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O60674 (JAK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 157. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase JAK2

EC=2.7.10.2
Alternative name(s):
Janus kinase 2
Short name=JAK-2
Gene names
Name:JAK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1132 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.13 Ref.15 Ref.16

Catalytic activity

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

Enzyme regulation

Regulated by autophosphorylation, can both activate or decrease activity By similarity. Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008. Ref.14

Subunit structure

Interacts with EPOR, LYN, SIRPA, SH2B1 and TEC By similarity. Interacts with IL23R, SKB1 and STAM2. Ref.5 Ref.6 Ref.7

Subcellular location

Endomembrane system; Peripheral membrane protein By similarity. Cytoplasm. Nucleus Ref.13.

Tissue specificity

Ubiquitously expressed throughout most tissues. Ref.12

Domain

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.

Post-translational modification

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. Ref.19

Involvement in disease

Chromosomal aberrations involving JAK2 are found in both chronic and acute forms of eosinophilic, lymphoblastic and myeloid leukemia. Translocation t(8;9)(p22;p24) with PCM1 links the protein kinase domain of JAK2 to the major portion of PCM1. Translocation t(9;12)(p24;p13) with ETV6.

Budd-Chiari syndrome (BDCHS) [MIM:600880]: A syndrome caused by obstruction of hepatic venous outflow involving either the hepatic veins or the terminal segment of the inferior vena cava. Obstructions are generally caused by thrombosis and lead to hepatic congestion and ischemic necrosis. Clinical manifestations observed in the majority of patients include hepatomegaly, right upper quadrant pain and abdominal ascites. Budd-Chiari syndrome is associated with a combination of disease states including primary myeloproliferative syndromes and thrombophilia due to factor V Leiden, protein C deficiency and antithrombin III deficiency. Budd-Chiari syndrome is a rare but typical complication in patients with polycythemia vera.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Polycythemia vera (PV) [MIM:263300]: A myeloproliferative disorder characterized by abnormal proliferation of all hematopoietic bone marrow elements, erythroid hyperplasia, an absolute increase in total blood volume, but also by myeloid leukocytosis, thrombocytosis and splenomegaly.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20 Ref.23 Ref.24 Ref.27

Thrombocythemia 3 (THCYT3) [MIM:614521]: A myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes.
Note: The disease may be caused by mutations affecting the gene represented in this entry. Ref.22 Ref.30

Myelofibrosis (MYELOF) [MIM:254450]: A disorder characterized by replacement of the bone marrow by fibrous tissue, occurring in association with a myeloproliferative disorder. Clinical manifestations may include anemia, pallor, splenomegaly, hypermetabolic state, petechiae, ecchymosis, bleeding, lymphadenopathy, hepatomegaly, portal hypertension.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.

Contains 1 FERM domain.

Contains 2 protein kinase domains.

Contains 1 SH2 domain.

Ontologies

Keywords
   Biological processAdaptive immunity
Immunity
Innate immunity
   Cellular componentCytoplasm
Membrane
Nucleus
   Coding sequence diversityChromosomal rearrangement
Polymorphism
   DiseaseDisease mutation
Proto-oncogene
   DomainRepeat
SH2 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionChromatin regulator
Kinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

JAK-STAT cascade

Traceable author statement PubMed 9670957. Source: ProtInc

JAK-STAT cascade involved in growth hormone signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

STAT protein import into nucleus

Inferred from sequence or structural similarity. Source: BHF-UCL

actin filament polymerization

Non-traceable author statement PubMed 10925297. Source: BHF-UCL

activation of JAK2 kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

activation of MAPKK activity

Inferred from electronic annotation. Source: Ensembl

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: BHF-UCL

activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

apoptotic process

Inferred from sequence or structural similarity. Source: BHF-UCL

axon regeneration

Inferred from electronic annotation. Source: Ensembl

blood coagulation

Traceable author statement. Source: Reactome

cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular component movement

Traceable author statement PubMed 9670957. Source: ProtInc

cytokine-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

enzyme linked receptor protein signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

erythrocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

extrinsic apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

growth hormone receptor signaling pathway

Inferred from direct assay PubMed 10925297. Source: BHF-UCL

histone H3-Y41 phosphorylation

Inferred from direct assay Ref.13. Source: UniProtKB

hormone-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

host programmed cell death induced by symbiont

Inferred from electronic annotation. Source: Ensembl

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

interleukin-12-mediated signaling pathway

Inferred from direct assay PubMed 7528775. Source: BHF-UCL

intracellular signal transduction

Inferred from sequence or structural similarity. Source: BHF-UCL

intrinsic apoptotic signaling pathway in response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

mammary gland epithelium development

Inferred from sequence or structural similarity. Source: BHF-UCL

mesoderm development

Traceable author statement PubMed 9590174. Source: ProtInc

mineralocorticoid receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of DNA binding

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

negative regulation of heart contraction

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: BHF-UCL

platelet-derived growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of DNA binding

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell activation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell-substrate adhesion

Inferred from direct assay PubMed 10925297. Source: BHF-UCL

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of growth hormone receptor signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of inflammatory response

Inferred from electronic annotation. Source: Ensembl

positive regulation of insulin secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-1 beta production

Inferred from electronic annotation. Source: Ensembl

positive regulation of nitric oxide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of nitric-oxide synthase biosynthetic process

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of phosphoprotein phosphatase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein import into nucleus, translocation

Inferred from electronic annotation. Source: Ensembl

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of tumor necrosis factor production

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of tyrosine phosphorylation of Stat3 protein

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of tyrosine phosphorylation of Stat5 protein

Inferred from sequence or structural similarity. Source: BHF-UCL

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Traceable author statement PubMed 9670957. Source: ProtInc

regulation of inflammatory response

Inferred from direct assay PubMed 10925297. Source: BHF-UCL

regulation of interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

response to antibiotic

Inferred from direct assay PubMed 16280321. Source: MGI

response to hydroperoxide

Inferred from electronic annotation. Source: Ensembl

response to interleukin-12

Inferred from direct assay PubMed 7528775. Source: BHF-UCL

response to lipopolysaccharide

Inferred from sequence or structural similarity. Source: BHF-UCL

response to tumor necrosis factor

Inferred from direct assay PubMed 8609418. Source: BHF-UCL

signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

tumor necrosis factor-mediated signaling pathway

Inferred from direct assay PubMed 8609418. Source: BHF-UCL

tyrosine phosphorylation of STAT protein

Inferred from sequence or structural similarity. Source: BHF-UCL

tyrosine phosphorylation of Stat1 protein

Inferred from electronic annotation. Source: Ensembl

tyrosine phosphorylation of Stat3 protein

Inferred from electronic annotation. Source: Ensembl

tyrosine phosphorylation of Stat5 protein

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcaveola

Inferred from sequence or structural similarity. Source: BHF-UCL

cytoplasm

Inferred from direct assay PubMed 10502458. Source: BHF-UCL

cytoskeleton

Inferred from electronic annotation. Source: InterPro

cytosol

Traceable author statement. Source: Reactome

endosome lumen

Traceable author statement. Source: Reactome

membrane raft

Inferred from sequence or structural similarity. Source: BHF-UCL

nuclear matrix

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.13. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

SH2 domain binding

Inferred from physical interaction PubMed 9727029. Source: UniProtKB

growth hormone receptor binding

Inferred from sequence or structural similarity. Source: BHF-UCL

heme binding

Inferred from direct assay Ref.14. Source: UniProtKB

histone binding

Inferred from direct assay Ref.13. Source: UniProtKB

histone kinase activity (H3-Y41 specific)

Inferred from direct assay Ref.13. Source: UniProtKB

interleukin-12 receptor binding

Inferred from sequence or structural similarity. Source: BHF-UCL

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein kinase activity

Non-traceable author statement PubMed 9670957. Source: ProtInc

protein kinase binding

Inferred from direct assay PubMed 10925297. Source: BHF-UCL

protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

receptor binding

Inferred from physical interaction PubMed 11201744. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11321132Tyrosine-protein kinase JAK2
PRO_0000088112

Regions

Domain37 – 380344FERM
Domain401 – 48282SH2; atypical
Domain545 – 809265Protein kinase 1
Domain849 – 1124276Protein kinase 2
Nucleotide binding855 – 8639ATP By similarity
Region1 – 239239Interaction with cytokine/interferon/growth hormone receptors By similarity

