Ubiquitin thioesterase OTUB1 (OTUB1)

Ubiquitin thioesterase OTUB1 is a human deubiquitinating enzyme (DUB) belonging to the OTU (ovarian tumor) superfamily of cysteine proteases[1][3][7]. It preferentially cleaves Lys48-linked polyubiquitin chains, regulating ubiquitin-dependent protein degradation and other signaling pathways such as the DNA damage response. OTUB1 functions by direct substrate deubiquitination and by a unique non-catalytic mechanism where it inhibits the E2 ubiquitin-conjugating enzyme UBC13, thereby suppressing Lys63-linked polyubiquitination involved in DNA repair[2]. OTUB1 participates in various multi-protein complexes, influencing processes such as RNA processing and cell adhesion[3]. Dysregulation of OTUB1 has been linked to cancer and abnormal immune responses. While no approved drugs currently target OTUB1, engineered ubiquitin variants selectively modulate its enzymatic activity in experimental settings[5].

Other names

Otubain-1OTU domain-containing ubiquitin aldehyde-binding protein 1OTUB1_HUMAN[4][6][7]

Inhibition of deubiquitinase activity; Modulation of Lys48-linked polyubiquitin chain cleavage; Non-canonical inhibition of E2 ubiquitin-conjugating enzymes (specifically UBC13)