O60674 (JAK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase JAK2
EC=2.7.10.2

Alternative name(s):
Janus kinase 2
Short name=JAK-2

Gene names

Name:

JAK2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1132 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Adaptive immunity Immunity Innate immunity
Cellular component	Cytoplasm Membrane Nucleus
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Disease mutation Proto-oncogene
Domain	Repeat SH2 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Chromatin regulator Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara 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: Compara activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL axon regeneration Inferred from electronic annotation. Source: Compara blood coagulation Traceable author statement. Source: Reactome cellular component movement Traceable author statement PubMed 9670957. Source: ProtInc elevation of cytosolic calcium ion concentration Inferred from electronic annotation. Source: Compara erythrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB hormone-mediated signaling pathway Inferred from electronic annotation. Source: Compara interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome interleukin-12-mediated signaling pathway Inferred from direct assay PubMed 7528775. Source: BHF-UCL intrinsic apoptotic signaling pathway in response to oxidative stress Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara negative regulation of heart contraction Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara platelet-derived growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of DNA binding Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cell activation Inferred from electronic annotation. Source: Compara positive regulation of cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of cell migration Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of cell-substrate adhesion Inferred from direct assay PubMed 10925297. Source: BHF-UCL 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: Compara positive regulation of insulin secretion Inferred from electronic annotation. Source: Compara positive regulation of interleukin-1 beta production Inferred from electronic annotation. Source: Compara positive regulation of nitric oxide biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of nitric-oxide synthase biosynthetic process Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of phosphatidylinositol 3-kinase cascade Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of phosphoprotein phosphatase activity Inferred from electronic annotation. Source: Compara positive regulation of protein import into nucleus, translocation Inferred from electronic annotation. Source: Compara positive regulation of sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara 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 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: Compara response to lipopolysaccharide Inferred from sequence or structural similarity. Source: BHF-UCL 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: Compara tyrosine phosphorylation of Stat3 protein Inferred from electronic annotation. Source: Compara tyrosine phosphorylation of Stat5 protein Inferred from electronic annotation. Source: Compara
Cellular_component	caveola Inferred from sequence or structural similarity. Source: BHF-UCL cytoskeleton Inferred from electronic annotation. Source: InterPro cytosol Traceable author statement. Source: Reactome endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell endosome lumen Traceable author statement. Source: Reactome nuclear matrix Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay Ref.13. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW 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: EC protein kinase binding Inferred from direct assay PubMed 10925297. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CSF2RB	P32927	3	EBI-518647,EBI-1809771
NCK1	P16333	2	EBI-518647,EBI-389883

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1132

1132

Tyrosine-protein kinase JAK2

PRO_0000088112

Regions

Domain

37 – 380

344

FERM

Domain

401 – 482

82

SH2; atypical

Domain

545 – 809

265

Protein kinase 1

Domain

849 – 1124

276

Protein kinase 2

Nucleotide binding

855 – 863

9

ATP By similarity

Region

1 – 239

239

Interaction with cytokine/interferon/growth hormone receptors By similarity

Sites

Active site

976

1

Proton acceptor By similarity

Binding site

882

1

ATP By similarity

Site

352 – 353

2

Breakpoint for translocation to form PCM1-JAK2 fusion protein

Site

442 – 443

2

Breakpoint for translocation to form PCM1-JAK2 fusion protein

Site

450 – 451

2

Breakpoint for translocation to form PCM1-JAK2 fusion protein

Site

504 – 505

2

Breakpoint for translocation to form PCM1-JAK2 fusion protein

Site

710 – 711

2

Breakpoint for translocation to form PCM1-JAK2 fusion protein

Amino acid modifications

Modified residue

119

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

372

1

Phosphotyrosine By similarity

Modified residue

373

1

Phosphotyrosine By similarity

Modified residue

523

1

Phosphoserine By similarity

Modified residue

570

1

Phosphotyrosine By similarity

Modified residue

813

1

Phosphotyrosine By similarity

Modified residue

868

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

966

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

972

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

1007

1

Phosphotyrosine; by autocatalysis Ref.19

Modified residue

1008

1

Phosphotyrosine; by autocatalysis Probable

Natural variations

Natural variant

127

1

G → D. Ref.29
Corresponds to variant rs56118985 [ dbSNP | Ensembl ].

