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P52333

- JAK3_HUMAN

UniProt

P52333 - JAK3_HUMAN

Protein

Tyrosine-protein kinase JAK3

Gene

JAK3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 164 (01 Oct 2014)
      Sequence version 2 (19 Jul 2004)
      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.4 Publications

    Catalytic activityi

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei855 – 8551ATPPROSITE-ProRule annotation
    Active sitei949 – 9491Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi828 – 8369ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
    3. protein binding Source: IntAct
    4. protein phosphatase binding Source: UniProtKB
    5. protein tyrosine kinase activity Source: BHF-UCL

    GO - Biological processi

    1. B cell differentiation Source: BHF-UCL
    2. enzyme linked receptor protein signaling pathway Source: BHF-UCL
    3. innate immune response Source: UniProtKB-KW
    4. interleukin-4-mediated signaling pathway Source: BHF-UCL
    5. intracellular signal transduction Source: BHF-UCL
    6. JAK-STAT cascade involved in growth hormone signaling pathway Source: UniProtKB
    7. negative regulation of dendritic cell cytokine production Source: BHF-UCL
    8. negative regulation of FasL biosynthetic process Source: BHF-UCL
    9. negative regulation of interleukin-10 production Source: BHF-UCL
    10. negative regulation of interleukin-12 production Source: BHF-UCL
    11. negative regulation of T cell activation Source: BHF-UCL
    12. negative regulation of T-helper 1 cell differentiation Source: BHF-UCL
    13. negative regulation of thymocyte apoptotic process Source: BHF-UCL
    14. peptidyl-tyrosine phosphorylation Source: BHF-UCL
    15. positive regulation of dendritic cell apoptotic process Source: Ensembl
    16. positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
    17. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    18. protein phosphorylation Source: ProtInc
    19. regulation of T cell apoptotic process Source: BHF-UCL
    20. response to interleukin-15 Source: BHF-UCL
    21. response to interleukin-2 Source: BHF-UCL
    22. response to interleukin-4 Source: BHF-UCL
    23. response to interleukin-9 Source: BHF-UCL
    24. STAT protein import into nucleus Source: UniProtKB
    25. T cell homeostasis Source: UniProtKB
    26. tyrosine phosphorylation of STAT protein Source: UniProtKB

    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. 2681.
    ReactomeiREACT_115529. Interleukin-7 signaling.
    REACT_23891. Interleukin receptor SHC signaling.
    REACT_27283. Interleukin-2 signaling.
    SignaLinkiP52333.

    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
    Leukocyte janus kinase
    Short name:
    L-JAK
    Gene namesi
    Name:JAK3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:6193. JAK3.

    Subcellular locationi

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

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cytoplasm, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID) [MIM:600802]: A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.5 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti58 – 581Missing in T(-)B(+)NK(-) SCID. 1 Publication
    VAR_019337
    Natural varianti100 – 1001Y → C in T(-)B(+)NK(-) SCID. 1 Publication
    VAR_006284
    Natural varianti151 – 1511P → R in T(-)B(+)NK(-) SCID. 2 Publications
    Corresponds to variant rs55778349 [ dbSNP | Ensembl ].
    VAR_010492
    Natural varianti169 – 1691D → E in T(-)B(+)NK(-) SCID. 1 Publication
    VAR_019338
    Natural varianti481 – 4811E → G in T(-)B(+)NK(-) SCID. 1 Publication
    VAR_010493
    Natural varianti582 – 5821R → W in T(-)B(+)NK(-) SCID. 1 Publication
    VAR_010494
    Natural varianti586 – 5927Missing in T(-)B(+)NK(-) SCID; lack of phosphorylation in response to cytokine stimulation.
    VAR_010495
    Natural varianti589 – 5891G → S in T(-)B(+)NK(-) SCID. 1 Publication
    VAR_019339
    Natural varianti759 – 7591C → R in T(-)B(+)NK(-) SCID; constitutive phosphorylation. 1 Publication
    VAR_010497
    Natural varianti910 – 9101L → S in T(-)B(+)NK(-) SCID. 1 Publication
    VAR_010498

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi785 – 7851Y → F: Strong decrease of JAK3 phosphorylation. 1 Publication
    Mutagenesisi855 – 8551K → A: More than 90% loss of STAT5a activation. 1 Publication
    Mutagenesisi904 – 9041Y → F: About 40% loss of STAT5a activation. 1 Publication
    Mutagenesisi939 – 9391Y → F: About 80% loss of STAT5a activation. 1 Publication

