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FLASH GENE
Symbol JAK2 contributors: mct/shn - updated : 10-08-2011
HGNC name Janus kinase 2
HGNC id 6192
Corresponding disease
MPD Ph1-negative myeloproliferative disorders, JAK2 mutated
PRV polycythemia rubra vera
Location 9p24.1      Physical location : 4.985.244 - 5.128.182
Synonym name
  • Janus kinase 2 (a protein tyrosine kinase)
  • tyrosine-protein kinase JAK2
  • Synonym symbol(s) EVI139, JTK10
    EC.number 2.7.1.112, 2.7.10.1
    DNA
    TYPE functioning gene
    STRUCTURE 142.94 kb     25 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - D9S1686 - D9S1810 - JAK2 - D9S1681 - D9S1852 - cen
    Physical map
    KIAA0020 9p24.2 KIAA0020 LOC392281 9 similar to G protein pathway suppressor 2 LOC138234 9p24.2 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit d pseudogene CARM1L 9p24.2 coactivator associated arginine methyltransferase 1-like RFX3 9p24 regulatory factor X, 3 (influences HLA class II expression) ZNF515 9p24.2 zinc finger protein 515 C9orf70 9p24.2 chromosome 9 open reading frame 70 SLC1A1 9p24 solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1 C9orf68 9p24.2 chromosome 9 open reading frame 68 HARC 9p24.1 chromosome 9 open reading frame 68 AK3L1 9p24.1-p24.3 adenylate kinase 3 like 1 LOC392282 9 similar to ribosomal protein S5 RCL1 9p24.1-p23 RNA terminal phosphate cyclase-like 1 JAK2 9p24 Janus kinase 2 (a protein tyrosine kinase) INSL6 9p24 insulin-like 6 INSL4 9p24.1-p23.3 insulin-like 4 (placenta) RLN2 9pter-q12 relaxin 2 (H2) RLN1 9pter-q12 relaxin 1 (H1) C9orf46 9p24.1 chromosome 9 open reading frame 46 PDCD1LG1 9p24 programmed cell death 1 ligand 1 PDCD1LG2 9p24.2 programmed cell death 1 ligand 2 KIAA1432 9p24.1 KIAA1432 KIAA1815 9p24 KIAA1815 MLANA 9p24.1 melan-A KIAA2026 9p24.1 KIAA2026 RANBP6 12p13.31 RAN binding protein 6 C9orf26 9p24.1 chromosome 9 open reading frame 26 (NF-HEV) LOC389704 9 similar to Selenoprotein T NYD-SP25 9p24.1 protein kinase NYD-SP25 NIRF 9p24.1 Np95-like ring finger protein C9orf38 9p24.1 chromosome 9 open reading frame 38 GLDC 9p24-p23 glycine dehydrogenase (decarboxylating; glycine decarboxylase, glycine cleavage system protein P) LOC392283 9 similar to ribosomal protein S3a; 40S ribosomal protein S3a; v-fos transformation effector protein 1 LOC392284 9 hypothetical gene supported by AK091574 GASC1 9p24-p23 hypothetical gene supported by AK091574 LOC158352 9p24.1 similar to small nuclear ribonucleoprotein E
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    25 - 5285 - 1132 - 2009 19181784
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Digestiveintestinesmall intestine  moderately Homo sapiens
     intestinelarge intestinecolon moderately Homo sapiens
    Endocrinepancreas   lowly Homo sapiens
    Lymphoid/Immunespleen   highly Homo sapiens
     thymus   moderately Homo sapiens
    Nervousbrain   lowly Homo sapiens
    Reproductivefemale systemplacenta  moderately Homo sapiens
     female systemovary  moderately Homo sapiens
     male systemtestis  highly Homo sapiens
     male systemprostate  lowly Homo sapiens
    Respiratorylung   lowly Homo sapiens
    Urinarykidney   lowly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatum  highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a C terminal kinase domain
  • a JH2 pseudokinase domain tandemly linked to the N site of the former and seven JAK homology (JH), and functioning as a negative regulator and is presumed to be a catalytically inactive pseudokinase
  • N terminus region (JH6, JH7) critical for receptor binding domains
  • two phosphotransferase domains
