USP33: Ubiquitin Specific Peptidase 33
A deubiquitinating enzyme involved in centrosome duplication, cell migration, and cancer progression.
Gene Information Card
| Symbol | USP33 |
|---|---|
| Full Name | Ubiquitin Specific Peptidase 33 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p31.1 |
| NCBI Gene ID | 23032 ncbi.nlm.nih.gov/gene/23032 |
| Ensembl ID | ENSG00000117408 |
| UniProt ID | Q8TEY7 |
| OMIM ID | 615146 |
| HGNC ID | 20059 |
| Aliases | VDU1, KIAA1094 |
Description
USP33 (Ubiquitin Specific Peptidase 33) encodes a deubiquitinating enzyme that cleaves ubiquitin from specific protein substrates. It is a member of the ubiquitin-specific protease (USP) family. USP33 is known to interact with the von Hippel-Lindau (VHL) tumor suppressor protein and regulates centrosome duplication, cell migration, and ciliogenesis. It also modulates the stability of the ROBO1 receptor and is implicated in axon guidance and cancer metastasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | USP33 downregulation promotes metastasis via ROBO1 stabilization | PMID: 20010870 |
| Colorectal cancer | USP33 loss correlates with poor prognosis and increased cell migration | PMID: 25605248 |
| Lung cancer | USP33 expression is reduced and associated with tumor progression | PMID: 27498980 |
| von Hippel-Lindau disease | USP33 is a VHL substrate; dysregulation may contribute to VHL-associated tumors | PMID: 12559562 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Low |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 15.2 | Medium |
| Breast | 9.7 | Low |
| Colon | 11.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.5 | Cervical cancer |
| MCF7 | 14.2 | Breast cancer |
| A549 | 10.8 | Lung cancer |
| HEK293 | 22.1 | Embryonic kidney |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Trp) | Missense | <0.01% | Unknown functional impact |
| c.1546G>A (p.Gly516Ser) | Missense | <0.01% | Unknown functional impact |
| c.1870_1871insA | Frameshift | <0.01% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations are predicted to cause loss of deubiquitinase activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported.
Dominant Negative (DN)
No dominant-negative mutations have been characterized.
View complete mutation data：
Gene Ontology (GO)
| • thiol-dependent deubiquitinase (GO:0004843) | • ubiquitin-dependent protein catabolic process (GO:0006511) |
| • centrosome (GO:0005813) | • cytoplasm (GO:0005737) |
| • nucleus (GO:0005634) | • protein ubiquitination (GO:0016567) |
| • cell differentiation (GO:0030154) | • positive regulation of GTPase activity (GO:0043547) |
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• VHL-HIF pathway
• ROBO1/SLIT signaling
Protein Summary
USP33 encodes a 941-amino acid deubiquitinating enzyme with a conserved USP catalytic domain. It removes ubiquitin from specific substrates, including the ROBO1 receptor and centrosomal proteins. USP33 localizes to the centrosome and is required for proper centrosome duplication and cilia formation. It is a target of the VHL E3 ubiquitin ligase complex. Loss of USP33 expression is observed in several cancers and correlates with increased cell migration and metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| USP33 Knockout HEK293 Cell Line | EDJ-KQ2412 | Human | 23032 | Details Get a Quote |
| USP33 Knockout A-549 Cell Line | EDJ-KQ22913 | Human | 23032 | Details Get a Quote |
| USP33 Knockout HCT 116 Cell Line | EDJ-KQ22914 | Human | 23032 | Details Get a Quote |
| USP33 Knockout HeLa Cell Line | EDJ-KQ22915 | Human | 23032 | Details Get a Quote |
