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Q62689

- JAK2_RAT

UniProt

Q62689 - JAK2_RAT

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Protein

Tyrosine-protein kinase JAK2

Gene
Jak2
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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. 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 activityi

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

Enzyme regulationi

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei882 – 8821ATP By similarity
Active sitei976 – 9761Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi855 – 8639ATP By similarity

GO - Molecular functioni

  1. acetylcholine receptor binding Source: RGD
  2. ATP binding Source: UniProtKB-KW
  3. growth hormone receptor binding Source: BHF-UCL
  4. heme binding Source: UniProtKB
  5. histone binding Source: UniProtKB
  6. histone kinase activity (H3-Y41 specific) Source: UniProtKB
  7. insulin receptor substrate binding Source: RGD
  8. non-membrane spanning protein tyrosine kinase activity Source: Reactome
  9. peptide hormone receptor binding Source: RGD
  10. phosphatidylinositol 3-kinase binding Source: RGD
  11. protein binding Source: IntAct
  12. protein C-terminus binding Source: RGD
  13. protein tyrosine kinase activity Source: UniProtKB
  14. type 1 angiotensin receptor binding Source: RGD

GO - Biological processi

  1. activation of JAK2 kinase activity Source: UniProtKB
  2. activation of MAPKK activity Source: RGD
  3. axon regeneration Source: RGD
  4. cytokine-mediated signaling pathway Source: UniProtKB
  5. erythrocyte differentiation Source: UniProtKB
  6. extrinsic apoptotic signaling pathway Source: Ensembl
  7. G-protein coupled receptor signaling pathway Source: RGD
  8. histone H3-Y41 phosphorylation Source: UniProtKB
  9. hormone-mediated signaling pathway Source: RGD
  10. host programmed cell death induced by symbiont Source: Ensembl
  11. interferon-gamma-mediated signaling pathway Source: BHF-UCL
  12. interleukin-12-mediated signaling pathway Source: Ensembl
  13. intrinsic apoptotic signaling pathway in response to oxidative stress Source: RGD
  14. JAK-STAT cascade Source: RGD
  15. JAK-STAT cascade involved in growth hormone signaling pathway Source: UniProtKB
  16. mammary gland epithelium development Source: Ensembl
  17. mineralocorticoid receptor signaling pathway Source: RGD
  18. negative regulation of cell-cell adhesion Source: RGD
  19. negative regulation of cell proliferation Source: Ensembl
  20. negative regulation of DNA binding Source: Ensembl
  21. negative regulation of heart contraction Source: RGD
  22. negative regulation of neuron apoptotic process Source: RGD
  23. platelet-derived growth factor receptor signaling pathway Source: RGD
  24. positive regulation of apoptotic process Source: RGD
  25. positive regulation of apoptotic signaling pathway Source: Ensembl
  26. positive regulation of cell activation Source: RGD
  27. positive regulation of cell differentiation Source: RGD
  28. positive regulation of cell migration Source: RGD
  29. positive regulation of cell proliferation Source: RGD
  30. positive regulation of cell-substrate adhesion Source: Ensembl
  31. positive regulation of cytosolic calcium ion concentration Source: RGD
  32. positive regulation of DNA binding Source: RGD
  33. positive regulation of inflammatory response Source: RGD
  34. positive regulation of insulin secretion Source: RGD
  35. positive regulation of interleukin-1 beta production Source: RGD
  36. positive regulation of nitric oxide biosynthetic process Source: RGD
  37. positive regulation of nitric-oxide synthase biosynthetic process Source: BHF-UCL
  38. positive regulation of phosphoprotein phosphatase activity Source: RGD
  39. positive regulation of protein import into nucleus, translocation Source: RGD
  40. positive regulation of sequence-specific DNA binding transcription factor activity Source: RGD
  41. positive regulation of tyrosine phosphorylation of Stat3 protein Source: UniProtKB
  42. protein autophosphorylation Source: UniProtKB
  43. response to antibiotic Source: Ensembl
  44. response to hydroperoxide Source: RGD
  45. response to oxidative stress Source: RGD
  46. signal transduction Source: UniProtKB
  47. STAT protein import into nucleus Source: Ensembl
  48. tumor necrosis factor-mediated signaling pathway Source: Ensembl
  49. tyrosine phosphorylation of Stat1 protein Source: RGD
  50. tyrosine phosphorylation of Stat3 protein Source: RGD
  51. tyrosine phosphorylation of Stat5 protein Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Adaptive immunity, Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 5301.
ReactomeiREACT_195025. Signaling by SCF-KIT.
REACT_195204. Signaling by Leptin.
REACT_196232. Factors involved in megakaryocyte development and platelet production.
REACT_196425. Growth hormone receptor signaling.
REACT_196446. Interferon gamma signaling.
REACT_196448. Regulation of IFNG signaling.
REACT_199232. Prolactin receptor signaling.
REACT_199244. Interleukin-6 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase JAK2 (EC:2.7.10.2)
Alternative name(s):
Janus kinase 2
Short name:
JAK-2
Gene namesi
Name:Jak2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 1

Organism-specific databases

RGDi2939. Jak2.

