HGNC Approved Gene Symbol: USP1Cytogenetic location: 1p31.3 Genomic coordinates (GRCh38): 1:62,436,394-62,451,803 (from NCBI)▼ DescriptionUSP1 is the catalyt...
HGNC Approved Gene Symbol: USP1
Cytogenetic location: 1p31.3 Genomic coordinates (GRCh38): 1:62,436,394-62,451,803 (from NCBI)
USP1 is the catalytic component of the nuclear USP1-UAF1 (WDR48; 612167) deubiquitinating complex. By removing an activating ubiquitin modification, the USP1-UAF1 complex deactivates monoubiquitinated FANCD2 (613984) and monoubiquitinated PCNA (176740), which are required in DNA damage repair and translesional synthesis, respectively (Cohn et al., 2007).
▼ Cloning and Expression
Deubiquitinating enzymes (DUBs) possess conserved catalytic regions known as the 'cys domain' and the 'his domain.' There are 2 distinct families of DUBs: ubiquitin-specific processing proteases (UBPs, or USPs) and ubiquitin C-terminal hydrolases (UCHs). By computerized sequence analysis of human fetal brain cDNAs, Fujiwara et al. (1998) identified a cDNA encoding a novel UBP family member, which they designated USP1. The predicted 785-amino acid USP1 protein contains a cys domain and a his domain, as well as conserved asp and KRF domains.
▼ Gene Function
Fujiwara et al. (1998) showed that recombinant USP1 protein exhibited UBP activity.
By mass spectrometric analysis, Cohn et al. (2007) found that USP1 and UAF1 formed a stoichiometric complex that immunopurified from HeLa cell nuclear extracts. USP1 was present in the complex as both a full-length protein and as autocleaved N- and C-terminal fragments, with the catalytic cysteine box in the N-terminal fragment and the catalytic histidine box in the C-terminal fragment. UAF1 apparently bridged the 2 fragments together. USP1 alone showed little catalytic activity against monoubiquitinated FANCD2 or a synthetic monoubiquitinated fluorogenic substrate. However, addition of UAF1 increased the catalytic activity of USP1 up to 35-fold. Knockdown of UAF1 in HeLa cells via short hairpin RNA reduced the level of both full-length and hydrolyzed USP1, resulting in accumulation of monoubiquitinated FANCD2 and monoubiquitinated PCNA. Transcription of USP1 was rapidly suppressed and USP1 protein was degraded in response to ultraviolet irradiation, allowing cellular accumulation of monoubiquitinated FANCD2 for an effective DNA damage response. Cohn et al. (2007) noted that while all USP1 was found in complex with UAF1, a subfraction of UAF1 was not bound to USP1, suggesting additional cellular functions.
By analysis of radiation hybrids and by fluorescence in situ hybridization, Fujiwara et al. (1998) mapped the USP1 gene to 1p32.1-p31.3.