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Ubiquitin carboxyl-terminal hydrolase 1

Developmental stage

Cell cycle-regulated. Highest level during S phase.

Function

Negative regulator of DNA damage repair which specifically deubiquitinates monoubiquitinated FANCD2 (PubMed:15694335). Also involved in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA (PubMed:16531995, PubMed:20147293). Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity (PubMed:18082604, PubMed:26388029).

Post-translational modifications

Autocatalytic cleavage of USP1 following UV irradiation inactivates it, leading to an increase in ubiquitinated PCNA, recruitment of POLH and translesion synthesis.

Ubiquitin carboxyl-terminal hydrolase 1, N-terminal fragment

Ubiquitinated by the CRL2(KLHDC2) complex following autocatalytic cleavage, leading to its degradation: the CRL2(KLHDC2) complex recognizes the diglycine (Gly-Gly) at the C-terminus.

Sequence Similarities

Belongs to the peptidase C19 family.

Cellular localization

Alternative names

Ubiquitin carboxyl-terminal hydrolase 1, Deubiquitinating enzyme 1, Ubiquitin thioesterase 1, Ubiquitin-specific-processing protease 1, hUBP, USP1

swissprot:O94782 entrezGene:7398 omim:603478