P28330 (ACADL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Long-chain specific acyl-CoA dehydrogenase, mitochondrial
Short name=LCAD
EC=1.3.99.13

Gene names

Name:

ACADL

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	430 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Catalytic activity	Acyl-CoA + acceptor = 2,3-dehydroacyl-CoA + reduced acceptor.
Cofactor	FAD.
Pathway	Lipid metabolism; mitochondrial fatty acid beta-oxidation.
Subunit structure	Homotetramer.
Subcellular location	Mitochondrion matrix.
Involvement in disease	Defects in ACADL are a cause of 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.
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 process	Fatty acid metabolism Lipid metabolism
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transit peptide
Ligand	FAD Flavoprotein
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	carnitine 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 fatty acid beta-oxidation using acyl-CoA dehydrogenase Inferred from sequence or structural similarity. Source: BHF-UCL 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 regulation of cholesterol metabolic process Inferred from sequence or structural similarity. Source: BHF-UCL temperature homeostasis Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular function	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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 30	30	Mitochondrion
	Chain	31 – 430	400	Long-chain specific acyl-CoA dehydrogenase, mitochondrial		PRO_0000000509
Natural variations
	Natural variant	303	1	S → T. Ref.7 Corresponds to variant rs1801204 [ dbSNP | Ensembl ].		VAR_000328
	Natural variant	333	1	K → Q. Ref.3 Ref.7 Corresponds to variant rs2286963 [ dbSNP | Ensembl ].		VAR_000329

Sequences

	Sequence		Length	Mass (Da)
	P28330 [UniParc]. Last modified February 10, 2009. Version 2. Checksum: 72F9803685406DF9	FASTA	430	47,656
	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

References

	« Hide 'large scale' referencesShow '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: 1774065] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Erratum Indo Y., Yang-Feng T., Glassberg R., Tanaka K. Genomics 12:626-626(1992) [PubMed: 1559716] [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. , 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: 14702039] [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. , 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: 15815621] [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. , 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: 15489334] [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.
IPI	IPI00292695.
PIR	A40559.
RefSeq	NP_001599.1. NM_001608.3.
UniGene	Hs.471277.
3D structure databases
ProteinModelPortal	P28330.
SMR	P28330. Positions 53-426.
ModBase	Search...
Protein-protein interaction databases
STRING	P28330.
PTM databases
PhosphoSite	P28330.
Polymorphism databases
DMDM	223590148.
Proteomic databases
PRIDE	P28330.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000233710; ENSP00000233710; ENSG00000115361.
GeneID	33.
KEGG	hsa:33.
Organism-specific databases
CTD	33.
GeneCards	GC02M211016.
H-InvDB	HIX0200331.
HGNC	HGNC:88. ACADL.
HPA	HPA010611. HPA011990.
MIM	201475. phenotype. 609576. gene.
neXtProt	NX_P28330.
Orphanet	99900. Long chain Acyl-CoA dehydrogenase deficiency.
PharmGKB	PA24424.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG06056.
GeneTree	ENSGT00590000082906.
HOGENOM	HBG699365.
HOVERGEN	HBG104903.
InParanoid	P28330.
OMA	VSRELWE.
OrthoDB	EOG4FR0RR.
PhylomeDB	P28330.
Enzyme and pathway databases
Reactome	REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	P28330.
Bgee	P28330.
CleanEx	HS_ACADL.
Genevestigator	P28330.
GermOnline	ENSG00000115361. Homo sapiens.
Family and domain databases
InterPro	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. [Graphical view]
Gene3D	G3DSA:2.40.110.10. Acyl_CoA_DH/ox_M. 1 hit. G3DSA:1.10.540.10. AcylCoA_DH/ox_N. 1 hit. G3DSA:1.20.140.10. AcylCoA_DH_1/2_C. 1 hit.
KO	K00255.
Pfam	PF00441. Acyl-CoA_dh_1. 1 hit. PF02770. Acyl-CoA_dh_M. 1 hit. PF02771. Acyl-CoA_dh_N. 1 hit. [Graphical view]
SUPFAM	SSF56645. AcylCoA_dehyd_NM. 1 hit. SSF47203. AcylCoADH_C_like. 1 hit.
PROSITE	PS00072. ACYL_COA_DH_1. 1 hit. PS00073. ACYL_COA_DH_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

ACADL_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 119 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.