    Keywords - Diseasei

    Disease mutation, SCID

    Organism-specific databases

    MIMi600802. phenotype.
    Orphaneti35078. T-B+ severe combined immunodeficiency due to JAK3 deficiency.
    PharmGKBiPA29990.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11241124Tyrosine-protein kinase JAK3PRO_0000088115Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei785 – 7851Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei904 – 9041Phosphotyrosine2 Publications
    Modified residuei939 – 9391Phosphotyrosine2 Publications
    Modified residuei980 – 9801Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei981 – 9811Phosphotyrosine; by autocatalysis2 Publications

    Post-translational modificationi

    Tyrosine phosphorylated in response to IL-2 and IL-4. Dephosphorylation of Tyr-980 and Tyr-981 by PTPN2 negatively regulates cytokine-mediated signaling Probable.4 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP52333.
    PaxDbiP52333.
    PRIDEiP52333.

    PTM databases

    PhosphoSiteiP52333.

    Expressioni

    Tissue specificityi

    In NK cells and an NK-like cell line but not in resting T-cells or in other tissues. The S-form is more commonly seen in hematopoietic lines, whereas the B-form is detected in cells both of hematopoietic and epithelial origins.1 Publication

    Gene expression databases

    ArrayExpressiP52333.
    BgeeiP52333.
    CleanExiHS_JAK3.
    GenevestigatoriP52333.

    Interactioni

    Subunit structurei

    Interacts with STAM2 and MYO18A By similarity. Interacts with SHB.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    KHDRBS1Q076662EBI-518246,EBI-1364

    Protein-protein interaction databases

    BioGridi109921. 32 interactions.
    DIPiDIP-274N.
    IntActiP52333. 12 interactions.
    MINTiMINT-1497014.
    STRINGi9606.ENSP00000391676.

    Structurei

    Secondary structure

    1
    1124
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi816 – 8183
    Helixi819 – 8213
    Beta strandi822 – 83110
    Beta strandi834 – 8418
    Beta strandi845 – 8473
    Beta strandi849 – 85911
    Helixi862 – 87615
    Beta strandi886 – 8916
    Beta strandi893 – 8953
    Beta strandi897 – 9037
    Helixi910 – 9178
    Helixi918 – 9203
    Helixi923 – 94220
    Helixi952 – 9543
    Beta strandi955 – 9595
    Beta strandi962 – 9654
    Helixi968 – 9703
    Beta strandi979 – 9824
    Helixi991 – 9933
    Helixi996 – 10016
    Beta strandi1003 – 10053
    Helixi1006 – 102116
    Turni1022 – 10243
    Helixi1026 – 10283
    Helixi1030 – 10378
    Beta strandi1041 – 10433
    Helixi1046 – 105510
    Helixi1068 – 107710
    Helixi1082 – 10843
    Helixi1088 – 109710

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1YVJX-ray2.55A814-1103[»]
    3LXKX-ray2.00A806-1124[»]
    3LXLX-ray1.74A806-1124[»]
    3PJCX-ray2.20A812-1124[»]
    3ZC6X-ray2.42A/B/C/D813-1100[»]
    3ZEPX-ray2.35A/B/C/D813-1047[»]
    A/B/C/D813-1100[»]
    4HVDX-ray1.85A811-1124[»]
    4HVGX-ray2.75A811-1124[»]
    4HVHX-ray2.30A811-1124[»]
    4HVIX-ray2.40A811-1124[»]
    4I6QX-ray1.85A811-1124[»]
    ProteinModelPortaliP52333.
    SMRiP52333. Positions 24-780, 787-1103.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP52333.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini24 – 356333FERMPROSITE-ProRule annotationAdd
    BLAST
    Domaini375 – 475101SH2; atypicalAdd
    BLAST
    Domaini521 – 781261Protein kinase 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini822 – 1111290Protein kinase 2PROSITE-ProRule annotationAdd
    BLAST

    Region

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

    Domaini

    Possesses two phosphotransferase domains. The second one probably contains the catalytic domain By similarity, while the presence of slight differences suggest a different role for domain 1.1 Publication

    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.
    InParanoidiP52333.
    KOiK11218.
    OMAiNCMESFL.
    OrthoDBiEOG7BW0HM.
    PhylomeDBiP52333.
    TreeFamiTF327041.

    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]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 2 (identifier: P52333-1) [UniParc]FASTAAdd to Basket

    Also known as: JAK3S, Spleen-JAK3

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAPPSEETPL IPQRSCSLLS TEAGALHVLL PARGPGPPQR LSFSFGDHLA     50
    EDLCVQAAKA SGILPVYHSL FALATEDLSC WFPPSHIFSV EDASTQVLLY 100
    RIRFYFPNWF GLEKCHRFGL RKDLASAILD LPVLEHLFAQ HRSDLVSGRL 150
    PVGLSLKEQG ECLSLAVLDL ARMAREQAQR PGELLKTVSY KACLPPSLRD 200
    LIQGLSFVTR RRIRRTVRRA LRRVAACQAD RHSLMAKYIM DLERLDPAGA 250
    AETFHVGLPG ALGGHDGLGL LRVAGDGGIA WTQGEQEVLQ PFCDFPEIVD 300
    ISIKQAPRVG PAGEHRLVTV TRTDNQILEA EFPGLPEALS FVALVDGYFR 350
    LTTDSQHFFC KEVAPPRLLE EVAEQCHGPI TLDFAINKLK TGGSRPGSYV 400
    LRRSPQDFDS FLLTVCVQNP LGPDYKGCLI RRSPTGTFLL VGLSRPHSSL 450
    RELLATCWDG GLHVDGVAVT LTSCCIPRPK EKSNLIVVQR GHSPPTSSLV 500
    QPQSQYQLSQ MTFHKIPADS LEWHENLGHG SFTKIYRGCR HEVVDGEARK 550
    TEVLLKVMDA KHKNCMESFL EAASLMSQVS YRHLVLLHGV CMAGDSTMVQ 600
    EFVHLGAIDM YLRKRGHLVP ASWKLQVVKQ LAYALNYLED KGLPHGNVSA 650
    RKVLLAREGA DGSPPFIKLS DPGVSPAVLS LEMLTDRIPW VAPECLREAQ 700
    TLSLEADKWG FGATVWEVFS GVTMPISALD PAKKLQFYED RQQLPAPKWT 750
    ELALLIQQCM AYEPVQRPSF RAVIRDLNSL ISSDYELLSD PTPGALAPRD 800
    GLWNGAQLYA CQDPTIFEER HLKYISQLGK GNFGSVELCR YDPLGDNTGA 850
    LVAVKQLQHS GPDQQRDFQR EIQILKALHS DFIVKYRGVS YGPGRQSLRL 900
    VMEYLPSGCL RDFLQRHRAR LDASRLLLYS SQICKGMEYL GSRRCVHRDL 950
    AARNILVESE AHVKIADFGL AKLLPLDKDY YVVREPGQSP IFWYAPESLS 1000
    DNIFSRQSDV WSFGVVLYEL FTYCDKSCSP SAEFLRMMGC ERDVPALCRL 1050
    LELLEEGQRL PAPPACPAEV HELMKLCWAP SPQDRPSFSA LGPQLDMLWS 1100
    GSRGCETHAF TAHPEGKHHS LSFS 1124
    Length:1,124
    Mass (Da):125,099
    Last modified:July 19, 2004 - v2
    Checksum:i895D8563439B2B7C
    GO
    Isoform 1 (identifier: P52333-2) [UniParc]FASTAAdd to Basket

    Also known as: JAK3B, Breast-JAK3

    The sequence of this isoform differs from the canonical sequence as follows:
         1071-1124: HELMKLCWAP...EGKHHSLSFS → SAAGLASVSQSVDWAGVSGKPAGA

    Note: May be inactive as it lacks some part of the kinase domain.

