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 27-MAR-2024, entry version 223. 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 CC (2S)-2-methylbutanoyl-CoA (PubMed:12855692). kcat is 7600 sec(-1) for CC the dehydrogenation of hexanoyl-CoA (PubMed:12855692). kcat is 2900 CC sec(-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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 72. DR IntAct; P45954; 22. 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; 9606-ENSP00000357873; -. DR PeptideAtlas; P45954; -. DR ProteomicsDB; 4844; -. DR ProteomicsDB; 55690; -. [P45954-1] DR Pumba; P45954; -. DR Antibodypedia; 19074; 169 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 AGR; HGNC:91; -. DR CTD; 36; -. DR DisGeNET; 36; -. DR GeneCards; ACADSB; -. DR HGNC; HGNC:91; ACADSB. DR HPA; ENSG00000196177; Tissue enriched (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; DAMFSYC; -. DR OrthoDB; 275353at2759; -. DR PhylomeDB; P45954; -. DR TreeFam; TF105055; -. DR BioCyc; MetaCyc:HS10828-MONOMER; -. 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 1154 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 195 other cell types or tissues. DR ExpressionAtlas; P45954; baseline and differential. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. 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:0004085; F:butyryl-CoA dehydrogenase activity; IEA:RHEA. 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-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 CDD; cd01158; SCAD_SBCAD; 1. DR Gene3D; 1.10.540.10; Acyl-CoA dehydrogenase/oxidase, N-terminal domain; 1. DR Gene3D; 2.40.110.10; Butyryl-CoA Dehydrogenase, subunit A, domain 2; 1. DR Gene3D; 1.20.140.10; Butyryl-CoA Dehydrogenase, subunit A, domain 3; 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_sf. DR PANTHER; PTHR43884; ACYL-COA DEHYDROGENASE; 1. DR PANTHER; PTHR43884:SF1; SHORT_BRANCHED CHAIN SPECIFIC ACYL-COA DEHYDROGENASE, MITOCHONDRIAL; 1. 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; Acyl-CoA dehydrogenase C-terminal domain-like; 1. DR SUPFAM; SSF56645; Acyl-CoA dehydrogenase NM domain-like; 1. DR PROSITE; PS00072; ACYL_COA_DH_1; 1. DR PROSITE; PS00073; ACYL_COA_DH_2; 1. DR Genevisible; P45954; HS. 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 //