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

Q63272 (JAK3_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. 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 JAK3

EC=2.7.10.2
Alternative name(s):
Janus kinase 3
Short name=JAK-3
Gene names
Name:Jak3
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1100 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, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. 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, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion By similarity.

Catalytic activity

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

Subunit structure

Interacts with STAM2 and MYO18A. Interacts with SHB By similarity.

Subcellular location

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

Tissue specificity

In contrast with the ubiquitous expression of the other JAKs, JAK3 is predominantly expressed in hematopoietic tissues.

Domain

Possesses two phosphotransferase domains. The second one contains the catalytic domain, while the presence of a pseudokinase domain is required for suppression of basal activity of JAK3.

Post-translational modification

Autophosphorylated, leading to regulate its activity. IL2 promotes phosphorylation on tyrosine residues, including autophosphorylation on Tyr-781 By similarity. Dephosphorylation of Tyr-976 and Tyr-977 by PTPN2 negatively regulates cytokine-mediated signaling 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
   DomainRepeat
SH2 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

T cell homeostasis

Inferred from sequence or structural similarity. Source: BHF-UCL

cytokine-mediated signaling pathway

Inferred from direct assay PubMed 7518451. Source: RGD

enzyme linked receptor protein signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular signal transduction

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of FasL biosynthetic process

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of T cell activation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of T-helper 1 cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of dendritic cell cytokine production

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of interleukin-10 production

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of interleukin-12 production

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of thymocyte apoptotic process

Inferred from sequence or structural similarity. Source: BHF-UCL

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of T cell proliferation

Inferred from direct assay PubMed 9637481. Source: BHF-UCL

positive regulation of activated T cell proliferation

Inferred from mutant phenotype PubMed 11781254. Source: RGD

positive regulation of calcium ion transport

Inferred from mutant phenotype PubMed 16371324. Source: RGD

positive regulation of cytosolic calcium ion concentration

Inferred from mutant phenotype PubMed 16371324. Source: RGD

positive regulation of immune response

Inferred from mutant phenotype PubMed 11781254. Source: RGD

protein autophosphorylation

Inferred from mutant phenotype PubMed 11781254. Source: RGD

regulation of T cell apoptotic process

Inferred from sequence or structural similarity. Source: BHF-UCL

tyrosine phosphorylation of Stat5 protein

Inferred from mutant phenotype PubMed 11781254. Source: RGD

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 9030713. Source: RGD

cytoskeleton

Inferred from electronic annotation. Source: InterPro

endomembrane system

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein tyrosine kinase activity

Inferred from mutant phenotype PubMed 11781254. Source: RGD

transcription factor binding

Inferred by curator PubMed 11781254. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11001100Tyrosine-protein kinase JAK3
PRO_0000088117

Regions

Domain24 – 353330FERM
Domain372 – 472101SH2; atypical
Domain517 – 777261Protein kinase 1
Domain818 – 1091274Protein kinase 2
Nucleotide binding824 – 8329ATP By similarity
Region1 – 223223cytokine/interferon/growth hormone receptors By similarity

Sites

Active site9451Proton acceptor By similarity
Binding site8511ATP By similarity

Amino acid modifications

Modified residue7811Phosphotyrosine; by autocatalysis By similarity
Modified residue9001Phosphotyrosine By similarity
Modified residue9351Phosphotyrosine By similarity
Modified residue9761Phosphotyrosine; by autocatalysis By similarity
Modified residue9771Phosphotyrosine; by autocatalysis By similarity

Sequences

Sequence LengthMass (Da)Tools
Q63272 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: 1D59CA05F4DD7EE2

FASTA1,100122,561
        10         20         30         40         50         60 
MAPPSEETPL ISQRSCSLSS SEAGALHVLL PPRGPGPPQR LSFSFGDYLA EDLCVRAAKA 

        70         80         90        100        110        120 
CGILPVYHSL FALATEDLSC WFPPSHIFSI EDVDTQVLVY RLRFYFPGWF GLETCHRFGL 

       130        140        150        160        170        180 
HKDLTSAILD VHVLEHLFAQ HRSDLVSGRL PVGLSLKDQG EFLSLAVLDL AQMARKQAQR 

