Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

JAK3 (P52333) - Overview - Molecular Target Synopsis


JAK3, Tyrosine-protein kinase JAK3
Enzyme Classification
UniProt P52333

Also Known as JAK3_HUMAN, 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. Interacts with STAM2 and MYO18A (By similarity). Interacts with SHB.

Inspect Structure
See all 3D Structures for JAK3

Isoforms / Transcripts (Protein Coding)

Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
1124ENSG00000105639ENST00000458235, ENST00000527670ENSP00000391676, ENSP00000432511P52333-1

Sub-cellular localization

UniProt: JAK3 is active in the following subcellular-locations: cytoplasm, endomembrane system.
GO terms: JAK3 is active in the following subcellular-locations: cytoskeleton, cytosol, endosome, plasma membrane.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project JAK3 has gain in 1 cell-lines, loss in 1 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: SR, MOLT_4, CCRF_CEM

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SR, SU-DHL-1, SR-786

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: CD34-positive mobilized cell, CD20-positive B cell, GM12878

(see details)

RNA Interference

JAK3 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: HELA, H358. (see details)

3D Structures

For JAK3 there are:
33 structures (53 chains) solved
33 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

JAK3 is solved in complex with the approved drug(s):


(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

JAK3 has been screened with 3237 compounds (4306 bioactivities), 1509 compounds have bioactivities that show binding affinity of <= 500nM (1823 bioactivities). (see details)