UBASH3B Gene: Function, Expression, and Clinical Significance

UBASH3B (Ubiquitin Associated and SH3 Domain Containing B) encodes a protein that functions as a negative regulator of T-cell receptor (TCR) signaling. The protein contains an N-terminal ubiquitin-associated (UBA) domain, a central SH3 domain, and a C-terminal phosphoglycerate mutase (PGM) domain with phosphatase activity. It dephosphorylates specific tyrosine residues on signaling proteins such as ZAP-70 and Syk, thereby attenuating TCR-mediated activation. UBASH3B is also implicated in the regulation of growth factor receptor signaling and may act as a tumor suppressor in certain cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• T cell receptor signaling pathway (Reactome: R-HSA-202403)

• Signaling by EGFR (Reactome: R-HSA-177929)

• Adaptive Immune System (Reactome: R-HSA-1280218)

The UBASH3B protein (also known as STS-2 or TULA-2) is a 647-amino acid phosphatase that negatively regulates TCR signaling by dephosphorylating ZAP-70 and Syk. It contains a UBA domain for ubiquitin binding, an SH3 domain for protein-protein interactions, and a PGM domain with phosphatase activity. The protein is predominantly expressed in lymphoid tissues and is involved in modulating immune responses. Altered expression and mutations have been observed in several cancers, suggesting a potential tumor suppressor role.