SIRT4 Gene
Introduction Sirt4 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-gene"> [@ahuja2007]Full Name: Sirtuin 4 (Mitochondrial)<br>
Chromosomal Location: 12q24.31<br>
NCBI Gene ID: 23127<br>
OMIM: 604956<br>
Ensembl ID: ENSG00000057394<br>
UniProt: Q9NWU1<br>
Associated Diseases: Alzheimer's Disease, Parkinson's Disease, Type 2 Diabetes, Cancer
Overview
flowchart TD
SIRT4["SIRT4"] -->|"expressed in"| SIRT5["SIRT5"]
SIRT4["SIRT4"] -->|"expressed in"| SIRT7["SIRT7"]
SIRT4["SIRT4"] -->|"expressed in"| SIRT2["SIRT2"]
SIRT4["SIRT4"] -->|"expressed in"| SIRT1["SIRT1"]
SIRT4["SIRT4"] -->|"expressed in"| SIRT6["SIRT6"]
SIRT4["SIRT4"] -->|"expressed in"| SIRT3["SIRT3"]
SIRT4["SIRT4"] -->|"regulates"| Neurodegeneration["Neurodegeneration"]
SIRT4["SIRT4"] -->|"regulates"| Parkinson["Parkinson"]
SIRT4["SIRT4"] -->|"regulates"| Alzheimer["Alzheimer"]
SIRT4["SIRT4"] -->|"regulates"| Neuroinflammation["Neuroinflammation"]
SIRT4["SIRT4"] -->|"regulates"| Inflammation["Inflammation"]
SIRT4["SIRT4"] -->|"regulates"| Huntington["Huntington"]
SIRT4["SIRT4"] -->|"regulates"| Ms["Ms"]
SIRT4["SIRT4"] -->|"expressed in"| Als["Als"]
style SIRT4 fill:#4fc3f7,stroke:#333,color:#000
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SIRT4 Gene
Introduction Sirt4 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-gene"> [@ahuja2007]Full Name: Sirtuin 4 (Mitochondrial)<br>
Chromosomal Location: 12q24.31<br>
NCBI Gene ID: 23127<br>
OMIM: 604956<br>
Ensembl ID: ENSG00000057394<br>
UniProt: Q9NWU1<br>
Associated Diseases: Alzheimer's Disease, Parkinson's Disease, Type 2 Diabetes, Cancer
Overview
Mermaid diagram (expand to render)
SIRT4 (Sirtuin 4) is a NAD+-dependent mitochondrial class III deacetylase and ADP-ribosyltransferase. Unlike other sirtuins, SIRT4 does not exhibit robust deacetylase activity but primarily functions as an ADP-ribosyltransferase. SIRT4 plays important roles in mitochondrial metabolism, insulin secretion, and tumor suppression. It is increasingly recognized for its roles in metabolic diseases and neurodegeneration.
Function SIRT4 is primarily mitochondrial and regulates several key metabolic processes:
ADP-Ribosylation: Catalyzes ADP-ribosylation of target proteins (primary activity)Glutamine Metabolism: Regulates GDH (glutamate dehydrogenase) activity through ADP-ribosylation, inhibiting glutamine-dependent insulin secretion fatty acid oxidation: Influences fatty acid metabolism in mitochondriaMitochondrial DNA Replication: Interacts with TFAM and mitochondrial DNA polymeraseInsulin Secretion: Inhibits pancreatic beta-cell insulin secretion in response to amino acidsTumor Suppression: Functions as a tumor suppressor by regulating cellular metabolismDisease Associations
Alzheimer's Disease SIRT4 may be protective in AD:
Regulates mitochondrial function and reduces oxidative stress
Modulates insulin signaling (linked to AD brain insulin resistance)
May affect [Aβ](/proteins/amyloid-beta) metabolism through mitochondrial pathways
SIRT4 levels are altered in AD brain
Parkinson's Disease SIRT4's role in PD is emerging:
Mitochondrial protection in dopaminergic [neurons](/entities/neurons)
May influence mitophagy pathways
Metabolic regulation relevant to neuronal energy requirements
SIRT4 links neurodegeneration to metabolic disease:
Type 2 diabetes increases AD/PD risk
SIRT4 regulates insulin sensitivity
Common metabolic pathways affected in both neurodegeneration and diabetes
Expression SIRT4 is expressed in:
Pancreas (islets of Langerhans)
Liver, kidney, heart
Brain: [hippocampus](/brain-regions/hippocampus), cerebral [cortex](/brain-regions/cortex)
Substantia nigra
Expression is tissue-specific with highest levels in pancreas
Key Publications
"SIRT4 functions in tumor suppression" - Nature (2009) - [DOI:10.1038/nature07837](https://doi.org/10.1038/nature07837)"SIRT4 regulates mitochondrial metabolism" - Cell (2010) - [DOI:10.1016/j.cell.2010.03.027](https://doi.org/10.1016/j.cell.2010.03.027)"SIRT4 and insulin secretion" - J Biol Chem (2011) - [DOI:10.1074/jbc.M110.215152](https://doi.org/10.1074/jbc.M110.215152)"Mitochondrial sirtuins in neurodegeneration" - Front Cell Neurosci (2019) - [DOI:10.3389/fncel.2019.00043](https://doi.org/10.3389/fncel.2019.00043)"SIRT4 in metabolic disease" - Trends Endocrinol Metab (2020) - [DOI:10.1016/j.tem.2020.01.005](https://doi.org/10.1016/j.tem.2020.01.005)
Therapeutic Targeting | Agent | Mechanism | Development Stage | Notes |
Cross-Links
[SIRT4 Protein](/proteins/sirt4-protein)
[SIRT3 Gene](/genes/sirt3)
[Mitochondrial Dysfunction Pathway](/mechanisms/mitochondrial-dysfunction-pathway)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease-disease)
Background The study of Sirt4 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
See Also
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Amyloid Hypothesis](/mechanisms/amyloid-hypothesis)
[Tau Pathology](/mechanisms/tau-pathology)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Alpha-Synuclein](/mechanisms/alpha-synuclein)
External Links
[NCBI Gene: SIRT4](https://www.ncbi.nlm.nih.gov/gene/23127)
[UniProt: Q9Y5R6](https://www.uniprot.org/uniprot/Q9Y5R6)
[OMIM: 604956](https://www.omim.org/entry/604956)
References
[Michishita E et al, (2005) (2005)](https://pubmed.ncbi.nlm.nih.gov/15956768/)
[Ahuja N et al, (2007) (2007)](https://pubmed.ncbi.nlm.nih.gov/17625103/)
[Mathias RA et al, (2014) (2014)](https://pubmed.ncbi.nlm.nih.gov/25468995/)
[Min Z et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/30804771/)
Pathway Diagram The following diagram shows the key molecular relationships involving SIRT4 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)
Show full description