Reviewed, UniProtKB/Swiss-Prot O60674 (JAK2_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1132 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Plays a role in leptin signaling and control of body weight By similarity. Tyrosine kinase of the non-receptor type, involved in interleukin-3 and probably interleukin-23 signal transduction.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with SIRPA and SH2B1 By similarity. Interacts with IL23R, SKB1 and STAM2.
Subcellular location	Endomembrane system; Peripheral membrane protein By similarity. Note: Wholly intracellular, possibly membrane associated By similarity.
Tissue specificity	Expressed in blood, bone marrow and lymph node. Ref.12
Domain	Possesses two phosphotransferase domains. The second one probably contains the catalytic domain By similarity, while the presence of slight differences suggest a different role for domain 1.
Post-translational modification	Leptin promotes phosphorylation on tyrosine residues, including phosphorylation on Tyr-813 By similarity.
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. Defects in JAK2 are a cause of susceptibility to Budd-Chiari syndrome [MIM:600880]. Budd-Chiari syndrome is a spectrum of disease states, including anatomic abnormalities and hypercoagulable disorders, resulting in hepatic venous outflow occlusion. Clinical manifestations observed in the majority of patients include hepatomegaly, right upper quadrant pain, and abdominal ascites. Defects in JAK2 are associated with polycythemia vera (PV) [MIM:263300]. PV, the most common form of primary polycythemia, is caused by somatic mutation in a single hematopoietic stem cell leading to clonal hematopoiesis. PV is a myeloproliferative disorder characterized predominantly by erythroid hyperplasia, but also by myeloid leukocytosis, thrombocytosis, and splenomegaly. Familial cases of PV are very rare and usually manifest in elderly patients. Ref.14 Ref.17 Ref.18 Ref.21 Defects in JAK2 gene may be a cause of essential thrombocythemia (ET) [MIM:187950]. ET is characterized by elevated platelet levels due to sustained proliferation of megakaryocytes, and frequently lead to thrombotic and haemorrhagic complications. Ref.3 Ref.16 Defects in JAK2 are associated with familial myelofibrosis [MIM:254450]. Myelofibrosis with myeloid metaplasia is a myeloproliferative disease with annual incidence of 0.5-1.5 cases per 100,000 individuals and age at diagnosis around 60 (an increased prevalence is noted in Ashkenazi Jews). Clinical manifestations depend on the type of blood cell affected and may include anemia, pallor, splenomegaly, hypermetabolic state, petechiae, ecchymosis, bleeding, lymphadenopathy, hepatomegaly, portal hypertension. Defects in JAK2 are a cause of acute myelogenous leukemia (AML) [MIM:601626]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development. Ref.20
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily. Contains 1 FERM domain. Contains 1 protein kinase domain. Contains 1 SH2 domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Disease mutation Proto-oncogene
Domain	Repeat SH2 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell motion Traceable author statement. Source: ProtInc mesoderm development Traceable author statement. Source: ProtInc 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: UniProtKB response to antibiotic Inferred from direct assay. Source: MGI
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB cytoskeleton Inferred from electronic annotation. Source: InterPro endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW SH2 domain binding Inferred from physical interaction. Source: UniProtKB growth hormone receptor binding Inferred from sequence or structural similarity. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CSF2RB	P32927	2	EBI-518647,EBI-1809771
GRB2	P62993	1	EBI-518647,EBI-401755
NCK1	P16333	1	EBI-518647,EBI-389883
PIK3R1	P27986	1	EBI-518647,EBI-79464
PLCG1	P19174	1	EBI-518647,EBI-79387
PTPRJ	Q12913	1	EBI-518647,EBI-2264500

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

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

523

1

Phosphoserine By similarity

Modified residue

570

1

Phosphotyrosine By similarity

Modified residue

813

1

Phosphotyrosine By similarity

Modified residue

1007

1

Phosphotyrosine; by autocatalysis Ref.13

Modified residue

1008

1

Phosphotyrosine Ref.13

Natural variations

Natural variant

127

1

G → D Ref.23

VAR_041716

Natural variant

191

1

K → Q in an ovarian serous carcinoma sample; somatic mutation. Ref.23

VAR_041717

Natural variant

346

1

K → R Ref.23

VAR_041718

Natural variant

377

1

A → E Ref.23

VAR_041719

Natural variant

393

1

L → V: dbSNP rs2230723. Ref.23

VAR_041720

Natural variant

537 – 539

3

FHK → L in myeloproliferative disorder with erythrocytosis. Ref.22

VAR_032693

Natural variant

538 – 539

2

HK → QL in myeloproliferative disorder with erythrocytosis. Ref.22

VAR_032694

Natural variant

539

1

K → L in myeloproliferative disorder with erythrocytosis; requires 2 nucleotide substitutions. Ref.22

VAR_032695

Natural variant

584

1

D → E: dbSNP rs17490221.

