SENP6 (SUMO Specific Peptidase 6)
A key regulator of SUMOylation dynamics involved in genome stability, cell cycle control, and cancer.
Gene Information Card
| Symbol | SENP6 |
|---|---|
| Full Name | SUMO specific peptidase 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p12.3 |
| NCBI Gene ID | 26054 ncbi.nlm.nih.gov/gene/26054 |
| Ensembl ID | ENSG00000112759 |
| UniProt ID | Q9GZR1 |
| OMIM ID | 612137 |
| HGNC ID | 20944 |
| Aliases | SENP6, SSP1, SUSP1, FLJ12649, KIAA0477 |
Description
SENP6 (SUMO specific peptidase 6) encodes a member of the SUMO (small ubiquitin-like modifier) specific protease family. The protein specifically deconjugates SUMO2 and SUMO3 from target proteins, playing a critical role in regulating SUMOylation dynamics. SENP6 is involved in multiple cellular processes including cell cycle progression, DNA repair, chromosome segregation, and maintenance of genome stability. It is localized to the nucleoplasm and is essential for proper mitotic progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | SENP6 overexpression promotes cell proliferation and migration; altered SUMOylation of key oncoproteins. | PMID: 31409811 |
| Colorectal cancer | SENP6 upregulation correlates with poor prognosis; enhances Wnt/β-catenin signaling. | PMID: 31591468 |
| Hepatocellular carcinoma | SENP6 knockdown reduces tumor growth; regulates p53 and NF-κB pathways. | PMID: 30523322 |
| Prostate cancer | SENP6 expression linked to androgen receptor signaling and therapy resistance. | PMID: 32015549 |
| Lung adenocarcinoma | SENP6 amplification and overexpression associated with metastasis. | PMID: 32697937 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Lymph node | 10.2 | Medium |
| Bone marrow | 9.8 | Medium |
| Spleen | 8.7 | Medium |
| Brain | 4.1 | Low |
| Heart | 3.5 | Low |
| Liver | 2.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.3 | Embryonic kidney; high expression |
| HeLa | 12.1 | Cervical carcinoma; moderate |
| MCF7 | 11.4 | Breast cancer; moderate |
| A549 | 10.8 | Lung cancer; moderate |
| HepG2 | 9.2 | Liver cancer; moderate |
| K562 | 8.5 | Leukemia; moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1873C>T (p.Arg625Trp) | Missense | 0.01% (gnomAD) | Unknown; located in catalytic domain |
| c.2444G>A (p.Arg815Gln) | Missense | 0.005% (gnomAD) | Unknown; may affect substrate binding |
| c.3190C>T (p.Arg1064*) | Nonsense | <0.001% | Loss of function; truncation |
| c.1126_1127insA (p.Thr376Asnfs*2) | Frameshift | <0.001% | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg1064*, p.Thr376Asnfs*2) are predicted to cause loss of function by truncating the protein or inducing nonsense-mediated decay.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SENP6.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported in SENP6.
View complete mutation data：
Gene Ontology (GO)
Pathways
• SUMOylation pathway (Reactome: R-HSA-2990846)
• Cell Cycle
• Mitotic (Reactome: R-HSA-69278)
• DNA Repair (Reactome: R-HSA-73894)
• Regulation of TP53 Activity (Reactome: R-HSA-5633007)
Protein Summary
SENP6 is a 1112-amino acid protein (UniProt Q9GZR1) belonging to the peptidase C48 family. It contains a conserved C-terminal catalytic domain with a Cys-His-Asp triad essential for isopeptidase activity. SENP6 specifically cleaves SUMO2/3 from modified proteins, reversing SUMOylation. It is critical for proper mitotic progression, chromosome segregation, and genome stability. The protein interacts with multiple partners including the anaphase-promoting complex/cyclosome (APC/C) and is involved in DNA damage response. Dysregulation of SENP6 expression is implicated in several cancers.
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