USP1 Gene: Ubiquitin Specific Peptidase 1
A key regulator of DNA damage response and Fanconi anemia pathway
Gene Information Card
| Symbol | USP1 |
|---|---|
| Full Name | Ubiquitin Specific Peptidase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p31.3 |
| NCBI Gene ID | 7398 ncbi.nlm.nih.gov/gene/7398 |
| Ensembl ID | ENSG00000162607 |
| UniProt ID | O94782 |
| OMIM ID | 603478 |
| HGNC ID | 12607 |
| Aliases | UBP, USP1, deubiquitinating enzyme 1 |
Description
USP1 (Ubiquitin Specific Peptidase 1) encodes a deubiquitinating enzyme that removes ubiquitin from specific target proteins, playing a critical role in DNA damage repair, cell cycle regulation, and the Fanconi anemia pathway. It deubiquitinates FANCD2 and PCNA, thereby regulating their activity in response to DNA damage. USP1 is also involved in the regulation of stem cell differentiation and is frequently altered in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Fanconi anemia complementation group S (FANCS) | Loss-of-function mutations in USP1 impair FANCD2 deubiquitination, disrupting the Fanconi anemia DNA repair pathway and leading to bone marrow failure and cancer predisposition. | OMIM #617243; ClinVar |
| Breast cancer | USP1 overexpression or gain-of-function mutations may promote genomic instability and tumorigenesis by altering DNA repair dynamics. | COSMIC; literature |
| Lung cancer | Somatic mutations and altered expression of USP1 have been reported in non-small cell lung cancer, potentially affecting chemoresistance. | COSMIC; literature |
| Colorectal cancer | USP1 upregulation is associated with poor prognosis and may contribute to resistance to DNA-damaging chemotherapies. | COSMIC; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Bone marrow | 8.2 | Low |
| Lymph node | 6.7 | Low |
| Brain | 4.1 | Low |
| Liver | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 15.3 | High expression |
| A549 (lung carcinoma) | 10.1 | Medium expression |
| MCF7 (breast carcinoma) | 9.4 | Medium expression |
| HEK293 (embryonic kidney) | 7.2 | Low expression |
| K562 (leukemia) | 6.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.152C>T (p.Ser51Leu) | Missense | <0.01% | Loss of deubiquitinase activity; associated with Fanconi anemia |
| c.409G>A (p.Glu137Lys) | Missense | <0.01% | Impaired FANCD2 interaction; Fanconi anemia |
| c.1234A>G (p.Lys412Glu) | Missense | 0.02% | Reduced catalytic activity; reported in cancer |
| c.1685T>C (p.Ile562Thr) | Missense | 0.01% | Unknown functional effect; somatic in lung cancer |
Mutation functional classification
Loss of Function (LOF)
Germline missense mutations (e.g., p.Ser51Leu, p.Glu137Lys) reduce or abolish USP1 deubiquitinase activity, leading to Fanconi anemia phenotype.
Gain of Function (GOF)
Overexpression or activating mutations (e.g., p.Lys412Glu) may increase deubiquitination of PCNA, promoting DNA repair and chemoresistance in cancer.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported; however, some missense variants may interfere with wild-type USP1 function in heterozygous state.
View complete mutation data：
Gene Ontology (GO)
| • thiol-dependent deubiquitinase (GO:0004843) | • ubiquitin-dependent protein catabolic process (GO:0006511) |
| • DNA repair (GO:0006281) | • cellular response to DNA damage stimulus (GO:0006974) |
| • nucleus (GO:0005634) | • cytoplasm (GO:0005737) |
Pathways
• Fanconi anemia pathway (Reactome: R-HSA-6783310)
• Translesion synthesis by Y-family polymerases (Reactome: R-HSA-110313)
• Ubiquitin-mediated proteolysis (KEGG: hsa04120)
Protein Summary
USP1 is a 785-amino acid deubiquitinating enzyme (UniProt O94782) that specifically cleaves ubiquitin from FANCD2 and PCNA. It contains a catalytic domain with a conserved cysteine box and a ubiquitin-binding domain. USP1 is regulated by autocleavage and interaction with UAF1 (USP1-associated factor 1). Its activity is essential for the proper activation of the Fanconi anemia pathway and for regulating DNA damage tolerance during replication.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| Dusp1 Knockout ID8 Cell Line | EDJ-KQ78171 | Mouse | 19252 | Details Get a Quote |
| DUSP16 Knockout HEK293 Cell Line | EDJ-KQ156 | Human | 80824 | Details Get a Quote |
| USP13 Knockout HEK293 Cell Line | EDJ-KQ459 | Human | 8975 | Details Get a Quote |
| DUSP1 Knockout HEK293 Cell Line | EDJ-KQ639 | Human | 1843 | Details Get a Quote |
| DUSP10 Knockout HEK293 Cell Line | EDJ-KQ640 | Human | 11221 | Details Get a Quote |
| USP1 Knockout HEK293 Cell Line | EDJ-KQ2430 | Human | 7398 | Details Get a Quote |
| USP18 Knockout HEK293 Cell Line | EDJ-KQ2453 | Human | 11274 | Details Get a Quote |
| USP10 Knockout HEK293 Cell Line | EDJ-KQ2504 | Human | 9100 | Details Get a Quote |
| USP15 Knockout HEK293 Cell Line | EDJ-KQ2671 | Human | 9958 | Details Get a Quote |
| USP11 Knockout HEK293 Cell Line | EDJ-KQ2750 | Human | 8237 | Details Get a Quote |
| USP16 Knockout HEK293 Cell Line | EDJ-KQ3856 | Human | 10600 | Details Get a Quote |
| DUSP11 Knockout HEK293 Cell Line | EDJ-KQ6242 | Human | 8446 | Details Get a Quote |
| USP19 Knockout HEK293 Cell Line | EDJ-KQ7199 | Human | 10869 | Details Get a Quote |
| DUSP14 Knockout HEK293 Cell Line | EDJ-KQ7270 | Human | 11072 | Details Get a Quote |
| USP12 Knockout HEK293 Cell Line | EDJ-KQ8183 | Human | 219333 | Details Get a Quote |
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