SIRT5
Sirtuin 5, a mitochondrial lysine deacylase regulating metabolism and oxidative stress
Gene Information Card
| Symbol | SIRT5 |
|---|---|
| Full Name | Sirtuin 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p23 |
| NCBI Gene ID | 23408 ncbi.nlm.nih.gov/gene/23408 |
| Ensembl ID | ENSG00000124523 |
| UniProt ID | Q9NXA8 |
| OMIM ID | 604483 |
| HGNC ID | 14933 |
| Aliases | SIR2L5, SIR2-like 5 |
Description
SIRT5 is a member of the sirtuin family of NAD+-dependent deacylases, localized primarily to the mitochondria. It catalyzes the removal of succinyl, malonyl, and glutaryl groups from lysine residues, regulating key metabolic enzymes involved in fatty acid oxidation, the urea cycle, and the tricarboxylic acid cycle. SIRT5 also modulates oxidative stress responses and has been implicated in cancer, metabolic disorders, and aging.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | SIRT5 overexpression or underexpression alters metabolic reprogramming (e.g., desuccinylation of IDH2, SOD1) promoting tumor growth or suppression | COSMIC, PubMed |
| Metabolic syndrome | SIRT5 regulates mitochondrial metabolism; deficiency impairs fatty acid oxidation and ketogenesis | OMIM, PubMed |
| Neurological disorders | SIRT5 modulates oxidative stress and mitochondrial function; variants linked to Parkinson's disease risk | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.3 | Medium |
| Heart | 8.9 | Medium |
| Brain | 6.2 | Low |
| Skeletal Muscle | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.2 | Hepatocellular carcinoma cell line |
| HEK293 | 9.8 | Embryonic kidney cells |
| SH-SY5Y | 7.4 | Neuroblastoma cell line |
| MCF7 | 6.1 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.302C>T (p.Ala101Val) | Missense | <0.01% | Reduced deacylase activity; associated with metabolic phenotypes |
| c.457G>A (p.Gly153Ser) | Missense | <0.01% | Unknown functional effect; reported in ClinVar |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Likely loss of function; rare population variant |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., Ala101Val) reduce enzymatic activity; start-loss variant Met1Val abolishes protein production.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SIRT5.
Dominant Negative (DN)
No evidence for dominant-negative effects; SIRT5 functions as a monomer.
View complete mutation data：ClinVar: https://www.clinvar.com/gene/23408 COSMIC: https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=SIRT5
Gene Ontology (GO)
| • GO:0017136 - NAD-dependent histone deacetylase activity | • GO:0042802 - identical protein binding |
| • GO:0005739 - mitochondrion | • GO:0018394 - peptidyl-lysine desuccinylation |
| • GO:0018395 - peptidyl-lysine demalonylation | • GO:0006120 - mitochondrial electron transport |
| • NADH to ubiquinone |
Pathways
• Urea cycle (Reactome: R-HSA-70635)
• Fatty acid metabolism (Reactome: R-HSA-8978868)
• TCA cycle and respiratory electron transport (Reactome: R-HSA-1428517)
• Sirtuin-mediated regulation (KEGG: hsa05034)
Protein Summary
SIRT5 is a 310-amino acid mitochondrial sirtuin with a conserved catalytic core domain. It removes succinyl, malonyl, and glutaryl groups from lysine residues in a NAD+-dependent manner. Key substrates include carbamoyl phosphate synthase 1 (CPS1), isocitrate dehydrogenase 2 (IDH2), and superoxide dismutase 1 (SOD1). Through these modifications, SIRT5 regulates ammonia detoxification, fatty acid oxidation, and antioxidant defense. Its activity is modulated by NAD+ availability and post-translational modifications.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIRT5 Knockout HEK293 Cell Line | EDC07605 | Human | 23408 | Details Get a Quote |
| SIRT5 Knockout A-549 Cell Line | EDJ-KQ24842 | Human | 23408 | Details Get a Quote |
| SIRT5 Knockout HCT 116 Cell Line | EDJ-KQ24843 | Human | 23408 | Details Get a Quote |
| SIRT5 Knockout HeLa Cell Line | EDJ-KQ24844 | Human | 23408 | Details Get a Quote |
| Sirt5 Knockout HL-1 Cell Line | EDJ-KZ464 | Mouse | 68346 | Details Get a Quote |
| SIRT5 Knockout Hep-G2 Cell Line | EDJ-KQ78081 | Human | 23408 | Details Get a Quote |
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