Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P28330 (ACADL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Long-chain specific acyl-CoA dehydrogenase, mitochondrial

Short name=LCAD
EC=1.3.8.8
Gene names
Name:ACADL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length430 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Catalytic activity

Long-chain-acyl-CoA + electron-transfer flavoprotein = long-chain-2,3-dehydroacyl-CoA + reduced electron-transfer flavoprotein.

Cofactor

FAD.

Pathway

Lipid metabolism; mitochondrial fatty acid beta-oxidation.

Subunit structure

Homotetramer.

Subcellular location

Mitochondrion matrix.

Post-translational modification

Acetylation at Lys-318 and Lys-322 in proximity of the cofactor-binding sites strongly reduces catalytic activity. These sites are deacetylated by SIRT3 By similarity.

Involvement in disease

Acyl-CoA dehydrogenase very long-chain deficiency (ACADVLD) [MIM:201475]: An inborn error of mitochondrial fatty acid beta-oxidation which leads to impaired long-chain fatty acid beta-oxidation. It is clinically heterogeneous, with three major phenotypes: a severe childhood form characterized by early onset, high mortality and high incidence of cardiomyopathy; a milder childhood form with later onset, characterized by hypoketotic hypoglycemia, low mortality and rare cardiomyopathy; an adult form, with isolated skeletal muscle involvement, rhabdomyolysis and myoglobinuria, usually triggered by exercise or fasting.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Miscellaneous

A number of straight-chain acyl-CoA dehydrogenases of different substrate specificities are present in mammalian tissues.

Sequence similarities

Belongs to the acyl-CoA dehydrogenase family.

Ontologies

Keywords
   Biological processFatty acid metabolism
Lipid metabolism
   Cellular componentMitochondrion
   Coding sequence diversityPolymorphism
   DomainTransit peptide
   LigandFAD
Flavoprotein
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcarnitine catabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

carnitine metabolic process, CoA-linked

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular lipid catabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular lipid metabolic process

Traceable author statement. Source: Reactome

fatty acid beta-oxidation

Traceable author statement. Source: Reactome

fatty acid beta-oxidation using acyl-CoA dehydrogenase

Inferred from sequence or structural similarity. Source: BHF-UCL

long-chain fatty acid catabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of fatty acid biosynthetic process

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of fatty acid oxidation

Inferred from sequence or structural similarity. Source: BHF-UCL

oxidation-reduction process

Inferred from sequence or structural similarity. Source: BHF-UCL

protein homotetramerization

Inferred from electronic annotation. Source: Ensembl

regulation of cholesterol metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

small molecule metabolic process

Traceable author statement. Source: Reactome

temperature homeostasis

Inferred from sequence or structural similarity. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

mitochondrial matrix

Traceable author statement. Source: Reactome

mitochondrial membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from direct assay. Source: HPA

   Molecular_functionacyl-CoA dehydrogenase activity

Traceable author statement. Source: Reactome

fatty-acyl-CoA binding

Inferred from electronic annotation. Source: Ensembl

flavin adenine dinucleotide binding

Inferred from electronic annotation. Source: Ensembl

long-chain-acyl-CoA dehydrogenase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

palmitoyl-CoA oxidase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3030Mitochondrion
Chain31 – 430400Long-chain specific acyl-CoA dehydrogenase, mitochondrial
PRO_0000000509

Amino acid modifications

Modified residue421N6-acetyllysine By similarity
Modified residue661N6-acetyllysine; alternate By similarity
Modified residue661N6-succinyllysine; alternate By similarity
Modified residue811N6-acetyllysine; alternate By similarity
Modified residue811N6-succinyllysine; alternate By similarity
Modified residue921N6-acetyllysine By similarity
Modified residue951N6-acetyllysine By similarity
Modified residue1651N6-succinyllysine By similarity
Modified residue2401N6-succinyllysine By similarity
Modified residue2541N6-acetyllysine; alternate By similarity
Modified residue2541N6-succinyllysine; alternate By similarity
Modified residue2791N6-acetyllysine; alternate By similarity
Modified residue2791N6-succinyllysine; alternate By similarity
Modified residue3181N6-acetyllysine By similarity
Modified residue3221N6-acetyllysine; alternate By similarity
Modified residue3221N6-succinyllysine; alternate By similarity
Modified residue3581N6-acetyllysine By similarity

Natural variations

Natural variant3031S → T. Ref.7
Corresponds to variant rs1801204 [ dbSNP | Ensembl ].
VAR_000328
Natural variant3331K → Q. Ref.3 Ref.7
Corresponds to variant rs2286963 [ dbSNP | Ensembl ].
VAR_000329

Sequences

Sequence LengthMass (Da)Tools
P28330 [UniParc].

Last modified February 10, 2009. Version 2.
Checksum: 72F9803685406DF9

FASTA43047,656
        10         20         30         40         50         60 
MAARLLRGSL RVLGGHRAPR QLPAARCSHS GGEERLETPS AKKLTDIGIR RIFSPEHDIF 

        70         80         90        100        110        120 
RKSVRKFFQE EVIPHHSEWE KAGEVSREVW EKAGKQGLLG VNIAEHLGGI GGDLYSAAIV 

       130        140        150        160        170        180 
WEEQAYSNCS GPGFSIHSGI VMSYITNHGS EEQIKHFIPQ MTAGKCIGAI AMTEPGAGSD 

       190        200        210        220        230        240 
LQGIKTNAKK DGSDWILNGS KVFISNGSLS DVVIVVAVTN HEAPSPAHGI SLFLVENGMK 

       250        260        270        280        290        300 
GFIKGRKLHK MGLKAQDTAE LFFEDIRLPA SALLGEENKG FYYIMKELPQ ERLLIADVAI 

       310        320        330        340        350        360 
SASEFMFEET RNYVKQRKAF GKTVAHLQTV QHKLAELKTH ICVTRAFVDN CLQLHEAKRL 

       370        380        390        400        410        420 
DSATACMAKY WASELQNSVA YDCVQLHGGW GYMWEYPIAK AYVDARVQPI YGGTNEIMKE 

       430 
LIAREIVFDK 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and nucleotide sequence of cDNAs encoding human long-chain acyl-CoA dehydrogenase and assignment of the location of its gene (ACADL) to chromosome 2."
Indo Y., Yang-Feng T., Glassberg R., Tanaka K.
Genomics 11:609-620(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]Erratum
Indo Y., Yang-Feng T., Glassberg R., Tanaka K.
Genomics 12:626-626(1992) [PubMed] [Europe PMC] [Abstract]
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-333.
Tissue: Brain.
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain and Colon.
[7]"The molecular basis of human long chain acyl-CoA dehydrogenase deficiency."
Kelly D., Ogden M., Hale D., Hainline B., Strauss A.
Am. J. Hum. Genet. 49:409-409(1991)
Cited for: VARIANTS THR-303 AND GLN-333.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M74096 mRNA. Translation: AAA51565.1.
AK313498 mRNA. Translation: BAG36280.1.
AC006994 Genomic DNA. Translation: AAY14881.1.
CH471063 Genomic DNA. Translation: EAW70481.1.
BC039063 mRNA. Translation: AAH39063.1.
BC064549 mRNA. Translation: AAH64549.1.
CCDSCCDS2389.1.
PIRA40559.
RefSeqNP_001599.1. NM_001608.3.
UniGeneHs.471277.

3D structure databases

ProteinModelPortalP28330.
SMRP28330. Positions 51-426.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106551. 2 interactions.
STRING9606.ENSP00000233710.

PTM databases

PhosphoSiteP28330.

Polymorphism databases

DMDM223590148.

Proteomic databases

MaxQBP28330.
PaxDbP28330.
PRIDEP28330.

Protocols and materials databases

DNASU33.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000233710; ENSP00000233710; ENSG00000115361.
GeneID33.
KEGGhsa:33.
UCSCuc002vdz.4. human.

Organism-specific databases

CTD33.
GeneCardsGC02M211052.
HGNCHGNC:88. ACADL.
HPAHPA010611.
HPA011990.
MIM201475. phenotype.
609576. gene.
neXtProtNX_P28330.
Orphanet99900. Long chain acyl-CoA dehydrogenase deficiency.
PharmGKBPA24424.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1960.
HOGENOMHOG000131659.
HOVERGENHBG104903.
InParanoidP28330.
KOK00255.
OMAYMWEYPV.
OrthoDBEOG77126W.
PhylomeDBP28330.
TreeFamTF105054.

Enzyme and pathway databases

BioCycMetaCyc:HS03876-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP28330.
UniPathwayUPA00660.

Gene expression databases

ArrayExpressP28330.
BgeeP28330.
CleanExHS_ACADL.
GenevestigatorP28330.

Family and domain databases

Gene3D1.10.540.10. 1 hit.
2.40.110.10. 1 hit.
InterProIPR006089. Acyl-CoA_DH_CS.
IPR006091. Acyl-CoA_Oxase/DH_cen-dom.
IPR009075. AcylCo_DH/oxidase_C.
IPR013786. AcylCoA_DH/ox_N.
IPR009100. AcylCoA_DH/oxidase_NM_dom.
[Graphical view]
PfamPF00441. Acyl-CoA_dh_1. 1 hit.
PF02770. Acyl-CoA_dh_M. 1 hit.
PF02771. Acyl-CoA_dh_N. 1 hit.
[Graphical view]
SUPFAMSSF47203. SSF47203. 1 hit.
SSF56645. SSF56645. 1 hit.
PROSITEPS00072. ACYL_COA_DH_1. 1 hit.
PS00073. ACYL_COA_DH_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi33.
NextBio127.
PROP28330.
SOURCESearch...

Entry information

Entry nameACADL_HUMAN
AccessionPrimary (citable) accession number: P28330
Secondary accession number(s): B2R8T3, Q8IUN8
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: February 10, 2009
Last modified: July 9, 2014
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM