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Q63272

- JAK3_RAT

UniProt

Q63272 - JAK3_RAT

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Protein
Tyrosine-protein kinase JAK3
Gene
Jak3
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

Functioni

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 activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei851 – 8511ATP By similarity
Active sitei945 – 9451Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi824 – 8329ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
  3. protein tyrosine kinase activity Source: RGD
  4. transcription factor binding Source: RGD

GO - Biological processi

  1. B cell differentiation Source: BHF-UCL
  2. T cell homeostasis Source: BHF-UCL
  3. cytokine-mediated signaling pathway Source: RGD
  4. enzyme linked receptor protein signaling pathway Source: BHF-UCL
  5. innate immune response Source: UniProtKB-KW
  6. intracellular signal transduction Source: BHF-UCL
  7. negative regulation of FasL biosynthetic process Source: BHF-UCL
  8. negative regulation of T cell activation Source: BHF-UCL
  9. negative regulation of T-helper 1 cell differentiation Source: BHF-UCL
  10. negative regulation of dendritic cell cytokine production Source: BHF-UCL
  11. negative regulation of interleukin-10 production Source: BHF-UCL
  12. negative regulation of interleukin-12 production Source: BHF-UCL
  13. negative regulation of thymocyte apoptotic process Source: BHF-UCL
  14. peptidyl-tyrosine phosphorylation Source: BHF-UCL
  15. positive regulation of T cell proliferation Source: BHF-UCL
  16. positive regulation of activated T cell proliferation Source: RGD
  17. positive regulation of calcium ion transport Source: RGD
  18. positive regulation of cytosolic calcium ion concentration Source: RGD
  19. positive regulation of immune response Source: RGD
  20. protein autophosphorylation Source: RGD
  21. regulation of T cell apoptotic process Source: BHF-UCL
  22. tyrosine phosphorylation of Stat5 protein Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

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.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase JAK3 (EC:2.7.10.2)
Alternative name(s):
Janus kinase 3
Short name:
JAK-3
Gene namesi
Name:Jak3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi2940. Jak3.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: RGD
  2. cytoskeleton Source: InterPro
  3. endomembrane system Source: UniProtKB-SubCell
  4. membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11001100Tyrosine-protein kinase JAK3
PRO_0000088117Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei781 – 7811Phosphotyrosine; by autocatalysis By similarity
Modified residuei900 – 9001Phosphotyrosine By similarity
Modified residuei935 – 9351Phosphotyrosine By similarity
Modified residuei976 – 9761Phosphotyrosine; by autocatalysis By similarity
Modified residuei977 – 9771Phosphotyrosine; by autocatalysis By similarity

Post-translational modificationi

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.

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiQ63272.

PTM databases

PhosphoSiteiQ63272.

Expressioni

Tissue specificityi

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

Gene expression databases

GenevestigatoriQ63272.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000032301.

Structurei

3D structure databases

ProteinModelPortaliQ63272.
SMRiQ63272. Positions 810-1098.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 353330FERM
Add
BLAST
Domaini372 – 472101SH2; atypical
Add
BLAST
Domaini517 – 777261Protein kinase 1
Add
BLAST
Domaini818 – 1091274Protein kinase 2
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 223223cytokine/interferon/growth hormone receptors By similarity
Add
BLAST

Domaini

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.

Sequence similaritiesi

Contains 1 FERM domain.
Contains 1 SH2 domain.

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000049158.
HOVERGENiHBG006195.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR019749. 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]
PfamiPF07714. Pkinase_Tyr. 2 hits.
[Graphical view]
PIRSFiPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSiPR01823. JANUSKINASE.
PR01826. JANUSKINASE3.
PR00109. TYRKINASE.
SMARTiSM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMiSSF55550. 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.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q63272-1 [UniParc]FASTAAdd to Basket