    Show »
    Length:1,094
    Mass (Da):121,268
    Checksum:iD491FADB3D772693
    GO
    Isoform 3 (identifier: P52333-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         597-619: TMVQEFVHLGAIDMYLRKRGHLV → ESPPPTHPTPASPKSRLFFPPLF
         620-1124: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:619
    Mass (Da):68,279
    Checksum:i2DA342038998636C
    GO

    Sequence cautioni

    The sequence AAC50227.1 differs from that shown. Reason: Wrong choice of CDS. Was erroneously described as an isoform JAK3M while it is a fragmentary mRNA of INSL3.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti34 – 341G → A in AAA19626. (PubMed:8022790)Curated
    Sequence conflicti45 – 451F → S in AAC50950. (PubMed:8921370)Curated
    Sequence conflicti103 – 1031R → RS in AAC50950. (PubMed:8921370)Curated
    Sequence conflicti147 – 1471Missing in AAC50542. (PubMed:8662778)Curated
    Sequence conflicti187 – 1871T → A in AAC50542. (PubMed:8662778)Curated
    Sequence conflicti212 – 2121R → A in AAA19626. (PubMed:8022790)Curated
    Sequence conflicti212 – 2121R → A in AAC50950. (PubMed:8921370)Curated
    Sequence conflicti222 – 2221R → P in AAA19626. (PubMed:8022790)Curated
    Sequence conflicti222 – 2221R → P in AAC50950. (PubMed:8921370)Curated
    Sequence conflicti271 – 2711L → F in AAC50950. (PubMed:8921370)Curated
    Sequence conflicti287 – 2871Missing in AAC50950. (PubMed:8921370)Curated
    Sequence conflicti610 – 6101M → I in AAC50226. (PubMed:7559633)Curated
    Sequence conflicti845 – 8462GD → AH in AAA19626. (PubMed:8022790)Curated
    Sequence conflicti895 – 8973RQS → EPE in AAC50950. (PubMed:8921370)Curated
    Sequence conflicti896 – 8972QS → PE in AAA19626. (PubMed:8022790)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti12 – 121P → L.1 Publication
    Corresponds to variant rs56061056 [ dbSNP | Ensembl ].
    VAR_041722
    Natural varianti40 – 401R → H.1 Publication
    Corresponds to variant rs56384680 [ dbSNP | Ensembl ].
    VAR_041723
    Natural varianti58 – 581Missing in T(-)B(+)NK(-) SCID. 1 Publication
    VAR_019337
    Natural varianti100 – 1001Y → C in T(-)B(+)NK(-) SCID. 1 Publication
    VAR_006284
    Natural varianti132 – 1321P → T.2 Publications
    Corresponds to variant rs3212723 [ dbSNP | Ensembl ].
    VAR_019336
    Natural varianti151 – 1511P → R in T(-)B(+)NK(-) SCID. 2 Publications
    Corresponds to variant rs55778349 [ dbSNP | Ensembl ].
    VAR_010492
    Natural varianti169 – 1691D → E in T(-)B(+)NK(-) SCID. 1 Publication
    VAR_019338
    Natural varianti481 – 4811E → G in T(-)B(+)NK(-) SCID. 1 Publication
    VAR_010493
    Natural varianti521 – 5211L → V.1 Publication
    Corresponds to variant rs55666418 [ dbSNP | Ensembl ].
    VAR_041724
    Natural varianti527 – 5271L → P in a gastric adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_041725
    Natural varianti582 – 5821R → W in T(-)B(+)NK(-) SCID. 1 Publication
    VAR_010494
    Natural varianti586 – 5927Missing in T(-)B(+)NK(-) SCID; lack of phosphorylation in response to cytokine stimulation.
    VAR_010495
    Natural varianti589 – 5891G → S in T(-)B(+)NK(-) SCID. 1 Publication
    VAR_019339
    Natural varianti688 – 6881I → F.1 Publication
    Corresponds to variant rs35785705 [ dbSNP | Ensembl ].
    VAR_041726
    Natural varianti722 – 7221V → I.4 Publications
    Corresponds to variant rs3213409 [ dbSNP | Ensembl ].
    VAR_010496
    Natural varianti759 – 7591C → R in T(-)B(+)NK(-) SCID; constitutive phosphorylation. 1 Publication
    VAR_010497
    Natural varianti910 – 9101L → S in T(-)B(+)NK(-) SCID. 1 Publication
    VAR_010498