Subcellular locationi

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

GO - Cellular componenti

  1. caveola Source: Ensembl
  2. cytoplasm Source: RGD
  3. cytoskeleton Source: InterPro
  4. cytosol Source: RGD
  5. endomembrane system Source: UniProtKB-SubCell
  6. nuclear matrix Source: RGD
  7. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11321132Tyrosine-protein kinase JAK2PRO_0000088114Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei119 – 1191Phosphotyrosine; by autocatalysis By similarity
Modified residuei372 – 3721Phosphotyrosine By similarity
Modified residuei373 – 3731Phosphotyrosine By similarity
Modified residuei523 – 5231Phosphoserine By similarity
Modified residuei813 – 8131Phosphotyrosine By similarity
Modified residuei868 – 8681Phosphotyrosine; by autocatalysis By similarity
Modified residuei966 – 9661Phosphotyrosine; by autocatalysis By similarity
Modified residuei972 – 9721Phosphotyrosine; by autocatalysis By similarity
Modified residuei1007 – 10071Phosphotyrosine; by autocatalysis By similarity
Modified residuei1008 – 10081Phosphotyrosine; by autocatalysis By similarity

Post-translational modificationi

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.

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiQ62689.

PTM databases

PhosphoSiteiQ62689.

Expressioni

Tissue specificityi

Ubiquitously expressed throughout most tissues.1 Publication

Gene expression databases

GenevestigatoriQ62689.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
InsrP151272EBI-8656708,EBI-7472166
Ptpn11P414993EBI-8656708,EBI-7180604

Protein-protein interaction databases

BioGridi246670. 10 interactions.
DIPiDIP-491N.
IntActiQ62689. 3 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ62689.
SMRiQ62689. Positions 840-1132.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini37 – 380344FERMAdd
BLAST
Domaini401 – 48282SH2; atypicalAdd
BLAST
Domaini545 – 809265Protein kinase 1Add
BLAST
Domaini849 – 1126278Protein kinase 2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 239239Interaction with cytokine/interferon/growth hormone receptors By similarityAdd
BLAST

Domaini

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.

Sequence similaritiesi

Contains 1 FERM domain.
Contains 1 SH2 domain.

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00710000106680.
HOGENOMiHOG000049158.
HOVERGENiHBG006195.
InParanoidiQ62689.
KOiK04447.
OMAiCHGPISM.
OrthoDBiEOG7BW0HM.
PhylomeDBiQ62689.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR019749. 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]
PfamiPF07714. Pkinase_Tyr. 2 hits.
PF00017. SH2. 1 hit.
[Graphical view]
PIRSFiPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSiPR01823. JANUSKINASE.
PR01825. JANUSKINASE2.
PR00109. TYRKINASE.
SMARTiSM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50057. 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]

Sequencei

Sequence statusi: Complete.

