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UniProtKB - O60674 (JAK2_HUMAN)

Protein

Tyrosine-protein kinase JAK2

Gene

JAK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). 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).7 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

Activity 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 (PubMed:21036157).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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

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-1059683 Interleukin-6 signaling
R-HSA-110056 MAPK3 (ERK1) activation
R-HSA-112411 MAPK1 (ERK2) activation
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-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-5673000 RAF activation
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6785807 Interleukin-4 and Interleukin-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-8854691 Interleukin-20 family signaling
R-HSA-8984722 Interleukin-35 Signalling
R-HSA-9020591 Interleukin-12 signaling
R-HSA-9020933 Interleukin-23 signaling
R-HSA-9020956 Interleukin-27 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:2.7.10.23 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

EuPathDBiHostDB:ENSG00000096968.12
HGNCiHGNC:6192 JAK2
MIMi147796 gene
neXtProtiNX_O60674

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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:rs77375493EnsemblClinVar.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_067534617V → I in THCYT3. 1 PublicationCorresponds to variant dbSNP:rs77375493EnsemblClinVar.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:rs121912472EnsemblClinVar.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
729 Polycythemia vera
824 Primary myelofibrosis
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). Phosphorylated on tyrosine residues in response to a signaling cascade that is activated by increased cellular retinol (PubMed:21368206).By similarity3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO60674
MaxQBiO60674
PaxDbiO60674
PeptideAtlasiO60674
PRIDEiO60674
ProteomicsDBi49519

PTM databases

iPTMnetiO60674
PhosphoSitePlusiO60674

Expressioni

Tissue specificityi

Ubiquitously expressed throughout most tissues.1 Publication

Gene expression databases

BgeeiENSG00000096968 Expressed in 212 organ(s), highest expression level in popliteal artery
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). Interacts with STRA6 (PubMed:21368206). Interacts with RHEX; this interaction occurs in a erythropoietin (EPO)-dependent manner (PubMed:25092874).By similarity9 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi109920, 108 interactors
ComplexPortaliCPX-382 Interleukin-12-receptor complex
CPX-383 Interleukin-23-receptor complex
CORUMiO60674
DIPiDIP-33880N
IntActiO60674, 35 interactors
MINTiO60674
STRINGi9606.ENSP00000371067

Chemistry databases

BindingDBiO60674

Structurei

Secondary structure

11132
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
GeneTreeiENSGT00900000140909
HOGENOMiHOG000049158
HOVERGENiHBG006195
InParanoidiO60674
KOiK04447
OMAiHCKATAR
OrthoDBiEOG091G01IS
PhylomeDBiO60674
TreeFamiTF327041

Family and domain databases

CDDicd13333 FERM_C_JAK2, 1 hit
cd05078 PTK_Jak2_rpt1, 1 hit
cd14205 PTKc_Jak2_rpt2, 1 hit
cd10379 SH2_Jak2, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR019749 Band_41_domain
IPR035963 FERM_2
IPR000299 FERM_domain
IPR037838 JAK2_FERM_C-lobe
IPR035860 JAK2_SH2
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR035588 PTK_Jak2_rpt1
IPR035589 PTKc_Jak2_rpt2
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
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
SSF55550 SSF55550, 1 hit
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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

O60674-1 [UniParc]FASTAAdd to basket
« Hide
        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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1B0GTR9A0A1B0GTR9_HUMAN
Tyrosine-protein kinase
JAK2
710Annotation score:
A0A1B0GVR5A0A1B0GVR5_HUMAN
Tyrosine-protein kinase JAK2
JAK2
26Annotation score:

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:rs56118985EnsemblClinVar.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:rs2230723EnsemblClinVar.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:rs121912473EnsemblClinVar.1
Natural variantiVAR_043129584D → E. Corresponds to variant dbSNP:rs17490221Ensembl.1
Natural variantiVAR_032696607K → N in AML. 1 PublicationCorresponds to variant dbSNP:rs121912472EnsemblClinVar.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:rs77375493EnsemblClinVar.1
Natural variantiVAR_067534617V → I in THCYT3. 1 PublicationCorresponds to variant dbSNP:rs77375493EnsemblClinVar.1
Natural variantiVAR_0417211063R → H1 PublicationCorresponds to variant dbSNP:rs41316003EnsemblClinVar.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

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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

