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JAK3 Gene

protein-coding   GIFtS: 73
GCID: GC19M017935

Janus Kinase 3

  See JAK3-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Janus Kinase 31 2 3     JAKL2 5
Leukocyte Janus Kinase1 2 3     JAK3_HUMAN2
Tyrosine-Protein Kinase JAK31 2     LJAK2
JAK-32 3     Janus Kinase 3 (A Protein Tyrosine Kinase, Leukocyte)2
L-JAK2 3     EC 2.7.108
EC 2.7.10.23 8     

External Ids:    HGNC: 61931   Entrez Gene: 37182   Ensembl: ENSG000001056397   OMIM: 6001735   UniProtKB: P523333   

Export aliases for JAK3 gene to outside databases

Previous GC identifers: GC19M018430 GC19M018328 GC19M017780 GC19M017797 GC19M017789 GC19M017790 GC19M017500


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for JAK3 Gene:
The protein encoded by this gene is a member of the Janus kinase (JAK) family of tyrosine kinases involved in
cytokine receptor-mediated intracellular signal transduction. It is predominantly expressed in immune cells and
transduces a signal in response to its activation via tyrosine phosphorylation by interleukin receptors.
Mutations in this gene are associated with autosomal SCID (severe combined immunodeficiency disease). (provided
by RefSeq, Jul 2008)

GeneCards Summary for JAK3 Gene:
JAK3 (Janus kinase 3) is a protein-coding gene. Diseases associated with JAK3 include scid, autosomal recessive, t-negative/b-positive type, and severe combined immune deficiency, autosomal recessive, t cell-negative, b cell-positive, nk cell-negative, jak3-related. GO annotations related to this gene include non-membrane spanning protein tyrosine kinase activity and protein tyrosine kinase activity. An important paralog of this gene is SYK.

UniProtKB/Swiss-Prot: JAK3_HUMAN, P52333
Function: 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

summary for JAK3 Gene:
JAKs (or Janus kinases) are a family of tyrosine kinases that associated with cytokine receptors. Upon
receptor activation JAKs phosphorylate the transcription factors known as STATs and initiate the JAK-STAT
signaling pathway. Four JAK family members have been identified (JAK1, JAK2, JAK3 and Tyk2), which share a
similar protein domain structure: a kinase domain, a regulatory pseudo -kinase domain, a SH2 domain and a
FERM domain. The FERM domain of JAK family members mediates the association of JAK with other enzymes and
cytokine receptors. The JAK Tyk2 associates with the IFN-1, IL-6, 10, 12, and 23 cytokine receptor families.
JAK1 mediates signals from IFN-alpha, beta, gamma and IL-2, 6 receptors. JAK2 transduces signals from the
single chain and IL-3 cytokine receptor families, and from the IFN-gamma receptors. JAK3 associates with the
IL-2 receptor gamma-chain.

Gene Wiki entry for JAK3 (Janus kinase 3) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000019.9  NT_011295.12  NC_018930.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the JAK3 gene promoter:
         STAT5B   Sp1   AP-1   ATF-2   MyoD   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidJAK3 promoter sequence
   Search Chromatin IP Primers for JAK3

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat JAK3


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19p13.1   Ensembl cytogenetic band:  19p13.11   HGNC cytogenetic band: 19p13-p12

JAK3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
JAK3 gene location

GeneLoc information about chromosome 19         GeneLoc Exon Structure

GeneLoc location for GC19M017935:  view genomic region     (about GC identifiers)