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei597 – 61923TMVQE…RGHLV → ESPPPTHPTPASPKSRLFFP PLF in isoform 3. 1 PublicationVSP_054165Add
    BLAST
    Alternative sequencei620 – 1124505Missing in isoform 3. 1 PublicationVSP_054166Add
    BLAST
    Alternative sequencei1071 – 112454HELMK…SLSFS → SAAGLASVSQSVDWAGVSGK PAGA in isoform 1. 1 PublicationVSP_004989Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U09607 mRNA. Translation: AAA19626.1.
    U31601 mRNA. Translation: AAC50226.1.
    U31602 mRNA. Translation: AAC50227.1. Sequence problems.
    U70065 Genomic DNA. Translation: AAC50950.1.
    AF513860 Genomic DNA. Translation: AAM44860.1.
    AC007201 Genomic DNA. Translation: AAD22741.1.
    CH471106 Genomic DNA. Translation: EAW84639.1.
    BC028068 mRNA. Translation: AAH28068.1.
    U57096 mRNA. Translation: AAC50542.1.
    CCDSiCCDS12366.1. [P52333-1]
    PIRiA55747.
    RefSeqiNP_000206.2. NM_000215.3. [P52333-1]
    XP_006722808.1. XM_006722745.1. [P52333-1]
    UniGeneiHs.515247.

    Genome annotation databases

    EnsembliENST00000458235; ENSP00000391676; ENSG00000105639. [P52333-1]
    ENST00000527670; ENSP00000432511; ENSG00000105639. [P52333-1]
    ENST00000534444; ENSP00000436421; ENSG00000105639. [P52333-2]
    GeneIDi3718.
    KEGGihsa:3718.
    UCSCiuc002nhn.4. human. [P52333-1]
    uc002nho.2. human. [P52333-2]
    uc010xpx.1. human.

    Polymorphism databases

    DMDMi50403745.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology
    JAK3base

    JAK3 mutation db

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U09607 mRNA. Translation: AAA19626.1 .
    U31601 mRNA. Translation: AAC50226.1 .
    U31602 mRNA. Translation: AAC50227.1 . Sequence problems.
    U70065 Genomic DNA. Translation: AAC50950.1 .
    AF513860 Genomic DNA. Translation: AAM44860.1 .
    AC007201 Genomic DNA. Translation: AAD22741.1 .
    CH471106 Genomic DNA. Translation: EAW84639.1 .
    BC028068 mRNA. Translation: AAH28068.1 .
    U57096 mRNA. Translation: AAC50542.1 .
    CCDSi CCDS12366.1. [P52333-1 ]
    PIRi A55747.
    RefSeqi NP_000206.2. NM_000215.3. [P52333-1 ]
    XP_006722808.1. XM_006722745.1. [P52333-1 ]
    UniGenei Hs.515247.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1YVJ X-ray 2.55 A 814-1103 [» ]
    3LXK X-ray 2.00 A 806-1124 [» ]
    3LXL X-ray 1.74 A 806-1124 [» ]
    3PJC X-ray 2.20 A 812-1124 [» ]
    3ZC6 X-ray 2.42 A/B/C/D 813-1100 [» ]
    3ZEP X-ray 2.35 A/B/C/D 813-1047 [» ]
    A/B/C/D 813-1100 [» ]
    4HVD X-ray 1.85 A 811-1124 [» ]
    4HVG X-ray 2.75 A 811-1124 [» ]
    4HVH X-ray 2.30 A 811-1124 [» ]
    4HVI X-ray 2.40 A 811-1124 [» ]
    4I6Q X-ray 1.85 A 811-1124 [» ]
    ProteinModelPortali P52333.
    SMRi P52333. Positions 24-780, 787-1103.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109921. 32 interactions.
    DIPi DIP-274N.
    IntActi P52333. 12 interactions.
    MINTi MINT-1497014.
    STRINGi 9606.ENSP00000391676.

    Chemistry

    BindingDBi P52333.
    ChEMBLi CHEMBL2148.
    GuidetoPHARMACOLOGYi 2049.

    PTM databases

    PhosphoSitei P52333.

    Polymorphism databases

    DMDMi 50403745.

    Proteomic databases

    MaxQBi P52333.
    PaxDbi P52333.
    PRIDEi P52333.

    Protocols and materials databases

    DNASUi 3718.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000458235 ; ENSP00000391676 ; ENSG00000105639 . [P52333-1 ]
    ENST00000527670 ; ENSP00000432511 ; ENSG00000105639 . [P52333-1 ]
    ENST00000534444 ; ENSP00000436421 ; ENSG00000105639 . [P52333-2 ]
    GeneIDi 3718.
    KEGGi hsa:3718.
    UCSCi uc002nhn.4. human. [P52333-1 ]
    uc002nho.2. human. [P52333-2 ]
    uc010xpx.1. human.