VAR_043129

Natural variant

607

1

K → N in AML. Ref.20

VAR_032696

Natural variant

617

1

V → F in PV 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.

VAR_032697

Natural variant

1063

1

R → H: dbSNP rs41316003. Ref.23

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

846 – 848

3

Beta strand

849 – 858

10

Beta strand

861 – 868

8

Beta strand

872 – 874

3

Beta strand

878 – 886

9

Helix

889 – 903

15

Beta strand

913 – 917

5

Beta strand

926 – 930

5

Helix

937 – 943

7

Turn

945 – 947

3

Helix

950 – 969

20

Helix

979 – 981

3

Beta strand

982 – 986

5

Beta strand

989 – 992

4

Helix

1018 – 1020

3

Helix

1023 – 1027

5

Helix

1033 – 1048

16

Turn

1049 – 1051

3

Helix

1053 – 1055

3

Helix

1057 – 1065

9

Helix

1073 – 1083

11

Helix

1096 – 1105

10

Helix

1110 – 1112

3

Helix

1116 – 1131

16

Sequences

	Sequence		Length	Mass (Da)
	O60674-1 [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: 9618263] [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: 9446644] [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: 9326218] [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: 15164053] [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: 10531356] [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: 10899310] [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: 12023369] [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: 15805263] [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: 16034466] [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: 16091753] [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: 16769584] [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: 16424865] [Abstract] Cited for: TISSUE SPECIFICITY, CHROMOSOMAL TRANSLOCATION WITH PCM1.
[13]	"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: 16174768] [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.
[14]	"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: 15781101] [Abstract] Cited for: VARIANT PV PHE-617.
[15]	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)
[16]	"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: 16325696] [Abstract] Cited for: VARIANT ET PHE-617.
[17]	"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: 15793561] [Abstract] Cited for: VARIANT PV PHE-617, CHARACTERIZATION OF VARIANT PV PHE-617.
[18]	"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: 15858187] [Abstract] Cited for: VARIANT PV PHE-617.
[19]	"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: 16707754] [Abstract] Cited for: ASSOCIATION OF VARIANT PHE-617 WITH SUSCEPTIBILITY BUDD-CHIARI SYNDROME.
[20]	"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: 16247455] [Abstract] Cited for: VARIANTS AML ASN-607 AND PHE-617.
[21]	"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: 16603627] [Abstract] Cited for: VARIANT PV PHE-617.
[22]	"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: 17267906] [Abstract] Cited for: VARIANTS MYELOPROLIFERATIVE DISORDER WITH ERYTHROCYTOSIS 537-PHE--LYS-539 DELINS LEU; 538-GLN-LEU-539 AND LEU-539.
[23]	"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: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASP-127; GLN-191; ARG-346; GLU-377; VAL-393 AND HIS-1063.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

UniGene

Hs.656213

3D structure databases

PDBPDBe

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	[»]
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	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O60674. 11 interactions.

PTM databases

PhosphoSite

O60674.

Proteomic databases

PRIDE

O60674.

Genome annotation databases

Ensembl

ENSG00000096968. Homo sapiens. [Contig view]

GeneID

3717.

KEGG

hsa:3717.

Organism-specific databases

GeneCards

GC09P004975.

H-InvDB

HIX0025698.

HGNC

HGNC:6192. JAK2.

HPA

CAB013089.

MIM

147796. gene.
187950. phenotype.
254450. phenotype.
263300. phenotype.
600880. phenotype.
601626. phenotype.

Orphanet

824. Myelofibrosis with myeloid metaplasia.
729. Polycythemia vera.
3318. Thrombocythemia, essential.

PharmGKB

PA29989.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O60674.

HOVERGEN

O60674.

OMA

O60674. CHGPISM.

Enzyme and pathway databases

BRENDA

2.7.10.2. 247.

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).

Gene expression databases

ArrayExpress

O60674.

Bgee

O60674.

CleanEx

HS_JAK2.

Family and domain databases

InterPro

IPR019749. Band_41_domain.
IPR019747. FERM_CS.
IPR000299. FERM_domain.
IPR009127. JAK.
IPR009129. JAK2.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR000980. SH2.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
IPR016251. TyrPK_Jak.
[Graphical view]

Gene3D

G3DSA:3.30.505.10. SH2. 1 hit.

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.

ProDom

PD000001. Prot_kinase. 2 hits.
PD000093. SH2. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

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

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 Resources

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:	June 16, 2009
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)