Start:
17,935,589 bp from pter      End:
17,958,880 bp from pter
Size:
23,292 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: JAK3_HUMAN, P52333 (See protein sequence)
Recommended Name: Tyrosine-protein kinase JAK3  
Size: 1124 amino acids; 125099 Da
Subunit: Interacts with STAM2 and MYO18A (By similarity). Interacts with SHB
Sequence caution: Sequence=AAC50227.1; Type=Miscellaneous discrepancy; Note=Wrong choice of CDS. Was erroneously
described as an isoform JAK3M while it is a fragmentary mRNA of INSL3;
Selected PDB 3D structures from and Proteopedia for JAK3 (see all 11):
1YVJ (3D)        3LXK (3D)        3LXL (3D)        3PJC (3D)        3ZC6 (3D)        3ZEP (3D)    
Secondary accessions: Q13259 Q13260 Q13611 Q99699 Q9Y6S2
Alternative splicing: 2 isoforms:  P52333-1   P52333-2   (May be inactive as it lacks some part of the kinase domain)

Explore the universe of human proteins at neXtProt for JAK3: NX_P52333

Explore proteomics data for JAK3 at MOPED

Post-translational modifications: 

  • 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)1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for JAK3 (P52333) (see all 9)
     FEERHLK  RDLAARN  TEVLLKV  ASLMSQVS 


    See JAK3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_000206.2  
    ENSEMBL proteins: 
     ENSP00000432511   ENSP00000436421   ENSP00000391676  
    Reactome Protein details: P52333

    JAK3 Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant JAK3 Protein
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    Novus Biologicals JAK3 Proteins
    Novus Biologicals JAK3 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for JAK3

     
    Search eBioscience for Proteins for JAK3 

    JAK3 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of JAK3
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    JAK3 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    GenScript Custom Assay Services for JAK3
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for JAK3
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    Search eBioscience for ELISAs for JAK3 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    IUPHAR Guide to PHARMACOLOGY protein family classification: Janus kinase 3
    Janus kinase (JakA) family

    Selected InterPro protein domains (see all 11):
     IPR017441 Protein_kinase_ATP_BS
     IPR011009 Kinase-like_dom
     IPR000719 Prot_kinase_dom
     IPR020775 Tyr_kinase_non-rcpt_Jak3
     IPR001245 Ser-Thr/Tyr_kinase_cat_dom

    Graphical View of Domain Structure for InterPro Entry P52333

    ProtoNet protein and cluster: P52333

    2 Blocks protein domains:
    IPB008266 Tyrosine protein kinase
    IPB009127 Janus kinase family signature


    UniProtKB/Swiss-Prot: JAK3_HUMAN, P52333
    Domain: 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
    Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily
    Similarity: Contains 1 FERM domain
    Similarity: Contains 2 protein kinase domains
    Similarity: Contains 1 SH2 domain


    Find genes that share domains with JAK3           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: JAK3_HUMAN, P52333
    Function: 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
    Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

         Genatlas biochemistry entry for JAK3:
    Janus tyrosine kinase 3,non receptor type,class III ,cytosolic,tightly linked with INSL3 locus,expressed in
    natural killer cells and other activated leukocytes,associating primarily with IL receptors common gamma
    chain,involved in their signal transduction,also critical for lymphoid development,also potential modulator of
    CD40 (TNFRSF5) signaling

         Enzyme Numbers (IUBMB): EC 2.7.10.21 2 EC 2.7.102

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity ----
    GO:0004713protein tyrosine kinase activity TAS--
    GO:0004715non-membrane spanning protein tyrosine kinase activity IEA--
    GO:0005515protein binding IPI9045636
    GO:0005524ATP binding IEA--
         
    Find genes that share ontologies with JAK3           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for JAK3:
     Decreased viability in HMC1.1  

         5 MGI mutant phenotypes (inferred from 8 alleles(MGI details for Jak3):
     cellular  digestive/alimentary  hematopoietic system  immune system  mortality/aging 

    Find genes that share phenotypes with JAK3           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for JAK3: Jak3tm1Jni Jak3tm1Tks Jak3tm1Ljb Jak3tm1Flv

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for JAK3
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for JAK3

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for JAK3
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for JAK3

    miRNA
    Products:
        
    miRTarBase miRNAs that target JAK3:
    hsa-mir-335-5p (MIRT017636)

    Block miRNA regulation of human, mouse, rat JAK3 using miScript Target Protectors
    3 qRT-PCR Assays for microRNAs that regulate JAK3:
    hsa-miR-9* hsa-miR-377 hsa-miR-181a-2*
    SwitchGear 3'UTR luciferase reporter plasmidJAK3 3' UTR sequence
    Inhib. RNA
    Products:
        
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    Predesigned siRNA for gene silencing in human, mouse, rat JAK3

    Gene Editing
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    Clone
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    GenScript: all cDNA clones in your preferred vector: JAK3 (NM_000215)
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    Addgene plasmids for JAK3 

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    eBioscience FlowRNA Probe Sets ( VA1-12357) for JAK3 


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    JAK3_HUMAN, P52333: Endomembrane system; Peripheral membrane protein (By similarity). Cytoplasm (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol4
    cytoskeleton2
    extracellular2
    nucleus2
    plasma membrane2
    endosome1
    peroxisome1

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005829cytosol TAS--
    GO:0005856cytoskeleton IEA--
    GO:0012505endomembrane system IEA--
    GO:0016020membrane IEA--

    Find genes that share ontologies with JAK3           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for JAK3 About   (see all 41)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1IL-9 Signaling Pathways
    IL-9 Signaling Pathways0.90
    IL-4 Signaling Pathways0.84
    IL-7 Signaling Pathways0.90
    IL-9 Signaling Pathway0.42
    IL-21 Signaling Pathways0.90
    Immune response IL 9 signaling pathway0.42
    Common Cytokine Receptor Gamma-Chain Family Signaling Pathways0.90
    IL-7 Signaling Pathway0.40
    2IL2-mediated signaling events
    IL-2 Signaling pathway0.49
    IL2-mediated signaling events0.49
    3Signaling by Interleukins
    Interleukin receptor SHC signaling0.67
    Signaling by Interleukins0.42
    Interleukin-2 signaling0.67
    Interleukin-7 signaling0.00
    Interleukin-3, 5 and GM-CSF signaling0.59
    4Peptide ligand-binding receptors
    Class A/1 (Rhodopsin-like receptors)0.71
    Peptide ligand-binding receptors0.60
    GPCR ligand binding0.71
    Relaxin receptors0.00
    5Signaling by GPCR
    Signaling by GPCR0.90
    Signal Transduction0.58
    GPCR downstream signaling0.90


    Find genes that share SuperPaths with JAK3           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected R&D Systems Pathways for JAK3 (see all 9)
        IL-21 Signaling Pathways
    IL-2 Signaling Pathways
    IL-4 Signaling Pathways
    IL-7 Signaling Pathways
    Common Cytokine Receptor Gamma-Chain Family Signaling Pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for JAK3 (see all 16)
        IL-4 Pathway
    Molecular Mechanisms of Cancer
    PDGF Pathway
    IL-2 Pathway
    Signaling Involved in Cardiac Hypertrophy

    1 Cell Signaling Technology (CST) Pathway for JAK3
        Jak/Stat Pathway

    5 GeneGo (Thomson Reuters) Pathways for JAK3
        Immune response IL-4 signaling pathway
    Immune response IL-22 signaling pathway
    Immune response IL-9 signaling pathway
    Cytokine production by Th17 cells in CF (Mouse model)
    Immune response IL-2 activation and signaling pathway

    Selected BioSystems Pathways for JAK3 (see all 11)
        Oncostatin M Signaling Pathway
    IL-4 signaling Pathway
    IL-7 Signaling Pathway
    IL-9 Signaling Pathway
    IL-2 Signaling pathway

    1 Sino Biological Pathway for JAK3
        Death Receptor Signaling

    3 Reactome Pathways for JAK3
        Interleukin-7 signaling
    Interleukin receptor SHC signaling
    Interleukin-2 signaling


