ACDSB_HUMAN
ID ACDSB_HUMAN Reviewed; 432 AA.
AC P45954; B4DQ51; Q5SQN6; Q96CX7;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial {ECO:0000305|PubMed:7698750};
DE Short=SBCAD {ECO:0000303|PubMed:7698750};
DE EC=1.3.8.5 {ECO:0000269|PubMed:10832746, ECO:0000269|PubMed:21430231};
DE AltName: Full=2-methyl branched chain acyl-CoA dehydrogenase;
DE Short=2-MEBCAD;
DE AltName: Full=2-methylbutyryl-coenzyme A dehydrogenase;
DE Short=2-methylbutyryl-CoA dehydrogenase;
DE Flags: Precursor;
GN Name=ACADSB {ECO:0000312|HGNC:HGNC:91};
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), FUNCTION, CATALYTIC ACTIVITY,
RP SUBSTRATE SPECIFICITY, AND TRANSIT PEPTIDE.
RC TISSUE=Liver;
RX PubMed=7698750; DOI=10.1006/geno.1994.1617;
RA Rozen R., Vockley J., Zhou L., Milos R., Willard J., Fu K., Vicanek C.,
RA Low-Nang L., Torban E., Fournier B.;
RT "Isolation and expression of a cDNA encoding the precursor for a novel
RT member (ACADSB) of the acyl-CoA dehydrogenase gene family.";
RL Genomics 24:280-287(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP INVOLVEMENT IN SBCADD, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=11013134; DOI=10.1086/303105;
RA Andresen B.S., Christensen E., Corydon T.J., Bross P., Pilgaard B.,
RA Wanders R.J.A., Ruiter J.P.N., Simonsen H., Winter V., Knudsen I.,
RA Schroeder L.D., Gregersen N., Skovby F.;
RT "Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA
RT dehydrogenase deficiency: identification of a new enzyme defect, resolution
RT of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases
RT in isoleucine and valine metabolism.";
RL Am. J. Hum. Genet. 67:1095-1103(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Esophagus, and Mammary gland;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LYS-13.
RC TISSUE=Mammary gland;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-432 (ISOFORM 1), AND VARIANTS
RP LYS-13 AND VAL-316.
RC TISSUE=Skeletal muscle;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=8660691; DOI=10.1006/abbi.1996.0290;
RA Willard J., Vicanek C., Battaile K.P., van Veldhoven P.P., Fauq A.H.,
RA Rozen R., Vockley J.;
RT "Cloning of a cDNA for short/branched chain acyl-Coenzyme A dehydrogenase
RT from rat and characterization of its tissue expression and substrate
RT specificity.";
RL Arch. Biochem. Biophys. 331:127-133(1996).
RN [9]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF
RP VAL-137; PHE-138; SER-210 AND ALA-416.
RX PubMed=12855692; DOI=10.1074/jbc.m306882200;
RA He M., Burghardt T.P., Vockley J.;
RT "A novel approach to the characterization of substrate specificity in
RT short/branched chain Acyl-CoA dehydrogenase.";
RL J. Biol. Chem. 278:37974-37986(2003).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-284, AND IDENTIFICATION BY MASS
RP 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 [11]
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 [12]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=21430231; DOI=10.1124/dmd.110.037606;
RA Luis P.B., Ruiter J.P., Ijlst L., Tavares de Almeida I., Duran M.,
RA Mohsen A.W., Vockley J., Wanders R.J., Silva M.F.;
RT "Role of isovaleryl-CoA dehydrogenase and short branched-chain acyl-CoA
RT dehydrogenase in the metabolism of valproic acid: implications for the
RT branched-chain amino acid oxidation pathway.";
RL Drug Metab. Dispos. 39:1155-1160(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183, AND IDENTIFICATION BY
RP 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 [14]
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 [15]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 52-432 IN COMPLEX WITH FAD AND
RP SUBSTRATE ANALOG, COFACTOR, SUBUNIT, AND ACTIVE SITE.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human short-branched chain acyl-CoA dehydrogenase.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [16]
RP VARIANT SBCADD PHE-255, CHARACTERIZATION OF VARIANT SBCADD PHE-255,
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10832746; DOI=10.1203/00006450-200006000-00025;
RA Gibson K.M., Burlingame T.G., Hogema B., Jakobs C., Schutgens R.B.H.,
RA Millington D., Roe C.R., Roe D.S., Sweetman L., Steiner R.D., Linck L.,
RA Pohowalla P., Sacks M., Kiss D., Rinaldo P., Vockley J.;
RT "2-methylbutyryl-coenzyme A dehydrogenase deficiency: a new inborn error of
RT L-isoleucine metabolism.";
RL Pediatr. Res. 47:830-833(2000).
