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UniProtKB - O60674 (JAK2_HUMAN)

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Protein

Tyrosine-protein kinase JAK2

Gene

JAK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (PubMed:7615558). Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:9618263). 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 (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). 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 (PubMed:19783980).6 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation2 Publications

Cofactori

Mg2+CuratedNote: Mn2+ was used in the in vitro kinase assay but Mg2+ is likely to be the in vivo cofactor.1 Publication

Enzyme regulationi

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.By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei882ATPPROSITE-ProRule annotation1
Active sitei976Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi855 – 863ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • acetylcholine receptor binding Source: Ensembl
  • ATP binding Source: UniProtKB-KW
  • growth hormone receptor binding Source: BHF-UCL
  • heme binding Source: UniProtKB
  • histone binding Source: UniProtKB
  • histone kinase activity (H3-Y41 specific) Source: UniProtKB
  • insulin receptor substrate binding Source: Ensembl
  • interleukin-12 receptor binding Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: Reactome
  • peptide hormone receptor binding Source: Ensembl
  • phosphatidylinositol 3-kinase binding Source: Ensembl
  • protein C-terminus binding Source: Ensembl
  • protein kinase activity Source: ProtInc
  • protein kinase binding Source: BHF-UCL
  • protein tyrosine kinase activity Source: CACAO
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • receptor binding Source: UniProtKB
  • SH2 domain binding Source: UniProtKB
  • type 1 angiotensin receptor binding Source: Ensembl
Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Keywordsi

Molecular functionChromatin regulator, Kinase, Transferase, Tyrosine-protein kinase
Biological processAdaptive immunity, Immunity, Innate immunity
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-110056. MAPK3 (ERK1) activation.
R-HSA-112411. MAPK1 (ERK2) activation.
R-HSA-114604. GPVI-mediated activation cascade.
R-HSA-1170546. Prolactin receptor signaling.
R-HSA-1433557. Signaling by SCF-KIT.
R-HSA-2586552. Signaling by Leptin.
R-HSA-3214858. RMTs methylate histone arginines.
R-HSA-392451. G beta:gamma signalling through PI3Kgamma.
R-HSA-447115. Interleukin-12 family signaling.
R-HSA-512988. Interleukin-3, 5 and GM-CSF signaling.
R-HSA-5673000. RAF activation.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6783589. Interleukin-6 family signaling.
R-HSA-6785807. Interleukin-4 and 13 signaling.
R-HSA-6788467. IL-6-type cytokine receptor ligand interactions.
R-HSA-6802946. Signaling by moderate kinase activity BRAF mutants.
R-HSA-6802949. Signaling by RAS mutants.
R-HSA-6802952. Signaling by BRAF and RAF fusions.
R-HSA-6802955. Paradoxical activation of RAF signaling by kinase inactive BRAF.
R-HSA-69231. Cyclin D associated events in G1.
R-HSA-877300. Interferon gamma signaling.
R-HSA-877312. Regulation of IFNG signaling.
R-HSA-912526. Interleukin receptor SHC signaling.
R-HSA-982772. Growth hormone receptor signaling.
R-HSA-983231. Factors involved in megakaryocyte development and platelet production.
SignaLinkiO60674.
SIGNORiO60674.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase JAK2 (EC:2.7.10.22 Publications)
Alternative name(s):
Janus kinase 2
Short name:
JAK-2
Gene namesi
Name:JAK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:6192. JAK2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

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)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:600880
Polycythemia vera (PV)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:263300
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032697617V → 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. 6 PublicationsCorresponds to variant dbSNP:rs77375493Ensembl.1
Thrombocythemia 3 (THCYT3)2 Publications
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes.
See also OMIM:614521
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032697617V → 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. 6 PublicationsCorresponds to variant dbSNP:rs77375493Ensembl.1
Natural variantiVAR_067534617V → I in THCYT3. 1 PublicationCorresponds to variant dbSNP:rs77375493Ensembl.1
Myelofibrosis (MYELOF)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:254450
Leukemia, acute myelogenous (AML)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:601626
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032696607K → N in AML. 1 PublicationCorresponds to variant dbSNP:rs121912472Ensembl.1
Natural variantiVAR_032697617V → 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. 6 PublicationsCorresponds to variant dbSNP:rs77375493Ensembl.1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei352 – 353Breakpoint for translocation to form PCM1-JAK2 fusion protein2
Sitei442 – 443Breakpoint for translocation to form PCM1-JAK2 fusion protein2
Sitei450 – 451Breakpoint for translocation to form PCM1-JAK2 fusion protein2
Sitei504 – 505Breakpoint for translocation to form PCM1-JAK2 fusion protein2
Sitei710 – 711Breakpoint for translocation to form PCM1-JAK2 fusion protein2

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi3717.
MalaCardsiJAK2.
MIMi254450. phenotype.
263300. phenotype.
600880. phenotype.
601626. phenotype.
614521. phenotype.
OpenTargetsiENSG00000096968.
Orphaneti131. Budd-Chiari syndrome.
3318. Essential thrombocythemia.
71493. Familial thrombocytosis.
824. Myelofibrosis with myeloid metaplasia.
729. Polycythemia vera.
PharmGKBiPA29989.

Chemistry databases

ChEMBLiCHEMBL2971.
DrugBankiDB07162. 4-(3-amino-1H-indazol-5-yl)-N-tert-butylbenzenesulfonamide.
DB08067. 4-[(2-{4-[(CYCLOPROPYLCARBAMOYL)AMINO]-1H-PYRAZOL-3-YL}-1H-BENZIMIDAZOL-6-YL)METHYL]MORPHOLIN-4-IUM.
DB07161. 5-phenyl-1H-indazol-3-amine.
DB08877. Ruxolitinib.
DB08895. Tofacitinib.
DB05243. XL019.
GuidetoPHARMACOLOGYi2048.

Polymorphism and mutation databases

BioMutaiJAK2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000881121 – 1132Tyrosine-protein kinase JAK2Add BLAST1132

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei119Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei372PhosphotyrosineBy similarity1
Modified residuei373PhosphotyrosineBy similarity1
Modified residuei523PhosphoserineBy similarity1
Modified residuei570PhosphotyrosineCombined sources1
Modified residuei813PhosphotyrosineBy similarity1
Modified residuei868Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei966Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei972Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1007Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1008Phosphotyrosine; by autocatalysis1 Publication1

Post-translational modificationi

Autophosphorylated, leading to regulate its activity. Leptin promotes phosphorylation on tyrosine residues, including phosphorylation on Tyr-813 (By similarity). Autophosphorylation on Tyr-119 in response to EPO down-regulates its kinase activity (By similarity). Autophosphorylation on Tyr-868, Tyr-966 and Tyr-972 in response to growth hormone (GH) are required for maximal kinase activity (By similarity). Also phosphorylated by TEC (By similarity). Phosphorylated on tyrosine residues in response to interferon gamma signaling (PubMed:7615558, PubMed:7673114).By similarity2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO60674.
MaxQBiO60674.
PaxDbiO60674.
PeptideAtlasiO60674.
PRIDEiO60674.

PTM databases

iPTMnetiO60674.
PhosphoSitePlusiO60674.

Expressioni

Tissue specificityi

Ubiquitously expressed throughout most tissues.1 Publication

Gene expression databases

BgeeiENSG00000096968.
CleanExiHS_JAK2.
ExpressionAtlasiO60674. baseline and differential.
GenevisibleiO60674. HS.

Organism-specific databases

HPAiCAB013089.
HPA040820.
HPA043870.

Interactioni

Subunit structurei

Interacts with EPOR, LYN, SIRPA, SH2B1 and TEC (By similarity). Interacts with IL23R (PubMed:12023369). Interacts with SKB1 (PubMed:10531356). Interacts with STAM2 (PubMed:10899310). Interacts with IFNGR2 (via intracellular domain) (PubMed:7673114, PubMed:7615558). Interacts with LEPR (Isoform B) (By similarity). Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner (PubMed:20353823).By similarity7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Complete GO annotation...

Protein-protein interaction databases

BioGridi109920. 93 interactors.
DIPiDIP-33880N.
IntActiO60674. 31 interactors.
MINTiMINT-158048.
STRINGi9606.ENSP00000371067.

Chemistry databases

BindingDBiO60674.

