UBE3C

E3 ubiquitin-protein ligase that specifically catalyzes 'Lys-29'- and 'Lys-48'-linked polyubiquitin chains (PubMed:11278995, PubMed:12692129, PubMed:16341092, PubMed:16601690, PubMed:24158444, PubMed:24811749, PubMed:25752573, PubMed:25752577, PubMed:32039437, PubMed:33637724, PubMed:34239127). Accepts ubiquitin from the E2 ubiquitin-conjugating enzyme UBE2D1 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:32039437, PubMed:9575161). Associates with the proteasome and promotes elongation of ubiquitin chains on substrates bound to the 26S proteasome (PubMed:24158444, PubMed:28396413, PubMed:31375563). Also catalyzes 'Lys-29'- and 'Lys-48'-linked ubiquitination of 26S proteasome subunit ADRM1/RPN13 in response to proteotoxic stress, impairing the ability of the proteasome to bind and degrade ubiquitin-conjugated proteins (PubMed:24811749, PubMed:31375563). Acts as a negative regulator of autophagy by mediating 'Lys-29'- and 'Lys-48'-linked ubiquitination of PIK3C3/VPS34, promoting its degradation (PubMed:33637724). Can assemble unanchored poly-ubiquitin chains in either 'Lys-29'- or 'Lys-48'-linked polyubiquitin chains; with some preference for 'Lys-48' linkages (PubMed:11278995, PubMed:16601690, PubMed:25752577). Acts as a negative regulator of type I interferon by mediating 'Lys-48'-linked ubiquitination of IRF3 and IRF7, leading to their degradation by the proteasome (PubMed:21167755). Catalyzes ubiquitination and degradation of CAND2 (PubMed:12692129).

Neurodevelopmental disorder with absent speech and movement and behavioral abnormalities

NEDSMB

An autosomal recessive disorder characterized by global developmental delay apparent in infancy, severely impaired intellectual development, absent speech, and aggressive behavior.

None

The disease may be caused by variants affecting the gene represented in this entry.

Protein modification; protein ubiquitination.

Autoubiquitinated; promoting its own degradation.

Belongs to the UBE3C family.

Highly expressed in skeletal muscle. Detected at much lower levels in kidney and pancreas.

KIAA0010, KIAA10, UBE3C, Ubiquitin-protein ligase E3C, HECT-type ubiquitin transferase E3C, Homologous to E6AP carboxyl terminus homologous protein 2, RTA-associated ubiquitin ligase, HectH2, RAUL

• entrezGene:9690
• omim:614454
• swissprot:Q15386

Proteins

Oncology

123923Da