    Organism-specific databases

    CTDi 3718.
    GeneCardsi GC19M017935.
    HGNCi HGNC:6193. JAK3.
    MIMi 600173. gene.
    600802. phenotype.
    neXtProti NX_P52333.
    Orphaneti 35078. T-B+ severe combined immunodeficiency due to JAK3 deficiency.
    PharmGKBi PA29990.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000049158.
    HOVERGENi HBG006195.
    InParanoidi P52333.
    KOi K11218.
    OMAi NCMESFL.
    OrthoDBi EOG7BW0HM.
    PhylomeDBi P52333.
    TreeFami TF327041.

    Enzyme and pathway databases

    BRENDAi 2.7.10.2. 2681.
    Reactomei REACT_115529. Interleukin-7 signaling.
    REACT_23891. Interleukin receptor SHC signaling.
    REACT_27283. Interleukin-2 signaling.
    SignaLinki P52333.

    Miscellaneous databases

    EvolutionaryTracei P52333.
    GeneWikii Janus_kinase_3.
    GenomeRNAii 3718.
    NextBioi 14571.
    PROi P52333.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P52333.
    Bgeei P52333.
    CleanExi HS_JAK3.
    Genevestigatori P52333.

    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 L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes."
      Kawamura M., McVicar D.W., Johnston J.A., Blake T.B., Chen Y.-Q., Lal B.K., Lloyd A.R., Kelvin D.J., Staples J.E., Ortaldo J.R., O'Shea J.J.
      Proc. Natl. Acad. Sci. U.S.A. 91:6374-6378(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    2. "A kinase-deficient splice variant of the human JAK3 is expressed in hematopoietic and epithelial cancer cells."
      Lai K.S., Jin Y., Graham D.K., Witthuhn B.A., Ihle J.N., Liu E.T.
      J. Biol. Chem. 270:25028-25036(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORM 2).
    3. "Genomic sequence, organization, and chromosomal localization of human JAK3."
      Riedy M.C., Dutra A.S., Blake T.B., Modi W., Lal B.K., Davis J., Bosse A., O'Shea J.J., Johnston J.A.
      Genomics 37:57-61(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. SeattleSNPs variation discovery resource
      Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-132 AND ILE-722.
    5. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
      Tissue: Blood.
    8. "Expression of Janus kinase 3 in human endothelial and other non-lymphoid and non-myeloid cells."
      Verbsky J.W., Bach E.A., Fang Y.F., Yang L., Randolph D.A., Fields L.E.
      J. Biol. Chem. 271:13976-13980(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 36-191.
    9. "Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2."
      Johnston J.A., Kawamura M., Kirken R.A., Chen Y.Q., Blake T.B., Shibuya K., Ortaldo J.R., McVicar D.W., O'Shea J.J.
      Nature 370:151-153(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN IL2 SIGNALING PATHWAY.
    10. "JAK3 protein tyrosine kinase mediates interleukin-7-induced activation of phosphatidylinositol-3' kinase."
      Sharfe N., Dadi H.K., Roifman C.M.
      Blood 86:2077-2085(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN IL7 SIGNALING PATHWAY.
    11. "Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7."
      Musso T., Johnston J.A., Linnekin D., Varesio L., Rowe T.K., O'Shea J.J., McVicar D.W.
      J. Exp. Med. 181:1425-1431(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    12. Cited for: INTERACTION WITH STAM2.
      Tissue: Fetal brain.
    13. "IL-2 receptor signaling through the Shb adapter protein in T and NK cells."
      Lindholm C.K.
      Biochem. Biophys. Res. Commun. 296:929-936(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SHB.
    14. "The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3."
      Simoncic P.D., Lee-Loy A., Barber D.L., Tremblay M.L., McGlade C.J.
      Curr. Biol. 12:446-453(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CYTOKINE SIGNALING, PHOSPHORYLATION, DEPHOSPHORYLATION AT TYR-980 AND TYR-981 BY PTPN2.
    15. "The pseudokinase domain is required for suppression of basal activity of Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of signal transduction."
      Saharinen P., Silvennoinen O.
      J. Biol. Chem. 277:47954-47963(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOMAIN.
    16. "Tyrosine 813 is a site of JAK2 autophosphorylation critical for activation of JAK2 by SH2-B beta."
