Ubiquitin-associated and SH3 domain-containing protein B (UBASH3B)

Ubiquitin-associated and SH3 domain-containing protein B (UBASH3B) is an atypical protein tyrosine phosphatase that serves as a critical regulator of cellular signaling, protein ubiquitination, and immune cell activation. The molecule is composed of a ubiquitin-binding (UBA) domain, a centrally located Src-homology 3 (SH3) domain, and a C-terminal histidine phosphatase domain. UBASH3B dephosphorylates multiple key signaling kinases (such as Syk, Zap-70, EGFR, Cbl) and thereby negatively regulates receptor-mediated signaling, especially in lymphoid and hematopoietic cells. Overexpression of UBASH3B is implicated in cancer progression (notably triple-negative breast cancer and acute myeloid leukemia), where it promotes invasion, metastasis, and therapeutic resistance by modulating EGFR signaling via dephosphorylation and inactivation of Cbl, preventing EGFR degradation. UBASH3B also plays roles in immune regulation, autoimmunity, cell proliferation, mitosis, and autophagy, making it a potential therapeutic target and biomarker in multiple disease contexts[1][2][3].

Other names

STS-1TULA-2KIAA1959Cbl-interacting protein p70Suppressor of T-cell receptor signaling 1T-cell ubiquitin ligand 2Tyrosine-protein phosphatase STS1/TULA2SH3 domain-containing 70 kDa protein

Drugs or inhibitors would act by blocking protein tyrosine phosphatase activity or disrupting SH3 domain-mediated interactions to inhibit dephosphorylation of key substrates (e.g., Cbl), impairing EGFR stabilization and downstream oncogenic signaling[2][3].