RN [17]
RP VARIANT SBCADD PHE-255.
RX PubMed=16317551; DOI=10.1007/s00439-005-0070-4;
RA Madsen P.P., Kibaek M., Roca X., Sachidanandam R., Krainer A.R.,
RA Christensen E., Steiner R.D., Gibson K.M., Corydon T.J., Knudsen I.,
RA Wanders R.J., Ruiter J.P.N., Gregersen N., Andresen B.S.;
RT "Short/branched-chain acyl-CoA dehydrogenase deficiency due to an IVS3+3A>G
RT mutation that causes exon skipping.";
RL Hum. Genet. 118:680-690(2006).
CC -!- FUNCTION: Short and branched chain specific acyl-CoA dehydrogenase that
CC catalyzes the removal of one hydrogen from C-2 and C-3 of the fatty
CC acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA
CC (PubMed:7698750, PubMed:11013134, PubMed:21430231, PubMed:10832746).
CC Among the different mitochondrial acyl-CoA dehydrogenases, acts
CC specifically on short and branched chain acyl-CoA derivatives such as
CC (S)-2-methylbutyryl-CoA as well as short straight chain acyl-CoAs such
CC as butyryl-CoA (PubMed:7698750, PubMed:11013134, PubMed:21430231,
CC PubMed:10832746). Plays an important role in the metabolism of L-
CC isoleucine by catalyzing the dehydrogenation of 2-methylbutyryl-CoA,
CC one of the steps of the L-isoleucine catabolic pathway
CC (PubMed:11013134, PubMed:10832746). Can also act on valproyl-CoA, a
CC metabolite of valproic acid, an antiepileptic drug (PubMed:8660691).
CC {ECO:0000269|PubMed:10832746, ECO:0000269|PubMed:11013134,
CC ECO:0000269|PubMed:21430231, ECO:0000269|PubMed:7698750,
CC ECO:0000269|PubMed:8660691}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylbutanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-2-methylbut-2-enoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:43780, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57336,
CC ChEBI:CHEBI:57337, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307; EC=1.3.8.5;
CC Evidence={ECO:0000269|PubMed:10832746, ECO:0000269|PubMed:21430231};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43781;
CC Evidence={ECO:0000269|PubMed:10832746};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S)-2-methylbutanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-2-methylbut-2-enoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:48256, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57337,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:88166;
CC Evidence={ECO:0000269|PubMed:11013134, ECO:0000269|PubMed:12855692,
CC ECO:0000269|PubMed:7698750};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48257;
CC Evidence={ECO:0000305|PubMed:7698750};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-2-methylbutanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = ethylacryloyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:65296, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:156439, ChEBI:CHEBI:156440;
CC Evidence={ECO:0000250|UniProtKB:P70584};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65297;
CC Evidence={ECO:0000250|UniProtKB:P70584};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=butanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-butenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:24004, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57332, ChEBI:CHEBI:57371,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307;
CC Evidence={ECO:0000269|PubMed:7698750};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24005;
CC Evidence={ECO:0000305|PubMed:7698750};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylpropanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = (2E)-2-methylpropenoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:44180, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57338,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:62500;
CC Evidence={ECO:0000269|PubMed:7698750};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44181;
CC Evidence={ECO:0000305|PubMed:7698750};
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:12855692, ECO:0000269|PubMed:7698750};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43465;
CC Evidence={ECO:0000305|PubMed:7698750};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylhexanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = 2-methylhexenoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:48272, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:90156, ChEBI:CHEBI:90157;
CC Evidence={ECO:0000269|PubMed:7698750};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48273;
CC Evidence={ECO:0000305|PubMed:7698750};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + oxidized [electron-transfer flavoprotein] + valproyl-
CC CoA = (2E)-2-propylpent-2-enoyl-CoA + reduced [electron-transfer
CC flavoprotein]; Xref=Rhea:RHEA:65344, Rhea:RHEA-COMP:10685, Rhea:RHEA-
CC COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:156457, ChEBI:CHEBI:156458;
CC Evidence={ECO:0000269|PubMed:8660691};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65345;
CC Evidence={ECO:0000305|PubMed:8660691};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|Ref.15};
CC -!- ACTIVITY REGULATION: Competitively inhibited by valproyl-CoA.