       190        200        210        220        230        240 
PGELLKSVSY KACLPPSLRD LIQGQSFVTR RRIRRTVVQA LAPCSSLPSR PYALMAKYIL 

       250        260        270        280        290        300 
DLERLHPAAT TESFLVGLPG AQEEPGCLRV TGDNGIAWSS KDQELFQTFC DFPEIVDVSI 

       310        320        330        340        350        360 
KQAPRVGPAG EHRLVTITRM DGHILEAEFP GLPEALSFVA LVDGYFRLIC DSRHFFCKEV 

       370        380        390        400        410        420 
APPRLLEEEA ELCHGPITLD FAIHKLKAAG SLPGSYILRR SPQDYDSFLL TACVQTPLGP 

       430        440        450        460        470        480 
DYKGCLIRQD PSGAFSLVGL SQLHRSLQEL LTACWHSGLQ VDGTALNLTS CCVPRPKEKS 

       490        500        510        520        530        540 
NLIVVRRGRN PTPAPGHSPS CCALTKLSFH TIPADSLEWH ENLGHGSFTK IFHGHRREVV 

       550        560        570        580        590        600 
DGETHDTEVL LKVMDSRHQN CMESFLEAAS LMSQVSYPHL VLLHGVCMAG DSIMVQEFVY 

       610        620        630        640        650        660 
LGAIDTYLRK RGHLVPASWK LQVTKQLAYA LNYLEDKGLP HGNVSARKVL LAREGVDGNP 

       670        680        690        700        710        720 
PFIKLSDPGV SPTVLSLEML TDRIPWVAPE CLQEAGTLNL EADKWGFGAT TWEVFSGAPM 

       730        740        750        760        770        780 
HITSLEPAKK LKFYEDRGQL PALKWTELEG LIAQCMAYDP GRRPSFRAIL RDLNGLITSD 

       790        800        810        820        830        840 
YELLSDPTPG IPNPRDELCG GAQLYACQDP AIFEERHLKY ISLLGKGNFG SVELCRYDPL 

       850        860        870        880        890        900 
GDNTGPLVAV KQLQHSGPEQ QRDFQREIQI LKALHCDFIV KYRGVSYGPG RQELRLVMEY 

       910        920        930        940        950        960 
LPSGCLRDFL QRHRARLHND RLLLFAWQIC KGMEYLGARR CVHRDLAARN ILVESEAHVK 

       970        980        990       1000       1010       1020 
IADFGLAKLL PLGKDYYVVR VPGQSPIFWY APESLSDNIF SRQSDVWSFG VVLYELFTYS 

      1030       1040       1050       1060       1070       1080 
DKSCSPSTEF LRMIGPEREG SPLCHLLELL AEGRRLPPPS TCPTEVQELM QLCWSPNPQD 

      1090       1100 
RPAFDTLSPQ LDALWRGSPG 

« Hide

References

[1]"Molecular cloning of rat JAK3, a novel member of the JAK family of protein tyrosine kinases."
Takahashi T., Shirasawa T.
FEBS Lett. 342:124-128(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Spleen.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D28508 mRNA. Translation: BAA05868.1.
PIRS43677.
UniGeneRn.11159.

3D structure databases

ProteinModelPortalQ63272.
SMRQ63272. Positions 810-1098.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000032301.

PTM databases

PhosphoSiteQ63272.

Proteomic databases

PRIDEQ63272.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

UCSCRGD:2940. rat.

Organism-specific databases

RGD2940. Jak3.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000049158.
HOVERGENHBG006195.

Enzyme and pathway databases

BRENDA2.7.10.2. 5301.

Gene expression databases

GenevestigatorQ63272.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR019749. Band_41_domain.
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.
IPR020775. Tyr_kinase_non-rcpt_Jak3.
[Graphical view]
PfamPF07714. Pkinase_Tyr. 2 hits.
[Graphical view]
PIRSFPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSPR01823. JANUSKINASE.
PR01826. JANUSKINASE3.
PR00109. TYRKINASE.
SMARTSM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMSSF55550. 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.
[Graphical view]
ProtoNetSearch...

Other

NextBio13955491.
PROQ63272.

Entry information

Entry nameJAK3_RAT
AccessionPrimary (citable) accession number: Q63272
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: April 16, 2014
This is version 123 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