Names & Taxonomy

Uniprot ID:
P52333
Entry Name:
JAK3_HUMAN
Status:
reviewed
Protein Names:
Tyrosine-protein kinase JAK3 (EC 2.7.10.2) (Janus kinase 3) (JAK-3) (Leukocyte janus kinase) (L-JAK)
Gene Names:
JAK3
Gene Names Primary:
JAK3
Organism:
Homo sapiens (Human)

Structure

Length:
1124
Sequence:
MAPPSEETPLIPQRSCSLLSTEAGALHVLLPARGPGPPQRLSFSFGDHLAEDLCVQAAKASGILPVYHSLFALATEDLSCWFPPSHIFSVEDASTQVLLYRIRFYFPNWFGLEKCHRFGLRKDLASAILDLPVLEHLFAQHRSDLVSGRLPVGLSLKEQGECLSLAVLDLARMAREQAQRPGELLKTVSYKACLPPSLRDLIQGLSFVTRRRIRRTVRRALRRVAACQADRHSLMAKYIMDLERLDPAGAAETFHVGLPGALGGHDGLGLLRVAGDGGIAWTQGEQEVLQPFCDFPEIVDISIKQAPRVGPAGEHRLVTVTRTDNQILEAEFPGLPEALSFVALVDGYFRLTTDSQHFFCKEVAPPRLLEEVAEQCHGPITLDFAINKLKTGGSRPGSYVLRRSPQDFDSFLLTVCVQNPLGPDYKGCLIRRSPTGTFLLVGLSRPHSSLRELLATCWDGGLHVDGVAVTLTSCCIPRPKEKSNLIVVQRGHSPPTSSLVQPQSQYQLSQMTFHKIPADSLEWHENLGHGSFTKIYRGCRHEVVDGEARKTEVLLKVMDAKHKNCMESFLEAASLMSQVSYRHLVLLHGVCMAGDSTMVQEFVHLGAIDMYLRKRGHLVPASWKLQVVKQLAYALNYLEDKGLPHGNVSARKVLLAREGADGSPPFIKLSDPGVSPAVLSLEMLTDRIPWVAPECLREAQTLSLEADKWGFGATVWEVFSGVTMPISALDPAKKLQFYEDRQQLPAPKWTELALLIQQCMAYEPVQRPSFRAVIRDLNSLISSDYELLSDPTPGALAPRDGLWNGAQLYACQDPTIFEERHLKYISQLGKGNFGSVELCRYDPLGDNTGALVAVKQLQHSGPDQQRDFQREIQILKALHSDFIVKYRGVSYGPGRQSLRLVMEYLPSGCLRDFLQRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKDYYVVREPGQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYCDKSCSPSAEFLRMMGCERDVPALCRLLELLEEGQRLPAPPACPAEVHELMKLCWAPSPQDRPSFSALGPQLDMLWSGSRGCETHAFTAHPEGKHHSLSFS
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Endomembrane system

Function

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.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Active Site:
ACT_SITE 949 949 Proton acceptor.
Cross Reference Drug Bank:
DB08895
Gene Ontology Go:
cytoskeleton
cytosol
endomembrane system
extrinsic component of cytoplasmic side of plasma membrane
ATP binding
non-membrane spanning protein tyrosine kinase activity
protein phosphatase binding
protein tyrosine kinase activity
receptor binding
activation of MAPKK activity
adaptive immune response
axon guidance
B cell differentiation
cell migration
enzyme linked receptor protein signaling pathway
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
innate immune response
insulin receptor signaling pathway
interleukin-4-mediated signaling pathway
intracellular signal transduction
JAK-STAT cascade involved in growth hormone signaling pathway
MAPK cascade
negative regulation of dendritic cell cytokine production
negative regulation of FasL biosynthetic process
negative regulation of interleukin-10 production
negative regulation of interleukin-12 production
negative regulation of T cell activation
negative regulation of T-helper 1 cell differentiation
negative regulation of thymocyte apoptotic process
neurotrophin TRK receptor signaling pathway
peptidyl-tyrosine autophosphorylation
peptidyl-tyrosine phosphorylation
positive regulation of activated T cell proliferation
positive regulation of calcium ion transport
positive regulation of cytosolic calcium ion concentration
positive regulation of immune response
positive regulation of T cell proliferation
protein phosphorylation
Ras protein signal transduction
regulation of T cell apoptotic process
response to interleukin-15
response to interleukin-2
response to interleukin-4
response to interleukin-9
small GTPase mediated signal transduction
STAT protein import into nucleus
T cell homeostasis
tyrosine phosphorylation of STAT protein
tyrosine phosphorylation of Stat5 protein
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Biological Process:
activation of MAPKK activity
adaptive immune response
axon guidance
B cell differentiation
cell migration
enzyme linked receptor protein signaling pathway
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
innate immune response
insulin receptor signaling pathway
interleukin-4-mediated signaling pathway
intracellular signal transduction
JAK-STAT cascade involved in growth hormone signaling pathway
MAPK cascade
negative regulation of dendritic cell cytokine production
negative regulation of FasL biosynthetic process
negative regulation of interleukin-10 production
negative regulation of interleukin-12 production
negative regulation of T cell activation
negative regulation of T-helper 1 cell differentiation
negative regulation of thymocyte apoptotic process
neurotrophin TRK receptor signaling pathway
peptidyl-tyrosine autophosphorylation
peptidyl-tyrosine phosphorylation
positive regulation of activated T cell proliferation
positive regulation of calcium ion transport
positive regulation of cytosolic calcium ion concentration
positive regulation of immune response
positive regulation of T cell proliferation
protein phosphorylation
Ras protein signal transduction
regulation of T cell apoptotic process
response to interleukin-15
response to interleukin-2
response to interleukin-4
response to interleukin-9
small GTPase mediated signal transduction
STAT protein import into nucleus
T cell homeostasis
tyrosine phosphorylation of Stat5 protein
tyrosine phosphorylation of STAT protein
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Molecular Function:
ATP binding
non-membrane spanning protein tyrosine kinase activity
protein phosphatase binding
protein tyrosine kinase activity
receptor binding
Gene Ontology Cellular Component:
cytoskeleton
cytosol
endomembrane system
extrinsic component of cytoplasmic side of plasma membrane
Keywords:
3D-structure
ATP-binding
Adaptive immunity
Alternative splicing
Complete proteome
Cytoplasm
Disease mutation
Immunity
Innate immunity
Kinase
Membrane
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome
Repeat
SCID
SH2 domain
Transferase
Tyrosine-protein kinase
Interacts With:
Q07666; Q9UNF1; P55209

Publication

PubMed ID:
8022790 7559633 8921370 15057824 15489334 8662778 8022485 7662955 7535338 10899310 12200137 11909529 12351625 15121872 15592455 18250158 19290934 19369195 19690332 20440074 15831699 7659163 9354668 9753072 10982185 14615376 17344846