Protein: Ubiquilin-4 (Ataxin-1 interacting ubiquitin-like protein) (A1Up) (Ataxin-1 ubiquitin-like-interacting protein A1U) (Connexin43-interacting protein of 75 kDa) (CIP75) (Q9NRR5)
Organism: Homo sapiens (Human)
Function: Regulator of protein degradation that mediates the proteasomal targeting of misfolded, mislocalized or accumulated proteins. Acts by binding polyubiquitin chains of target proteins via its UBA domain and by interacting with subunits of the proteasome via its ubiquitin-like domain. Key regulator of DNA repair that represses homologous recombination repair: in response to DNA damage, recruited to sites of DNA damage following phosphorylation by ATM and acts by binding and removing ubiquitinated MRE11 from damaged chromatin, leading to MRE11 degradation by the proteasome. MRE11 degradation prevents homologous recombination repair, redirecting double-strand break repair toward non-homologous end joining (NHEJ). Specifically recognizes and binds mislocalized transmembrane-containing proteins and targets them to proteasomal degradation. Collaborates with DESI1/POST in the export of ubiquitinated proteins from the nucleus to the cytoplasm. Also plays a role in the regulation of the proteasomal degradation of non-ubiquitinated GJA1 (By similarity). Acts as an adapter protein that recruits UBQLN1 to the autophagy machinery. Mediates the association of UBQLN1 with autophagosomes and the autophagy-related protein LC3 (MAP1LC3A/B/C) and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome-lysosome fusion.
Subcellular location: Nucleus {ECO:0000269|PubMed:11001934, ECO:0000269|PubMed:15280365, ECO:0000269|PubMed:29666234, ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:34245648}. Cytoplasm {ECO:0000269|PubMed:29666234, ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:34245648}. Chromosome {ECO:0000269|PubMed:30612738}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q99NB8}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q99NB8}. Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:23459205}. Note=Colocalizes with the proteasome, both in nucleus and cytoplasm (PubMed:15280365). Exported from the nucleus following interaction with DESI1/POST (PubMed:29666234). In response to DNA damage and phosphorylation at Ser-318 by ATM, localizes to the nucleus and is recruited to sites of DNA damage (PubMed:30612738). {ECO:0000269|PubMed:15280365, ECO:0000269|PubMed:29666234, ECO:0000269|PubMed:30612738}.
Interaction partners:
- 26S proteasome non-ATPase regulatory subunit 4
- 26S proteasome non-ATPase regulatory subunit 14
- Desumoylating isopeptidase 1
- 26S proteasome non-ATPase regulatory subunit 1
- 26S proteasome non-ATPase regulatory subunit 8
- 26S proteasome non-ATPase regulatory subunit 12
- 26S proteasome non-ATPase regulatory subunit 13
- 26S proteasome non-ATPase regulatory subunit 6
- 26S proteasome non-ATPase regulatory subunit 11
- 26S proteasome regulatory subunit 7
Sequence:
MAEPSGAETRPPIRVTVKTPKDKEEIVICDRASVKEFKEEISRRFKAQQDQLVLIFAGKILKDGDTLNQHGIKDGLTVHLVIKTPQKAQDPAAATASSPSTPDPASAPSTTPASPATPAQPSTSGSASSDAGSGSRRSSGGGPSPGAGEGSPSATASILSGFGGILGLGSLGLGSANFMELQQQMQRQLMSNPEMLSQIMENPLVQDMMSNPDLMRHMIMANPQMQQLMERNPEISHMLNNPELMRQTMELARNPAMMQEMMRNQDRALSNLESIPGGYNALRRMYTDIQEPMFSAAREQFGNNPFSSLAGNSDSSSSQPLRTENREPLPNPWSPSPPTSQAPGSGGEGTGGSGTSQVHPTVSNPFGINAASLGSGMFNSPEMQALLQQISENPQLMQNVISAPYMRSMMQTLAQNPDFAAQMMVNVPLFAGNPQLQEQLRLQLPVFLQQMQNPESLSILTNPRAMQALLQIQQGLQTLQTEAPGLVPSLGSFGISRTPAPSAGSNAGSTPEAPTSSPATPATSSPTGASSAQQQLMQQMIQLLAGSGNSQVQTPEVRFQQQLEQLNSMGFINREANLQALIATGGDINAAIERLLGSQLS