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[»]
5USYX-ray2.00A/B840-1132[»]
5USZX-ray2.10A536-812[»]
5UT0X-ray2.10A536-812[»]
5UT1X-ray1.95A536-812[»]
5UT2X-ray1.75A536-812[»]
5UT3X-ray1.50A536-812[»]
5UT4X-ray2.00A536-812[»]
5UT5X-ray1.90A536-812[»]
5UT6X-ray1.65A536-812[»]
5WEVX-ray1.85A833-1132[»]
5WIJX-ray2.04A536-812[»]
5WIKX-ray2.60B536-812[»]
5WILX-ray2.20A536-812[»]
5WIMX-ray2.55A536-812[»]
5WINX-ray2.38A536-812[»]
6AAJX-ray2.37A/B834-1132[»]
6BBVX-ray1.80A837-1132[»]
6BRWX-ray2.03A536-812[»]
6BS0X-ray1.54A536-812[»]
6BSSX-ray2.10A536-812[»]
6DRWX-ray2.30A840-1132[»]
6E2PX-ray2.83A/B36-514[»]
6E2QX-ray2.65A/B/C/D36-514[»]
6M9HX-ray1.79A536-812[»]
ProteinModelPortaliO60674
SMRiO60674
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109920, 108 interactors
ComplexPortaliCPX-382 Interleukin-12-receptor complex
CPX-383 Interleukin-23-receptor complex
CORUMiO60674
DIPiDIP-33880N
IntActiO60674, 35 interactors
MINTiO60674
STRINGi9606.ENSP00000371067

Chemistry databases

BindingDBiO60674
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

PTM databases

iPTMnetiO60674
PhosphoSitePlusiO60674

Polymorphism and mutation databases

BioMutaiJAK2

Proteomic databases

EPDiO60674
MaxQBiO60674
PaxDbiO60674
PeptideAtlasiO60674
PRIDEiO60674
ProteomicsDBi49519

Protocols and materials databases

DNASUi3717
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3717
DisGeNETi3717
EuPathDBiHostDB:ENSG00000096968.12
GeneCardsiJAK2
HGNCiHGNC:6192 JAK2
HPAiCAB013089
HPA040820
HPA043870
MalaCardsiJAK2
MIMi147796 gene
254450 phenotype
263300 phenotype
600880 phenotype
601626 phenotype
614521 phenotype
neXtProtiNX_O60674
OpenTargetsiENSG00000096968
Orphaneti131 Budd-Chiari syndrome
3318 Essential thrombocythemia
71493 Familial thrombocytosis
729 Polycythemia vera
824 Primary myelofibrosis
PharmGKBiPA29989
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00900000140909
HOGENOMiHOG000049158
HOVERGENiHBG006195
InParanoidiO60674
KOiK04447
OMAiHCKATAR
OrthoDBiEOG091G01IS
PhylomeDBiO60674
TreeFamiTF327041

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-1059683 Interleukin-6 signaling
R-HSA-110056 MAPK3 (ERK1) activation
R-HSA-112411 MAPK1 (ERK2) activation
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-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-5673000 RAF activation
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6785807 Interleukin-4 and Interleukin-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-8854691 Interleukin-20 family signaling
R-HSA-8984722 Interleukin-35 Signalling
R-HSA-9020591 Interleukin-12 signaling
R-HSA-9020933 Interleukin-23 signaling
R-HSA-9020956 Interleukin-27 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

Miscellaneous databases

ChiTaRSiJAK2 human
EvolutionaryTraceiO60674
GeneWikiiJanus_kinase_2
GenomeRNAii3717
PROiPR:O60674
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000096968 Expressed in 212 organ(s), highest expression level in popliteal artery
CleanExiHS_JAK2
ExpressionAtlasiO60674 baseline and differential
GenevisibleiO60674 HS

Family and domain databases

CDDicd13333 FERM_C_JAK2, 1 hit
cd05078 PTK_Jak2_rpt1, 1 hit
cd14205 PTKc_Jak2_rpt2, 1 hit
cd10379 SH2_Jak2, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR019749 Band_41_domain
IPR035963 FERM_2
IPR000299 FERM_domain
IPR037838 JAK2_FERM_C-lobe
IPR035860 JAK2_SH2
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR035588 PTK_Jak2_rpt1
IPR035589 PTKc_Jak2_rpt2
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
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
SSF55550 SSF55550, 1 hit
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
ProtoNetiSearch...

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: November 7, 2018
This is version 208 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. SIMILARITY comments
    Index of protein domains and families
  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 chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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