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Protein

Tyrosine-protein kinase JAK3

Gene

Jak3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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).By similarity

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei851 – 8511ATPPROSITE-ProRule annotation
Active sitei945 – 9451Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi824 – 8329ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • hormone receptor binding Source: GO_Central
  • non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  • protein tyrosine kinase activity Source: RGD
  • transcription factor binding Source: RGD

GO - Biological processi

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 Componenti: Unplaced

Organism-specific databases

RGDi2940. Jak3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: RGD
  • cytoskeleton Source: InterPro
  • cytosol Source: GOC
  • endomembrane system Source: UniProtKB-SubCell
  • extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11001100Tyrosine-protein kinase JAK3PRO_0000088117Add
BLAST

Amino acid modifications

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

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000025312.

Structurei

3D structure databases

ProteinModelPortaliQ63272.
SMRiQ63272. Positions 810-1098.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 353330FERMPROSITE-ProRule annotationAdd
BLAST
Domaini372 – 472101SH2; atypicalAdd
BLAST
Domaini517 – 777261Protein kinase 1PROSITE-ProRule annotationAdd
BLAST
Domaini818 – 1091274Protein kinase 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 223223cytokine/interferon/growth hormone receptorsBy similarityAdd
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

Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.PROSITE-ProRule annotation
Contains 1 FERM domain.PROSITE-ProRule annotation
Contains 2 protein kinase domains.PROSITE-ProRule annotation
Contains 1 SH2 domain.Curated

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000049158.
HOVERGENiHBG006195.
InParanoidiQ63272.

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

« Hide

        10         20         30         40         50
MAPPSEETPL ISQRSCSLSS SEAGALHVLL PPRGPGPPQR LSFSFGDYLA
60 70 80 90 100
EDLCVRAAKA CGILPVYHSL FALATEDLSC WFPPSHIFSI EDVDTQVLVY
110 120 130 140 150
RLRFYFPGWF GLETCHRFGL HKDLTSAILD VHVLEHLFAQ HRSDLVSGRL
160 170 180 190 200
PVGLSLKDQG EFLSLAVLDL AQMARKQAQR PGELLKSVSY KACLPPSLRD
210 220 230 240 250
LIQGQSFVTR RRIRRTVVQA LAPCSSLPSR PYALMAKYIL DLERLHPAAT
260 270 280 290 300
TESFLVGLPG AQEEPGCLRV TGDNGIAWSS KDQELFQTFC DFPEIVDVSI
310 320 330 340 350
KQAPRVGPAG EHRLVTITRM DGHILEAEFP GLPEALSFVA LVDGYFRLIC
360 370 380 390 400
DSRHFFCKEV APPRLLEEEA ELCHGPITLD FAIHKLKAAG SLPGSYILRR
410 420 430 440 450
SPQDYDSFLL TACVQTPLGP DYKGCLIRQD PSGAFSLVGL SQLHRSLQEL
460 470 480 490 500
LTACWHSGLQ VDGTALNLTS CCVPRPKEKS NLIVVRRGRN PTPAPGHSPS
510 520 530 540 550
CCALTKLSFH TIPADSLEWH ENLGHGSFTK IFHGHRREVV DGETHDTEVL
560 570 580 590 600
LKVMDSRHQN CMESFLEAAS LMSQVSYPHL VLLHGVCMAG DSIMVQEFVY
610 620 630 640 650
LGAIDTYLRK RGHLVPASWK LQVTKQLAYA LNYLEDKGLP HGNVSARKVL
660 670 680 690 700
LAREGVDGNP PFIKLSDPGV SPTVLSLEML TDRIPWVAPE CLQEAGTLNL
710 720 730 740 750
EADKWGFGAT TWEVFSGAPM HITSLEPAKK LKFYEDRGQL PALKWTELEG
760 770 780 790 800
LIAQCMAYDP GRRPSFRAIL RDLNGLITSD YELLSDPTPG IPNPRDELCG
810 820 830 840 850
GAQLYACQDP AIFEERHLKY ISLLGKGNFG SVELCRYDPL GDNTGPLVAV
860 870 880 890 900
KQLQHSGPEQ QRDFQREIQI LKALHCDFIV KYRGVSYGPG RQELRLVMEY
910 920 930 940 950
LPSGCLRDFL QRHRARLHND RLLLFAWQIC KGMEYLGARR CVHRDLAARN
960 970 980 990 1000
ILVESEAHVK IADFGLAKLL PLGKDYYVVR VPGQSPIFWY APESLSDNIF
1010 1020 1030 1040 1050
SRQSDVWSFG VVLYELFTYS DKSCSPSTEF LRMIGPEREG SPLCHLLELL
1060 1070 1080 1090 1100
AEGRRLPPPS TCPTEVQELM QLCWSPNPQD RPAFDTLSPQ LDALWRGSPG
Length:1,100
Mass (Da):122,561
Last modified:November 1, 1997 - v1
Checksum:i1D59CA05F4DD7EE2
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D28508 mRNA. Translation: BAA05868.1.
PIRiS43677.
UniGeneiRn.11159.

Genome annotation databases

UCSCiRGD:2940. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D28508 mRNA. Translation: BAA05868.1.
PIRiS43677.
UniGeneiRn.11159.

3D structure databases

ProteinModelPortaliQ63272.
SMRiQ63272. Positions 810-1098.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000025312.

PTM databases

PhosphoSiteiQ63272.

Proteomic databases

PRIDEiQ63272.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:2940. rat.

Organism-specific databases

RGDi2940. Jak3.

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000049158.
HOVERGENiHBG006195.
InParanoidiQ63272.

Enzyme and pathway databases

BRENDAi2.7.10.2. 5301.

Miscellaneous databases

NextBioi13955491.
PROiQ63272.

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]
ProtoNetiSearch...

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: June 24, 2015
This is version 129 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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.