      Kurzer J.H., Argetsinger L.S., Zhou Y.J., Kouadio J.L., O'Shea J.J., Carter-Su C.
      Mol. Cell. Biol. 24:4557-4570(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-785, MUTAGENESIS OF TYR-785.
    17. "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
      Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
      Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    18. "Phosphorylation of human Jak3 at tyrosines 904 and 939 positively regulates its activity."
      Cheng H., Ross J.A., Frost J.A., Kirken R.A.
      Mol. Cell. Biol. 28:2271-2282(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-904 AND TYR-939, MUTAGENESIS OF LYS-855; TYR-904 AND TYR-939.
    19. Cited for: REVIEW ON FUNCTION.
    20. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    21. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    22. "IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease-associated inflammation and lymphomagenesis."
      Malamut G., El Machhour R., Montcuquet N., Martin-Lanneree S., Dusanter-Fourt I., Verkarre V., Mention J.J., Rahmi G., Kiyono H., Butz E.A., Brousse N., Cellier C., Cerf-Bensussan N., Meresse B.
      J. Clin. Invest. 120:2131-2143(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN IL15 SIGNALING PATHWAY.
    23. "Crystal structure of the Jak3 kinase domain in complex with a staurosporine analog."
      Boggon T.J., Li Y., Manley P.W., Eck M.J.
      Blood 106:996-1002(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 814-1103 IN COMPLEX WITH STAUROSPORINE ANALOG AFN941, PHOSPHORYLATION AT TYR-980 AND TYR-981.
    24. "Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)."
      Macchi P., Villa A., Giliani S., Sacco M.G., Frattini A., Porta F., Ugazio A.G., Johnston J.A., Candotti F., O'Shea J.J., Vezzoni P., Notarangelo L.D.
      Nature 377:65-68(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT T(-)B(+)NK(-) SCID CYS-100.
    25. "Structural and functional basis for JAK3-deficient severe combined immunodeficiency."
      Candotti F., Oakes S.A., Johnston J.A., Giliani S., Schumacher R.F., Mella P., Fiorini M., Ugazio A.G., Badolato R., Notarangelo L.D., Bozzi F., Macchi P., Strina D., Vezzoni P., Blaese R.M., O'Shea J.J., Villa A.
      Blood 90:3996-4003(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS T(-)B(+)NK(-) SCID GLY-481; 586-LEU--MET-592 DEL AND ARG-759.
    26. "Molecular and biochemical characterization of JAK3 deficiency in a patient with severe combined immunodeficiency over 20 years after bone marrow transplantation: implications for treatment."
      Bozzi F., Lefranc G., Villa A., Badolato R., Schumacher R.F., Khalil G., Loiselet J., Bresciani S., O'Shea J.J., Vezzoni P., Notarangelo L.D., Candotti F.
      Br. J. Haematol. 102:1363-1366(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT T(-)B(+)NK(-) SCID TRP-582.
    27. "Complete genomic organization of the human JAK3 gene and mutation analysis in severe combined immunodeficiency by single-strand conformation polymorphism."
      Schumacher R.F., Mella P., Badolato R., Fiorini M., Savoldi G., Giliani S., Villa A., Candotti F., Tampalini A., O'Shea J.J., Notarangelo L.D.
      Hum. Genet. 106:73-79(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS T(-)B(+)NK(-) SCID ARG-151 AND SER-910, VARIANT ILE-722.
    28. "Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation."
      Roberts J.L., Lengi A., Brown S.M., Chen M., Zhou Y.-J., O'Shea J.J., Buckley R.H.
      Blood 103:2009-2018(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS T(-)B(+)NK(-) SCID ALA-58 DEL; GLU-169 AND SER-589, VARIANT ILE-722.
    29. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-12; HIS-40; THR-132; ARG-151; VAL-521; PRO-527; PHE-688 AND ILE-722.

    Entry informationi

    Entry nameiJAK3_HUMAN
    AccessioniPrimary (citable) accession number: P52333
    Secondary accession number(s): Q13259
    , Q13260, Q13611, Q8N1E8, Q99699, Q9Y6S2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: July 19, 2004
    Last modified: October 1, 2014
    This is version 164 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3