VAR_041716

Natural variant

191

1

K → Q in an ovarian serous carcinoma sample; somatic mutation. Ref.29

VAR_041717

Natural variant

346

1

K → R. Ref.29
Corresponds to variant rs55667734 [ dbSNP | Ensembl ].

VAR_041718

Natural variant

377

1

A → E. Ref.29
Corresponds to variant rs55953208 [ dbSNP | Ensembl ].

VAR_041719

Natural variant

393

1

L → V. Ref.29
Corresponds to variant rs2230723 [ dbSNP | Ensembl ].

VAR_041720

Natural variant

537 – 539

3

FHK → L in myeloproliferative disorder with erythrocytosis.

VAR_032693

Natural variant

538 – 539

2

HK → QL in myeloproliferative disorder with erythrocytosis.

VAR_032694

Natural variant

539

1

K → L in myeloproliferative disorder with erythrocytosis; requires 2 nucleotide substitutions. Ref.28

VAR_032695

Natural variant

584

1

D → E.
Corresponds to variant rs17490221 [ dbSNP | Ensembl ].

VAR_043129

Natural variant

607

1

K → N in AML. Ref.26

VAR_032696

Natural variant

617

1

V → 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 variant

617

1

V → I in THCYT3. Ref.30

VAR_067534

Natural variant

1063

1

R → H. Ref.29
Corresponds to variant rs41316003 [ dbSNP | Ensembl ].

VAR_041721

Experimental info

Sequence conflict

321

1

P → S in AAC23982. Ref.1

Sequence conflict

1126

1

I → V in AAC23653. Ref.2

Secondary structure

1

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1132

Helix Strand Turn

Details...

Helix

542 – 544

3

Beta strand

545 – 554

10

Beta strand

557 – 567

11

Helix

569 – 571

3

Beta strand

573 – 583

11

Helix

585 – 590

6

Helix

591 – 602

12

Beta strand

612 – 616

5

Beta strand

623 – 627

5

Helix

634 – 640

7

Helix

642 – 644

3

Helix

647 – 666

20

Helix

676 – 678

3

Beta strand

679 – 683

5

Helix

687 – 689

3

Beta strand

694 – 697

4

Turn

704 – 706

3

Helix

709 – 714

6

Turn

715 – 718

4

Helix

721 – 725

5

Helix

727 – 729

3

Helix

732 – 747

16

Turn

748 – 750

3

Turn

753 – 756

4

Helix

759 – 767

9

Helix

781 – 787

7

Helix

792 – 794

3

Helix

798 – 806

9

Beta strand

836 – 838

3

Helix

846 – 848

3

Beta strand

849 – 857

9

Beta strand

859 – 868

10

Beta strand

872 – 874

3

Beta strand

877 – 885

9

Helix

889 – 903

15

Beta strand

913 – 917

5

Helix

919 – 922

4

Beta strand

926 – 930

5

Helix

937 – 943

7

Helix

945 – 947

3

Helix

950 – 969

20

Helix

979 – 981

3

Beta strand

982 – 986

5

Beta strand

989 – 992

4

Helix

995 – 997

3

Beta strand

1006 – 1009

4

Helix

1017 – 1020

4

Helix

1023 – 1028

6

Beta strand

1030 – 1032

3

Helix

1033 – 1049

17

Helix

1053 – 1055

3

Helix

1057 – 1065

9

Helix

1072 – 1083

12

Helix

1096 – 1105

10

Helix

1110 – 1112

3

Helix

1116 – 1128

13

Sequences

	Sequence		Length	Mass (Da)
	O60674 [UniParc]. Last modified January 24, 2001. Version 2. Checksum: C30669EF1A7DA80C	FASTA	1,132	130,674
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, 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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00031016.

PIR

JW0091.

RefSeq

NP_004963.1. NM_004972.3.

