Sirt4 Protein 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-protein"> [@du2011] <div class="infobox-header">SIRT4</div> [@csibi2013] <div class="infobox-content">
Protein Name: Sirtuin 4 (Mitochondrial)<br>
Gene: SIRT4<br>
UniProt ID: Q9Y5R6<br>
PDB Structures: 3RJR, 4IG0<br>
Molecular Weight: 35 kDa<br>
Subcellular Localization: Mitochondria matrix<br>
Protein Family: Sirtuin family (Class III deacetylases) </div> </div>
Overview
SIRT4 (Sirtuin 4) is a mitochondrial NAD+-dependent enzyme that primarily functions as an ADP-ribosyltransferase, with weaker deacetylation activity. It is one of three mitochondrial sirtuins (SIRT3, SIRT4, SIRT5) that regulate mitochondrial metabolism and function. SIRT4 plays important roles in metabolic regulation, insulin secretion, tumor suppression, and is increasingly studied in the context of neurodegeneration.
Structure
SIRT4 contains the conserved sirtuin core domain with:
Rossmann-fold NAD+-binding domain: Characteristic of sirtuin family
Small domain: Involved in substrate binding
Catalytic core: His and Asp residues for ADP-ribosylation
N-terminal mitochondrial targeting sequence: Directs import to mitochondria
The crystal structure reveals a unique substrate-binding pocket that accommodates ADP-ribosylation substrates.
Normal Function
...
SIRT4 Protein
Introduction
Sirt4 Protein 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-protein"> [@du2011] <div class="infobox-header">SIRT4</div> [@csibi2013] <div class="infobox-content">
Protein Name: Sirtuin 4 (Mitochondrial)<br>
Gene: SIRT4<br>
UniProt ID: Q9Y5R6<br>
PDB Structures: 3RJR, 4IG0<br>
Molecular Weight: 35 kDa<br>
Subcellular Localization: Mitochondria matrix<br>
Protein Family: Sirtuin family (Class III deacetylases) </div> </div>
Overview
SIRT4 (Sirtuin 4) is a mitochondrial NAD+-dependent enzyme that primarily functions as an ADP-ribosyltransferase, with weaker deacetylation activity. It is one of three mitochondrial sirtuins (SIRT3, SIRT4, SIRT5) that regulate mitochondrial metabolism and function. SIRT4 plays important roles in metabolic regulation, insulin secretion, tumor suppression, and is increasingly studied in the context of neurodegeneration.
Structure
SIRT4 contains the conserved sirtuin core domain with:
Rossmann-fold NAD+-binding domain: Characteristic of sirtuin family
Small domain: Involved in substrate binding
Catalytic core: His and Asp residues for ADP-ribosylation
N-terminal mitochondrial targeting sequence: Directs import to mitochondria
The crystal structure reveals a unique substrate-binding pocket that accommodates ADP-ribosylation substrates.
Normal Function
ADP-Ribosylation
SIRT4's primary enzymatic activity is ADP-ribosylation:
Transfers ADP-ribose from NAD+ to target proteins
GDH (glutamate dehydrogenase) is a major substrate
The study of Sirt4 Protein 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.