ACSF3 acyl-CoA synthetase family member 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ACSF3provided by HGNC
Official Full Name: acyl-CoA synthetase family member 3provided by HGNC
Primary source: HGNC:HGNC:27288
See related: Ensembl:ENSG00000176715 MIM:614245; AllianceGenome:HGNC:27288
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
Summary: This gene encodes a member of the acyl-CoA synthetase family of enzymes that activate fatty acids by catalyzing the formation of a thioester linkage between fatty acids and coenzyme A. The encoded protein is localized to mitochondria, has high specificity for malonate and methylmalonate and possesses malonyl-CoA synthetase activity. Mutations in this gene are a cause of combined malonic and methylmalonic aciduria. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Sep 2013]
Expression: Ubiquitous expression in duodenum (RPKM 1.5), lymph node (RPKM 1.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16q24.3

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (89093852..89156233)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (95173811..95236254)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (89160260..89222641)

Chromosome 16 - NC_000016.10 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: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Causal ACSF3 mutations were identified in all patients.
Title: Combined malonic and methylmalonic aciduria due to ACSF3 mutations: Benign clinical course in an unselected cohort.
ACSF3 catalyzes the first step of mitochondrial fatty acid biosynthesis (mtFASII). Hypofunctional mtFASII impairs mitochondrial flexibility and lipoylation degree. Defective mtFASII leads to reduced glycolytic flux and upregulation of beta-oxidation.
Title: The emerging role of the mitochondrial fatty-acid synthase (mtFASII) in the regulation of energy metabolism.
ACSF3-derived malonyl-CoA can be used to malonylate lysine residues on proteins within the matrix of mitochondria, possibly adding another regulatory layer to post-translational control of mitochondrial metabolism.
Title: Role of the malonyl-CoA synthetase ACSF3 in mitochondrial metabolism.
an essential role for ACSF3 in dictating the metabolic fate of mitochondrial malonate and malonyl-CoA in mammalian metabolism
Title: The Mammalian Malonyl-CoA Synthetase ACSF3 Is Required for Mitochondrial Protein Malonylation and Metabolic Efficiency.
ACSF3 was significantly upregulated, and was involved in fatty acid and lipid metabolism and accelerated liver injury in alcoholic liver disease.
Title: Analysis of differentially expressed genes and microRNAs in alcoholic liver disease.
data indicate that the CBFA2T3/ACSF3 locus is a novel recurrent oncogenic target of immunoglobulin heavy chain translocations, which might contribute to the pathogenesis of pediatric GC-derived B-cell lymphoma.
Title: The CBFA2T3/ACSF3 locus is recurrently involved in IGH chromosomal translocation t(14;16)(q32;q24) in pediatric B-cell lymphoma with germinal center phenotype.
ACSF3 is a candidate gene for non-classical CMAMMA observed in our patients.
Title: Combined malonic and methylmalonic aciduria: exome sequencing reveals mutations in the ACSF3 gene in patients with a non-classic phenotype.
Mammalian ACSF3 protein is a malonyl-CoA synthetase that supplies the chain extender units for mitochondrial fatty acid synthesis.
Title: Mammalian ACSF3 protein is a malonyl-CoA synthetase that supplies the chain extender units for mitochondrial fatty acid synthesis.
mutations in ACSF3, encoding a putative methylmalonyl-CoA and malonyl-CoA synthetase, were identified as a cause of combined malonic and methylmalonic aciduria.
Title: Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.