UniGene

Hs.656213.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2B7A	X-ray	2.00	A/B	840-1132	[»]
2W1I	X-ray	2.60	A/B	835-1132	[»]
2XA4	X-ray	2.04	A/B	835-1132	[»]
3E62	X-ray	1.92	A	839-1131	[»]
3E63	X-ray	1.90	A	839-1131	[»]
3E64	X-ray	1.80	A	839-1131	[»]
3FUP	X-ray	2.40	A/B	840-1132	[»]
3IO7	X-ray	2.60	A	842-1132	[»]
3IOK	X-ray	2.10	A	842-1132	[»]
3JY9	X-ray	2.10	A	842-1130	[»]
3KCK	X-ray	2.20	A	842-1132	[»]
3KRR	X-ray	1.80	A	840-1132	[»]
3LPB	X-ray	2.00	A/B	840-1132	[»]
3Q32	X-ray	2.50	A/B	839-1132	[»]
3RVG	X-ray	2.50	A	835-1132	[»]
3TJC	X-ray	2.40	A/B	837-1132	[»]
3TJD	X-ray	2.90	A/B	837-1132	[»]
3UGC	X-ray	1.34	A	840-1132	[»]
4AQC	X-ray	1.90	A/B	835-1132	[»]
4BBE	X-ray	1.90	A/B/C/D	839-1132	[»]
4BBF	X-ray	2.00	A/B/C/D	839-1132	[»]
4E4M	X-ray	2.25	A/B/D/E	833-1132	[»]
4E6D	X-ray	2.22	A/B	835-1132	[»]
4E6Q	X-ray	1.95	A/B	835-1132	[»]
4F08	X-ray	2.82	A/B	833-1132	[»]
4F09	X-ray	2.40	A	833-1132	[»]
4FVP	X-ray	2.01	A	536-812	[»]
4FVQ	X-ray	1.75	A	536-812	[»]
4FVR	X-ray	2.00	A	536-812	[»]
4HGE	X-ray	2.30	A/B	833-1132	[»]

ProteinModelPortal

O60674.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33880N.

IntAct

O60674. 15 interactions.

MINT

MINT-158048.

STRING

9606.ENSP00000371067.

PTM databases

PhosphoSite

O60674.

Proteomic databases

PaxDb

O60674.

PRIDE

O60674.

Protocols and materials databases

DNASU

3717.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000381652; ENSP00000371067; ENSG00000096968.
ENST00000539801; ENSP00000440387; ENSG00000096968.

GeneID

3717.

KEGG

hsa:3717.

UCSC

uc003ziw.3. human.

Organism-specific databases

CTD

3717.

GeneCards

GC09P004985.

HGNC

HGNC:6192. JAK2.

HPA

CAB013089.

MIM

147796. gene.
254450. phenotype.
263300. phenotype.
600880. phenotype.
601626. phenotype.
614521. phenotype.

neXtProt

NX_O60674.

Orphanet

131. Budd-Chiari syndrome.
3318. Essential thrombocythemia.
71493. Familial thrombocytosis.
824. Myelofibrosis with myeloid metaplasia.
729. Polycythemia vera.

PharmGKB

PA29989.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000049158.

HOVERGEN

HBG006195.

InParanoid

O60674.

KO

K04447.

OMA

CHGPISM.

OrthoDB

EOG4PZJ5W.

PhylomeDB

O60674.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Pathway_Interaction_DB

endothelinpathway. Endothelins.
epopathway. EPO signaling pathway.
ifngpathway. IFN-gamma pathway.
il12_2pathway. IL12-mediated signaling events.
il23pathway. IL23-mediated signaling events.
il27pathway. IL27-mediated signaling events.
il4_2pathway. IL4-mediated signaling events.
il6_7pathway. IL6-mediated signaling events.
a4b1_paxindep_pathway. Paxillin-independent events mediated by a4b1 and a4b7.
s1p_s1p3_pathway. S1P3 pathway.
ptp1bpathway. Signaling events mediated by PTP1B.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).

Reactome

REACT_111102. Signal Transduction.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

O60674.

Bgee

O60674.

CleanEx

HS_JAK2.

Genevestigator

O60674.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR019749. Band_41_domain.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_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]

Pfam

PF07714. Pkinase_Tyr. 2 hits.
PF00017. SH2. 1 hit.
[Graphical view]

PIRSF

PIRSF000636. TyrPK_Jak. 1 hit.

PRINTS

PR01823. JANUSKINASE.
PR01825. JANUSKINASE2.
PR00109. TYRKINASE.

SMART

SM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]

SUPFAM

SSF47031. FERM_3-hlx. 1 hit.
SSF56112. Kinase_like. 2 hits.

PROSITE

PS00660. FERM_1. False negative.
PS00661. FERM_2. False negative.
PS50057. FERM_3. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O60674.

ChEMBL

CHEMBL2971.

ChiTaRS

JAK2. human.

EvolutionaryTrace

O60674.

GenomeRNAi

3717.

NextBio

14567.

SOURCE

Search...

Entry information

Entry name

JAK2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 146 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.