Sites

Active site9761Proton acceptor By similarity
Binding site8821ATP By similarity
Site352 – 3532Breakpoint for translocation to form PCM1-JAK2 fusion protein
Site442 – 4432Breakpoint for translocation to form PCM1-JAK2 fusion protein
Site450 – 4512Breakpoint for translocation to form PCM1-JAK2 fusion protein
Site504 – 5052Breakpoint for translocation to form PCM1-JAK2 fusion protein
Site710 – 7112Breakpoint for translocation to form PCM1-JAK2 fusion protein

Amino acid modifications

Modified residue1191Phosphotyrosine; by autocatalysis By similarity
Modified residue3721Phosphotyrosine By similarity
Modified residue3731Phosphotyrosine By similarity
Modified residue5231Phosphoserine By similarity
Modified residue8131Phosphotyrosine By similarity
Modified residue8681Phosphotyrosine; by autocatalysis By similarity
Modified residue9661Phosphotyrosine; by autocatalysis By similarity
Modified residue9721Phosphotyrosine; by autocatalysis By similarity
Modified residue10071Phosphotyrosine; by autocatalysis Ref.19
Modified residue10081Phosphotyrosine; by autocatalysis Probable

Natural variations

Natural variant1271G → D. Ref.29
Corresponds to variant rs56118985 [ dbSNP | Ensembl ].
VAR_041716
Natural variant1911K → Q in an ovarian serous carcinoma sample; somatic mutation. Ref.29
VAR_041717
Natural variant3461K → R. Ref.29
Corresponds to variant rs55667734 [ dbSNP | Ensembl ].
VAR_041718
Natural variant3771A → E. Ref.29
Corresponds to variant rs55953208 [ dbSNP | Ensembl ].
VAR_041719
Natural variant3931L → V. Ref.29
Corresponds to variant rs2230723 [ dbSNP | Ensembl ].
VAR_041720
Natural variant537 – 5393FHK → L in myeloproliferative disorder with erythrocytosis.
VAR_032693
Natural variant538 – 5392HK → QL in myeloproliferative disorder with erythrocytosis.
VAR_032694
Natural variant5391K → L in myeloproliferative disorder with erythrocytosis; requires 2 nucleotide substitutions. Ref.28
VAR_032695
Natural variant5841D → E.
Corresponds to variant rs17490221 [ dbSNP | Ensembl ].
VAR_043129
Natural variant6071K → N in AML. Ref.26
VAR_032696
Natural variant6171V → F in PV, THCYT3 and AML; associated with susceptibility to Budd-Chiari syndrome; somatic mutation in a high percentage of patients with essential thrombocythemia or myelofibrosis; leads to constitutive tyrosine phosphorylation activity that promotes cytokine hypersensitivity. Ref.20 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27
VAR_032697
Natural variant6171V → I in THCYT3. Ref.30
VAR_067534
Natural variant10631R → H. Ref.29
Corresponds to variant rs41316003 [ dbSNP | Ensembl ].
VAR_041721

Experimental info

Sequence conflict3211P → S in AAC23982. Ref.1
Sequence conflict11261I → V in AAC23653. Ref.2

Secondary structure

......................................................................................................... 1132
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O60674 [UniParc].

Last modified January 24, 2001. Version 2.
Checksum: C30669EF1A7DA80C

FASTA1,132130,674
        10         20         30         40         50         60 
MGMACLTMTE MEGTSTSSIY QNGDISGNAN SMKQIDPVLQ VYLYHSLGKS EADYLTFPSG 

        70         80         90        100        110        120 
EYVAEEICIA ASKACGITPV YHNMFALMSE TERIWYPPNH VFHIDESTRH NVLYRIRFYF 

       130        140        150        160        170        180 
PRWYCSGSNR AYRHGISRGA EAPLLDDFVM SYLFAQWRHD FVHGWIKVPV THETQEECLG 

       190        200        210        220        230        240 
MAVLDMMRIA KENDQTPLAI YNSISYKTFL PKCIRAKIQD YHILTRKRIR YRFRRFIQQF 

