Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q62689 (JAK2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase JAK2

EC=2.7.10.2
Alternative name(s):
Janus kinase 2
Short name=JAK-2
Gene names
Name:Jak2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1132 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin By similarity.

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Enzyme regulation

Regulated by autophosphorylation, can both activate or decrease activity. Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008 By similarity.

Subunit structure

Interacts with EPOR, SIRPA and SH2B1. Interacts with IL23R, LYN, SKB1, STAM2 and TEC By similarity.

Subcellular location

Endomembrane system; Peripheral membrane protein By similarity. Cytoplasm By similarity. Nucleus By similarity.

Tissue specificity

Ubiquitously expressed throughout most tissues. Ref.1

Domain

The N-terminal domain of JAKs mediates their interaction with cytokine/interferon/growth hormone receptors. Possesses 2 protein kinase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for protein kinase 1 By similarity.

Post-translational modification

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

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.

Contains 1 FERM domain.

Contains 2 protein kinase domains.

Contains 1 SH2 domain.

Ontologies

Keywords
   Biological processAdaptive immunity
Immunity
Innate immunity
   Cellular componentCytoplasm
Membrane
Nucleus
   DomainRepeat
SH2 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionChromatin regulator
Kinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from mutant phenotype PubMed 17021051. Source: RGD

JAK-STAT cascade

Inferred from direct assay PubMed 11064147. Source: RGD

JAK-STAT cascade involved in growth hormone signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

STAT protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

activation of JAK2 kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

activation of MAPKK activity

Inferred from mutant phenotype PubMed 16567515. Source: RGD

axon regeneration

Inferred from mutant phenotype PubMed 15716400. Source: RGD

cytokine-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

erythrocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

extrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

histone H3-Y41 phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

hormone-mediated signaling pathway

Inferred from direct assay PubMed 11064147. Source: RGD

host programmed cell death induced by symbiont

Inferred from electronic annotation. Source: Ensembl

interferon-gamma-mediated signaling pathway

Inferred from direct assay PubMed 11536325. Source: BHF-UCL

interleukin-12-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

intrinsic apoptotic signaling pathway in response to oxidative stress

Inferred from mutant phenotype PubMed 15659221. Source: RGD

mammary gland epithelium development

Inferred from electronic annotation. Source: Ensembl

mineralocorticoid receptor signaling pathway

Inferred from mutant phenotype PubMed 15932931. Source: RGD

negative regulation of DNA binding

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell-cell adhesion

Inferred from mutant phenotype PubMed 15530849. Source: RGD

negative regulation of heart contraction

Inferred from mutant phenotype PubMed 12595539. Source: RGD

negative regulation of neuron apoptotic process

Inferred from mutant phenotype PubMed 12244045. Source: RGD

platelet-derived growth factor receptor signaling pathway

Inferred from mutant phenotype PubMed 15948243. Source: RGD

positive regulation of DNA binding

Inferred from mutant phenotype PubMed 15322111. Source: RGD

positive regulation of apoptotic process

Inferred from mutant phenotype PubMed 16269269. Source: RGD

positive regulation of apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell activation

Inferred from mutant phenotype PubMed 15256805. Source: RGD

positive regulation of cell differentiation

Inferred from mutant phenotype PubMed 16514419. Source: RGD

positive regulation of cell migration

Inferred from mutant phenotype PubMed 15530849. Source: RGD

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 16567515. Source: RGD

positive regulation of cell-substrate adhesion

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytosolic calcium ion concentration

Inferred from mutant phenotype PubMed 16597920. Source: RGD

positive regulation of inflammatory response

Inferred from mutant phenotype PubMed 16934228. Source: RGD

positive regulation of insulin secretion

Inferred from mutant phenotype PubMed 16597920. Source: RGD

positive regulation of interleukin-1 beta production

Inferred from mutant phenotype PubMed 16934228. Source: RGD

positive regulation of nitric oxide biosynthetic process

Inferred from mutant phenotype PubMed 12595539. Source: RGD

positive regulation of nitric-oxide synthase biosynthetic process

Inferred from direct assay PubMed 11536325. Source: BHF-UCL

positive regulation of phosphoprotein phosphatase activity

Inferred from mutant phenotype PubMed 17021051. Source: RGD

positive regulation of protein import into nucleus, translocation

Inferred from mutant phenotype PubMed 15530849. Source: RGD

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from mutant phenotype PubMed 15322111. Source: RGD

