Q63272 (JAK3_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase JAK3
EC=2.7.10.2

Alternative name(s):
Janus kinase 3
Short name=JAK-3

Gene names

Name:

Jak3

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1100 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
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 process	Adaptive immunity Immunity Innate immunity
Cellular component	Cytoplasm Membrane
Domain	Repeat SH2 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B 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 elevation of cytosolic calcium ion concentration Inferred from mutant phenotype PubMed 16371324. 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 negative regulation of FasL biosynthetic process 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 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 immune response Inferred from mutant phenotype PubMed 11781254. Source: RGD protein autophosphorylation Inferred from mutant phenotype PubMed 11781254. Source: RGD tyrosine phosphorylation of Stat5 protein Inferred from mutant phenotype PubMed 11781254. Source: RGD
Cellular_component	cytoplasm 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_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1100	1100	Tyrosine-protein kinase JAK3		PRO_0000088117
Regions
	Domain	24 – 353	330	FERM
	Domain	372 – 472	101	SH2; atypical
	Domain	517 – 777	261	Protein kinase 1
	Domain	818 – 1091	274	Protein kinase 2
	Nucleotide binding	824 – 832	9	ATP By similarity
	Region	1 – 223	223	cytokine/interferon/growth hormone receptors By similarity
Sites
	Active site	945	1	Proton acceptor By similarity
	Binding site	851	1	ATP By similarity
Amino acid modifications
	Modified residue	8	1	Phosphothreonine By similarity
	Modified residue	781	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	900	1	Phosphotyrosine By similarity
	Modified residue	935	1	Phosphotyrosine By similarity
	Modified residue	976	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	977	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1023	1	Phosphoserine By similarity
	Modified residue	1027	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q63272 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 1D59CA05F4DD7EE2	FASTA	1,100	122,561
	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

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.
IPI	IPI00207004.
PIR	S43677.
UniGene	Rn.11159.
3D structure databases
ProteinModelPortal	Q63272.
SMR	Q63272. Positions 810-1098.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000032301.
PTM databases
PhosphoSite	Q63272.
Proteomic databases
PRIDE	Q63272.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	RGD:2940. rat.
Organism-specific databases
RGD	2940. Jak3.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000049158.
HOVERGEN	HBG006195.
OrthoDB	EOG4001HH.
Enzyme and pathway databases
BRENDA	2.7.10.2. 5301.
Gene expression databases
ArrayExpress	Q63272.
Genevestigator	Q63272.
GermOnline	ENSRNOG00000018669. Rattus norvegicus.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR019749. Band_41_domain. IPR000299. FERM_domain. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_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]
Pfam	PF07714. Pkinase_Tyr. 2 hits. [Graphical view]
PIRSF	PIRSF000636. TyrPK_Jak. 1 hit.
PRINTS	PR01823. JANUSKINASE. PR01826. JANUSKINASE3. PR00109. TYRKINASE.
SMART	SM00295. B41. 1 hit. SM00252. SH2. 1 hit. SM00219. TyrKc. 2 hits. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 2 hits.
PROSITE	PS00660. FERM_1. False negative. PS00661. FERM_2. False negative. 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. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	13955491.

Entry information

Entry name

JAK3_RAT

Accession

Primary (citable) accession number: Q63272

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	April 3, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program