InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: JAK3

Summary

InnateDB Protein

IDBP-375657.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

JAK3

Protein Name

Janus kinase 3

Synonyms

JAK-3; JAK3_HUMAN; JAKL; L-JAK; LJAK;

Species

Homo sapiens

Ensembl Protein

ENSP00000391676

InnateDB Gene

IDBG-37201 (JAK3)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:11909529, ECO:0000269PubMed:20440074, ECO:0000269PubMed:7662955, ECO:0000269PubMed:8022485}.

Subcellular Localization

Endomembrane system {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Cytoplasm {ECO:0000250}.

Disease Associations

Severe combined immunodeficiency autosomal recessive T- cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID) [MIM:600802]: A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. {ECO:0000269PubMed:10982185, ECO:0000269PubMed:14615376, ECO:0000269PubMed:7659163, ECO:0000269PubMed:9354668, ECO:0000269PubMed:9753072}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

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. {ECO:0000269PubMed:7535338}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 56 experimentally validated interaction(s) in this database.
They are also associated with 12 interaction(s) predicted by orthology.

Experimentally validated
Total	56 [view]
Protein-Protein	56 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	12 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019903	protein phosphatase binding

Biological Process

GO:0002731	negative regulation of dendritic cell cytokine production
GO:0006468	protein phosphorylation
GO:0007167	enzyme linked receptor protein signaling pathway
GO:0007260	tyrosine phosphorylation of STAT protein
GO:0007262	STAT protein import into nucleus
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0019221	cytokine-mediated signaling pathway
GO:0030183	B cell differentiation
GO:0032693	negative regulation of interleukin-10 production
GO:0032695	negative regulation of interleukin-12 production
GO:0035556	intracellular signal transduction
GO:0035771	interleukin-4-mediated signaling pathway
GO:0043029	T cell homeostasis
GO:0045087	innate immune response (InnateDB)
GO:0045221	negative regulation of FasL biosynthetic process
GO:0045626	negative regulation of T-helper 1 cell differentiation
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0050868	negative regulation of T cell activation
GO:0060397	JAK-STAT cascade involved in growth hormone signaling pathway
GO:0070232	regulation of T cell apoptotic process
GO:0070244	negative regulation of thymocyte apoptotic process
GO:0070669	response to interleukin-2
GO:0070670	response to interleukin-4
GO:0070672	response to interleukin-15
GO:0071104	response to interleukin-9
GO:2000670	positive regulation of dendritic cell apoptotic process
GO:2001241	positive regulation of extrinsic apoptotic signaling pathway in absence of ligand

Cellular Component

GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0012505	endomembrane system
GO:0016020	membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000299 FERM domain
IPR000719 Protein kinase domain
IPR000980 SH2 domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR016251 Tyrosine-protein kinase, non-receptor Jak/Tyk2
IPR019748 FERM central domain
IPR019749 Band 4.1 domain
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR020775 Tyrosine-protein kinase, non-receptor Jak3

PFAM

PF00069
PF00017
PF14633
PF07714
PF00373

PRINTS

PR00401
PR00109
PR01823
PR01826

PIRSF

PIRSF000636

SMART

SM00252
SM00220
SM00295
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References