HERC2

This gene belongs to the HERC gene family that encodes a group of unusually large proteins, which contain multiple structural domains. All members have at least 1 copy of an N-terminal region showing homology to the cell cycle regulator RCC1 and a C-terminal HECT (homologous to E6-AP C terminus) domain found in a number of E3 ubiquitin protein ligases. Genetic variations in this gene are associated with skin/hair/eye pigmentation variability. Multiple pseudogenes of this gene are located on chromosomes 15 and 16.

HECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 2

E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. Recruited to sites of DNA damage in response to ionizing radiation (IR) and facilitates the assembly of UBE2N and RNF8 promoting DNA damage-induced formation of 'Lys-63'-linked ubiquitin chains. Acts as a mediator of binding specificity between UBE2N and RNF8. Involved in the maintenance of RNF168 levels. E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of XPA which influences the circadian oscillation of DNA excision repair activity. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333).

Cellular response to DNA damage stimulus Source: UniProtKB
DNA repair Source: UniProtKB-KW
Intracellular protein transport Source: UniProtKB
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: Ensembl
Protein ubiquitination Source: UniProtKB
Spermatogenesis Source: Ensembl

Centriole; Nucleus; Cytoplasm. Recruited to sites of DNA damage in response to ionizing radiation (IR) via its interaction with RNF8. May loose association with centrosomes during mitosis.

Mental retardation, autosomal recessive 38 (MRT38):
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT38 is characterized by global developmental delay affecting motor, speech, adaptive, and social development. Patients manifest autistic features, aggression, self-injury, impulsivity, and distractibility.

Phosphorylation at Thr-4827 is required for interaction with RNF8.
Sumoylated with SUMO1 by PIAS4 in response to double-strand breaks (DSBs), promoting the interaction with RNF8.