Structurei

Secondary structure

11132
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi38 – 45Combined sources8
Turni47 – 49Combined sources3
Beta strandi53 – 57Combined sources5
Beta strandi59 – 63Combined sources5
Helixi64 – 75Combined sources12
Helixi79 – 82Combined sources4
Beta strandi85 – 89Combined sources5
Turni90 – 92Combined sources3
Beta strandi101 – 104Combined sources4
Beta strandi109 – 116Combined sources8
Turni121 – 124Combined sources4
Beta strandi131 – 133Combined sources3
Turni136 – 139Combined sources4
Helixi147 – 162Combined sources16
Helixi172 – 192Combined sources21
Helixi197 – 201Combined sources5
Helixi206 – 209Combined sources4
Helixi212 – 219Combined sources8
Helixi223 – 239Combined sources17
Helixi247 – 261Combined sources15
Helixi263 – 265Combined sources3
Beta strandi268 – 271Combined sources4
Beta strandi286 – 291Combined sources6
Turni292 – 294Combined sources3
Beta strandi295 – 300Combined sources6
Beta strandi315 – 318Combined sources4
Helixi320 – 322Combined sources3
Beta strandi323 – 329Combined sources7
Beta strandi340 – 349Combined sources10
Beta strandi351 – 357Combined sources7
Helixi359 – 376Combined sources18
Turni385 – 387Combined sources3
Helixi390 – 397Combined sources8
Helixi406 – 415Combined sources10
Beta strandi423 – 427Combined sources5
Beta strandi432 – 443Combined sources12
Beta strandi446 – 455Combined sources10
Helixi474 – 481Combined sources8
Beta strandi485 – 488Combined sources4
Beta strandi491 – 495Combined sources5
Beta strandi510 – 513Combined sources4
Helixi542 – 544Combined sources3
Beta strandi545 – 554Combined sources10
Beta strandi557 – 567Combined sources11
Helixi569 – 571Combined sources3
Beta strandi573 – 584Combined sources12
Helixi588 – 602Combined sources15
Beta strandi612 – 616Combined sources5
Beta strandi618 – 627Combined sources10
Helixi634 – 640Combined sources7
Turni641 – 643Combined sources3
Helixi647 – 666Combined sources20
Helixi676 – 678Combined sources3
Beta strandi679 – 683Combined sources5
Turni687 – 690Combined sources4
Beta strandi694 – 697Combined sources4
Turni704 – 706Combined sources3
Helixi709 – 714Combined sources6
Turni715 – 718Combined sources4
Helixi721 – 725Combined sources5
Helixi727 – 729Combined sources3
Helixi732 – 746Combined sources15
Turni747 – 750Combined sources4
Turni753 – 756Combined sources4
Helixi759 – 767Combined sources9
Helixi778 – 780Combined sources3
Helixi781 – 787Combined sources7
Helixi792 – 794Combined sources3
Helixi798 – 807Combined sources10
Beta strandi836 – 838Combined sources3
Helixi846 – 848Combined sources3
Beta strandi849 – 857Combined sources9
Beta strandi859 – 868Combined sources10
Beta strandi872 – 874Combined sources3
Beta strandi877 – 885Combined sources9
Helixi889 – 903Combined sources15
Beta strandi913 – 917Combined sources5
Helixi919 – 922Combined sources4
Beta strandi926 – 930Combined sources5
Helixi937 – 943Combined sources7
Helixi945 – 947Combined sources3
Helixi950 – 969Combined sources20
Helixi979 – 981Combined sources3
Beta strandi982 – 986Combined sources5
Beta strandi989 – 992Combined sources4
Helixi995 – 997Combined sources3
Beta strandi1006 – 1009Combined sources4
Helixi1017 – 1020Combined sources4
Helixi1023 – 1028Combined sources6
Beta strandi1030 – 1032Combined sources3
Helixi1033 – 1049Combined sources17
Helixi1053 – 1055Combined sources3
Helixi1057 – 1065Combined sources9
Beta strandi1069 – 1071Combined sources3
Helixi1072 – 1083Combined sources12
Turni1084 – 1086Combined sources3
Helixi1096 – 1105Combined sources10
Helixi1110 – 1112Combined sources3
Helixi1116 – 1128Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4D0WX-ray1.77A835-1132[»]
4D0XX-ray1.82A835-1132[»]
4D1SX-ray1.66A835-1132[»]
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[»]
4P7EX-ray2.40A/B840-1132[»]
4YTCX-ray2.16A842-1132[»]
4YTFX-ray1.78A842-1132[»]
4YTHX-ray2.04A842-1132[»]
4YTIX-ray2.52A842-1132[»]
4Z32X-ray3.04A/B/C/D/E/F/G/H31-516[»]
4ZIMX-ray2.65A/B839-1132[»]
5AEPX-ray1.95A835-1132[»]
5CF4X-ray2.38A/B839-1132[»]
5CF5X-ray2.45A/B839-1132[»]
5CF6X-ray2.50A/B839-1132[»]
5CF8X-ray1.80A/B839-1132[»]
5HEZX-ray2.66A/B/C/D833-1132[»]
5I4NX-ray1.54A535-812[»]
5L3AX-ray1.98A840-1132[»]
5TQ3X-ray2.69A/B837-1132[»]
5TQ4X-ray2.30A837-1132[»]
5TQ5X-ray2.30A837-1132[»]
5TQ6X-ray2.06A/B837-1132[»]
5TQ7X-ray2.10A/B837-1132[»]
5TQ8X-ray1.59A837-1132[»]
ProteinModelPortaliO60674.
SMRiO60674.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60674.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini37 – 380FERMPROSITE-ProRule annotationAdd BLAST344
Domaini401 – 482SH2; atypicalPROSITE-ProRule annotationAdd BLAST82
Domaini545 – 809Protein kinase 1PROSITE-ProRule annotationAdd BLAST265
Domaini849 – 1124Protein kinase 2PROSITE-ProRule annotationAdd BLAST276

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 239Interaction with cytokine/interferon/growth hormone receptorsBy similarityAdd BLAST239

Domaini

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).By similarity

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118799.
HOGENOMiHOG000049158.
HOVERGENiHBG006195.
InParanoidiO60674.
KOiK04447.
OMAiSNCHGPI.
OrthoDBiEOG091G01IS.
PhylomeDBiO60674.
TreeFamiTF327041.

Family and domain databases

Gene3Di1.20.80.10. 1 hit.
3.30.505.10. 1 hit.
InterProiView protein in InterPro
IPR019749. Band_41_domain.
IPR014352. FERM/acyl-CoA-bd_prot_3-hlx.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
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.
PfamiView protein in Pfam
PF07714. Pkinase_Tyr. 2 hits.
PF00017. SH2. 1 hit.
PIRSFiPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSiPR01823. JANUSKINASE.
PR01825. JANUSKINASE2.
PR00109. TYRKINASE.
SMARTiView protein in SMART
SM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiView protein in PROSITE
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.

Sequencei

Sequence statusi: Complete.

O60674-1 [UniParc]FASTAAdd to basket

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        10         20         30         40         50
MGMACLTMTE MEGTSTSSIY QNGDISGNAN SMKQIDPVLQ VYLYHSLGKS 
        60         70         80         90        100
EADYLTFPSG EYVAEEICIA ASKACGITPV YHNMFALMSE TERIWYPPNH 
       110        120        130        140        150
VFHIDESTRH NVLYRIRFYF PRWYCSGSNR AYRHGISRGA EAPLLDDFVM 
       160        170        180        190        200
SYLFAQWRHD FVHGWIKVPV THETQEECLG MAVLDMMRIA KENDQTPLAI 
       210        220        230        240        250
YNSISYKTFL PKCIRAKIQD YHILTRKRIR YRFRRFIQQF SQCKATARNL 
       260        270        280        290        300
KLKYLINLET LQSAFYTEKF EVKEPGSGPS GEEIFATIII TGNGGIQWSR 
       310        320        330        340        350
GKHKESETLT EQDLQLYCDF PNIIDVSIKQ ANQEGSNESR VVTIHKQDGK 
       360        370        380        390        400
NLEIELSSLR EALSFVSLID GYYRLTADAH HYLCKEVAPP AVLENIQSNC 
       410        420        430        440        450
HGPISMDFAI SKLKKAGNQT GLYVLRCSPK DFNKYFLTFA VERENVIEYK 
       460        470        480        490        500
HCLITKNENE EYNLSGTKKN FSSLKDLLNC YQMETVRSDN IIFQFTKCCP 
       510        520        530        540        550
PKPKDKSNLL VFRTNGVSDV PTSPTLQRPT HMNQMVFHKI RNEDLIFNES 
       560        570        580        590        600
LGQGTFTKIF KGVRREVGDY GQLHETEVLL KVLDKAHRNY SESFFEAASM 
       610        620        630        640        650
MSKLSHKHLV LNYGVCVCGD ENILVQEFVK FGSLDTYLKK NKNCINILWK 
       660        670        680        690        700
LEVAKQLAWA MHFLEENTLI HGNVCAKNIL LIREEDRKTG NPPFIKLSDP 
       710        720        730        740        750
GISITVLPKD ILQERIPWVP PECIENPKNL NLATDKWSFG TTLWEICSGG 
       760        770        780        790        800
DKPLSALDSQ RKLQFYEDRH QLPAPKWAEL ANLINNCMDY EPDFRPSFRA 
       810        820        830        840        850
IIRDLNSLFT PDYELLTEND MLPNMRIGAL GFSGAFEDRD PTQFEERHLK 
       860        870        880        890        900
FLQQLGKGNF GSVEMCRYDP LQDNTGEVVA VKKLQHSTEE HLRDFEREIE 
