ACSF3

Protein identityUniProt · HPA

UniProt accession

Q4G176

Gene

ACSF3

Ensembl

ENSG00000176715

Chromosome

16

Canonical length

576 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Mitochondria

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

576 residues, UniProt reviewed canonical sequence.

>Q4G176|ACSF3
     1  MLPHVVLTFR RLGCALASCR LAPARHRGSG LLHTAPVARS DRSAPVFTRA LAFGDRIALV
    61  DQHGRHTYRE LYSRSLRLSQ EICRLCGCVG GDLREERVSF LCANDASYVV AQWASWMSGG
   121  VAVPLYRKHP AAQLEYVICD SQSSVVLASQ EYLELLSPVV RKLGVPLLPL TPAIYTGAVE
   181  EPAEVPVPEQ GWRNKGAMII YTSGTTGRPK GVLSTHQNIR AVVTGLVHKW AWTKDDVILH
   241  VLPLHHVHGV VNALLCPLWV GATCVMMPEF SPQQVWEKFL SSETPRINVF MAVPTIYTKL
   301  MEYYDRHFTQ PHAQDFLRAV CEEKIRLMVS GSAALPLPVL EKWKNITGHT LLERYGMTEI
   361  GMALSGPLTT AVRLPGSVGT PLPGVQVRIV SENPQREACS YTIHAEGDER GTKVTPGFEE
   421  KEGELLVRGP SVFREYWNKP EETKSAFTLD GWFKTGDTVV FKDGQYWIRG RTSVDIIKTG
   481  GYKVSALEVE WHLLAHPSIT DVAVIGVPDM TWGQRVTAVV TLREGHSLSH RELKEWARNV
   541  LAPYAVPSEL VLVEEIPRNQ MGKIDKKALI RHFHPS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ACSF3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

35 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ACSF3.

Disease | AllUniProt

Conditions ACSF3 is implicated in, by any mechanism.

• Combined malonic and methylmalonic aciduria (CMAMMA) MIM:614265

Disease | GeneticClinVar

186 pathogenic / likely-pathogenic of 1,113 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Combined malonic and methylmalonic acidemia
• ACSF3-related disorder
• Methylmalonic acidemia
• Inborn genetic diseases
• Sarcoma

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.77

gnomAD pLI

0

gnomAD missense Z

-1.3

DepMap mean gene effect

0.14

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• fatty acid biosynthetic process
• fatty acid metabolic process
• long-chain fatty-acyl-CoA biosynthetic process
• malonate catabolic process

Molecular functions

• ATP binding
• CoA-ligase activity
• very long-chain fatty acid-CoA ligase activity
• malonyl-CoA synthetase activity

Cellular components

• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• AMP-dependent synthetase/ligase domain
• AMP-binding, conserved site
• AMP-binding enzyme, C-terminal domain
• ANL, N-terminal domain
• AMP-binding enzyme domain superfamily
• AMP-binding enzyme
• AMP-binding enzyme C-terminal domain

KeywordsUniProt

• ATP-binding
• Fatty acid metabolism
• Ligase
• Lipid metabolism
• Mitochondrion
• Nucleotide-binding
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of ACSF3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HSPD1