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Q5RB23 (JAK2_PONAB) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 77. 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·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
OrganismPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) [Reference proteome]
Taxonomic identifier9601 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo

Protein attributes

Sequence length1132 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript 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.

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_processJAK-STAT cascade involved in growth hormone signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

activation of JAK2 kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

cytokine-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

erythrocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

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

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoskeleton

Inferred from electronic annotation. Source: InterPro

endomembrane system

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

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

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11321132Tyrosine-protein kinase JAK2
PRO_0000324094

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
Q5RB23 [UniParc].

Last modified December 21, 2004. Version 1.
Checksum: 25EA1ADCB4B2B918

FASTA1,132130,704
        10         20         30         40         50         60 
MGMACLTMTE MEGTSTSSIY QNGDISGNAN SMKQIDPVLL VYLYHSLGKS EADYLTFPSG 

        70         80         90        100        110        120 
EYVAEEICIA ASKACGITPV YHNMFALMSE TERIWYPPNH VFHIDESTRH NVLYRIRFYF 

       130        140        150        160        170        180 
PRWYCSGSNR AYRHGISRGA EAPLLDDFVM SYLFAQWRHD FVHGWIKVPV THETQEECLG 

       190        200        210        220        230        240 
MAVLDMMRIA KENDQTPLAI YNSISYKTFL PKCIRAKIQD YHILTRKRIR YRFRRFIQQF 

       250        260        270        280        290        300 
SQCKATARNL KLKYLINLET LQSAFYTEKF EVKEPGSGPS GEEIFATIII TGNGGIQWSR 

       310        320        330        340        350        360 
GKHKESETLT EQDLQLYCDF PNIIDVSIKQ ANQEGSNESR VVTIHKQDGK NLEIELSSLR 

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

       430        440        450        460        470        480 
GLYVLRCSPK DFNKYFLTFA VERENVIEYK HCLITKNENE EYNLSGTKKN FSSLKDLLNC 

       490        500        510        520        530        540 
YQMETVRSDN IIFQFTKCCP PKPKDKSNLL VFRTNGVSDV PTSPTLQRPT HMNQMVFHKI 

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

       610        620        630        640        650        660 
MSKLSHKHLV LNYGVCVCGD ENILVQEFVK FGSLDTYLKK NKNCINILWK LEVAKQLAWA 

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

       730        740        750        760        770        780 
PECIENPKNL NLATDKWSFG TTLWEICSGG DKPLSALDSQ RKLQFYEDRH QLPAPKWAEL 

       790        800        810        820        830        840 
ANLINNCMDY EPDFRPSFRA IIRDLNSLFT PDYELLTEND MLPNMRIGAL GFSGAFEDRD 

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

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

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

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

      1090       1100       1110       1120       1130 
LLKNNGRLPR PDGCPDEIYM IMTECWNNNV NQRPSFRDLA LRVDQIRDNM AG 

« Hide

References

[1]The German cDNA consortium
Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
CR858835 mRNA. Translation: CAH91037.1.
RefSeqNP_001125600.1. NM_001132128.1.
UniGenePab.11396.

3D structure databases

ProteinModelPortalQ5RB23.
SMRQ5RB23. Positions 840-1132.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100172517.
KEGGpon:100172517.

Organism-specific databases

CTD3717.

Phylogenomic databases

HOGENOMHOG000049158.
HOVERGENHBG006195.
InParanoidQ5RB23.
KOK04447.

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.
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...

Entry information

Entry nameJAK2_PONAB
AccessionPrimary (citable) accession number: Q5RB23
Entry history
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: December 21, 2004
Last modified: February 19, 2014
This is version 77 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