E3 ubiquitin-protein ligase HERC2
Domain
The ZZ-type zinc finger mediates binding to SUMO1, and at low level SUMO2.
The RCC1 repeats are grouped into three seven-bladed beta-propeller regions.
Function
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). Modulates also iron metabolism by regulating the basal turnover of FBXL5 (PubMed:24778179).
Involvement in disease
Intellectual developmental disorder, 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.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
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.
Cellular localization
- Cytoplasm
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Centriole
- Nucleus
- Recruited to sites of DNA damage in response to ionizing radiation (IR) via its interaction with RNF8. May loose association with centrosomes during mitosis.
Alternative names
E3 ubiquitin-protein ligase HERC2, HECT domain and RCC1-like domain-containing protein 2, HECT-type E3 ubiquitin transferase HERC2, HERC2