CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008491
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
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
830KYISQLGKGNFGSVEubiquitination[1]
Reference
 [1] 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
MAPPSEETPL IPQRSCSLLS TEAGALHVLL PARGPGPPQR LSFSFGDHLA EDLCVQAAKA 60
SGILPVYHSL FALATEDLSC WFPPSHIFSV EDASTQVLLY RIRFYFPNWF GLEKCHRFGL 120
RKDLASAILD LPVLEHLFAQ HRSDLVSGRL PVGLSLKEQG ECLSLAVLDL ARMAREQAQR 180
PGELLKTVSY KACLPPSLRD LIQGLSFVTR RRIRRTVRRA LRRVAACQAD RHSLMAKYIM 240
DLERLDPAGA AETFHVGLPG ALGGHDGLGL LRVAGDGGIA WTQGEQEVLQ PFCDFPEIVD 300
ISIKQAPRVG PAGEHRLVTV TRTDNQILEA EFPGLPEALS FVALVDGYFR LTTDSQHFFC 360
KEVAPPRLLE EVAEQCHGPI TLDFAINKLK TGGSRPGSYV LRRSPQDFDS FLLTVCVQNP 420
LGPDYKGCLI RRSPTGTFLL VGLSRPHSSL RELLATCWDG GLHVDGVAVT LTSCCIPRPK 480
EKSNLIVVQR GHSPPTSSLV QPQSQYQLSQ MTFHKIPADS LEWHENLGHG SFTKIYRGCR 540
HEVVDGEARK TEVLLKVMDA KHKNCMESFL EAASLMSQVS YRHLVLLHGV CMAGDSTMVQ 600
EFVHLGAIDM YLRKRGHLVP ASWKLQVVKQ LAYALNYLED KGLPHGNVSA RKVLLAREGA 660
DGSPPFIKLS DPGVSPAVLS LEMLTDRIPW VAPECLREAQ TLSLEADKWG FGATVWEVFS 720
GVTMPISALD PAKKLQFYED RQQLPAPKWT ELALLIQQCM AYEPVQRPSF RAVIRDLNSL 780
ISSDYELLSD PTPGALAPRD GLWNGAQLYA CQDPTIFEER HLKYISQLGK GNFGSVELCR 840
YDPLGDNTGA LVAVKQLQHS GPDQQRDFQR EIQILKALHS DFIVKYRGVS YGPGRQSLRL 900
VMEYLPSGCL RDFLQRHRAR LDASRLLLYS SQICKGMEYL GSRRCVHRDL AARNILVESE 960
AHVKIADFGL AKLLPLDKDY YVVREPGQSP IFWYAPESLS DNIFSRQSDV WSFGVVLYEL 1020
FTYCDKSCSP SAEFLRMMGC ERDVPALCRL LELLEEGQRL PAPPACPAEV SAAGLASVSQ 1080
SVDWAGVSGK PAGA 1094 
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.