  • one SH2 domain
  • a FERM domain and a kinase domain binding to CDKN1B
  • HOMOLOGY
    interspecies ortholog to Jak2, Mus musculus
    ortholog to Jak2, Rattus norvegicus
    ortholog to JAK2, Pan troglodytes
    ortholog to jak2b, Danio rerio
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • JAK subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    basic FUNCTION
  • cytokine receptor signaling pathways, playing pivotal functions for signal transduction from hematopoietic cytokine receptors
  • involved in GH induced activation of the GH receptor
  • involved in c-Myc protein induction by Bcr-Abl (
  • required in definitive erythropoiesis and has a nonredundant role in the function of a specific group of cytokines receptors (
  • mediating an increase of c-MYC RNA expression by BCR-ABL but also interfering with proteasome-dependent degradation of c-Myc protein
  • stimulates homologous recombination and genetic instability, and a single mutation can give rise to different myeloproliferative disorders
  • regulates BCR-ABL signaling in chronic myeloid leukemia
  • essential role signaling in GnRH neurons for normal reproductive development and fertility (
  • could enhance SLC5A1 protein abundance by influencing transcription of SLC5A1 or a regulator thereof
  • enhances the SLC5A1 protein abundance in the cell membrane and thus stimulates electrogenic glucose uptake by this carrier
  • may modify SLC5A1 activity by direct interaction with the carrier or by phosphorylating other signaling molecules regulating SLC5A1
  • up-regulates SLC6A19 activity which may foster amino acid uptake into JAK2 expressing cells
  • could enhance SLC6A19 protein abundance by either accelerating carrier insertion into the cell membrane or delaying the carrier retrieval from the cell membrane
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • IFN-gamma (
  • IFN-gamma receptor, IFN-gamma R (
  • synaptophysin, Syp (
  • AT1 receptor (
  • beta c chain of the GM-CSF receptor (
  • erythropoietin receptor, EPOR (
  • c-kit proto-oncogene (
  • PP2A, P13K, and Yes (
  • interleukin-12 receptor subunits beta1 and beta2 (
  • signal transducer and activator of transcription 5, STAT5 (
  • SHC (Src homology 2 domain containing) transforming protein, Shc (
  • signal transducer and activator of transcription 3, STAT3 (
  • SH2-Bbeta (
  • midkine-receptor (
  • tec protein tyrosine kinase, TEC (
  • insulin receptor, IR and the insulin-like growth factor-1 receptor, IGF1 (
  • tumor necrosis factor receptor 1, TNFR1 (
  • interleukin-5 (IL-5) receptor alpha and betac (
  • p125 focal adhesion kinase, FAK (
  • growth factor receptor-bound protein 10, Grb10 (
  • interleukin-12 receptor beta 2, IL-12R beta 2 (
  • cytokine-inducible SH2 protein 3, CIS3 (
  • growth hormone receptor, GHR (
  • chemokine (C-X-C motif) receptor 4, CXCR4 (
  • Skb1 and Hsl7p (
  • SH2-Containing protein tyrosine phosphatase-1, SHP-1 (
  • thyroid stimulating hormone receptor, TSHR (
  • SIRPalpha (
  • box 1-like motif in the cytoplasmic tail of CTLA-4 molecule (
  • cytokine receptor-like molecule 2, CRLM-2 (
  • signal transducing adaptor molecule (SH3 domain and ITAM motif) 1, STAM1 and signal transducing adaptor molecule (SH3 domain and ITAM motif) 2, STAM2 (
  • hTid-1(S) or hTid-1(L) (
  • protein tyrosine phosphatase, non-receptor type 1B, PTP1B (
  • protein tyrosine phosphatase-PEST, PTP-PEST (
  • G protein-coupled AngII type 1, AT(1) and protein tyrosine kinase 2 beta, PYK2B (
  • v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian), ERBB2 (