       250        260        270        280        290        300 
SQCKATARNL KLKYLINLET LQSAFYTEKF EVKEPGSGPS GEEIFATIII TGNGGIQWSR 

       310        320        330        340        350        360 
GKHKESETLT EQDLQLYCDF PNIIDVSIKQ ANQEGSNESR VVTIHKQDGK NLEIELSSLR 

       370        380        390        400        410        420 
EALSFVSLID GYYRLTADAH HYLCKEVAPP AVLENIQSNC HGPISMDFAI SKLKKAGNQT 

       430        440        450        460        470        480 
GLYVLRCSPK DFNKYFLTFA VERENVIEYK HCLITKNENE EYNLSGTKKN FSSLKDLLNC 

       490        500        510        520        530        540 
YQMETVRSDN IIFQFTKCCP PKPKDKSNLL VFRTNGVSDV PTSPTLQRPT HMNQMVFHKI 

       550        560        570        580        590        600 
RNEDLIFNES LGQGTFTKIF KGVRREVGDY GQLHETEVLL KVLDKAHRNY SESFFEAASM 

       610        620        630        640        650        660 
MSKLSHKHLV LNYGVCVCGD ENILVQEFVK FGSLDTYLKK NKNCINILWK LEVAKQLAWA 

       670        680        690        700        710        720 
MHFLEENTLI HGNVCAKNIL LIREEDRKTG NPPFIKLSDP GISITVLPKD ILQERIPWVP 

       730        740        750        760        770        780 
PECIENPKNL NLATDKWSFG TTLWEICSGG DKPLSALDSQ RKLQFYEDRH QLPAPKWAEL 

       790        800        810        820        830        840 
ANLINNCMDY EPDFRPSFRA IIRDLNSLFT PDYELLTEND MLPNMRIGAL GFSGAFEDRD 

       850        860        870        880        890        900 
PTQFEERHLK FLQQLGKGNF GSVEMCRYDP LQDNTGEVVA VKKLQHSTEE HLRDFEREIE 

       910        920        930        940        950        960 
ILKSLQHDNI VKYKGVCYSA GRRNLKLIME YLPYGSLRDY LQKHKERIDH IKLLQYTSQI 

       970        980        990       1000       1010       1020 
CKGMEYLGTK RYIHRDLATR NILVENENRV KIGDFGLTKV LPQDKEYYKV KEPGESPIFW 

      1030       1040       1050       1060       1070       1080 
YAPESLTESK FSVASDVWSF GVVLYELFTY IEKSKSPPAE FMRMIGNDKQ GQMIVFHLIE 