positive regulation of tyrosine phosphorylation of Stat3 protein

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

response to antibiotic

Inferred from electronic annotation. Source: Ensembl

response to hydroperoxide

Inferred from mutant phenotype PubMed 15659221. Source: RGD

response to oxidative stress

Inferred from mutant phenotype PubMed 16269269. Source: RGD

signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

tumor necrosis factor-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

tyrosine phosphorylation of Stat1 protein

Inferred from mutant phenotype PubMed 15659221. Source: RGD

tyrosine phosphorylation of Stat3 protein

Inferred from mutant phenotype PubMed 15659221PubMed 17920330. Source: RGD

tyrosine phosphorylation of Stat5 protein

Inferred from mutant phenotype PubMed 17920330. Source: RGD

   Cellular_componentcaveola

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 8756581. Source: RGD

cytoskeleton

Inferred from electronic annotation. Source: InterPro

cytosol

Inferred from direct assay PubMed 16972141. Source: RGD

endomembrane system

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear matrix

Inferred from direct assay PubMed 8756581. Source: RGD

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

acetylcholine receptor binding

Inferred from physical interaction PubMed 12244045. Source: RGD

growth hormone receptor binding

Inferred from physical interaction PubMed 10502458. Source: BHF-UCL

heme binding

Inferred from sequence or structural similarity. Source: UniProtKB

histone binding

Inferred from sequence or structural similarity. Source: UniProtKB

histone kinase activity (H3-Y41 specific)

Inferred from sequence or structural similarity. Source: UniProtKB

insulin receptor substrate binding

Inferred from physical interaction PubMed 15701573. Source: RGD

non-membrane spanning protein tyrosine kinase activity

Traceable author statement. Source: Reactome

peptide hormone receptor binding

Inferred from physical interaction PubMed 11244571. Source: RGD

phosphatidylinositol 3-kinase binding

Inferred from physical interaction PubMed 15530849. Source: RGD

protein C-terminus binding

Inferred from physical interaction PubMed 9287353. Source: RGD

protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

type 1 angiotensin receptor binding

Inferred from physical interaction PubMed 9287353PubMed 9314843. Source: RGD

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11321132Tyrosine-protein kinase JAK2
PRO_0000088114

Regions

Domain37 – 380344FERM
Domain401 – 48282SH2; atypical
Domain545 – 809265Protein kinase 1
Domain849 – 1126278Protein kinase 2
Nucleotide binding855 – 8639ATP By similarity
Region1 – 239239Interaction with cytokine/interferon/growth hormone receptors By similarity

Sites

Active site9761Proton acceptor By similarity
Binding site8821ATP By similarity

Amino acid modifications

Modified residue1191Phosphotyrosine; by autocatalysis By similarity
Modified residue3721Phosphotyrosine By similarity
Modified residue3731Phosphotyrosine By similarity
Modified residue5231Phosphoserine By similarity
Modified residue8131Phosphotyrosine By similarity
Modified residue8681Phosphotyrosine; by autocatalysis By similarity
Modified residue9661Phosphotyrosine; by autocatalysis By similarity
Modified residue9721Phosphotyrosine; by autocatalysis By similarity
Modified residue10071Phosphotyrosine; by autocatalysis By similarity
Modified residue10081Phosphotyrosine; by autocatalysis By similarity

Sequences

Sequence LengthMass (Da)Tools
Q62689 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: C3AEDF2FECE8B95A

FASTA1,132130,585
        10         20         30         40         50         60 
MGMACLTMTE MEGTSTSPAH QNGDIPGNAN SVKQTEPVLQ VYLYHSLGQA EGDYLKFPNG 

        70         80         90        100        110        120 
EYVAEEICVA ASKACGITPV YHNMFALMSE TERIWYPPNH VFHIDESTRH NILYRIRFYF 

       130        140        150        160        170        180 
PHWYCSGSNR TYRYGVSRGA EAPLLDDFVM SYLFAQWRHD FVHGWIKVPV THETQEECLG 

       190        200        210        220        230        240 
MAVLDMMRIA KEKDQTPLAV YNSISYKTFL PKCVRAKIQD YHILTRKRIR YRFRRFIQQF 

       250        260        270        280        290        300 
SQCKATARNL KLKYLINLET LQSAFYTEQF EVKESARGPS GEEIFATIII TGNGGIQWSR 

       310        320        330        340        350        360 
GKHKESETLT EQDLQLYCDF PDIIDVSIKQ ANQECSTESR VVTVHKQDGK VLEIELSSLK 

       370        380        390        400        410        420 
EALSFVSLID GYYRLTADAH HYLCKEVAPP AVLENIHSNC HGPISMDFAI SKLKKAGNQT 

       430        440        450        460        470        480 
GLYVLRCSPK DFNKYFLTFA VERENVIEYK HCLITKNENG EYNLSGTKRN FSSLKDLLNC 

       490        500        510        520        530        540 
YQMETVRSDS IIFQFTKCCP PKPKDKSNLL VFRTNGVSDV QLSPTLQRHN NVNQMVFHKI 

       550        560        570        580        590        600 
RNEDLIFNES LGQGTFTKIF KGVRREVGDY GQLHETEVLL KVLDKAHRNY SESFFEAASM 

       610        620        630        640        650        660 
MSQLSHKHLV LNYGVCVCGE ENILVQEFVK FGSLDTYLKK NKNSINILWK LGVAKQLAWA 

       670        680        690        700        710        720 
MHFLEEKSLI HGNVCAKNIL LIREEDRKTG NPPFIKLSDP GISITVLPKD ILQERIPWVP 

       730        740        750        760        770        780 
PECIENPKNL TLATDKWSFG TTLWEICSGG DKPLSALDSQ RKLQFYEDKH QLPAPKWTEL 

       790        800        810        820        830        840 
ANLINTCMDY EPDFRPAFRA VIRDLNSLFT PDYELLTEND MLPNMRIGAL GFSGAFEDRD 

       850        860        870        880        890        900 
PTQFEERHLK FLQQLGKGNF GSVEMCRYDP LQDNTGEVVA VKKLQHSTEE HLRDFEREIE 

       910        920        930        940        950        960 
ILKSLQHDNI VKYKGVCYSA GRRNLRLIME YLPYGSLRDY LQKHKERIDH KKLLQYTSQI 

       970        980        990       1000       1010       1020 
CKGMEYLGTK RYIHRDLATR NILVENENRV KIGDFGLTKV LPQDKEYYKV KEPGESPIFW 

      1030       1040       1050       1060       1070       1080 
YAPESLTESK FSVASDVWSF GVVLYELFTY IEKSKSPPVE FMRMIGNDKQ GQMIVFHLIE 

      1090       1100       1110       1120       1130 
LLKNNGRLPR PEGCPDEIYV IMTECWNNNV NQRPSFRDLS LRVDQIRDSM AA 

« Hide

References

[1]"Cloning of the gene encoding rat JAK2, a protein tyrosine kinase."
Duhe R.J., Rui H., Greenwood J.D., Garvey K., Farrar W.L.
Gene 158:281-285(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U13396 mRNA. Translation: AAA79911.1.
PIRJC4127.
RefSeqNP_113702.1. NM_031514.1.
XP_006231257.1. XM_006231195.1.
UniGeneRn.18909.

3D structure databases

ProteinModelPortalQ62689.
SMRQ62689. Positions 840-1132.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid246670. 10 interactions.
DIPDIP-491N.
IntActQ62689. 3 interactions.

Chemistry

ChEMBLCHEMBL1075225.

PTM databases

PhosphoSiteQ62689.

Proteomic databases

PRIDEQ62689.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000021217; ENSRNOP00000021218; ENSRNOG00000015547.
GeneID24514.
KEGGrno:24514.
UCSCRGD:2939. rat.

Organism-specific databases

CTD3717.
RGD2939. Jak2.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00710000106680.
HOGENOMHOG000049158.
HOVERGENHBG006195.
InParanoidQ62689.
KOK04447.
OMACHGPISM.
OrthoDBEOG7BW0HM.
PhylomeDBQ62689.

Enzyme and pathway databases

BRENDA2.7.10.2. 5301.

Gene expression databases

GenevestigatorQ62689.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR019749. Band_41_domain.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
PANTHERPTHR24418:SF69. PTHR24418:SF69. 1 hit.
PfamPF07714. Pkinase_Tyr. 2 hits.
PF00017. SH2. 1 hit.
[Graphical view]
PIRSFPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSPR01823. JANUSKINASE.
PR01825. JANUSKINASE2.
PR00109. TYRKINASE.
SMARTSM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMSSF47031. SSF47031. 1 hit.
SSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEPS50057. 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]
ProtoNetSearch...

Other

NextBio603541.
PROQ62689.

Entry information

Entry nameJAK2_RAT
AccessionPrimary (citable) accession number: Q62689
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: April 16, 2014
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families