Human Gene ACSF3 (uc021tmq.1) Description and Page Index
  Description: Homo sapiens acyl-CoA synthetase family member 3 (ACSF3), nuclear gene encoding mitochondrial protein, transcript variant 4, mRNA.
RefSeq Summary (NM_001243279): 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].
Transcript (Including UTRs)
   Position: hg19 chr16:89,160,217-89,222,171 Size: 61,955 Total Exon Count: 11 Strand: +
Coding Region
   Position: hg19 chr16:89,167,090-89,220,615 Size: 53,526 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr16:89,160,217-89,222,171)mRNA (may differ from genome)Protein (576 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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H-INVHGNCLynxMGIneXtProtOMIM
PubMedReactomeStanford SOURCETreefamUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: ACSF3_HUMAN
DESCRIPTION: RecName: Full=Acyl-CoA synthetase family member 3, mitochondrial; EC=6.2.1.-; Flags: Precursor;
FUNCTION: Catalyzes the initial reaction in intramitochondrial fatty acid synthesis, by activating malonate and methylmalonate, but not acetate, into their respective CoA thioester. May have some preference toward very-long-chain substrates.
SUBCELLULAR LOCATION: Mitochondrion.
DISEASE: Defects in ACSF3 are the cause of combined malonic and methylmalonic aciduria (CMAMMA) [MIM:614265]. A metabolic disease characterized by malonic and methylmalonic aciduria, with urinary excretion of much larger amounts of methylmalonic acid than malonic acid, in the presence of normal malonyl-CoA decarboxylase activity. Clinical features include coma, ketoacidosis, hypoglycemia, failure to thrive, microcephaly, dystonia, axial hypotonia and/or developmental delay, and neurologic manifestations including seizures, psychiatric disease and/or cognitive decline.
SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
SEQUENCE CAUTION: Sequence=AAH72391.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): ACSF3
CDC HuGE Published Literature: ACSF3
Positive Disease Associations: Hemoglobin A, Glycosylated
Related Studies:
  1. Hemoglobin A, Glycosylated
    Andrew D Paterson et al. Diabetes 2010, A genome-wide association study identifies a novel major locus for glycemic control in type 1 diabetes, as measured by both A1C and glucose., Diabetes. [PubMed 19875614]
    A major locus for A1C and glucose in individuals with diabetes is near SORCS1. This may influence the design and analysis of genetic studies attempting to identify risk factors for long-term diabetic complications.

-  MalaCards Disease Associations
  MalaCards Gene Search: ACSF3
Diseases sorted by gene-association score: combined malonic and methylmalonic aciduria* (1693)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 6.75 RPKM in Adrenal Gland
Total median expression: 179.85 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -176.86381-0.464 Picture PostScript Text
3' UTR -634.811556-0.408 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR020845 - AMP-binding_CS
IPR000873 - AMP-dep_Synth/Lig

Pfam Domains:
PF00501 - AMP-binding enzyme
PF13193 - AMP-binding enzyme C-terminal domain

SCOP Domains:
56801 - Acetyl-CoA synthetase-like

ModBase Predicted Comparative 3D Structure on Q4G176
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003824 catalytic activity
GO:0005524 ATP binding
GO:0016874 ligase activity
GO:0016878 acid-thiol ligase activity
GO:0031957 very long-chain fatty acid-CoA ligase activity
GO:0090409 malonyl-CoA synthetase activity

Biological Process:
GO:0006629 lipid metabolic process
GO:0006631 fatty acid metabolic process
GO:0006633 fatty acid biosynthetic process
GO:0008152 metabolic process
GO:0035338 long-chain fatty-acyl-CoA biosynthetic process
GO:0090410 malonate catabolic process

Cellular Component:
GO:0005739 mitochondrion
GO:0005759 mitochondrial matrix


-  Descriptions from all associated GenBank mRNAs
  BC028399 - Homo sapiens acyl-CoA synthetase family member 3, mRNA (cDNA clone MGC:33480 IMAGE:4812335), complete cds.
AK290963 - Homo sapiens cDNA FLJ77772 complete cds.
BC064609 - Homo sapiens acyl-CoA synthetase family member 3, mRNA (cDNA clone IMAGE:5548791), partial cds.
BC072391 - Homo sapiens acyl-CoA synthetase family member 3, mRNA (cDNA clone MGC:90152 IMAGE:5728307), complete cds.
AK075499 - Homo sapiens cDNA PSEC0197 fis, clone HEMBA1001490, weakly similar to PEROXISOMAL-COENZYME A SYNTHETASE (EC 6.-.-.-).
JD173333 - Sequence 154357 from Patent EP1572962.
JD117400 - Sequence 98424 from Patent EP1572962.
JD435760 - Sequence 416784 from Patent EP1572962.
JD554876 - Sequence 535900 from Patent EP1572962.
JD256485 - Sequence 237509 from Patent EP1572962.
KJ900400 - Synthetic construct Homo sapiens clone ccsbBroadEn_09794 ACSF3 gene, encodes complete protein.
JD373851 - Sequence 354875 from Patent EP1572962.
AK096561 - Homo sapiens cDNA FLJ39242 fis, clone OCBBF2008138.
JD205880 - Sequence 186904 from Patent EP1572962.
AK098113 - Homo sapiens cDNA FLJ40794 fis, clone TRACH2007676.
JD128713 - Sequence 109737 from Patent EP1572962.
JD444925 - Sequence 425949 from Patent EP1572962.
JD202667 - Sequence 183691 from Patent EP1572962.
JD057287 - Sequence 38311 from Patent EP1572962.
JD260650 - Sequence 241674 from Patent EP1572962.
JD064993 - Sequence 46017 from Patent EP1572962.
JD547946 - Sequence 528970 from Patent EP1572962.
JD473190 - Sequence 454214 from Patent EP1572962.
JD371073 - Sequence 352097 from Patent EP1572962.
JD533613 - Sequence 514637 from Patent EP1572962.
JD200701 - Sequence 181725 from Patent EP1572962.
JD432151 - Sequence 413175 from Patent EP1572962.
JD560198 - Sequence 541222 from Patent EP1572962.
JD141645 - Sequence 122669 from Patent EP1572962.
JD126787 - Sequence 107811 from Patent EP1572962.
JD513844 - Sequence 494868 from Patent EP1572962.
JD114159 - Sequence 95183 from Patent EP1572962.
JD345023 - Sequence 326047 from Patent EP1572962.
JD061492 - Sequence 42516 from Patent EP1572962.
JD475025 - Sequence 456049 from Patent EP1572962.
JD392912 - Sequence 373936 from Patent EP1572962.
JD064868 - Sequence 45892 from Patent EP1572962.
JD403179 - Sequence 384203 from Patent EP1572962.
JD225240 - Sequence 206264 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q4G176 (Reactome details) participates in the following event(s):

R-HSA-5696007 ACSF3 ligates CoA-SH to VLCFA
R-HSA-75876 Synthesis of very long-chain fatty acyl-CoAs
R-HSA-75105 Fatty acyl-CoA biosynthesis
R-HSA-8978868 Fatty acid metabolism
R-HSA-556833 Metabolism of lipids
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: A8K4J8, ACSF3_HUMAN, C9JQL6, NM_001243279, NP_777577, PSEC0197, Q4G176, Q6INA0, Q8N2F7
UCSC ID: uc021tmq.1
RefSeq Accession: NM_001243279
Protein: Q4G176 (aka ACSF3_HUMAN)
CCDS: CCDS10974.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001243279.1
exon count: 11CDS single in 3' UTR: no RNA size: 3668
ORF size: 1731CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3167.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.