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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

Associated conditions

Description	Tests
Combined malonic and methylmalonic acidemia MedGen: C3280314 OMIM: 614265 GeneReviews: Not available	Compare labs

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

RH65209 (e-PCR)
- UniSTS:89140

RH79754 (e-PCR)
- UniSTS:88293

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables acid-thiol ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables malonyl-CoA synthetase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables very long-chain fatty acid-CoA ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables very long-chain fatty acid-CoA ligase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in fatty acid biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in fatty acid biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in fatty acid metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in long-chain fatty-acyl-CoA biosynthetic process	TAS Traceable Author Statement more info
involved_in malonate catabolic process	IDA Inferred from Direct Assay more info	PubMed

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

General protein information

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Preferred Names: malonate--CoA ligase ACSF3, mitochondrial

Names: acyl-CoA synthetase family member 3, mitochondrial; malonyl-CoA synthetase

NP_001120686.1

EC 6.2.1.76

NP_001230208.1

EC 6.2.1.76

NP_001271245.1

EC 6.2.1.76

NP_777577.2

EC 6.2.1.76

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.

Genomic

NG_031961.1 RefSeqGene

Range

5044..67425

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001127214.4 → NP_001120686.1 malonate--CoA ligase ACSF3, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_001120686.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 4 encode the same isoform (1).

Source sequence(s)

AC009113, AK290963, BM148793

Consensus CDS

CCDS10974.1

UniProtKB/Swiss-Prot

A8K4J8, C9JQL6, Q4G176, Q6INA0, Q8N2F7

UniProtKB/TrEMBL

A0A3B3ISK9

Related

ENSP00000384627.3, ENST00000406948.7

Conserved Domains (1) summary

cd05941
Location:55 → 571

MCS; Malonyl-CoA synthetase (MCS)
NM_001243279.3 → NP_001230208.1 malonate--CoA ligase ACSF3, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_001230208.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 4 encode the same isoform (1).

Source sequence(s)

AC009113, AC135782, BC028399, BM148793

Consensus CDS

CCDS10974.1

UniProtKB/Swiss-Prot

A8K4J8, C9JQL6, Q4G176, Q6INA0, Q8N2F7

UniProtKB/TrEMBL

A0A3B3ISK9

Related

ENSP00000479130.1, ENST00000614302.5

Conserved Domains (1) summary

cd05941
Location:55 → 571

MCS; Malonyl-CoA synthetase (MCS)
NM_001284316.2 → NP_001271245.1 malonate--CoA ligase ACSF3, mitochondrial isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two exons, one of which contains a portion of the 5' UTR and the other which contains a portion of the 5' coding region including the start codon, compared to variant 1. These differences cause translation initiation at a downstream start codon and result in an isoform (2) with a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AC009113, BI837487, BM148793, BQ953430, BX325026, BX402632

Consensus CDS

CCDS73926.1

UniProtKB/TrEMBL

F5H5A1, Q6P2C7

Related

ENSP00000367596.4, ENST00000378345.8

Conserved Domains (1) summary

cl17068
Location:1 → 306

AFD_class_I; Adenylate forming domain, Class I superfamily
NM_174917.5 → NP_777577.2 malonate--CoA ligase ACSF3, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_777577.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1). Variants 1, 2 and 4 encode the same isoform (1).

Source sequence(s)

AC009113, AC135782, AK075499, DA062861

Consensus CDS

CCDS10974.1

UniProtKB/Swiss-Prot

A8K4J8, C9JQL6, Q4G176, Q6INA0, Q8N2F7

UniProtKB/TrEMBL

A0A3B3ISK9

Related

ENSP00000320646.4, ENST00000317447.9

Conserved Domains (1) summary

cd05941
Location:55 → 571

MCS; Malonyl-CoA synthetase (MCS)

RNA

NR_045667.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC009113, AK075499, AK096561

Related

ENST00000537116.5
NR_104293.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (7) uses two alternate splice sites, one in the 5' and one in the 3' region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC009113, AC135782, BC072391, BM148793, BX404035, HY100877
NR_147928.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC009113, AC135782
NR_147929.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC009113, AC135782

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_000016.10 Reference GRCh38.p14 Primary Assembly

Range

89093852..89156233

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060940.1 Alternate T2T-CHM13v2.0

Range

95173811..95236254

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NR_045666.1: Suppressed sequence

Description

NR_045666.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.