JAK3 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. Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily. In NK cells and an NK-like cell line but not in resting T-cells or in other tissues. The S-form is more commonly seen in hematopoietic lines, whereas the B-form is detected in cells both of hematopoietic and epithelial origins. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC; JakA family; Kinase, protein; Protein kinase, TK; Protein kinase, tyrosine (non-receptor); TK group
Chromosomal Location of human Ortholog: 19p13.11
Cellular Component:  cytoskeleton; cytosol; endosome; plasma membrane
Molecular Function:  ATP binding; non-membrane spanning protein tyrosine kinase activity; protein binding; protein phosphatase binding; protein tyrosine kinase activity
Biological Process:  adaptive immune response; B cell differentiation; cytokine-mediated signaling pathway; enzyme linked receptor protein signaling pathway; innate immune response; interleukin-15-mediated signaling pathway; interleukin-2-mediated signaling pathway; interleukin-21-mediated signaling pathway; interleukin-4-mediated signaling pathway; interleukin-7-mediated signaling pathway; interleukin-9-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; peptidyl-tyrosine phosphorylation; protein phosphorylation; regulation of JAK-STAT cascade; regulation of T cell apoptotic process; response to interleukin-15; response to interleukin-2; response to interleukin-4; response to interleukin-9; T cell homeostasis; tyrosine phosphorylation of STAT protein
Disease: Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-negative, B Cell-positive, Nk Cell-negative
Reference #:  P52333 (UniProtKB)
Alt. Names/Synonyms: JAK-3; JAK3; JAK3_HUMAN; JAKL; Janus kinase 3; Janus kinase 3 (a protein tyrosine kinase, leukocyte); L-JAK; Leukocyte janus kinase; LJAK; Tyrosine-protein kinase JAK3
Gene Symbols: JAK3
Molecular weight: 125,099 Da
Basal Isoelectric point: 6.77  Predict pI for various phosphorylation states
CST Pathways:  ErbB/HER Signaling  |  IL6 Signaling  |  Inhibition of Apoptosis  |  Tyrosine Kinases & Substrates
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene