ID   ACADL_HUMAN             Reviewed;         430 AA.
AC   P28330; B2R8T3; Q8IUN8;
DT   01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT   10-FEB-2009, sequence version 2.
DT   25-JAN-2012, entry version 119.
DE   RecName: Full=Long-chain specific acyl-CoA dehydrogenase, mitochondrial;
DE            Short=LCAD;
DE            EC=1.3.99.13;
DE   Flags: Precursor;
GN   Name=ACADL;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=92128943; PubMed=1774065; DOI=10.1016/0888-7543(91)90068-P;
RA   Indo Y., Yang-Feng T., Glassberg R., Tanaka K.;
RT   "Molecular cloning and nucleotide sequence of cDNAs encoding human
RT   long-chain acyl-CoA dehydrogenase and assignment of the location of
RT   its gene (ACADL) to chromosome 2.";
RL   Genomics 11:609-620(1991).
RN   [2]
RP   ERRATUM.
RX   MEDLINE=92217993; PubMed=1559716; DOI=10.1016/0888-7543(92)90462-2;
RA   Indo Y., Yang-Feng T., Glassberg R., Tanaka K.;
RL   Genomics 12:626-626(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-333.
RC   TISSUE=Brain;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 4.";
RL   Nature 434:724-731(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain, and Colon;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   VARIANTS THR-303 AND GLN-333.
RA   Kelly D., Ogden M., Hale D., Hainline B., Strauss A.;
RT   "The molecular basis of human long chain acyl-CoA dehydrogenase
RT   deficiency.";
RL   Am. J. Hum. Genet. 49:409-409(1991).
CC   -!- CATALYTIC ACTIVITY: Acyl-CoA + acceptor = 2,3-dehydroacyl-CoA +
CC       reduced acceptor.
CC   -!- COFACTOR: FAD.
CC   -!- PATHWAY: Lipid metabolism; mitochondrial fatty acid beta-
CC       oxidation.
CC   -!- SUBUNIT: Homotetramer.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC   -!- DISEASE: Defects in ACADL are a cause of acyl-CoA dehydrogenase
CC       very long-chain deficiency (ACADVLD) [MIM:201475]. An inborn error
CC       of mitochondrial fatty acid beta-oxidation which leads to impaired
CC       long-chain fatty acid beta-oxidation. It is clinically
CC       heterogeneous, with three major phenotypes: a severe childhood
CC       form characterized by early onset, high mortality and high
CC       incidence of cardiomyopathy; a milder childhood form with later
CC       onset, characterized by hypoketotic hypoglycemia, low mortality
CC       and rare cardiomyopathy; an adult form, with isolated skeletal
CC       muscle involvement, rhabdomyolysis and myoglobinuria, usually
CC       triggered by exercise or fasting.
CC   -!- MISCELLANEOUS: A number of straight-chain acyl-CoA dehydrogenases
CC       of different substrate specificities are present in mammalian
CC       tissues.
CC   -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC   -----------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution-NoDerivs License
CC   -----------------------------------------------------------------------
DR   EMBL; M74096; AAA51565.1; -; mRNA.
DR   EMBL; AK313498; BAG36280.1; -; mRNA.
DR   EMBL; AC006994; AAY14881.1; -; Genomic_DNA.
DR   EMBL; CH471063; EAW70481.1; -; Genomic_DNA.
DR   EMBL; BC039063; AAH39063.1; -; mRNA.
DR   EMBL; BC064549; AAH64549.1; -; mRNA.
DR   IPI; IPI00292695; -.
DR   PIR; A40559; A40559.
DR   RefSeq; NP_001599.1; NM_001608.3.
DR   UniGene; Hs.471277; -.
DR   ProteinModelPortal; P28330; -.
DR   SMR; P28330; 53-426.
DR   STRING; P28330; -.
DR   PhosphoSite; P28330; -.
DR   DMDM; 223590148; -.
DR   PRIDE; P28330; -.
DR   Ensembl; ENST00000233710; ENSP00000233710; ENSG00000115361.
DR   GeneID; 33; -.
DR   KEGG; hsa:33; -.
DR   CTD; 33; -.
DR   GeneCards; GC02M211016; -.
DR   H-InvDB; HIX0200331; -.
DR   HGNC; HGNC:88; ACADL.
DR   HPA; HPA010611; -.
DR   HPA; HPA011990; -.
DR   MIM; 201475; phenotype.
DR   MIM; 609576; gene.
DR   neXtProt; NX_P28330; -.
DR   Orphanet; 99900; Long chain Acyl-CoA dehydrogenase deficiency.
DR   PharmGKB; PA24424; -.
DR   eggNOG; prNOG06056; -.
DR   GeneTree; ENSGT00590000082906; -.
DR   HOGENOM; HBG699365; -.
DR   HOVERGEN; HBG104903; -.
DR   InParanoid; P28330; -.
DR   OMA; VSRELWE; -.
DR   OrthoDB; EOG4FR0RR; -.
DR   PhylomeDB; P28330; -.
DR   Reactome; REACT_22258; Metabolism of lipids and lipoproteins.
DR   ArrayExpress; P28330; -.
DR   Bgee; P28330; -.
DR   CleanEx; HS_ACADL; -.
DR   Genevestigator; P28330; -.
DR   GermOnline; ENSG00000115361; Homo sapiens.
DR   GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR   GO; GO:0004466; F:long-chain-acyl-CoA dehydrogenase activity; ISS:BHF-UCL.
DR   GO; GO:0016401; F:palmitoyl-CoA oxidase activity; ISS:BHF-UCL.
DR   GO; GO:0042413; P:carnitine catabolic process; ISS:BHF-UCL.
DR   GO; GO:0019254; P:carnitine metabolic process, CoA-linked; ISS:BHF-UCL.
DR   GO; GO:0033539; P:fatty acid beta-oxidation using acyl-CoA dehydrogenase; ISS:BHF-UCL.
DR   GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; ISS:BHF-UCL.
DR   GO; GO:0046322; P:negative regulation of fatty acid oxidation; ISS:BHF-UCL.
DR   GO; GO:0090181; P:regulation of cholesterol metabolic process; ISS:BHF-UCL.
DR   GO; GO:0001659; P:temperature homeostasis; ISS:BHF-UCL.
DR   InterPro; IPR006089; Acyl-CoA_DH_CS.
DR   InterPro; IPR006092; Acyl-CoA_DH_N.
DR   InterPro; IPR006090; Acyl-CoA_Oxase/DH_1.
DR   InterPro; IPR006091; Acyl-CoA_Oxase/DH_cen-dom.
DR   InterPro; IPR009075; AcylCo_DH/oxidase_C.
DR   InterPro; IPR013786; AcylCoA_DH/ox_N.
DR   InterPro; IPR009100; AcylCoA_DH/oxidase.
DR   Gene3D; G3DSA:2.40.110.10; Acyl_CoA_DH/ox_M; 1.
DR   Gene3D; G3DSA:1.10.540.10; AcylCoA_DH/ox_N; 1.
DR   Gene3D; G3DSA:1.20.140.10; AcylCoA_DH_1/2_C; 1.
DR   KO; K00255; -.
DR   Pfam; PF00441; Acyl-CoA_dh_1; 1.
DR   Pfam; PF02770; Acyl-CoA_dh_M; 1.
DR   Pfam; PF02771; Acyl-CoA_dh_N; 1.
DR   SUPFAM; SSF56645; AcylCoA_dehyd_NM; 1.
DR   SUPFAM; SSF47203; AcylCoADH_C_like; 1.
DR   PROSITE; PS00072; ACYL_COA_DH_1; 1.
DR   PROSITE; PS00073; ACYL_COA_DH_2; 1.
PE   2: Evidence at transcript level;
KW   Complete proteome; FAD; Fatty acid metabolism; Flavoprotein;
KW   Lipid metabolism; Mitochondrion; Oxidoreductase; Polymorphism;
KW   Reference proteome; Transit peptide.
FT   TRANSIT       1     30       Mitochondrion.
FT   CHAIN        31    430       Long-chain specific acyl-CoA
FT                                dehydrogenase, mitochondrial.
FT                                /FTId=PRO_0000000509.
FT   VARIANT     303    303       S -> T (in dbSNP:rs1801204).
FT                                /FTId=VAR_000328.
FT   VARIANT     333    333       K -> Q (in dbSNP:rs2286963).
FT                                /FTId=VAR_000329.
SQ   SEQUENCE   430 AA;  47656 MW;  72F9803685406DF9 CRC64;
     MAARLLRGSL RVLGGHRAPR QLPAARCSHS GGEERLETPS AKKLTDIGIR RIFSPEHDIF
     RKSVRKFFQE EVIPHHSEWE KAGEVSREVW EKAGKQGLLG VNIAEHLGGI GGDLYSAAIV
     WEEQAYSNCS GPGFSIHSGI VMSYITNHGS EEQIKHFIPQ MTAGKCIGAI AMTEPGAGSD
     LQGIKTNAKK DGSDWILNGS KVFISNGSLS DVVIVVAVTN HEAPSPAHGI SLFLVENGMK
     GFIKGRKLHK MGLKAQDTAE LFFEDIRLPA SALLGEENKG FYYIMKELPQ ERLLIADVAI
     SASEFMFEET RNYVKQRKAF GKTVAHLQTV QHKLAELKTH ICVTRAFVDN CLQLHEAKRL
     DSATACMAKY WASELQNSVA YDCVQLHGGW GYMWEYPIAK AYVDARVQPI YGGTNEIMKE
     LIAREIVFDK
//