      1090       1100       1110       1120       1130 
LLKNNGRLPR PDGCPDEIYM IMTECWNNNV NQRPSFRDLA LRVDQIRDNM AG 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of human Jak-2 kinase: high mRNA expression in immune cells and muscle tissue."
Saltzman A., Stone M., Franks C., Searfoss G., Munro R., Jaye M., Ivashchenko Y.
Biochem. Biophys. Res. Commun. 246:627-633(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Cloning and characterization of the human homolog of mouse Jak2."
Dalal I., Arpaia E., Dadi H., Kulkarni S., Squire J., Roifman C.M.
Blood 91:844-851(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia."
Peeters P., Raynaud S.D., Cools J., Wlodarska I., Grosgeorge J., Philip P., Monpoux F., Van Rompaey L., Baens M., Van Den Berghe H., Marynen P.
Blood 90:2535-2540(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION WITH ETV6.
[4]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity."
Pollack B.P., Kotenko S.V., He W., Izotova L.S., Barnoski B.L., Pestka S.
J. Biol. Chem. 274:31531-31542(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SKB1.
[6]"STAM2, a new member of the STAM family, binding to the Janus kinases."
Endo K., Takeshita T., Kasai H., Sasaki Y., Tanaka N., Asao H., Kikuchi K., Yamada M., Chenb M., O'Shea J.J., Sugamura K.
FEBS Lett. 477:55-61(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STAM2.
Tissue: Fetal brain.
[7]"A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R."
Parham C., Chirica M., Timans J., Vaisberg E., Travis M., Cheung J., Pflanz S., Zhang R., Singh K.P., Vega F., To W., Wagner J., O'Farrell A.-M., McClanahan T.K., Zurawski S., Hannum C., Gorman D., Rennick D.M. expand/collapse author list , Kastelein R.A., de Waal Malefyt R., Moore K.W.
J. Immunol. 168:5699-5708(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH IL23R.
[8]"The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2."
Reiter A., Walz C., Watmore A., Schoch C., Blau I., Schlegelberger B., Berger U., Telford N., Aruliah S., Yin J.A., Vanstraelen D., Barker H.F., Taylor P.C., O'Driscoll A., Benedetti F., Rudolph C., Kolb H.-J., Hochhaus A. expand/collapse author list , Hehlmann R., Chase A., Cross N.C.P.
Cancer Res. 65:2662-2667(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH PCM1.
[9]"PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation."
Murati A., Gelsi-Boyer V., Adelaide J., Perot C., Talmant P., Giraudier S., Lode L., Letessier A., Delaval B., Brunel V., Imbert M., Garand R., Xerri L., Birnbaum D., Mozziconacci M.-J., Chaffanet M.
Leukemia 19:1692-1696(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH PCM1.
[10]"The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene."
Bousquet M., Quelen C., De Mas V., Duchayne E., Roquefeuil B., Delsol G., Laurent G., Dastugue N., Brousset P.
Oncogene 24:7248-7252(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH PCM1.
[11]"A combination of cytomorphology, cytogenetic analysis, fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction for establishing clonality in cases of persisting hypereosinophilia."
Bacher U., Reiter A., Haferlach T., Mueller L., Schnittger S., Kern W., Schoch C.
Haematologica 91:817-820(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH PCM1.
[12]"A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma."
Adelaide J., Perot C., Gelsi-Boyer V., Pautas C., Murati A., Copie-Bergman C., Imbert M., Chaffanet M., Birnbaum D., Mozziconacci M.-J.
Leukemia 20:536-537(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, CHROMOSOMAL TRANSLOCATION WITH PCM1.
[13]"JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin."
Dawson M.A., Bannister A.J., Gottgens B., Foster S.D., Bartke T., Green A.R., Kouzarides T.
Nature 461:819-822(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[14]"Heme controls the regulation of protein tyrosine kinases Jak2 and Src."
Yao X., Balamurugan P., Arvey A., Leslie C., Zhang L.
Biochem. Biophys. Res. Commun. 403:30-35(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[15]"The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure."
Guilluy C., Bregeon J., Toumaniantz G., Rolli-Derkinderen M., Retailleau K., Loufrani L., Henrion D., Scalbert E., Bril A., Torres R.M., Offermanns S., Pacaud P., Loirand G.
Nat. Med. 16:183-190(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"Phosphorylation of p27Kip1 by JAK2 directly links cytokine receptor signaling to cell cycle control."
Jakel H., Weinl C., Hengst L.
Oncogene 30:3502-3512(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CDKN1B.
[17]"Jak2 tyrosine kinase: a mediator of both housekeeping and ligand-dependent gene expression?"
Wallace T.A., Sayeski P.P.
Cell Biochem. Biophys. 44:213-222(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[18]"Janus kinases in immune cell signaling."
Ghoreschi K., Laurence A., O'Shea J.J.
Immunol. Rev. 228:273-287(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[19]"The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor."
Lucet I.S., Fantino E., Styles M., Bamert R., Patel O., Broughton S.E., Walter M., Burns C.J., Treutlein H., Wilks A.F., Rossjohn J.
Blood 107:176-183(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 840-1132 IN COMPLEX WITH SYNTHETIC INHIBITOR, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT TYR-1007 AND TYR-1008.
