UniProt Accession

 JAK3_HUMAN; P52333; Q13259; Q13260; Q13611; Q99699; Q9Y6S2 

Genbank Protein ID

 U09607; U31601; U31602; U70065; AF513860; AC007201; U57096 

Genbank Nucleotide ID

 AAA19626.1; AAC50226.1; AAC50227.1; AAC50950.1; AAM44860.1; AAD22741.1; AAC50542.1 

Protein Name

 Tyrosine-protein kinase JAK3 

Protein Synonyms/Alias

 Janus kinase 3; JAK-3; Leukocyte janus kinase; L-JAK 

Gene Name

 JAK3 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
186	QRPGELLKTVSYKAC	ubiquitination	[1]
237	DRHSLMAKYIMDLER	ubiquitination	[1]
361	DSQHFFCKEVAPPRL	ubiquitination	[1, 2, 3]
388	TLDFAINKLKTGGSR	ubiquitination	[1]
390	DFAINKLKTGGSRPG	ubiquitination	[1]
482	CIPRPKEKSNLIVVQ	ubiquitination	[1, 3]
652	HGNVSARKVLLAREG	ubiquitination	[1]
734	SALDPAKKLQFYEDR	ubiquitination	[1]
823	IFEERHLKYISQLGK	ubiquitination	[1, 2]
830	KYISQLGKGNFGSVE	ubiquitination	[1, 4]
855	TGALVAVKQLQHSGP	ubiquitination	[1]
876	QREIQILKALHSDFI	ubiquitination	[1]
935	LYSSQICKGMEYLGS	ubiquitination	[1]
972	IADFGLAKLLPLDKD	ubiquitination	[1, 2]
978	AKLLPLDKDYYVVRE	ubiquitination	[1]
1117	FTAHPEGKHHSLSFS	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 24 356 FERM.
 DOMAIN 375 475 SH2; atypical.
 DOMAIN 521 781 Protein kinase 1.
 DOMAIN 822 1111 Protein kinase 2.
 NP_BIND 828 836 ATP (By similarity).
 REGION 1 223 Interaction with
 ACT_SITE 949 949 Proton acceptor (By similarity).
 BINDING 855 855 ATP (By similarity).
 MOD_RES 8 8 Phosphothreonine (By similarity).
 MOD_RES 785 785 Phosphotyrosine; by autocatalysis.
 MOD_RES 904 904 Phosphotyrosine.
 MOD_RES 939 939 Phosphotyrosine.
 MOD_RES 980 980 Phosphotyrosine; by autocatalysis.
 MOD_RES 981 981 Phosphotyrosine; by autocatalysis.
 MOD_RES 1027 1027 Phosphoserine (By similarity).
 MOD_RES 1031 1031 Phosphoserine (By similarity).  

Keyword

 3D-structure; Adaptive immunity; Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; Disease mutation; Immunity; Innate immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Repeat; SCID; SH2 domain; Transferase; Tyrosine-protein kinase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1124 AA 

Protein Sequence

Gene Ontology

 GO:0005856; C:cytoskeleton; IEA:InterPro.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
 GO:0016020; C:membrane; IEA:UniProtKB-KW.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:EC.
 GO:0004713; F:protein tyrosine kinase activity; ISS:BHF-UCL.
 GO:0030183; P:B cell differentiation; ISS:BHF-UCL.
 GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
 GO:0035771; P:interleukin-4-mediated signaling pathway; IDA:BHF-UCL.
 GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; TAS:UniProtKB.
 GO:0002731; P:negative regulation of dendritic cell cytokine production; ISS:BHF-UCL.
 GO:0045221; P:negative regulation of FasL biosynthetic process; ISS:BHF-UCL.
 GO:0032693; P:negative regulation of interleukin-10 production; ISS:BHF-UCL.
 GO:0032695; P:negative regulation of interleukin-12 production; ISS:BHF-UCL.
 GO:0045626; P:negative regulation of T-helper 1 cell differentiation; ISS:BHF-UCL.
 GO:0070244; P:negative regulation of thymocyte apoptotic process; ISS:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0070672; P:response to interleukin-15; TAS:BHF-UCL.
 GO:0070669; P:response to interleukin-2; TAS:BHF-UCL.
 GO:0071104; P:response to interleukin-9; TAS:BHF-UCL.
 GO:0007262; P:STAT protein import into nucleus; TAS:UniProtKB.
 GO:0043029; P:T cell homeostasis; TAS:UniProtKB.
 GO:0007260; P:tyrosine phosphorylation of STAT protein; TAS:UniProtKB. 

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. 

Pfam

 PF07714; Pkinase_Tyr 

SMART

 SM00295; B41
 SM00252; SH2
 SM00219; TyrKc 

PROSITE

 PS00660; FERM_1
 PS00661; FERM_2
 PS50057; FERM_3
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS50001; SH2 

PRINTS

 PR01823; JANUSKINASE.
 PR01826; JANUSKINASE3.
 PR00109; TYRKINASE.