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MAPPSEETPL ISQRSCSLSS SEAGALHVLL PPRGPGPPQR LSFSFGDYLA     50
EDLCVRAAKA CGILPVYHSL FALATEDLSC WFPPSHIFSI EDVDTQVLVY 100
RLRFYFPGWF GLETCHRFGL HKDLTSAILD VHVLEHLFAQ HRSDLVSGRL 150
PVGLSLKDQG EFLSLAVLDL AQMARKQAQR PGELLKSVSY KACLPPSLRD 200
LIQGQSFVTR RRIRRTVVQA LAPCSSLPSR PYALMAKYIL DLERLHPAAT 250
TESFLVGLPG AQEEPGCLRV TGDNGIAWSS KDQELFQTFC DFPEIVDVSI 300
KQAPRVGPAG EHRLVTITRM DGHILEAEFP GLPEALSFVA LVDGYFRLIC 350
DSRHFFCKEV APPRLLEEEA ELCHGPITLD FAIHKLKAAG SLPGSYILRR 400
SPQDYDSFLL TACVQTPLGP DYKGCLIRQD PSGAFSLVGL SQLHRSLQEL 450
LTACWHSGLQ VDGTALNLTS CCVPRPKEKS NLIVVRRGRN PTPAPGHSPS 500
CCALTKLSFH TIPADSLEWH ENLGHGSFTK IFHGHRREVV DGETHDTEVL 550
LKVMDSRHQN CMESFLEAAS LMSQVSYPHL VLLHGVCMAG DSIMVQEFVY 600
LGAIDTYLRK RGHLVPASWK LQVTKQLAYA LNYLEDKGLP HGNVSARKVL 650
LAREGVDGNP PFIKLSDPGV SPTVLSLEML TDRIPWVAPE CLQEAGTLNL 700
EADKWGFGAT TWEVFSGAPM HITSLEPAKK LKFYEDRGQL PALKWTELEG 750
LIAQCMAYDP GRRPSFRAIL RDLNGLITSD YELLSDPTPG IPNPRDELCG 800
GAQLYACQDP AIFEERHLKY ISLLGKGNFG SVELCRYDPL GDNTGPLVAV 850
KQLQHSGPEQ QRDFQREIQI LKALHCDFIV KYRGVSYGPG RQELRLVMEY 900
LPSGCLRDFL QRHRARLHND RLLLFAWQIC KGMEYLGARR CVHRDLAARN 950
ILVESEAHVK IADFGLAKLL PLGKDYYVVR VPGQSPIFWY APESLSDNIF 1000
SRQSDVWSFG VVLYELFTYS DKSCSPSTEF LRMIGPEREG SPLCHLLELL 1050
AEGRRLPPPS TCPTEVQELM QLCWSPNPQD RPAFDTLSPQ LDALWRGSPG 1100
Length:1,100
Mass (Da):122,561
Last modified:November 1, 1997 - v1
Checksum:i1D59CA05F4DD7EE2
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D28508 mRNA. Translation: BAA05868.1.
PIRiS43677.
UniGeneiRn.11159.

Genome annotation databases

UCSCiRGD:2940. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D28508 mRNA. Translation: BAA05868.1 .
PIRi S43677.
UniGenei Rn.11159.

3D structure databases

ProteinModelPortali Q63272.
SMRi Q63272. Positions 810-1098.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000032301.

PTM databases

PhosphoSitei Q63272.

Proteomic databases

PRIDEi Q63272.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

UCSCi RGD:2940. rat.

Organism-specific databases

RGDi 2940. Jak3.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000049158.
HOVERGENi HBG006195.

Enzyme and pathway databases

BRENDAi 2.7.10.2. 5301.

Miscellaneous databases

NextBioi 13955491.
PROi Q63272.

Gene expression databases

Genevestigatori Q63272.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR019749. 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 ]
Pfami PF07714. Pkinase_Tyr. 2 hits.
[Graphical view ]
PIRSFi PIRSF000636. TyrPK_Jak. 1 hit.
PRINTSi PR01823. JANUSKINASE.
PR01826. JANUSKINASE3.
PR00109. TYRKINASE.
SMARTi SM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view ]
SUPFAMi 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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiJAK3_RAT
AccessioniPrimary (citable) accession number: Q63272
Entry historyi
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 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

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