  • suppressor of cytokine signaling 1, SOCS1 (
  • Hes1 and Hes5 (
  • FABP4 in a fatty acid-dependent manner
  • beta subunit of IFNgamma receptor and PKCepsilon
  • VHL is a SOCS1-cooperative negative regulator of JAK2
  • oncogenic LCK and JAK2 may utilize different mechanisms to upregulate LMO2 levels during oncogenic transformation
  • is a novel regulator of the GABA transporter SLC6A12 (the kinase up-regulates the carrier presumably by enhancing the insertion of carrier protein into the cell membrane)
  • contributes to the regulation of the inositol transporter (SLC5A3)
  • CCDC80 is a JAK2-binding partner
  • cell & other
    REGULATION
    activated by cytokine receptors
    monocyte chemotactic protein SCYA2 (MCP)
    BRCA1 (
    IL-13 in colon carcinoma cell lines (
    Other regulated by phosphorylation of tyrosine residues in the putative activation loop of the kinase domains
    ASSOCIATED DISORDERS
    corresponding disease(s) PRV , MPD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation    
    in acute lymphoblastic leukemia
    tumoral fusion     gain of function
    in leukemia or constitutively expressed in acute lymphoblastic leukemia with t(9;12) (p24;p13) and a chimeric fusion protein, 5' - ETV6 -JAK2 - 3'
    tumoral fusion      
    BCR-JAK2 fusion, result of a t(9;22)(p24;q11.2) translocation in a chronic myeloid leukemia
    tumoral   translocation    
    t(8;9)(p22;p24), in in atypical chronic myeloid leukaemia with a PCM1-JAK2 fusion
    tumoral fusion      
    with RPN1, in t(3;9)(q21;p24) in a patient with chronic idiopathic myelofibrosis (CIMF), a chronic myeloproliferative disorder
    constitutional germinal mutation      
    V617F mutation is associated with thrombosis and pregnancy loss
    tumoral fusion      
    with SSBP2 in a t(5;9)(q14.1;p24.1) in pre-B acute lymphocytic leukemia
    tumoral   amplification    
    V617F activating mutation in addition to KIT and FLT3 mutations is associated with clinical outcome in patients with t(8;21)(q22;q22) acute myeloid leukemia
    tumoral somatic mutation      
    somatic activating mutation in 18p 100 of Down syndrome acute lymphoblastic leukaemia
    tumoral somatic mutation      
    in pediatric acute lymphoblastic leukemia
    tumoral   translocation    
    t(4;9)(q21;p24) leading to a novel SEC31A-JAK2 fusion, in classical Hodgkin lymphoma
    Susceptibility to Budd-Chiari syndrome and portal vein thrombosis
    Variant & Polymorphism other
  • JAK2 46/1 haplotype associated with Budd-Chiari syndrome and portal vein thrombosis
  • Candidate gene
    Marker
    Therapy target
  • a possible therapeutic target for compounds with anti-tyrosine kinase activity
  • inhibition of JAK signaling is a logical target for therapeutic intervention in JAK mutated ALL
  • inhibition of CRLF2/JAK2 signaling may represent a therapeutic approach for high-risk B-ALL patients )
  • SystemTypeDisorderPubmed
    blood  
    JAK2-targeted therapy in individuals with Chuvash polycythemia
    ANIMAL & CELL MODELS
  • Jak2-deficient mice are lethal at embryonic stage due to the absence of definitive erythropoiesis (
  • Jak2-/- mouse embryos are anemic and die around day 12.5 postcoitum because of absence of definitive erythropoiesis (
  • GnRH neuron-specific Jak2 conditional knock-out mice display reduced GnRH mRNA levels, reduced secretion of GnRH and basal serum luteinizing hormone (LH) levels are ignificantly lower in female. Female Jak2 G(-/-) mice exhibit significantly delayed puberty and first estrus, abnormal estrous cyclicity, and impaired fertility (