    Selected Kegg Pathways  (Kegg details for JAK3) (see all 8):
        Chemokine signaling pathway
    PI3K-Akt signaling pathway
    Jak-STAT signaling pathway
    Measles
    HTLV-I infection

        Pathway & Disease-focused RT2 Profiler PCR Arrays including JAK3: 
              Th1/Th2 Response in human mouse rat
              T-Cell Anergy & Immune Tolerance in human mouse rat
              JAK / STAT Signaling Pathway in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for JAK3

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for JAK3 (P523331, 2, 3 ENSP000003916764) via UniProtKB, MINT, STRING, and/or I2D (see all 156)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    KHDRBS1Q076661, 3, ENSP000003138294EBI-518246,EBI-1364 I2D: score=2 STRING: ENSP00000313829
    ERBB3P218602, 3, ENSP000002671014MINT-74564 I2D: score=2 STRING: ENSP00000267101
    CXCR4P610733, ENSP000003868844I2D: score=4 STRING: ENSP00000386884
    CD247P209633, ENSP000003547824I2D: score=3 STRING: ENSP00000354782
    IL2RBP147843, ENSP000002162234I2D: score=3 STRING: ENSP00000216223
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 27):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002731negative regulation of dendritic cell cytokine production ISS--
    GO:0006468protein phosphorylation TAS8022790
    GO:0007167enzyme linked receptor protein signaling pathway ISS--
    GO:0007260tyrosine phosphorylation of STAT protein TAS19290934
    GO:0007262STAT protein import into nucleus TAS19290934

    Find genes that share ontologies with JAK3           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
    Selected ApexBio Compounds for JAK3 (see all 36)     About this table
    CompoundAction CAS #
    1,2,3,4,5,6-HexabromocyclohexanePotently and directly inhibits JAK2[1837-91-8]
    AZ 960novel inhibitor of JAKs[905586-69-8]
    AZD1480novel small-molecule JAK inhibitor[935666-88-9]
    Baricitinib (LY3009104, INCB028050)new selective orally bioavailable inhibitor of JAK1 or JAK2. [1187594-09-7]
    Baricitinib phosphateselective orally bioavailable JAK1/JAK2 inhibitor[1187595-84-1]
    BMS-911543potent and selective inhibitor of JAK2[1271022-90-2]
    CEP-33779highly selective, orally active inhibitor of JAK2[1257704-57-6]
    CercosporamidePotent inhibitor of Mnk2 and JAK3[131436-22-1]
    Cucurbitacin ISelective inhibitor of STAT3/JAK2[2222-7-3]
    CYT387potent and selective inhibitor of JAK1, JAK2,TYK2[1056634-68-4]

    Compounds for JAK3 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    CP 690550 citratePotent JAK inhibitor[540737-29-9]
    1,2,3,4,5,6-Hexabromocyclohexane Inhibits JAK2 autophosphorylation[1837-91-8]
    TCS 21311Potent JAK3 inhibitor. Also inhibits GSK-3beta and PKC[1260181-14-3]
    ZM 449829 Potent, selective JAK3 inhibitor [4452-06-6]
    Lestaurtinib JAK2, FLT3 and TrkA inhibitor [111358-88-4]

    2 HMDB Compounds for JAK3    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--

    2 DrugBank Compounds for JAK3    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    2-(1,1-DIMETHYLETHYL)9-FLUORO-3,6-DIHYDRO-7H-BENZ[H]-IMIDAZ[4,5-F]ISOQUINOLIN-7-ONE-- --target--10592235
    3-{(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}-3-oxopropanenitrile-- --target--10592235

