USP21: Ubiquitin Specific Peptidase 21

A deubiquitinating enzyme involved in cell cycle regulation, immune signaling, and cancer.

Gene Information Card

Symbol USP21
Full Name Ubiquitin Specific Peptidase 21
Gene Type Protein coding
Chromosomal Location 1q23.3
NCBI Gene ID 27005 ncbi.nlm.nih.gov/gene/27005
Ensembl ID ENSG00000143278
UniProt ID Q9UJX3
OMIM ID 617470
HGNC ID 12620
Aliases USP23, deubiquitinating enzyme 21

Description

USP21 (Ubiquitin Specific Peptidase 21) is a deubiquitinating enzyme (DUB) that removes ubiquitin from target proteins, regulating their stability, localization, and activity. It plays roles in cell cycle progression, DNA damage response, innate immune signaling, and apoptosis. USP21 is implicated in several cancers and inflammatory conditions.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Hepatocellular carcinoma USP21 overexpression promotes deubiquitination and stabilization of oncoproteins (e.g., β-catenin), enhancing proliferation. PMID: 28965875
Colorectal cancer USP21 deubiquitinates and stabilizes MYC, driving tumor growth. PMID: 31073040
Inflammatory bowel disease USP21 negatively regulates NF-κB signaling by deubiquitinating TRAF3, reducing inflammation. PMID: 27559042
Breast cancer USP21 overexpression correlates with poor prognosis; promotes cell migration via deubiquitination of SNAI1. PMID: 31570799

Expression Profile

Tissue Expression
Tissue nTPM level
Testis 12.3 Medium
Liver 8.7 Medium
Kidney 6.5 Low
Brain 4.2 Low
Heart 3.1 Low
Cell Line Expression
Cell Line nTPM Notes
HepG2 (liver cancer) 14.5 High expression
HEK293 (embryonic kidney) 9.8 Moderate expression
MCF7 (breast cancer) 7.2 Moderate expression
A549 (lung cancer) 5.6 Low expression
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.511C>T (p.Arg171Trp) Missense <0.01% Unknown; located in catalytic domain
c.1024G>A (p.Glu342Lys) Missense <0.01% Unknown; may affect substrate binding
c.1345_1346insA (p.Thr449Asnfs*5) Frameshift <0.01% Predicted loss of function
Mutation functional classification

Loss of Function (LOF)

Frameshift mutations (e.g., p.Thr449Asnfs*5) likely result in truncated, non-functional protein.

Gain of Function (GOF)

Not well characterized; overexpression in cancer suggests potential gain-of-function via increased deubiquitinase activity.

Dominant Negative (DN)

No known dominant-negative mutations reported.

Gene Ontology (GO)

• cysteine-type deubiquitinase activity • ubiquitin-specific protease activity
• protein deubiquitination • cell cycle regulation
• NF-κB signaling • apoptotic process
• DNA repair

Pathways

• Deubiquitination
• NF-κB signaling
• Wnt/β-catenin signaling
• p53 pathway

Protein Summary

USP21 is a 561-amino acid cysteine protease belonging to the ubiquitin-specific protease (USP) family. It contains a conserved catalytic domain (Cys-His-Asp triad) and a ubiquitin-binding domain. The enzyme removes ubiquitin chains from specific substrates, thereby preventing their proteasomal degradation. USP21 is localized to the cytoplasm and nucleus, and its activity is regulated by phosphorylation and protein-protein interactions.

Related Products

Product name Cat.No. Species Gene ID
USP21 Knockout HEK293 Cell Line EDJ-KQ2970 Human 27005 Details Get a Quote
USP21 Knockout A-549 Cell Line EDJ-KQ24131 Human 27005 Details Get a Quote
USP21 Knockout HCT 116 Cell Line EDJ-KQ24132 Human 27005 Details Get a Quote
USP21 Knockout HeLa Cell Line EDJ-KQ24133 Human 27005 Details Get a Quote

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