Reviewed,
UniProtKB/Swiss-Prot O60674 (JAK2_HUMAN)
Last modified
November 25, 2008.
Version 90.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
Third-party data |
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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 |
| ||
| 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 | Intracytoplasmic membrane; Peripheral membrane proteinBy similarity. Note= Wholly intracellular, possibly membrane associated By similarity. |
| Tissue specificity | Expressed in blood, bone marrow and lymph node. |
| 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. 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. 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. |
| 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
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| 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 |
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 | 570 | 1 | Phosphotyrosine By similarity | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 813 | 1 | Phosphotyrosine By similarity | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 1007 | 1 | Phosphotyrosine; by autocatalysis | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 1008 | 1 | Phosphotyrosine | |||||||||||||||||||||||||||||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 127 | 1 | G → D | VAR_041716 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 191 | 1 | K → Q in an ovarian serous carcinoma sample; somatic mutation. | VAR_041717 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 346 | 1 | K → R | VAR_041718 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 377 | 1 | A → E | VAR_041719 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 393 | 1 | L → V: dbSNP rs35844880. | 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. | VAR_032695 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 584 | 1 | D → E: dbSNP rs17490221. | VAR_043129 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 607 | 1 | K → N in AML. | 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. | 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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
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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: 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. 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] |

Clusters with