    Selected Novoseek inferred chemical compound relationships for JAK3 gene (see all 30)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tyrosine 82 277 10037026 (6), 17537734 (4), 7479924 (3), 19923221 (3) (see all 99)
    [alcl] 55.9 5 15385932 (1), 12934099 (1), 16763206 (1)
    leflunomide 41.9 4 9469413 (2), 12482141 (1), 16045735 (1)
    propanil 40.5 2 9133424 (1)
    phosphatidylinositol 35.7 1 9045636 (1)
    mg 132 35.7 3 16871283 (1), 16825495 (1), 16939498 (1)
    quinazoline 34 1 10632369 (1)
    wortmannin 30.1 3 14716795 (2), 15740849 (1)
    gp 130 21.2 5 9618263 (1), 10872892 (1), 11557047 (1)
    genistein 19.9 5 19086989 (2), 15183121 (1)



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    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for JAK3 gene: 
    NM_000215.3  

    Unigene Cluster for JAK3:

    Janus kinase 3
    Hs.515247  [show with all ESTs]
    Unigene Representative Sequence: NM_000215
    7 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000527031(uc010ebh.3) ENST00000527670 ENST00000534444(uc002nho.2)
    ENST00000526008(uc010xpx.1) ENST00000528705 ENST00000528293(uc010xpy.1)
    ENST00000458235(uc002nhn.4)
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    hsa-miR-9* hsa-miR-377 hsa-miR-181a-2*
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    Additional mRNA sequence: 

    AK296383.1 AK304392.1 U08340.1 U09607.1 U31317.1 U31601.1 U57096.1 

    8 DOTS entries:

    DT.95133732  DT.307733  DT.92415599  DT.92415598  DT.100016656  DT.95324786  DT.92021985  DT.95084104 

    Selected AceView cDNA sequences (see all 75):

    AA295850 NM_000215 AA252892 BC028068 BM561964 BM756498 BG397564 BQ709825 
    AI651109 AA233621 BX092592 AW500013 CF138282 CF143837 AI760261 AW502902 
    AW576431 BE300962 AI915567 U31601 U09607 BF512748 AW408832 AA233419 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for JAK3 (see all 7)    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19a · 19b ^ 20 ^ 21a · 21b ^ 22a · 22b ^
    SP1:                                                        -                                                           -                                   -   
    SP2:                                                        -                                                                                                   
    SP3:                                                                                                                                                            
    SP4:                                                                                                                                                            
    SP5:                                                                                                                                                        -   

    ExUns: 23a · 23b ^ 24a · 24b · 24c ^ 25 ^ 26a · 26b · 26c
    SP1:                                                      
    SP2:                                                      
    SP3:                                                      
    SP4:                                      -               
    SP5:                                                      


    ECgene alternative splicing isoforms for JAK3

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    JAK3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TAGCTTTAAA
    JAK3 Expression
    About this image

    JAK3 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    JAK3 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.515247

    UniProtKB/Swiss-Prot: JAK3_HUMAN, P52333
    Tissue specificity: 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

        Pathway & Disease-focused RT2 Profiler PCR Arrays including JAK3: 
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for JAK3 gene from Selected species (see all 11)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Jak31 , 5 Janus kinase 31, 5 80.12(n)1
    83.73(a)1
      8 (34.43 cM)5
    164531  NM_010589.61  NP_034719.21 
     716762965 
    chicken
    (Gallus gallus)
    Aves JAK31 Janus kinase 3 66.94(n)
    61.54(a)
      395845  NM_204996.1  NP_990327.1 
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia jak31 Janus kinase 3 (a protein tyrosine kinase, leukocyte) 57.94(n)
    54.38(a)
      100135373  NM_001114045.1  NP_001107517.1 
    zebrafish
    (Danio rerio)
    Actinopterygii jak31 Janus kinase 3 (a protein tyrosine kinase, leukocyte) 58.09(n)
    52.16(a)
      561370  XM_002663087.3  XP_002663133.3 


    ENSEMBL Gene Tree for JAK3 (if available)
    TreeFam Gene Tree for JAK3 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for JAK3 gene
    SYK2  TNK12  JAK22  TNK22  TYK22  ERBB42  JAK12  ERBB32  
    PTK22  ERBB22  ZAP702  EGFR2  PTK2B2  
    3 SIMAP similar genes for JAK3 using alignment to 2 protein entries:     JAK3_HUMAN (see all proteins):
    JAK2    EPHA2    JAK1

    Find genes that share paralogs with JAK3           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for JAK3 (see all 1012)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 19 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0417254
    A gastric adenocarcinoma sample4--see VAR_0417252 L P mis40--------
    rs23026031,2
    C,F,A,Hnon-pathogenic117872575(+) GGGGCT/CCTGGG 1 -- int113Minor allele frequency- C:0.40EA NS NA CSA WA EU 2113
    rs354585301,2
    C,Fnon-pathogenic117876826(+) AGCAGA/C/GGCCAG 2 A syn14NA EU 5959
    rs32127171,2
    C,Fnon-pathogenic117885924(-) CCCCCC/-AGCCC 1 -- int13Minor allele frequency- -:0.03NS CSA 86
    rs1378526251,2
    Cpathogenic117880102(-) AACTGA/CATGGA 2 * C stg10--------
    rs1378526261,2
    Cpathogenic117881747(-) TCAGCC/TGACCC 2 R * stg10--------
    rs22305891,2
    C,Fprobable-non-pathogenic117874738(-) ATCCTC/TAAAGC 2 L syn1 ese33Minor allele frequency- T:0.01MN NA EU 5937
    rs1939223631,2
    Cprobable-non-pathogenic117878112(-) AAACAA/GCTGGC 2 Q syn10--------
    rs557783491,2,,4
    C,Fprobable-pathogenic117885304(+) CCACGG/CGGAGG 2 /P /R mis12Minor allele frequency- C:0.01NA EU 3625
    rs32134091,2,,4
    C,F,Huntested117877051(-) GTGGCG/ATCACC 2 /I /V mis1 ese324Minor allele frequency- A:0.01NS EA NA EU 8438

    HapMap Linkage Disequilibrium report for JAK3 (17935589 - 17958880 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 9 variations for JAK3:    About this table    
    Variant IDTypeSubtypePubMed ID
    dgv3764n71CNV Loss21882294
    nsv911225CNV Loss21882294
    dgv50n68CNV Loss17160897
    nsv911220CNV Loss21882294
    nsv911214CNV Loss21882294
    nsv911219CNV Loss21882294
    dgv3766n71CNV Loss21882294
    nsv911209CNV Loss21882294
    nsv911221CNV Loss21882294

    Human Gene Mutation Database (HGMD): JAK3
    Locus Specific Mutation Databases (LSDB): JAK3

    4 Site Specific Mutation Identification with PCR Assays for JAK3:
    Cosmic IdAA Change
    34213p.V722I
    34172p.Q501H
    34214p.A572V
    34215p.A573V
    SeqTarget long-range PCR primers for resequencing JAK3
    DNA2.0 Custom Variant and Variant Library Synthesis for JAK3

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 600173   
    OMIM disorders: 600802  
    UniProtKB/Swiss-Prot: JAK3_HUMAN, P52333
  • 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. Note=The disease is caused by mutations
    affecting the gene represented in this entry

  • 5 diseases for JAK3:    
    About MalaCards
    scid, autosomal recessive, t-negative/b-positive type    severe combined immune deficiency, autosomal recessive, t cell-negative, b cell-positive, nk cell-negative, jak3-related    jacobsen syndrome    anaplastic large cell lymphoma
    severe combined immunodeficiency

    4 diseases from the University of Copenhagen DISEASES database for JAK3:
    Severe combined immunodeficiency     Leukemia     Lung cancer     Gastrointestinal stromal tumor

    Find genes that share disorders with JAK3           About GenesLikeMe

    Selected Novoseek inferred disease relationships for JAK3 gene (see all 39)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    severe combined immunodeficiency 84.2 39 16418296 (2), 15220007 (2), 10477719 (1), 10972897 (1) (see all 31)
    severe combined immunodeficiency, x-linked 82.8 7 7973658 (2), 9063412 (1), 9843216 (1), 8557662 (1) (see all 5)
    megakaryoblastic leukemia acute 72.7 9 18160671 (1), 18297515 (1), 16843266 (1), 17252020 (1) (see all 9)
    myeloproliferative disorders 62.7 6 18397343 (2), 18160671 (1), 17644747 (1), 18682296 (1) (see all 5)
    polycythemia vera 52.6 1 18291658 (1)
    leukemogenesis 49.1 3 19047679 (1), 16843266 (1)
    anaplastic large cell lymphoma 43 2 12934099 (1), 16554750 (1)
    leukemia 42.9 9 18397343 (3), 10389946 (1), 10229324 (1), 20211620 (1) (see all 5)
    lymphoma t-cell 39.9 4 10229324 (1), 19747563 (1), 9613985 (1), 16170336 (1)
    somatic mutations 33.8 2 18160671 (1), 18559588 (1)

    Genatlas disease: JAK3
    immunodeficiency,severe,combined,with decreased T and NK cells and normal B cells (T-B+NK-)

    Genetic Association Database (GAD): JAK3
    Human Genome Epidemiology (HuGE) Navigator: JAK3 (27 documents)

    Export disorders for JAK3 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for JAK3 gene, integrated from 10 sources (see all 514):
    (articles sorted by number of sources associating them with JAK3)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Genomic sequence, organization, and chromosomal localization of human JAK3. (PubMed id 8921370)1, 2, 3, 9 Riedy M.C.... Johnston J.A. (Genomics 1996)
    2. Phosphorylation of human Jak3 at tyrosines 904 and 939 positively regulates its activity. (PubMed id 18250158)1, 2, 9 Cheng H.... Kirken R.A. (Mol. Cell. Biol. 2008)
    3. Expression of Janus kinase 3 in human endothelial and other non- lymphoid and non-myeloid cells. (PubMed id 8662778)1, 2, 9 Verbsky J.W....Fields L.E. (J. Biol. Chem. 1996)
    4. A kinase-deficient splice variant of the human JAK3 is expressed in hematopoietic and epithelial cancer cells. (PubMed id 7559633)1, 2, 9 Lai K.S.... Liu E.T. (J. Biol. Chem. 1995)
    5. Structural and functional basis for JAK3-deficient severe combined immunodeficiency. (PubMed id 9354668)1, 2, 9 Candotti F....Villa A. (Blood 1997)
    6. Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7. (PubMed id 7535338)1, 2, 9 Musso T.... McVicar D.W. (J. Exp. Med. 1995)
    7. Association of single-nucleotide polymorphisms in JAK3, STAT4, and STAT6 with new cardiovascular events in incident dialysis patients. (PubMed id 19282076)1, 4, 9 Sperati C.J....Kao W.H. (Am. J. Kidney Dis. 2009)
    8. Janus kinases in immune cell signaling. (PubMed id 19290934)1, 2, 9 Ghoreschi K.... O'Shea J.J. (Immunol. Rev. 2009)
    9. The pseudokinase domain is required for suppression of basal activity of Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of signal transduction. (PubMed id 12351625)1, 2, 9 Saharinen P. and Silvennoinen O. (J. Biol. Chem. 2002)
    10. Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). (PubMed id 7659163)1, 2, 9 Macchi P....Notarangelo L.D. (Nature 1995)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 3718 HGNC: 6193 AceView: JAK3 Ensembl:ENSG00000105639 euGenes: HUgn3718
    ECgene: JAK3 Kegg: 3718 H-InvDB: JAK3

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for JAK3 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for JAK3 Genetics and Cytogenetics in Oncology and Haematology
    JAK3basehttp://bioinf.uta.fi/JAK3base/
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=JAK3[genesymbol]
    SeattleSNPshttp://pga.gs.washington.edu/data/jak3/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for JAK3 gene:
    Search GeneIP for patents involving JAK3

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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