Human Gene ACADVL (uc002gev.4) Description and Page Index
  Description: Homo sapiens acyl-CoA dehydrogenase, very long chain (ACADVL), nuclear gene encoding mitochondrial protein, transcript variant 1, mRNA.
RefSeq Summary (NM_000018): The protein encoded by this gene is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr17:7,123,150-7,128,586 Size: 5,437 Total Exon Count: 20 Strand: +
Coding Region
   Position: hg19 chr17:7,123,304-7,128,416 Size: 5,113 Coding Exon Count: 20 

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

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:7,123,150-7,128,586)mRNA (may differ from genome)Protein (655 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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neXtProtOMIMPubMedReactomeStanford SOURCEUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: ACADV_HUMAN
DESCRIPTION: RecName: Full=Very long-chain specific acyl-CoA dehydrogenase, mitochondrial; Short=VLCAD; EC=1.3.8.9; Flags: Precursor;
FUNCTION: Active toward esters of long-chain and very long chain fatty acids such as palmitoyl-CoA, mysritoyl-CoA and stearoyl-CoA. Can accommodate substrate acyl chain lengths as long as 24 carbons, but shows little activity for substrates of less than 12 carbons.
CATALYTIC ACTIVITY: A very-long-chain acyl-CoA + electron-transfer flavoprotein = a very-long-chain trans-2,3-dehydroacyl-CoA + reduced electron-transfer flavoprotein.
COFACTOR: FAD.
PATHWAY: Lipid metabolism; mitochondrial fatty acid beta- oxidation.
SUBUNIT: Homodimer.
SUBCELLULAR LOCATION: Mitochondrion inner membrane.
DISEASE: Defects in ACADVL are the cause of acyl-CoA dehydrogenase very long chain deficiency (ACADVLD) [MIM:201475]. ACADVLD is an autosomal recessive disease which leads to impaired long-chain fatty acid beta-oxidation. It is clinically heterogeneous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyopathy; a milder childhood form, with later onset, usually with hypoketotic hypoglycemia as the main presenting feature, low mortality, and rare cardiomyopathy; and an adult form, with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, usually triggered by exercise or fasting.
MISCELLANEOUS: A number of straight-chain acyl-CoA dehydrogenases of different substrate specificities are present in mammalian tissues.
SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ACADVL";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): ACADVL
CDC HuGE Published Literature: ACADVL

-  MalaCards Disease Associations
  MalaCards Gene Search: ACADVL
Diseases sorted by gene-association score: vlcad deficiency* (1679), pericardial effusion (19), acyl-coa dehydrogenase, medium chain, deficiency of (15), carnitine palmitoyltransferase ii deficiency (15), 3-hydroxyacyl-coa dehydrogenase deficiency (11), hypoglycemia (10), myoglobinuria recurrent (10), myoglobinuria (8), fatty acid oxidation disorders (8), cardiomyopathy (6), vitamin b12 deficiency (6), ventricular tachycardia, catecholaminergic polymorphic, 1 (3), myopathy (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  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: 463.95 RPKM in Adrenal Gland
Total median expression: 8555.62 RPKM



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

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -66.70154-0.433 Picture PostScript Text
3' UTR -46.60170-0.274 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
IPR006089 - Acyl-CoA_DH_CS
IPR006092 - Acyl-CoA_DH_N
IPR006090 - Acyl-CoA_Oxase/DH_1
IPR006091 - Acyl-CoA_Oxase/DH_cen-dom
IPR009075 - AcylCo_DH/oxidase_C
IPR013786 - AcylCoA_DH/ox_N
IPR009100 - AcylCoA_DH/oxidase

Pfam Domains:
PF00441 - Acyl-CoA dehydrogenase, C-terminal domain
PF02770 - Acyl-CoA dehydrogenase, middle domain
PF02771 - Acyl-CoA dehydrogenase, N-terminal domain
PF08028 - Acyl-CoA dehydrogenase, C-terminal domain

SCOP Domains:
47203 - Acyl-CoA dehydrogenase C-terminal domain-like
56645 - Acyl-CoA dehydrogenase NM domain-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help

2UXW
- X-ray MuPIT

3B96
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P49748
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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 orthologGenome BrowserGenome BrowserGenome BrowserNo orthologNo ortholog
 Gene Details Gene Details  
 Gene Sorter Gene Sorter  
 RGDEnsemblFlyBase  
 Protein SequenceProtein SequenceProtein Sequence  
 AlignmentAlignmentAlignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003995 acyl-CoA dehydrogenase activity
GO:0004466 long-chain-acyl-CoA dehydrogenase activity
GO:0016491 oxidoreductase activity
GO:0016627 oxidoreductase activity, acting on the CH-CH group of donors
GO:0050660 flavin adenine dinucleotide binding

Biological Process:
GO:0001659 temperature homeostasis
GO:0006629 lipid metabolic process
GO:0006631 fatty acid metabolic process
GO:0006635 fatty acid beta-oxidation
GO:0009062 fatty acid catabolic process
GO:0009409 response to cold
GO:0015980 energy derivation by oxidation of organic compounds
GO:0030855 epithelial cell differentiation
GO:0033539 fatty acid beta-oxidation using acyl-CoA dehydrogenase
GO:0036498 IRE1-mediated unfolded protein response
GO:0045717 negative regulation of fatty acid biosynthetic process
GO:0046322 negative regulation of fatty acid oxidation
GO:0055114 oxidation-reduction process
GO:0090181 regulation of cholesterol metabolic process

Cellular Component:
GO:0005634 nucleus
GO:0005730 nucleolus
GO:0005739 mitochondrion
GO:0005743 mitochondrial inner membrane
GO:0005759 mitochondrial matrix
GO:0005829 cytosol
GO:0016020 membrane
GO:0031966 mitochondrial membrane
GO:0042645 mitochondrial nucleoid


-  Descriptions from all associated GenBank mRNAs
  AK293549 - Homo sapiens cDNA FLJ55801 complete cds, highly similar to Very-long-chain specific acyl-CoAdehydrogenase, mitochondrial precursor (EC 1.3.99.-).
AK097243 - Homo sapiens cDNA FLJ39924 fis, clone SPLEN2021057, highly similar to ACYL-COA DEHYDROGENASE, VERY-LONG-CHAIN SPECIFIC, MITOCHONDRIAL PRECURSOR (EC 1.3.99.-).
AK293537 - Homo sapiens cDNA FLJ56425 complete cds, highly similar to Very-long-chain specific acyl-CoAdehydrogenase, mitochondrial precursor (EC 1.3.99.-).
AK056956 - Homo sapiens cDNA FLJ32394 fis, clone SKMUS2000078, highly similar to Very-long-chain specific acyl-CoA dehydrogenase, mitochondrial precursor (EC 1.3.99.-).
AK302653 - Homo sapiens cDNA FLJ58866 complete cds, highly similar to Very-long-chain specific acyl-CoAdehydrogenase, mitochondrial precursor (EC 1.3.99.-).
BC012912 - Homo sapiens acyl-Coenzyme A dehydrogenase, very long chain, mRNA (cDNA clone MGC:21196 IMAGE:4471040), complete cds.
X86556 - H.sapiens HVLCAD gene.
BC000399 - Homo sapiens acyl-Coenzyme A dehydrogenase, very long chain, mRNA (cDNA clone MGC:8529 IMAGE:2822593), complete cds.
JD195755 - Sequence 176779 from Patent EP1572962.
BC020218 - Homo sapiens acyl-Coenzyme A dehydrogenase, very long chain, mRNA (cDNA clone MGC:31908 IMAGE:5090104), complete cds.
AK056083 - Homo sapiens cDNA FLJ31521 fis, clone NT2RI2000255, highly similar to Very-long-chain specific acyl-CoAdehydrogenase, mitochondrial precursor (EC 1.3.99.-).
AK222518 - Homo sapiens mRNA for acyl-Coenzyme A dehydrogenase, very long chain precursor variant, clone: adSE00281.
AK058109 - Homo sapiens cDNA FLJ25380 fis, clone TST02157, highly similar to ACYL-COA DEHYDROGENASE, VERY-LONG-CHAIN SPECIFIC, MITOCHONDRIAL PRECURSOR (EC 1.3.99.-).
D43682 - Homo sapiens VLACD mRNA for very-long-chain acyl-CoA dehydrogenase, complete cds.
AB527421 - Synthetic construct DNA, clone: pF1KB5446, Homo sapiens ACADVL gene for acyl-Coenzyme A dehydrogenase, very long chain, without stop codon, in Flexi system.
KJ890613 - Synthetic construct Homo sapiens clone ccsbBroadEn_00007 ACADVL gene, encodes complete protein.
JD027692 - Sequence 8716 from Patent EP1572962.
JD404559 - Sequence 385583 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00071 - Fatty acid metabolism
hsa01100 - Metabolic pathways

BioCyc Knowledge Library
FAO-PWY - fatty acid β-oxidation I

Reactome (by CSHL, EBI, and GO)

Protein P49748 (Reactome details) participates in the following event(s):

R-HSA-77299 palmitoyl-CoA+FAD<=>trans-Hexadec-2-enoyl-CoA+FADH2
R-HSA-381038 XBP1(S) activates chaperone genes
R-HSA-381070 IRE1alpha activates chaperones
R-HSA-77305 Beta oxidation of palmitoyl-CoA to myristoyl-CoA
R-HSA-381119 Unfolded Protein Response (UPR)
R-HSA-77286 mitochondrial fatty acid beta-oxidation of saturated fatty acids
R-HSA-392499 Metabolism of proteins
R-HSA-77289 Mitochondrial Fatty Acid Beta-Oxidation
R-HSA-8978868 Fatty acid metabolism
R-HSA-556833 Metabolism of lipids
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: ACADV_HUMAN, NM_000018, NP_001257377, O76056, P49748, Q8WUL0, uc002gev.3, VLCAD
UCSC ID: uc002gev.4
RefSeq Accession: NM_000018
Protein: P49748 (aka ACADV_HUMAN or ACDV_HUMAN)
CCDS: CCDS11090.1, CCDS42249.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene ACADVL:
vlcad (Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000018.3
exon count: 20CDS single in 3' UTR: no RNA size: 2296
ORF size: 1968CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 4261.00frame shift in genome: no % Coverage: 99.83
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
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.