Q62689-1 [UniParc]FASTAAdd to Basket

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MGMACLTMTE MEGTSTSPAH QNGDIPGNAN SVKQTEPVLQ VYLYHSLGQA     50
EGDYLKFPNG EYVAEEICVA ASKACGITPV YHNMFALMSE TERIWYPPNH 100
VFHIDESTRH NILYRIRFYF PHWYCSGSNR TYRYGVSRGA EAPLLDDFVM 150
SYLFAQWRHD FVHGWIKVPV THETQEECLG MAVLDMMRIA KEKDQTPLAV 200
YNSISYKTFL PKCVRAKIQD YHILTRKRIR YRFRRFIQQF SQCKATARNL 250
KLKYLINLET LQSAFYTEQF EVKESARGPS GEEIFATIII TGNGGIQWSR 300
GKHKESETLT EQDLQLYCDF PDIIDVSIKQ ANQECSTESR VVTVHKQDGK 350
VLEIELSSLK EALSFVSLID GYYRLTADAH HYLCKEVAPP AVLENIHSNC 400
HGPISMDFAI SKLKKAGNQT GLYVLRCSPK DFNKYFLTFA VERENVIEYK 450
HCLITKNENG EYNLSGTKRN FSSLKDLLNC YQMETVRSDS IIFQFTKCCP 500
PKPKDKSNLL VFRTNGVSDV QLSPTLQRHN NVNQMVFHKI RNEDLIFNES 550
LGQGTFTKIF KGVRREVGDY GQLHETEVLL KVLDKAHRNY SESFFEAASM 600
MSQLSHKHLV LNYGVCVCGE ENILVQEFVK FGSLDTYLKK NKNSINILWK 650
LGVAKQLAWA MHFLEEKSLI HGNVCAKNIL LIREEDRKTG NPPFIKLSDP 700
GISITVLPKD ILQERIPWVP PECIENPKNL TLATDKWSFG TTLWEICSGG 750
DKPLSALDSQ RKLQFYEDKH QLPAPKWTEL ANLINTCMDY EPDFRPAFRA 800
VIRDLNSLFT PDYELLTEND MLPNMRIGAL GFSGAFEDRD PTQFEERHLK 850
FLQQLGKGNF GSVEMCRYDP LQDNTGEVVA VKKLQHSTEE HLRDFEREIE 900
ILKSLQHDNI VKYKGVCYSA GRRNLRLIME YLPYGSLRDY LQKHKERIDH 950
KKLLQYTSQI CKGMEYLGTK RYIHRDLATR NILVENENRV KIGDFGLTKV 1000
LPQDKEYYKV KEPGESPIFW YAPESLTESK FSVASDVWSF GVVLYELFTY 1050
IEKSKSPPVE FMRMIGNDKQ GQMIVFHLIE LLKNNGRLPR PEGCPDEIYV 1100
IMTECWNNNV NQRPSFRDLS LRVDQIRDSM AA 1132
Length:1,132
Mass (Da):130,585
Last modified:November 1, 1997 - v1
Checksum:iC3AEDF2FECE8B95A
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U13396 mRNA. Translation: AAA79911.1.
PIRiJC4127.
RefSeqiNP_113702.1. NM_031514.1.
XP_006231257.1. XM_006231195.1.
UniGeneiRn.18909.

Genome annotation databases

EnsembliENSRNOT00000021217; ENSRNOP00000021218; ENSRNOG00000015547.
GeneIDi24514.
KEGGirno:24514.
UCSCiRGD:2939. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U13396 mRNA. Translation: AAA79911.1 .
PIRi JC4127.
RefSeqi NP_113702.1. NM_031514.1.
XP_006231257.1. XM_006231195.1.
UniGenei Rn.18909.

3D structure databases

ProteinModelPortali Q62689.
SMRi Q62689. Positions 840-1132.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 246670. 10 interactions.
DIPi DIP-491N.
IntActi Q62689. 3 interactions.

Chemistry

ChEMBLi CHEMBL1075225.

PTM databases

PhosphoSitei Q62689.

Proteomic databases

PRIDEi Q62689.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000021217 ; ENSRNOP00000021218 ; ENSRNOG00000015547 .
GeneIDi 24514.
KEGGi rno:24514.
UCSCi RGD:2939. rat.

Organism-specific databases

CTDi 3717.
RGDi 2939. Jak2.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00710000106680.
HOGENOMi HOG000049158.
HOVERGENi HBG006195.
InParanoidi Q62689.
KOi K04447.
OMAi CHGPISM.
OrthoDBi EOG7BW0HM.
PhylomeDBi Q62689.

Enzyme and pathway databases

BRENDAi 2.7.10.2. 5301.
Reactomei REACT_195025. Signaling by SCF-KIT.
REACT_195204. Signaling by Leptin.
REACT_196232. Factors involved in megakaryocyte development and platelet production.
REACT_196425. Growth hormone receptor signaling.
REACT_196446. Interferon gamma signaling.
REACT_196448. Regulation of IFNG signaling.
REACT_199232. Prolactin receptor signaling.
REACT_199244. Interleukin-6 signaling.

Miscellaneous databases

NextBioi 603541.
PROi Q62689.

Gene expression databases

Genevestigatori Q62689.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR019749. 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 ]
Pfami PF07714. Pkinase_Tyr. 2 hits.
PF00017. SH2. 1 hit.
[Graphical view ]
PIRSFi PIRSF000636. TyrPK_Jak. 1 hit.
PRINTSi PR01823. JANUSKINASE.
PR01825. JANUSKINASE2.
PR00109. TYRKINASE.
SMARTi SM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view ]
SUPFAMi SSF47031. SSF47031. 1 hit.
SSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEi PS50057. FERM_3. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiJAK2_RAT
AccessioniPrimary (citable) accession number: Q62689
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: September 3, 2014
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi