ACADM_HUMAN
ID ACADM_HUMAN Reviewed; 421 AA.
AC P11310; Q5T4U4; Q9NYF1;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=Medium-chain specific acyl-CoA dehydrogenase, mitochondrial {ECO:0000305|PubMed:3035565};
DE Short=MCAD {ECO:0000303|PubMed:3035565};
DE EC=1.3.8.7 {ECO:0000269|PubMed:1970566, ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:8823175};
DE AltName: Full=Medium chain acyl-CoA dehydrogenase {ECO:0000303|PubMed:8823175};
DE Short=MCADH {ECO:0000303|PubMed:8823175};
DE Flags: Precursor;
GN Name=ACADM {ECO:0000312|HGNC:HGNC:89};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3035565; DOI=10.1073/pnas.84.12.4068;
RA Kelly D.P., Kim J.-J.P., Billadello J.J., Hainline B.E., Chu T.W.,
RA Strauss A.W.;
RT "Nucleotide sequence of medium-chain acyl-CoA dehydrogenase mRNA and its
RT expression in enzyme-deficient human tissue.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:4068-4072(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=1731887; DOI=10.1021/bi00116a013;
RA Zhang Z.F., Kelly D.P., Kim J.-J.P., Zhou Y.Q., Ogden M.L., Whelan A.J.,
RA Strauss A.W.;
RT "Structural organization and regulatory regions of the human medium-chain
RT acyl-CoA dehydrogenase gene.";
RL Biochemistry 31:81-89(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Colon;
RA Sun F., Wang Y., Block G.D.;
RT "Medium-chain acyl-CoA dehydrogenase.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Heart;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Liver;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 218-235, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 314-342, AND VARIANT ACADMD GLU-329.
RX PubMed=2393404; DOI=10.1016/0006-291x(90)91421-n;
RA Matsubara Y., Narisawa K., Miyabayashi S., Tada K., Coates P.M.,
RA Bachmann C., Elsas L.J. II, Pollitt R.J., Rhead W.J., Roe C.R.;
RT "Identification of a common mutation in patients with medium-chain acyl-CoA
RT dehydrogenase deficiency.";
RL Biochem. Biophys. Res. Commun. 171:498-505(1990).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF GLU-401, AND ACTIVE SITE.
RX PubMed=1970566; DOI=10.1016/s0021-9258(19)39086-6;
RA Bross P., Engst S., Strauss A.W., Kelly D.P., Rasched I., Ghisla S.;
RT "Characterization of wild-type and an active site mutant of human medium
RT chain acyl-CoA dehydrogenase after expression in Escherichia coli.";
RL J. Biol. Chem. 265:7116-7119(1990).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, AND MUTAGENESIS OF THR-280 AND GLU-401.
RX PubMed=8823175; DOI=10.1021/bi960785e;
RA Nandy A., Kieweg V., Kraeutle F.G., Vock P., Kuechler B., Bross P.,
RA Kim J.J., Rasched I., Ghisla S.;
RT "Medium-long-chain chimeric human Acyl-CoA dehydrogenase: medium-chain
RT enzyme with the active center base arrangement of long-chain Acyl-CoA
RT dehydrogenase.";
RL Biochemistry 35:12402-12411(1996).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=16020546; DOI=10.1074/jbc.m504460200;
RA Ensenauer R., He M., Willard J.M., Goetzman E.S., Corydon T.J.,
RA Vandahl B.B., Mohsen A.W., Isaya G., Vockley J.;
RT "Human acyl-CoA dehydrogenase-9 plays a novel role in the mitochondrial
RT beta-oxidation of unsaturated fatty acids.";
RL J. Biol. Chem. 280:32309-32316(2005).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-279 AND LYS-301, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=21237683; DOI=10.1016/j.ymgme.2010.12.005;
RA He M., Pei Z., Mohsen A.W., Watkins P., Murdoch G., Van Veldhoven P.P.,
RA Ensenauer R., Vockley J.;
RT "Identification and characterization of new long chain acyl-CoA
RT dehydrogenases.";
RL Mol. Genet. Metab. 102:418-429(2011).
RN [16]
RP ACETYLATION, AND DEACETYLATION BY SIRT3.
RX PubMed=24121500; DOI=10.1074/jbc.m113.510354;
RA Bharathi S.S., Zhang Y., Mohsen A.W., Uppala R., Balasubramani M.,
RA Schreiber E., Uechi G., Beck M.E., Rardin M.J., Vockley J., Verdin E.,
RA Gibson B.W., Hirschey M.D., Goetzman E.S.;
RT "SIRT3 regulates long-chain acyl-coA dehydrogenase by deacetylating
RT conserved lysines near the active site.";
RL J. Biol. Chem. 288:33837-33847(2013).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP FUNCTION.
RX PubMed=25416781; DOI=10.1074/jbc.m114.614115;
RA Malecki J., Ho A.Y., Moen A., Dahl H.A., Falnes P.O.;
RT "Human METTL20 is a mitochondrial lysine methyltransferase that targets the
RT beta subunit of electron transfer flavoprotein (ETFbeta) and modulates its
RT activity.";
RL J. Biol. Chem. 290:423-434(2015).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [20] {ECO:0007744|PDB:1EGC, ECO:0007744|PDB:1EGD, ECO:0007744|PDB:1EGE}
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 26-421 OF MUTANT GLU-255 AND
RP GLY-401 IN COMPLEX WITH FAD AND THE SUBSTRATE ANALOG OCTANOYL-COENZYME A,
RP COFACTOR, SUBUNIT, ACTIVE SITE, AND TRANSIT PEPTIDE.
RX PubMed=8823176; DOI=10.1021/bi9607867;
RA Lee H.J., Wang M., Paschke R., Nandy A., Ghisla S., Kim J.-J.P.;
RT "Crystal structures of the wild type and the Glu376Gly/Thr255Glu mutant of
RT human medium-chain acyl-CoA dehydrogenase: influence of the location of the
RT catalytic base on substrate specificity.";
RL Biochemistry 35:12412-12420(1996).
RN [21] {ECO:0007744|PDB:1T9G}
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 26-421 IN COMPLEXES WITH FAD AND
RP THE ETFA-ETFB HETERODIMER, FUNCTION, COFACTOR, MUTAGENESIS OF LEU-86;
RP LEU-98; LEU-100; ILE-108; GLU-237 AND GLU-384, AND SUBUNIT.
RX PubMed=15159392; DOI=10.1074/jbc.m404884200;
RA Toogood H.S., van Thiel A., Basran J., Sutcliffe M.J., Scrutton N.S.,
RA Leys D.;
RT "Extensive domain motion and electron transfer in the human electron
RT transferring flavoprotein.medium chain acyl-CoA dehydrogenase complex.";
RL J. Biol. Chem. 279:32904-32912(2004).
RN [22] {ECO:0007744|PDB:2A1T}
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEXES WITH FAD AND THE
RP ETFA-ETFB HETERODIMER, COFACTOR, SUBUNIT, AND MUTAGENESIS OF TRP-191;
RP GLU-237 AND GLU-384.
RX PubMed=15975918; DOI=10.1074/jbc.m505562200;
RA Toogood H.S., van Thiel A., Scrutton N.S., Leys D.;
RT "Stabilization of non-productive conformations underpins rapid electron
RT transfer to electron-transferring flavoprotein.";
RL J. Biol. Chem. 280:30361-30366(2005).
RN [23] {ECO:0007744|PDB:4P13}
RP X-RAY CRYSTALLOGRAPHY (1.73 ANGSTROMS) OF 35-421 OF VARIANT ACADMD GLU-329
RP IN COMPLEX WITH FAD, COFACTOR, AND SUBUNIT.
RA Battaile K.P., Mohsen A.-W., Vockley J.;
RT "Medium chain acyl-CoA dehydrogenase, K304E mutant.";
RL Submitted (FEB-2014) to the PDB data bank.
RN [24]
RP REVIEW ON VARIANTS ACADMD.
RX PubMed=1363805; DOI=10.1002/humu.1380010402;
RA Tanaka K., Yokota I., Coates P.M., Strauss A.W., Kelly D.P., Zhang Z.F.,
RA Gregersen N., Andresen B.S., Matsubara Y., Curtis D., Chen Y.-T.;
RT "Mutations in the medium chain acyl-CoA dehydrogenase (MCAD) gene.";
RL Hum. Mutat. 1:271-279(1992).
RN [25]
RP VARIANT ACADMD GLU-329.
RX PubMed=2394825; DOI=10.1172/jci114761;
RA Yokota I., Indo Y., Coates P.M., Tanaka K.;
RT "Molecular basis of medium chain acyl-coenzyme A dehydrogenase deficiency.
RT An A to G transition at position 985 that causes a lysine-304 to glutamate
RT substitution in the mature protein is the single prevalent mutation.";
RL J. Clin. Invest. 86:1000-1003(1990).
RN [26]
RP VARIANT ACADMD GLU-329, FUNCTION, AND PATHWAY.
RX PubMed=2251268; DOI=10.1073/pnas.87.23.9236;
RA Kelly D.P., Whelan A.J., Ogden M.L., Alpers R., Zhang Z.F., Bellus G.,
RA Gregersen N., Dorland L., Strauss A.W.;
RT "Molecular characterization of inherited medium-chain acyl-CoA
RT dehydrogenase deficiency.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:9236-9240(1990).
RN [27]
RP VARIANTS ACADMD ILE-149; ARG-244; ARG-267 AND THR-375.
RX PubMed=1684086;
RA Yokota I., Coates P.M., Hale D.E., Rinaldo P., Tanaka K.;
RT "Molecular survey of a prevalent mutation, 985A-to-G transition, and
RT identification of five infrequent mutations in the medium-chain Acyl-CoA
RT dehydrogenase (MCAD) gene in 55 patients with MCAD deficiency.";
RL Am. J. Hum. Genet. 49:1280-1291(1991).
RN [28]
RP VARIANT ACADMD GLU-329.
RX PubMed=1902818; DOI=10.1007/bf00201539;
RA Gregersen N., Andresen B.S., Bross P., Winter V., Ruediger N., Engst S.,
RA Christensen E., Kelly D., Strauss A.W., Koelvraa S., Bolund L., Ghisla S.;
RT "Molecular characterization of medium-chain acyl-CoA dehydrogenase (MCAD)
RT deficiency: identification of a lys329 to glu mutation in the MCAD gene,
RT and expression of inactive mutant enzyme protein in E. coli.";
RL Hum. Genet. 86:545-551(1991).
RN [29]
RP VARIANT ACADMD GLU-329 FREQUENCY.
RX PubMed=1671131; DOI=10.1016/0140-6736(91)90907-7;
RA Blakemore A.I., Singleton H., Pollitt R.J., Engel P.C., Kolvraa S.,
RA Gregersen N., Curtis D.;
RT "Frequency of the G985 MCAD mutation in the general population.";
RL Lancet 337:298-299(1991).
RN [30]
RP VARIANTS ACADMD THR-326 AND ARG-336.
RX PubMed=8198141;
RA Andresen B.S., Jensen T.G., Bross P., Knudsen I., Winter V., Koelvraa S.,
RA Bolund L., Ding J.-H., Chen Y.-T., van Hove J.L.K., Curtis D., Yokota I.,
RA Tanaka K., Kim J.-J.P., Gregersen N.;
RT "Disease-causing mutations in exon 11 of the medium-chain acyl-CoA
RT dehydrogenase gene.";
RL Am. J. Hum. Genet. 54:975-988(1994).
RN [31]
RP VARIANT ACADMD 115-GLY-CYS-116 DEL.
RX PubMed=7603790; DOI=10.1203/00006450-199505000-00021;
RA Ziadeh R., Hoffman E.P., Finegold D.N., Hoop R.C., Brackett J.C.,
RA Strauss A.W., Naylor E.W.;
RT "Medium chain acyl-CoA dehydrogenase deficiency in Pennsylvania: neonatal
RT screening shows high incidence and unexpected mutation frequencies.";
RL Pediatr. Res. 37:675-678(1995).
RN [32]
RP VARIANT ACADMD ARG-195.
RX PubMed=7929823; DOI=10.1172/jci117486;
RA Brackett J.C., Sims H.F., Steiner R.D., Nunge M., Zimmerman E.M.,
RA Demartinville B., Rinaldo P., Slaugh R., Strauss A.W.;
RT "A novel mutation in medium chain acyl-CoA dehydrogenase causes sudden
RT neonatal death.";
RL J. Clin. Invest. 94:1477-1483(1994).
RN [33]
RP VARIANTS ACADMD TYR-116; ALA-193 AND CYS-352.
RX PubMed=9158144; DOI=10.1093/hmg/6.5.695;
RA Andresen B.S., Bross P., Udvari S., Kirk J., Gray G., Kmoch S.,
RA Chamoles N., Knudsen I., Winter V., Wilcken B., Yokota I., Hart K.,
RA Packman S., Harpey J.P., Saudubray J.-M., Hale D.E., Bolund L.,
RA Koelvraa S., Gregersen N.;
RT "The molecular basis of medium-chain acyl-CoA dehydrogenase (MCAD)
RT deficiency in compound heterozygous patients: is there correlation between
RT genotype and phenotype?";
RL Hum. Mol. Genet. 6:695-707(1997).
RN [34]
RP CHARACTERIZATION OF VARIANT ACADMD ALA-193.
RX PubMed=9882619; DOI=10.1042/bj3370225;
RA Kuchler B., Abdel-Ghany A.G., Bross P., Nandy A., Rasched I., Ghisla S.;
RT "Biochemical characterization of a variant human medium-chain acyl-CoA
RT dehydrogenase with a disease-associated mutation localized in the active
RT site.";
RL Biochem. J. 337:225-230(1999).
RN [35]
RP VARIANTS ACADMD LEU-206 AND GLU-329.
RX PubMed=10767181; DOI=10.1006/mgme.2000.2978;
RA Yang B.-Z., Ding J.-H., Zhou C., Dimachkie M.M., Sweetman L., Dasouki M.J.,
RA Wilkinson J., Roe C.R.;
RT "Identification of a novel mutation in patients with medium-chain acyl-CoA
RT dehydrogenase deficiency.";
RL Mol. Genet. Metab. 69:259-262(2000).
RN [36]
RP VARIANTS ACADMD HIS-67; THR-78; ILE-121 AND ARG-310.
RX PubMed=11349232; DOI=10.1086/320602;
RA Andresen B.S., Dobrowolski S.F., O'Reilly L., Muenzer J., McCandless S.E.,
RA Frazier D.M., Udvari S., Bross P., Knudsen I., Banas R., Chace D.H.,
RA Engel P.C., Naylor E.W., Gregersen N.;
RT "Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-
RT based prospective screening of newborns differ from those observed in
RT patients with clinical symptoms: identification and characterization of a
RT new, prevalent mutation that results in mild MCAD deficiency.";
RL Am. J. Hum. Genet. 68:1408-1418(2001).
RN [37]
RP VARIANT ACADMD LEU-245.
RX PubMed=11409868; DOI=10.1007/s004390100501;
RA Zschocke J., Schulze A., Lindner M., Fiesel S., Olgemoller K.,
RA Hoffmann G.F., Penzien J., Ruiter J.P.N., Wanders R.J.A., Mayatepek E.;
RT "Molecular and functional characterization of mild MCAD deficiency.";
RL Hum. Genet. 108:404-408(2001).
RN [38]
RP VARIANTS ACADMD THR-281 AND GLU-329.
RX PubMed=11486912; DOI=10.1023/a:1010533408635;
RA Albers S., Levy H.L., Irons M., Strauss A.W., Marsden D.;
RT "Compound heterozygosity in four asymptomatic siblings with medium-chain
RT acyl-CoA dehydrogenase deficiency.";
RL J. Inherit. Metab. Dis. 24:417-418(2001).
RN [39]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-132.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Medium-chain specific acyl-CoA dehydrogenase is one of the
CC acyl-CoA dehydrogenases that catalyze the first step of mitochondrial
CC fatty acid beta-oxidation, an aerobic process breaking down fatty acids
CC into acetyl-CoA and allowing the production of energy from fats
CC (PubMed:1970566, PubMed:8823175, PubMed:21237683, PubMed:2251268). The
CC first step of fatty acid beta-oxidation consists in the removal of one
CC hydrogen from C-2 and C-3 of the straight-chain fatty acyl-CoA
CC thioester, resulting in the formation of trans-2-enoyl-CoA
CC (PubMed:2251268). Electron transfer flavoprotein (ETF) is the electron
CC acceptor that transfers electrons to the main mitochondrial respiratory
CC chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase)
CC (PubMed:25416781, PubMed:15159392). Among the different mitochondrial
CC acyl-CoA dehydrogenases, medium-chain specific acyl-CoA dehydrogenase
CC acts specifically on acyl-CoAs with saturated 6 to 12 carbons long
CC primary chains (PubMed:1970566, PubMed:8823175, PubMed:21237683,
CC PubMed:2251268). {ECO:0000269|PubMed:15159392,
CC ECO:0000269|PubMed:1970566, ECO:0000269|PubMed:21237683,
CC ECO:0000269|PubMed:2251268, ECO:0000269|PubMed:25416781,
CC ECO:0000269|PubMed:8823175}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a medium-chain 2,3-saturated fatty acyl-CoA + H(+) + oxidized
CC [electron-transfer flavoprotein] = a medium-chain (2E)-enoyl-CoA +
CC reduced [electron-transfer flavoprotein]; Xref=Rhea:RHEA:14477,
CC Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:83723,
CC ChEBI:CHEBI:83726; EC=1.3.8.7; Evidence={ECO:0000269|PubMed:1970566,
CC ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14478;
CC Evidence={ECO:0000305|PubMed:1970566};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + oxidized [electron-transfer flavoprotein] + pentanoyl-
CC CoA = (2E)-pentenoyl-CoA + reduced [electron-transfer flavoprotein];
CC Xref=Rhea:RHEA:43456, Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57389, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:86160;
CC Evidence={ECO:0000250|UniProtKB:P08503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43457;
CC Evidence={ECO:0000250|UniProtKB:P08503};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexanoyl-CoA + oxidized [electron-transfer
CC flavoprotein] = (2E)-hexenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:43464, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:62077, ChEBI:CHEBI:62620;
CC Evidence={ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43465;
CC Evidence={ECO:0000305|PubMed:8823175};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + octanoyl-CoA + oxidized [electron-transfer
CC flavoprotein] = (2E)-octenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:48180, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57386, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:62242;
CC Evidence={ECO:0000269|PubMed:1970566, ECO:0000269|PubMed:21237683,
CC ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48181;
CC Evidence={ECO:0000305|PubMed:1970566};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=decanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-decenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:48176, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:61406, ChEBI:CHEBI:61430;
CC Evidence={ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48177;
CC Evidence={ECO:0000305|PubMed:8823175};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-dodecenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:47296, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57330, ChEBI:CHEBI:57375,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307;
CC Evidence={ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47297;
CC Evidence={ECO:0000305|PubMed:8823175};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + oxidized [electron-transfer flavoprotein] +
CC tetradecanoyl-CoA = (2E)-tetradecenoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:47316, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57385,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:61405;
CC Evidence={ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47317;
CC Evidence={ECO:0000305|PubMed:8823175};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexadecanoyl-CoA + oxidized [electron-transfer
CC flavoprotein] = (2E)-hexadecenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:43448, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57379, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:61526;
CC Evidence={ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:8823175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43449;
CC Evidence={ECO:0000305|PubMed:8823175};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:15159392, ECO:0000269|PubMed:15975918,
CC ECO:0000269|PubMed:8823176, ECO:0000269|Ref.23};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=175 uM for butyryl-CoA {ECO:0000269|PubMed:8823175};
CC KM=15 uM for hexanoyl-CoA {ECO:0000269|PubMed:8823175};
CC KM=3.4 uM for octanoyl-CoA {ECO:0000269|PubMed:8823175};
CC KM=2.5 uM for decanoyl-CoA {ECO:0000269|PubMed:8823175};
CC KM=2.5 uM for dodecanoyl-CoA {ECO:0000269|PubMed:8823175};
CC KM=2.3 uM for tetradecanoyl-CoA {ECO:0000269|PubMed:8823175};
CC KM=1.6 uM for hexadecanoyl-CoA {ECO:0000269|PubMed:8823175};
CC -!- PATHWAY: Lipid metabolism; mitochondrial fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:2251268}.
CC -!- SUBUNIT: Homotetramer (PubMed:8823176, Ref.23). Interacts with the
CC heterodimeric electron transfer flavoprotein ETF.
CC {ECO:0000269|PubMed:15159392, ECO:0000269|PubMed:15975918,
CC ECO:0000269|PubMed:8823176, ECO:0000269|Ref.23}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:16020546}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P11310-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P11310-2; Sequence=VSP_038420;
CC -!- PTM: Acetylated. Could occur at proximity of the cofactor-binding sites
CC and reduce the catalytic activity. Could be deacetylated by SIRT3.
CC {ECO:0000269|PubMed:24121500}.
CC -!- DISEASE: Acyl-CoA dehydrogenase medium-chain deficiency (ACADMD)
CC [MIM:201450]: An inborn error of mitochondrial fatty acid beta-
CC oxidation which causes fasting hypoglycemia, hepatic dysfunction and
CC encephalopathy, often resulting in death in infancy.
CC {ECO:0000269|PubMed:10767181, ECO:0000269|PubMed:11349232,
CC ECO:0000269|PubMed:11409868, ECO:0000269|PubMed:11486912,
CC ECO:0000269|PubMed:1363805, ECO:0000269|PubMed:1671131,
CC ECO:0000269|PubMed:1684086, ECO:0000269|PubMed:1902818,
CC ECO:0000269|PubMed:2251268, ECO:0000269|PubMed:2393404,
CC ECO:0000269|PubMed:2394825, ECO:0000269|PubMed:7603790,
CC ECO:0000269|PubMed:7929823, ECO:0000269|PubMed:8198141,
CC ECO:0000269|PubMed:9158144, ECO:0000269|PubMed:9882619}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; M16827; AAA51566.1; -; mRNA.
DR EMBL; M91432; AAA59567.1; -; Genomic_DNA.
DR EMBL; M91421; AAA59567.1; JOINED; Genomic_DNA.
DR EMBL; M91422; AAA59567.1; JOINED; Genomic_DNA.
DR EMBL; M91423; AAA59567.1; JOINED; Genomic_DNA.
DR EMBL; M91425; AAA59567.1; JOINED; Genomic_DNA.
DR EMBL; M91426; AAA59567.1; JOINED; Genomic_DNA.
DR EMBL; M91427; AAA59567.1; JOINED; Genomic_DNA.
DR EMBL; M91428; AAA59567.1; JOINED; Genomic_DNA.
DR EMBL; M91429; AAA59567.1; JOINED; Genomic_DNA.
DR EMBL; M91430; AAA59567.1; JOINED; Genomic_DNA.
DR EMBL; M91431; AAA59567.1; JOINED; Genomic_DNA.
DR EMBL; AF251043; AAF63626.1; -; mRNA.
DR EMBL; AK312629; BAG35514.1; -; mRNA.
DR EMBL; AL357314; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX06401.1; -; Genomic_DNA.
DR EMBL; BC005377; AAH05377.1; -; mRNA.
DR EMBL; M60505; AAB59625.1; -; Genomic_DNA.
DR CCDS; CCDS44165.1; -. [P11310-2]
DR CCDS; CCDS668.1; -. [P11310-1]
DR PIR; A29031; DEHUCM.
DR RefSeq; NP_000007.1; NM_000016.5. [P11310-1]
DR RefSeq; NP_001120800.1; NM_001127328.2. [P11310-2]
DR PDB; 1EGC; X-ray; 2.60 A; A/B/C/D=26-421.
DR PDB; 1EGD; X-ray; 2.40 A; A/B/C/D=26-421.
DR PDB; 1EGE; X-ray; 2.75 A; A/B/C/D=26-421.
DR PDB; 1T9G; X-ray; 2.90 A; A/B/C/D=26-421.
DR PDB; 2A1T; X-ray; 2.80 A; A/B/C/D=1-421.
DR PDB; 4P13; X-ray; 1.73 A; A/B/C/D=35-421.
DR PDBsum; 1EGC; -.
DR PDBsum; 1EGD; -.
DR PDBsum; 1EGE; -.
DR PDBsum; 1T9G; -.
DR PDBsum; 2A1T; -.
DR PDBsum; 4P13; -.
DR AlphaFoldDB; P11310; -.
DR SMR; P11310; -.
DR BioGRID; 106552; 112.
DR DIP; DIP-34281N; -.
DR IntAct; P11310; 28.
DR MINT; P11310; -.
DR STRING; 9606.ENSP00000359871; -.
DR ChEMBL; CHEMBL4295713; -.
DR DrugBank; DB03415; 3-thiaoctanoyl-CoA.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR DrugBank; DB02910; Octanoyl-Coenzyme A.
DR SwissLipids; SLP:000001334; -.
DR GlyGen; P11310; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P11310; -.
DR PhosphoSitePlus; P11310; -.
DR SwissPalm; P11310; -.
DR BioMuta; ACADM; -.
DR DMDM; 113017; -.
DR REPRODUCTION-2DPAGE; IPI00005040; -.
DR UCD-2DPAGE; P11310; -.
DR EPD; P11310; -.
DR jPOST; P11310; -.
DR MassIVE; P11310; -.
DR MaxQB; P11310; -.
DR PaxDb; P11310; -.
DR PeptideAtlas; P11310; -.
DR PRIDE; P11310; -.
DR ProteomicsDB; 52743; -. [P11310-1]
DR ProteomicsDB; 52744; -. [P11310-2]
DR Antibodypedia; 1642; 468 antibodies from 38 providers.
DR DNASU; 34; -.
DR Ensembl; ENST00000370841.9; ENSP00000359878.5; ENSG00000117054.15. [P11310-1]
DR Ensembl; ENST00000420607.6; ENSP00000409612.2; ENSG00000117054.15. [P11310-2]
DR GeneID; 34; -.
DR KEGG; hsa:34; -.
DR MANE-Select; ENST00000370841.9; ENSP00000359878.5; NM_000016.6; NP_000007.1.
DR UCSC; uc001dgw.6; human. [P11310-1]
DR CTD; 34; -.
DR DisGeNET; 34; -.
DR GeneCards; ACADM; -.
DR GeneReviews; ACADM; -.
DR HGNC; HGNC:89; ACADM.
DR HPA; ENSG00000117054; Tissue enhanced (liver, skeletal muscle, tongue).
DR MalaCards; ACADM; -.
DR MIM; 201450; phenotype.
DR MIM; 607008; gene.
DR neXtProt; NX_P11310; -.
DR OpenTargets; ENSG00000117054; -.
DR Orphanet; 42; Medium chain acyl-CoA dehydrogenase deficiency.
DR PharmGKB; PA24425; -.
DR VEuPathDB; HostDB:ENSG00000117054; -.
DR eggNOG; KOG0140; Eukaryota.
DR GeneTree; ENSGT00940000158429; -.
DR InParanoid; P11310; -.
DR OMA; AMEELFW; -.
DR PhylomeDB; P11310; -.
DR TreeFam; TF105020; -.
DR BioCyc; MetaCyc:HS04089-MON; -.
DR BRENDA; 1.3.8.7; 2681.
DR PathwayCommons; P11310; -.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-77288; mitochondrial fatty acid beta-oxidation of unsaturated fatty acids.
DR Reactome; R-HSA-77346; Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA.
DR Reactome; R-HSA-77348; Beta oxidation of octanoyl-CoA to hexanoyl-CoA.
DR SABIO-RK; P11310; -.
DR SignaLink; P11310; -.
DR SIGNOR; P11310; -.
DR UniPathway; UPA00660; -.
DR BioGRID-ORCS; 34; 12 hits in 1079 CRISPR screens.
DR ChiTaRS; ACADM; human.
DR EvolutionaryTrace; P11310; -.
DR GenomeRNAi; 34; -.
DR Pharos; P11310; Tbio.
DR PRO; PR:P11310; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P11310; protein.
DR Bgee; ENSG00000117054; Expressed in jejunal mucosa and 204 other tissues.
DR ExpressionAtlas; P11310; baseline and differential.
DR Genevisible; P11310; HS.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:BHF-UCL.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:LIFEdb.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0003995; F:acyl-CoA dehydrogenase activity; IDA:BHF-UCL.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IDA:BHF-UCL.
DR GO; GO:0070991; F:medium-chain-acyl-CoA dehydrogenase activity; IDA:BHF-UCL.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0045329; P:carnitine biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0019254; P:carnitine metabolic process, CoA-linked; IMP:BHF-UCL.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IMP:UniProtKB.
DR GO; GO:0033539; P:fatty acid beta-oxidation using acyl-CoA dehydrogenase; IDA:UniProtKB.
DR GO; GO:0005978; P:glycogen biosynthetic process; IEA:Ensembl.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0051793; P:medium-chain fatty acid catabolic process; IDA:BHF-UCL.
DR GO; GO:0051791; P:medium-chain fatty acid metabolic process; IDA:BHF-UCL.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0006111; P:regulation of gluconeogenesis; IEA:Ensembl.
DR GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR GO; GO:0042594; P:response to starvation; IEA:Ensembl.
DR CDD; cd01157; MCAD; 1.
DR Gene3D; 1.10.540.10; -; 1.
DR Gene3D; 2.40.110.10; -; 1.
DR InterPro; IPR006089; Acyl-CoA_DH_CS.
DR InterPro; IPR006091; Acyl-CoA_Oxase/DH_mid-dom.
DR InterPro; IPR046373; Acyl-CoA_Oxase/DH_mid-dom_sf.
DR InterPro; IPR036250; AcylCo_DH-like_C.
DR InterPro; IPR009075; AcylCo_DH/oxidase_C.
DR InterPro; IPR013786; AcylCoA_DH/ox_N.
DR InterPro; IPR037069; AcylCoA_DH/ox_N_sf.
DR InterPro; IPR009100; AcylCoA_DH/oxidase_NM_dom.
DR InterPro; IPR034180; MCAD.
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; SSF47203; SSF47203; 1.
DR SUPFAM; SSF56645; SSF56645; 1.
DR PROSITE; PS00072; ACYL_COA_DH_1; 1.
DR PROSITE; PS00073; ACYL_COA_DH_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing;
KW Disease variant; FAD; Fatty acid metabolism; Flavoprotein;
KW Lipid metabolism; Mitochondrion; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..25
FT /note="Mitochondrion"
FT /evidence="ECO:0000305|PubMed:8823176"
FT CHAIN 26..421
FT /note="Medium-chain specific acyl-CoA dehydrogenase,
FT mitochondrial"
FT /id="PRO_0000000502"
FT ACT_SITE 401
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:1970566,
FT ECO:0000269|PubMed:8823176"
FT BINDING 158..167
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:15159392,
FT ECO:0000269|PubMed:15975918, ECO:0000269|PubMed:8823176,
FT ECO:0000269|Ref.23, ECO:0007744|PDB:1EGC,
FT ECO:0007744|PDB:1EGD, ECO:0007744|PDB:1EGE,
FT ECO:0007744|PDB:1T9G, ECO:0007744|PDB:2A1T,
FT ECO:0007744|PDB:4P13"
FT BINDING 167
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8823176"
FT BINDING 191..193
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:15159392,
FT ECO:0000269|PubMed:15975918, ECO:0000269|PubMed:8823176,
FT ECO:0000269|Ref.23, ECO:0007744|PDB:1EGC,
FT ECO:0007744|PDB:1EGD, ECO:0007744|PDB:1EGE,
FT ECO:0007744|PDB:1T9G, ECO:0007744|PDB:2A1T,
FT ECO:0007744|PDB:4P13"
FT BINDING 216
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8823176"
FT BINDING 278..281
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8823176"
FT BINDING 306..308
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:15159392,
FT ECO:0000269|PubMed:15975918, ECO:0000269|PubMed:8823176,
FT ECO:0000269|Ref.23, ECO:0007744|PDB:1EGC,
FT ECO:0007744|PDB:1EGD, ECO:0007744|PDB:1EGE,
FT ECO:0007744|PDB:1T9G, ECO:0007744|PDB:2A1T,
FT ECO:0007744|PDB:4P13"
FT BINDING 316..317
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:15159392,
FT ECO:0000269|PubMed:15975918, ECO:0000269|PubMed:8823176,
FT ECO:0000269|Ref.23, ECO:0007744|PDB:1EGC,
FT ECO:0007744|PDB:1EGD, ECO:0007744|PDB:1EGE,
FT ECO:0007744|PDB:1T9G, ECO:0007744|PDB:2A1T,
FT ECO:0007744|PDB:4P13"
FT BINDING 351
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P41367"
FT BINDING 374..378
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:15159392,
FT ECO:0000269|PubMed:15975918, ECO:0000269|PubMed:8823176,
FT ECO:0000269|Ref.23, ECO:0007744|PDB:1EGC,
FT ECO:0007744|PDB:1EGD, ECO:0007744|PDB:1EGE,
FT ECO:0007744|PDB:1T9G, ECO:0007744|PDB:2A1T,
FT ECO:0007744|PDB:4P13"
FT BINDING 401..405
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:15159392,
FT ECO:0000269|PubMed:15975918, ECO:0000269|PubMed:8823176,
FT ECO:0000269|Ref.23, ECO:0007744|PDB:1EGC,
FT ECO:0007744|PDB:1EGD, ECO:0007744|PDB:1EGE,
FT ECO:0007744|PDB:1T9G, ECO:0007744|PDB:2A1T,
FT ECO:0007744|PDB:4P13"
FT BINDING 413
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P41367"
FT MOD_RES 69
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P45952"
FT MOD_RES 69
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P45952"
FT MOD_RES 179
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P45952"
FT MOD_RES 212
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P45952"
FT MOD_RES 212
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P45952"
FT MOD_RES 217
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P45952"
FT MOD_RES 217
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P45952"
FT MOD_RES 259
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P45952"
FT MOD_RES 259
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P45952"
FT MOD_RES 271
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P45952"
FT MOD_RES 271
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P45952"
FT MOD_RES 279
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 301
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 351
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P45952"
FT VAR_SEQ 10
FT /note="R -> RCSLQ (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_038420"
FT VARIANT 53
FT /note="R -> C (in ACADMD; dbSNP:rs398123072)"
FT /id="VAR_000317"
FT VARIANT 67
FT /note="Y -> H (in ACADMD; mild; dbSNP:rs121434280)"
FT /evidence="ECO:0000269|PubMed:11349232"
FT /id="VAR_013698"
FT VARIANT 78
FT /note="I -> T (in ACADMD; dbSNP:rs398123074)"
FT /evidence="ECO:0000269|PubMed:11349232"
FT /id="VAR_015954"
FT VARIANT 115..116
FT /note="Missing (in ACADMD)"
FT /evidence="ECO:0000269|PubMed:7603790"
FT /id="VAR_000318"
FT VARIANT 116
FT /note="C -> Y (in ACADMD; dbSNP:rs875989859)"
FT /evidence="ECO:0000269|PubMed:9158144"
FT /id="VAR_015955"
FT VARIANT 121
FT /note="T -> I (in ACADMD; dbSNP:rs121434283)"
FT /evidence="ECO:0000269|PubMed:11349232"
FT /id="VAR_015956"
FT VARIANT 132
FT /note="P -> R (in a breast cancer sample; somatic mutation;
FT dbSNP:rs875989854)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035716"
FT VARIANT 149
FT /note="M -> I (in ACADMD; dbSNP:rs121434277)"
FT /evidence="ECO:0000269|PubMed:1684086"
FT /id="VAR_000319"
FT VARIANT 193
FT /note="T -> A (in ACADMD; the thermostability is markedly
FT decreased; dbSNP:rs121434279)"
FT /evidence="ECO:0000269|PubMed:9158144,
FT ECO:0000269|PubMed:9882619"
FT /id="VAR_000320"
FT VARIANT 195
FT /note="G -> R (in ACADMD; dbSNP:rs121434278)"
FT /evidence="ECO:0000269|PubMed:7929823"
FT /id="VAR_000321"
FT VARIANT 206
FT /note="R -> L (in ACADMD; dbSNP:rs200724875)"
FT /evidence="ECO:0000269|PubMed:10767181"
FT /id="VAR_015957"
FT VARIANT 244
FT /note="C -> R (in ACADMD; dbSNP:rs121434276)"
FT /evidence="ECO:0000269|PubMed:1684086"
FT /id="VAR_000322"
FT VARIANT 245
FT /note="S -> L (in ACADMD; dbSNP:rs121434281)"
FT /evidence="ECO:0000269|PubMed:11409868"
FT /id="VAR_013699"
FT VARIANT 267
FT /note="G -> R (in ACADMD; dbSNP:rs121434274)"
FT /evidence="ECO:0000269|PubMed:1684086"
FT /id="VAR_000323"
FT VARIANT 281
FT /note="R -> T (in ACADMD; mild or benign clinical
FT phenotype; dbSNP:rs121434282)"
FT /evidence="ECO:0000269|PubMed:11486912"
FT /id="VAR_013700"
FT VARIANT 310
FT /note="G -> R (in ACADMD; dbSNP:rs747268471)"
FT /evidence="ECO:0000269|PubMed:11349232"
FT /id="VAR_015958"
FT VARIANT 326
FT /note="M -> T (in ACADMD; dbSNP:rs786204631)"
FT /evidence="ECO:0000269|PubMed:8198141"
FT /id="VAR_000324"
FT VARIANT 329
FT /note="K -> E (in ACADMD; may alter splicing; decreased
FT fatty acid beta-oxidation; dbSNP:rs77931234)"
FT /evidence="ECO:0000269|PubMed:10767181,
FT ECO:0000269|PubMed:11486912, ECO:0000269|PubMed:1902818,
FT ECO:0000269|PubMed:2251268, ECO:0000269|PubMed:2393404,
FT ECO:0000269|PubMed:2394825"
FT /id="VAR_000325"
FT VARIANT 336
FT /note="S -> R (in ACADMD)"
FT /evidence="ECO:0000269|PubMed:8198141"
FT /id="VAR_000326"
FT VARIANT 352
FT /note="Y -> C (in ACADMD; dbSNP:rs1227800781)"
FT /evidence="ECO:0000269|PubMed:9158144"
FT /id="VAR_015959"
FT VARIANT 375
FT /note="I -> T (in ACADMD; dbSNP:rs121434275)"
FT /evidence="ECO:0000269|PubMed:1684086"
FT /id="VAR_000327"
FT MUTAGEN 86
FT /note="L->M: Strongly reduced rate of electron transfer to
FT ETF."
FT /evidence="ECO:0000269|PubMed:15159392"
FT MUTAGEN 98
FT /note="L->W: Strongly reduced rate of electron transfer to
FT ETF."
FT /evidence="ECO:0000269|PubMed:15159392"
FT MUTAGEN 100
FT /note="L->Y: Strongly reduced rate of electron transfer to
FT ETF."
FT /evidence="ECO:0000269|PubMed:15159392"
FT MUTAGEN 108
FT /note="I->M: Strongly reduced rate of electron transfer to
FT ETF."
FT /evidence="ECO:0000269|PubMed:15159392"
FT MUTAGEN 191
FT /note="W->A: Loss of electron transfer to ETF."
FT /evidence="ECO:0000269|PubMed:15975918"
FT MUTAGEN 191
FT /note="W->F: Reduces rate of electron transfer to ETF about
FT six-fold."
FT /evidence="ECO:0000269|PubMed:15975918"
FT MUTAGEN 237
FT /note="E->A: Strongly reduced rate of electron transfer to
FT ETF."
FT /evidence="ECO:0000269|PubMed:15159392,
FT ECO:0000269|PubMed:15975918"
FT MUTAGEN 280
FT /note="T->E: Narrower substrate specificity. Changed
FT substrate specificity towards longer acyl chains; when
FT associated with G-401. Loss of acyl-CoA dehydrogenase
FT activity; when associated with T-410."
FT /evidence="ECO:0000269|PubMed:8823175"
FT MUTAGEN 384
FT /note="E->A: Reduces rate of electron transfer to ETF
FT three-fold."
FT /evidence="ECO:0000269|PubMed:15159392,
FT ECO:0000269|PubMed:15975918"
FT MUTAGEN 384
FT /note="E->Q: Reduces rate of electron transfer to ETF two-
FT fold."
FT /evidence="ECO:0000269|PubMed:15159392,
FT ECO:0000269|PubMed:15975918"
FT MUTAGEN 401
FT /note="E->G: Changed substrate specificity towards longer
FT acyl chains; when associated with E-280."
FT /evidence="ECO:0000269|PubMed:8823175"
FT MUTAGEN 401
FT /note="E->Q: Loss of acyl-CoA dehydrogenase activity."
FT /evidence="ECO:0000269|PubMed:1970566"
FT MUTAGEN 401
FT /note="E->T: Loss of acyl-CoA dehydrogenase activity; when
FT associated with E-280."
FT /evidence="ECO:0000269|PubMed:8823175"
FT CONFLICT 356
FT /note="I -> T (in Ref. 3; AAF63626)"
FT /evidence="ECO:0000305"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:1EGD"
FT HELIX 43..58
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 61..70
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 75..83
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 102..115
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 117..136
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 139..145
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 147..151
FT /evidence="ECO:0007829|PDB:4P13"
FT STRAND 155..159
FT /evidence="ECO:0007829|PDB:4P13"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:4P13"
FT STRAND 175..179
FT /evidence="ECO:0007829|PDB:4P13"
FT STRAND 182..193
FT /evidence="ECO:0007829|PDB:4P13"
FT TURN 194..197
FT /evidence="ECO:0007829|PDB:4P13"
FT STRAND 198..206
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 215..218
FT /evidence="ECO:0007829|PDB:4P13"
FT STRAND 219..225
FT /evidence="ECO:0007829|PDB:4P13"
FT STRAND 231..236
FT /evidence="ECO:0007829|PDB:4P13"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:4P13"
FT STRAND 247..258
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:4P13"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:4P13"
FT TURN 266..268
FT /evidence="ECO:0007829|PDB:1EGE"
FT HELIX 269..303
FT /evidence="ECO:0007829|PDB:4P13"
FT STRAND 309..312
FT /evidence="ECO:0007829|PDB:1EGC"
FT HELIX 313..315
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 317..345
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 351..376
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 377..381
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 387..394
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 395..398
FT /evidence="ECO:0007829|PDB:4P13"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:4P13"
FT HELIX 404..417
FT /evidence="ECO:0007829|PDB:4P13"
SQ SEQUENCE 421 AA; 46588 MW; 7CD0B5832410581B CRC64;
MAAGFGRCCR VLRSISRFHW RSQHTKANRQ REPGLGFSFE FTEQQKEFQA TARKFAREEI
IPVAAEYDKT GEYPVPLIRR AWELGLMNTH IPENCGGLGL GTFDACLISE ELAYGCTGVQ
TAIEGNSLGQ MPIIIAGNDQ QKKKYLGRMT EEPLMCAYCV TEPGAGSDVA GIKTKAEKKG
DEYIINGQKM WITNGGKANW YFLLARSDPD PKAPANKAFT GFIVEADTPG IQIGRKELNM
GQRCSDTRGI VFEDVKVPKE NVLIGDGAGF KVAMGAFDKT RPVVAAGAVG LAQRALDEAT
KYALERKTFG KLLVEHQAIS FMLAEMAMKV ELARMSYQRA AWEVDSGRRN TYYASIAKAF
AGDIANQLAT DAVQILGGNG FNTEYPVEKL MRDAKIYQIY EGTSQIQRLI VAREHIDKYK
N