CC {ECO:0000269|PubMed:21430231}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12 uM for 2-methylbutanoyl-CoA (at pH 8.0 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:21430231};
CC KM=2.7 uM for (2S)-2-methylbutanoyl-CoA (at 32 degrees Celsius)
CC {ECO:0000269|PubMed:12855692};
CC KM=36 uM for hexanoyl-CoA (at 32 degrees Celsius)
CC {ECO:0000269|PubMed:12855692};
CC KM=130 uM for 2-methylpropanoyl-CoA (at 32 degrees Celsius)
CC {ECO:0000269|PubMed:12855692};
CC Vmax=12 umol/min/mg enzyme with 2-methylbutanoyl-CoA as substrate (at
CC pH 8.0 and 37 degrees Celsius) {ECO:0000269|PubMed:21430231};
CC Note=kcat is 9700 sec(-1) for the dehydrogenation of (2S)-2-
CC methylbutanoyl-CoA (PubMed:12855692). kcat is 7600 sec(-1) for the
CC dehydrogenation of hexanoyl-CoA (PubMed:12855692). kcat is 2900 sec(-
CC 1) for the dehydrogenation of hexanoyl-CoA (PubMed:12855692).
CC {ECO:0000269|PubMed:12855692};
CC -!- PATHWAY: Lipid metabolism; mitochondrial fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:11013134}.
CC -!- PATHWAY: Amino-acid degradation; L-isoleucine degradation.
CC {ECO:0000269|PubMed:11013134}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:11013134,
CC ECO:0000269|Ref.15}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000305|PubMed:11013134}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P45954-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P45954-2; Sequence=VSP_055778;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:8660691}.
CC -!- DISEASE: Short/branched-chain acyl-CoA dehydrogenase deficiency
CC (SBCADD) [MIM:610006]: Autosomal recessive disorder and consists of a
CC defect in catabolism of L-isoleucine which is characterized by an
CC increase of 2-methylbutyrylglycine and 2-methylbutyrylcarnitine in
CC blood and urine. Affected individuals have seizures and psychomotor
CC delay as the main clinical features. {ECO:0000269|PubMed:10832746,
CC ECO:0000269|PubMed:11013134, ECO:0000269|PubMed:16317551}. 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; U12778; AAA74424.1; -; mRNA.
DR EMBL; AF260678; AAF97921.1; -; Genomic_DNA.
DR EMBL; AF260668; AAF97921.1; JOINED; Genomic_DNA.
DR EMBL; AF260669; AAF97921.1; JOINED; Genomic_DNA.
DR EMBL; AF260670; AAF97921.1; JOINED; Genomic_DNA.
DR EMBL; AF260671; AAF97921.1; JOINED; Genomic_DNA.
DR EMBL; AF260672; AAF97921.1; JOINED; Genomic_DNA.
DR EMBL; AF260673; AAF97921.1; JOINED; Genomic_DNA.
DR EMBL; AF260674; AAF97921.1; JOINED; Genomic_DNA.
DR EMBL; AF260675; AAF97921.1; JOINED; Genomic_DNA.
DR EMBL; AF260676; AAF97921.1; JOINED; Genomic_DNA.
DR EMBL; AF260677; AAF97921.1; JOINED; Genomic_DNA.
DR EMBL; AK298638; BAG60813.1; -; mRNA.
DR EMBL; AK314241; BAG36909.1; -; mRNA.
DR EMBL; AC012391; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC073585; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL731666; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49291.1; -; Genomic_DNA.
DR EMBL; BC013756; AAH13756.1; -; mRNA.
DR EMBL; AL831821; CAD38535.2; -; mRNA.
DR CCDS; CCDS7634.1; -. [P45954-1]
DR CCDS; CCDS81518.1; -. [P45954-2]
DR PIR; A55680; A55680.
DR RefSeq; NP_001317103.1; NM_001330174.1. [P45954-2]
DR RefSeq; NP_001600.1; NM_001609.3. [P45954-1]
DR PDB; 2JIF; X-ray; 2.00 A; A/B/C/D=52-432.
DR PDBsum; 2JIF; -.
DR AlphaFoldDB; P45954; -.
DR SMR; P45954; -.
DR BioGRID; 106554; 57.
DR IntAct; P45954; 21.
DR MINT; P45954; -.
DR STRING; 9606.ENSP00000357873; -.
DR DrugBank; DB00167; Isoleucine.
DR DrugBank; DB00313; Valproic acid.
DR SwissLipids; SLP:000001415; -.
