneIDi100172517.
    KEGGipon:100172517.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    CR858835 mRNA. Translation: CAH91037.1 .
    RefSeqi NP_001125600.1. NM_001132128.1.
    UniGenei Pab.11396.

    3D structure databases

    ProteinModelPortali Q5RB23.
    SMRi Q5RB23. Positions 840-1132.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 100172517.
    KEGGi pon:100172517.

    Organism-specific databases

    CTDi 3717.

    Phylogenomic databases

    HOGENOMi HOG000049158.
    HOVERGENi HBG006195.
    InParanoidi Q5RB23.
    KOi K04447.

    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. The German cDNA consortium
      Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Kidney.

    Entry informationi

    Entry nameiJAK2_PONAB
    AccessioniPrimary (citable) accession number: Q5RB23
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 18, 2008
    Last sequence update: December 21, 2004
    Last modified: October 1, 2014
    This is version 80 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