       910        920        930        940        950
ILKSLQHDNI VKYKGVCYSA GRRNLKLIME YLPYGSLRDY LQKHKERIDH 
       960        970        980        990       1000
IKLLQYTSQI CKGMEYLGTK RYIHRDLATR NILVENENRV KIGDFGLTKV 
      1010       1020       1030       1040       1050
LPQDKEYYKV KEPGESPIFW YAPESLTESK FSVASDVWSF GVVLYELFTY 
      1060       1070       1080       1090       1100
IEKSKSPPAE FMRMIGNDKQ GQMIVFHLIE LLKNNGRLPR PDGCPDEIYM 
      1110       1120       1130 
IMTECWNNNV NQRPSFRDLA LRVDQIRDNM AG
Length:1,132
Mass (Da):130,674
Last modified:January 24, 2001 - v2
Checksum:iC30669EF1A7DA80C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti321P → S in AAC23982 (PubMed:9618263).Curated1
Sequence conflicti1126I → V in AAC23653 (PubMed:9446644).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041716127G → D1 PublicationCorresponds to variant dbSNP:rs56118985Ensembl.1
Natural variantiVAR_041717191K → Q in an ovarian serous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041718346K → R1 PublicationCorresponds to variant dbSNP:rs55667734Ensembl.1
Natural variantiVAR_041719377A → E1 PublicationCorresponds to variant dbSNP:rs55953208Ensembl.1
Natural variantiVAR_041720393L → V1 PublicationCorresponds to variant dbSNP:rs2230723Ensembl.1
Natural variantiVAR_032693537 – 539FHK → L in myeloproliferative disorder with erythrocytosis. 1 Publication3
Natural variantiVAR_032694538 – 539HK → QL in myeloproliferative disorder with erythrocytosis. 2
Natural variantiVAR_032695539K → L in myeloproliferative disorder with erythrocytosis; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs121912473Ensembl.1
Natural variantiVAR_043129584D → E. Corresponds to variant dbSNP:rs17490221Ensembl.1
Natural variantiVAR_032696607K → N in AML. 1 PublicationCorresponds to variant dbSNP:rs121912472Ensembl.1
Natural variantiVAR_032697617V → 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. 6 PublicationsCorresponds to variant dbSNP:rs77375493Ensembl.1
Natural variantiVAR_067534617V → I in THCYT3. 1 PublicationCorresponds to variant dbSNP:rs77375493Ensembl.1
Natural variantiVAR_0417211063R → H1 PublicationCorresponds to variant dbSNP:rs41316003Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF058925 mRNA. Translation: AAC23982.1.
AF001362 mRNA. Translation: AAC23653.1.
AF005216 mRNA. Translation: AAB82092.1.
AL161450 Genomic DNA. No translation available.
CCDSiCCDS6457.1.
PIRiJW0091.
RefSeqiNP_001309123.1. NM_001322194.1.
NP_001309124.1. NM_001322195.1.
NP_001309125.1. NM_001322196.1.
NP_001309133.1. NM_001322204.1.
NP_004963.1. NM_004972.3.
UniGeneiHs.656213.

Genome annotation databases

EnsembliENST00000381652; ENSP00000371067; ENSG00000096968.
GeneIDi3717.
KEGGihsa:3717.
UCSCiuc003ziw.3. human.

Keywords - Coding sequence diversityi

Chromosomal rearrangement, Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiJAK2_HUMAN
AccessioniPrimary (citable) accession number: O60674
Secondary accession number(s): O14636, O75297
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: January 24, 2001
Last modified: June 7, 2017
This is version 193 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families