DR iPTMnet; P45954; -.
DR PhosphoSitePlus; P45954; -.
DR SwissPalm; P45954; -.
DR BioMuta; ACADSB; -.
DR DMDM; 1168283; -.
DR EPD; P45954; -.
DR jPOST; P45954; -.
DR MassIVE; P45954; -.
DR MaxQB; P45954; -.
DR PaxDb; P45954; -.
DR PeptideAtlas; P45954; -.
DR PRIDE; P45954; -.
DR ProteomicsDB; 4844; -.
DR ProteomicsDB; 55690; -. [P45954-1]
DR Antibodypedia; 19074; 161 antibodies from 31 providers.
DR DNASU; 36; -.
DR Ensembl; ENST00000358776.7; ENSP00000357873.3; ENSG00000196177.13. [P45954-1]
DR Ensembl; ENST00000368869.8; ENSP00000357862.4; ENSG00000196177.13. [P45954-2]
DR GeneID; 36; -.
DR KEGG; hsa:36; -.
DR MANE-Select; ENST00000358776.7; ENSP00000357873.3; NM_001609.4; NP_001600.1.
DR UCSC; uc001lhb.4; human. [P45954-1]
DR CTD; 36; -.
DR DisGeNET; 36; -.
DR GeneCards; ACADSB; -.
DR HGNC; HGNC:91; ACADSB.
DR HPA; ENSG00000196177; Tissue enhanced (liver).
DR MalaCards; ACADSB; -.
DR MIM; 600301; gene.
DR MIM; 610006; phenotype.
DR neXtProt; NX_P45954; -.
DR OpenTargets; ENSG00000196177; -.
DR Orphanet; 79157; 2-methylbutyryl-CoA dehydrogenase deficiency.
DR PharmGKB; PA24427; -.
DR VEuPathDB; HostDB:ENSG00000196177; -.
DR eggNOG; KOG0139; Eukaryota.
DR GeneTree; ENSGT00940000156525; -.
DR HOGENOM; CLU_018204_0_0_1; -.
DR InParanoid; P45954; -.
DR OMA; LYREAPM; -.
DR OrthoDB; 663893at2759; -.
DR PhylomeDB; P45954; -.
DR TreeFam; TF105055; -.
DR BioCyc; MetaCyc:HS10828-MON; -.
DR PathwayCommons; P45954; -.
DR Reactome; R-HSA-70895; Branched-chain amino acid catabolism.
DR SignaLink; P45954; -.
DR UniPathway; UPA00364; -.
DR UniPathway; UPA00660; -.
DR BioGRID-ORCS; 36; 11 hits in 1075 CRISPR screens.
DR ChiTaRS; ACADSB; human.
DR EvolutionaryTrace; P45954; -.
DR GenomeRNAi; 36; -.
DR Pharos; P45954; Tbio.
DR PRO; PR:P45954; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P45954; protein.
DR Bgee; ENSG00000196177; Expressed in right lobe of liver and 193 other tissues.
DR ExpressionAtlas; P45954; baseline and differential.
DR Genevisible; P45954; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0047119; F:2-methyl-branched-chain-enoyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0003853; F:2-methylacyl-CoA dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0003995; F:acyl-CoA dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0102035; F:isobutyryl-CoA:FAD oxidoreductase activity; IEA:UniProtKB-EC.
DR GO; GO:0016937; F:short-branched-chain-acyl-CoA dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; IDA:UniProtKB.
DR GO; GO:0006550; P:isoleucine catabolic process; IMP:UniProtKB.
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 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; Disease variant; FAD;
KW Fatty acid metabolism; Flavoprotein; Lipid metabolism; Mitochondrion;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..33
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:7698750"
FT CHAIN 34..432
FT /note="Short/branched chain specific acyl-CoA
FT dehydrogenase, mitochondrial"
FT /id="PRO_0000000519"
FT ACT_SITE 414
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|Ref.15"
FT BINDING 174..183
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|Ref.15"
FT BINDING 183
FT /ligand="substrate"
FT /evidence="ECO:0000269|Ref.15"
FT BINDING 207..209
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|Ref.15"
FT BINDING 229
FT /ligand="substrate"
FT /evidence="ECO:0000269|Ref.15"
FT BINDING 283
FT /ligand="substrate"
FT /evidence="ECO:0000269|Ref.15"
FT BINDING 291..294
FT /ligand="substrate"
FT /evidence="ECO:0000269|Ref.15"
FT BINDING 319
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|Ref.15"
FT BINDING 330
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|Ref.15"
FT BINDING 387..391
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|Ref.15"
FT BINDING 416..418
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|Ref.15"
FT MOD_RES 70
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBL1"
FT MOD_RES 70
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBL1"
FT MOD_RES 183
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 284
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 284
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBL1"
FT MOD_RES 426
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBL1"
FT VAR_SEQ 1..102
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055778"
FT VARIANT 13
FT /note="R -> K (in dbSNP:rs12263012)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_048177"
FT VARIANT 209
FT /note="S -> G (in dbSNP:rs1799823)"
FT /id="VAR_014749"
FT VARIANT 255
FT /note="L -> F (in SBCADD; loss of protein expression; loss
FT of 2-methylbutyryl-CoA dehydrogenase activity;
FT dbSNP:rs137852649)"
FT /evidence="ECO:0000269|PubMed:10832746,
FT ECO:0000269|PubMed:16317551"
FT /id="VAR_013010"
FT VARIANT 316
FT /note="I -> V (in dbSNP:rs1131430)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_048178"
FT VARIANT 376
FT /note="E -> G (in dbSNP:rs12357783)"
FT /id="VAR_048179"
FT MUTAGEN 137
FT /note="V->L: Decreased acyl-CoA dehydrogenase activity."
FT /evidence="ECO:0000269|PubMed:12855692"
FT MUTAGEN 138
FT /note="F->L: Increased acyl-CoA dehydrogenase activity. No
FT effect on substrate specificity."
FT /evidence="ECO:0000269|PubMed:12855692"
FT MUTAGEN 210
FT /note="S->N: Increased acyl-CoA dehydrogenase activity.
FT Changed substrate specificity."
FT /evidence="ECO:0000269|PubMed:12855692"
FT MUTAGEN 416
FT /note="A->T: Increased acyl-CoA dehydrogenase activity. No
FT effect on substrate specificity."
FT /evidence="ECO:0000269|PubMed:12855692"
FT HELIX 59..75
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 80..86
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 91..99
FT /evidence="ECO:0007829|PDB:2JIF"
FT TURN 100..103
FT /evidence="ECO:0007829|PDB:2JIF"
FT STRAND 104..107
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 118..129
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 133..144
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 146..153
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 156..168
FT /evidence="ECO:0007829|PDB:2JIF"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:2JIF"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:2JIF"
FT STRAND 191..195
FT /evidence="ECO:0007829|PDB:2JIF"
FT STRAND 198..209
FT /evidence="ECO:0007829|PDB:2JIF"
FT TURN 210..213
FT /evidence="ECO:0007829|PDB:2JIF"
FT STRAND 215..223
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 225..231
FT /evidence="ECO:0007829|PDB:2JIF"
FT STRAND 232..238
FT /evidence="ECO:0007829|PDB:2JIF"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:2JIF"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:2JIF"
FT STRAND 260..271
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 272..274
FT /evidence="ECO:0007829|PDB:2JIF"
FT STRAND 275..278
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 282..318
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 326..328
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 330..358
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 364..389
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 390..394
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 400..407
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 408..411
FT /evidence="ECO:0007829|PDB:2JIF"
FT TURN 412..414
FT /evidence="ECO:0007829|PDB:2JIF"
FT HELIX 417..431
FT /evidence="ECO:0007829|PDB:2JIF"
SQ SEQUENCE 432 AA; 47485 MW; 1EB5F894B1944E99 CRC64;
MEGLAVRLLR GSRLLRRNFL TCLSSWKIPP HVSKSSQSEA LLNITNNGIH FAPLQTFTDE
EMMIKSSVKK FAQEQIAPLV STMDENSKME KSVIQGLFQQ GLMGIEVDPE YGGTGASFLS
TVLVIEELAK VDASVAVFCE IQNTLINTLI RKHGTEEQKA TYLPQLTTEK VGSFCLSEAG
AGSDSFALKT RADKEGDYYV LNGSKMWISS AEHAGLFLVM ANVDPTIGYK GITSFLVDRD
TPGLHIGKPE NKLGLRASST CPLTFENVKV PEANILGQIG HGYKYAIGSL NEGRIGIAAQ
MLGLAQGCFD YTIPYIKERI QFGKRLFDFQ GLQHQVAHVA TQLEAARLLT YNAARLLEAG
KPFIKEASMA KYYASEIAGQ TTSKCIEWMG GVGYTKDYPV EKYFRDAKIG TIYEGASNIQ
LNTIAKHIDA EY