[20]"Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders."
The cancer genome project
Baxter E.J., Scott L.M., Campbell P.J., East C., Fourouclas N., Swanton S., Vassiliou G.S., Bench A.J., Boyd E.M., Curtin N., Scott M.A., Erber W.N., Green A.R.
Lancet 365:1054-1061(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PV PHE-617.
[21]Erratum
The cancer genome project
Baxter E.J., Scott L.M., Campbell P.J., East C., Fourouclas N., Swanton S., Vassiliou G.S., Bench A.J., Boyd E.M., Curtin N., Scott M.A., Erber W.N., Green A.R.
Lancet 366:122-122(2005)
[22]"Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study."
The United Kingdom myeloproliferative disorders study group, The medical research council adult leukaemia working party, The Australasian leukaemia and lymphoma group
Campbell P.J., Scott L.M., Buck G., Wheatley K., East C.L., Marsden J.T., Duffy A., Boyd E.M., Bench A.J., Scott M.A., Vassiliou G.S., Milligan D.W., Smith S.R., Erber W.N., Bareford D., Wilkins B.S., Reilly J.T., Harrison C.N., Green A.R.
Lancet 366:1945-1953(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THCYT3 PHE-617.
[23]"A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera."
James C., Ugo V., Le Couedic J.-P., Staerk J., Delhommeau F., Lacout C., Garcon L., Raslova H., Berger R., Bennaceur-Griscelli A., Villeval J.L., Constantinescu S.N., Casadevall N., Vainchenker W.
Nature 434:1144-1148(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PV PHE-617, CHARACTERIZATION OF VARIANT PV PHE-617.
[24]"A gain-of-function mutation of JAK2 in myeloproliferative disorders."
Kralovics R., Passamonti F., Buser A.S., Teo S.-S., Tiedt R., Passweg J.R., Tichelli A., Cazzola M., Skoda R.C.
N. Engl. J. Med. 352:1779-1790(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PV PHE-617.
[25]"Case records of the Massachusetts General Hospital. Case 15-2006: a 46-year-old woman with sudden onset of abdominal distention."
Chung R.T., Iafrate A.J., Amrein P.C., Sahani D.V., Misdraji J.
N. Engl. J. Med. 354:2166-2175(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION OF VARIANT PHE-617 WITH SUSCEPTIBILITY BUDD-CHIARI SYNDROME.
[26]"The JAK2 V617F mutation in de novo acute myelogenous leukemias."
Lee J.W., Kim Y.G., Soung Y.H., Han K.J., Kim S.Y., Rhim H.S., Min W.S., Nam S.W., Park W.S., Lee J.Y., Yoo N.J., Lee S.H.
Oncogene 25:1434-1436(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AML ASN-607 AND PHE-617.
[27]"The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation."
Jamieson C.H.M., Gotlib J., Durocher J.A., Chao M.P., Mariappan M.R., Lay M., Jones C., Zehnder J.L., Lilleberg S.L., Weissman I.L.
Proc. Natl. Acad. Sci. U.S.A. 103:6224-6229(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PV PHE-617.
[28]"JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis."
Scott L.M., Tong W., Levine R.L., Scott M.A., Beer P.A., Stratton M.R., Futreal P.A., Erber W.N., McMullin M.F., Harrison C.N., Warren A.J., Gilliland D.G., Lodish H.F., Green A.R.
N. Engl. J. Med. 356:459-468(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MYELOPROLIFERATIVE DISORDER WITH ERYTHROCYTOSIS 537-PHE--LYS-539 DELINS LEU; 538-GLN-LEU-539 AND LEU-539.
[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. expand/collapse author list , 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] ASP-127; GLN-191; ARG-346; GLU-377; VAL-393 AND HIS-1063.
[30]"Germline JAK2 mutation in a family with hereditary thrombocytosis."
Mead A.J., Rugless M.J., Jacobsen S.E., Schuh A.
N. Engl. J. Med. 366:967-969(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THCYT3 ILE-617.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF058925 mRNA. Translation: AAC23982.1.
AF001362 mRNA. Translation: AAC23653.1.
AF005216 mRNA. Translation: AAB82092.1.
AL161450 Genomic DNA. Translation: CAD13329.1.
PIRJW0091.
RefSeqNP_004963.1. NM_004972.3.
XP_005251512.1. XM_005251455.2.
UniGeneHs.656213.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2B7AX-ray2.00A/B840-1132[»]
2W1IX-ray2.60A/B835-1132[»]
2XA4X-ray2.04A/B835-1132[»]
3E62X-ray1.92A839-1131[»]
3E63X-ray1.90A839-1131[»]
3E64X-ray1.80A839-1131[»]
3FUPX-ray2.40A/B840-1132[»]
3IO7X-ray2.60A842-1132[»]
3IOKX-ray2.10A842-1132[»]
3JY9X-ray2.10A842-1130[»]
3KCKX-ray2.20A842-1132[»]
3KRRX-ray1.80A840-1132[»]
3LPBX-ray2.00A/B840-1132[»]
3Q32X-ray2.50A/B839-1132[»]
3RVGX-ray2.50A835-1132[»]
3TJCX-ray2.40A/B837-1132[»]
3TJDX-ray2.90A/B837-1132[»]
3UGCX-ray1.34A840-1132[»]
3ZMMX-ray2.51A/B835-1132[»]
4AQCX-ray1.90A/B835-1132[»]
4BBEX-ray1.90A/B/C/D839-1132[»]
4BBFX-ray2.00A/B/C/D839-1132[»]
4C61X-ray2.45A/B835-1132[»]
4C62X-ray2.75A/B835-1132[»]
4E4MX-ray2.25A/B/D/E833-1132[»]
4E6DX-ray2.22A/B835-1132[»]
4E6QX-ray1.95A/B835-1132[»]
4F08X-ray2.82A/B833-1132[»]
4F09X-ray2.40A833-1132[»]
4FVPX-ray2.01A536-812[»]
4FVQX-ray1.75A536-812[»]
4FVRX-ray2.00A536-812[»]
4GFMX-ray2.30A833-1132[»]
4GMYX-ray2.40A833-1132[»]
4HGEX-ray2.30A/B833-1132[»]
4IVAX-ray1.50A833-1132[»]
4JI9X-ray2.40A/B833-1132[»]
4JIAX-ray1.85A833-1132[»]
ProteinModelPortalO60674.
SMRO60674. Positions 401-1132.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109920. 89 interactions.
DIPDIP-33880N.
IntActO60674. 22 interactions.
MINTMINT-158048.
STRING9606.ENSP00000371067.

Chemistry

BindingDBO60674.
ChEMBLCHEMBL2971.
GuidetoPHARMACOLOGY2048.

PTM databases

PhosphoSiteO60674.

Proteomic databases

PaxDbO60674.
PRIDEO60674.

Protocols and materials databases

DNASU3717.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000381652; ENSP00000371067; ENSG00000096968.
ENST00000539801; ENSP00000440387; ENSG00000096968.
GeneID3717.
KEGGhsa:3717.
UCSCuc003ziw.3. human.

Organism-specific databases

CTD3717.
GeneCardsGC09P004985.
HGNCHGNC:6192. JAK2.
HPACAB013089.
MIM147796. gene.
254450. phenotype.
263300. phenotype.
600880. phenotype.
601626. phenotype.
614521. phenotype.
neXtProtNX_O60674.
Orphanet131. Budd-Chiari syndrome.
3318. Essential thrombocythemia.
71493. Familial thrombocytosis.
824. Myelofibrosis with myeloid metaplasia.
729. Polycythemia vera.
PharmGKBPA29989.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000049158.
HOVERGENHBG006195.
InParanoidO60674.
KOK04447.
OMACHGPISM.
OrthoDBEOG7BW0HM.
PhylomeDBO60674.
TreeFamTF327041.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkO60674.

Gene expression databases

ArrayExpressO60674.
BgeeO60674.
CleanExHS_JAK2.
GenevestigatorO60674.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR019749. 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]
PANTHERPTHR24418:SF69. PTHR24418:SF69. 1 hit.
PfamPF07714. Pkinase_Tyr. 2 hits.
PF00017. SH2. 1 hit.
[Graphical view]
PIRSFPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSPR01823. JANUSKINASE.
PR01825. JANUSKINASE2.
PR00109. TYRKINASE.
SMARTSM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMSSF47031. SSF47031. 1 hit.
SSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEPS50057. 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]
ProtoNetSearch...

Other

ChiTaRSJAK2. human.
EvolutionaryTraceO60674.
GeneWikiJanus_kinase_2.
GenomeRNAi3717.
NextBio14567.
PROO60674.
SOURCESearch...

Entry information

Entry nameJAK2_HUMAN
AccessionPrimary (citable) accession number: O60674
Secondary accession number(s): O14636, O75297
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: January 24, 2001
Last modified: April 16, 2014
This is version 157 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM