SIRT4 sirtuin 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SIRT4provided by HGNC
Official Full Name: sirtuin 4provided by HGNC
Primary source: HGNC:HGNC:14932
See related: Ensembl:ENSG00000089163 MIM:604482; AllianceGenome:HGNC:14932
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: SIR2L4
Summary: This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class IV of the sirtuin family. [provided by RefSeq, Jul 2008]
Expression: Broad expression in testis (RPKM 2.4), kidney (RPKM 1.1) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q24.23-q24.31

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (120291780..120313249)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (120277808..120300434)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (120729992..120751052)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Decreased sirtuin 4 levels promote cellular proliferation and invasion in papillary thyroid carcinoma.
Title: Decreased sirtuin 4 levels promote cellular proliferation and invasion in papillary thyroid carcinoma.
SIRT4 promotes neuronal apoptosis in models of Alzheimer's disease via the STAT2-SIRT4-mTOR pathway.
Title: SIRT4 promotes neuronal apoptosis in models of Alzheimer's disease via the STAT2-SIRT4-mTOR pathway.
SIRT3 and SIRT4 double-genes remodeled the mitochondrial network to induce hepatocellular carcinoma cell line differentiation and suppress malignant phenotypes.
Title: SIRT3 and SIRT4 double-genes remodeled the mitochondrial network to induce hepatocellular carcinoma cell line differentiation and suppress malignant phenotypes.
SIRT4 as a novel interactor and candidate suppressor of C-RAF kinase in MAPK signaling.
Title: SIRT4 as a novel interactor and candidate suppressor of C-RAF kinase in MAPK signaling.
SIRT4 is a regulator of human skeletal muscle fatty acid metabolism influencing inner and outer mitochondrial membrane-mediated fusion.
Title: SIRT4 is a regulator of human skeletal muscle fatty acid metabolism influencing inner and outer mitochondrial membrane-mediated fusion.
SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation.
Title: SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation.
The Regulation of GLT-1 Degradation Pathway by SIRT4.
Title: The Regulation of GLT-1 Degradation Pathway by SIRT4.
Sirtuin4 impacts mitochondrial homeostasis in pancreatic cancer cells by reducing the stability of AlkB homolog 1 via deacetylation of the HRD1-SEL1L complex.
Title: Sirtuin4 impacts mitochondrial homeostasis in pancreatic cancer cells by reducing the stability of AlkB homolog 1 via deacetylation of the HRD1-SEL1L complex.
SIRT4 in ageing.
Title: SIRT4 in ageing.
Sirtuin 4 activates autophagy and inhibits tumorigenesis by upregulating the p53 signaling pathway.
Title: Sirtuin 4 activates autophagy and inhibits tumorigenesis by upregulating the p53 signaling pathway.

Submit: New GeneRIF Correction See all GeneRIFs (53)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:489829

RH46443 (e-PCR)
- UniSTS:89331

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables NAD+ binding	IBA Inferred from Biological aspect of Ancestor more info
enables NAD+ binding	IEA Inferred from Electronic Annotation more info
enables NAD+-protein ADP-ribosyltransferase activity	TAS Traceable Author Statement more info	PubMed
enables NAD+-protein poly-ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD+-protein poly-ADP-ribosyltransferase activity	TAS Traceable Author Statement more info	PubMed
enables NAD+-protein-cysteine ADP-ribosyltransferase activity	IEA Inferred from Electronic Annotation more info
enables NAD-dependent protein biotinidase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD-dependent protein lipoamidase activity	IDA Inferred from Direct Assay more info	PubMed
NOT enables NAD-dependent protein lysine deacetylase activity	IDA Inferred from Direct Assay more info	PubMed
enables histone deacetylase activity, NAD-dependent	IBA Inferred from Biological aspect of Ancestor more info
enables lipoamidase activity	IEA Inferred from Electronic Annotation more info
enables nucleotidyltransferase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in DNA damage response	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in glutamine metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in mitochondrion organization	TAS Traceable Author Statement more info
involved_in negative regulation of cardiac muscle cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of fatty acid oxidation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of fatty acid oxidation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of insulin secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein processing involved in protein targeting to mitochondrion	IEA Inferred from Electronic Annotation more info
involved_in peptidyl-lysine deacetylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of lipid biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of glutamine family amino acid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of pyruvate dehydrogenase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in tricarboxylic acid metabolic process	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in mitochondrial inner membrane	IEA Inferred from Electronic Annotation more info
is_active_in mitochondrial matrix	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrial matrix	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: NAD-dependent protein lipoamidase sirtuin-4, mitochondrial

Names: NAD-dependent ADP-ribosyltransferase sirtuin-4; NAD-dependent protein biotinylase sirtuin-4; NAD-dependent protein deacetylase sirtuin-4; SIR2-like protein 4; regulatory protein SIR2 homolog 4; sir2-like 4; sirtuin type 4

NP_001372662.1

EC 2.3.1.286

NP_001372663.1

EC 2.3.1.286

NP_001372664.1

EC 2.3.1.286

NP_036372.1

EC 2.3.1.286

XP_006719372.1

EC 2.3.1.286

XP_054227554.1

EC 2.3.1.286

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001385733.2 → NP_001372662.1 NAD-dependent protein lipoamidase sirtuin-4, mitochondrial isoform 1

Status: REVIEWED

Source sequence(s)

AC003982, AC004263

Consensus CDS

CCDS9194.1

UniProtKB/Swiss-Prot

O43346, Q32M33, Q9Y6E7

Conserved Domains (1) summary

cd01409
Location:47 → 308

SIRT4; Eukaryotic and prokaryotic group (class2) which includes human sirtuin SIRT4 and several bacterial homologs; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone ...
NM_001385734.1 → NP_001372663.1 NAD-dependent protein lipoamidase sirtuin-4, mitochondrial isoform 2

Status: REVIEWED

Source sequence(s)

AC003982

Conserved Domains (1) summary

cl00195
Location:47 → 217

SIR2; SIR2 superfamily of proteins includes silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation, where the acetyl group from the lysine epsilon-amino group is transferred to the ADP-ribose moiety of NAD+, ...
NM_001385735.2 → NP_001372664.1 NAD-dependent protein lipoamidase sirtuin-4, mitochondrial isoform 2

Status: REVIEWED

Source sequence(s)

AC003982, AC004263

Conserved Domains (1) summary

cl00195
Location:47 → 217

SIR2; SIR2 superfamily of proteins includes silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation, where the acetyl group from the lysine epsilon-amino group is transferred to the ADP-ribose moiety of NAD+, ...
NM_012240.3 → NP_036372.1 NAD-dependent protein lipoamidase sirtuin-4, mitochondrial isoform 1

See identical proteins and their annotated locations for NP_036372.1

Status: REVIEWED

Source sequence(s)

AC003982

Consensus CDS

CCDS9194.1

UniProtKB/Swiss-Prot

O43346, Q32M33, Q9Y6E7

Related

ENSP00000202967.4, ENST00000202967.4

Conserved Domains (1) summary

cd01409
Location:47 → 308

SIRT4; Eukaryotic and prokaryotic group (class2) which includes human sirtuin SIRT4 and several bacterial homologs; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

120291780..120313249

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006719309.5 → XP_006719372.1 NAD-dependent protein lipoamidase sirtuin-4, mitochondrial isoform X1

See identical proteins and their annotated locations for XP_006719372.1

UniProtKB/Swiss-Prot

O43346, Q32M33, Q9Y6E7

Conserved Domains (1) summary

cd01409
Location:47 → 308

SIRT4; Eukaryotic and prokaryotic group (class2) which includes human sirtuin SIRT4 and several bacterial homologs; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone ...