ID ACDSB_HUMAN Reviewed; 432 AA.
AC P45954; Q5SQN6; Q96CX7;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 01-MAY-2013, entry version 141.
DE RecName: Full=Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial;
DE Short=SBCAD;
DE EC=1.3.8.5;
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;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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.,
RA Vicanek C., 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].
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
RT acyl-CoA dehydrogenase deficiency: identification of a new enzyme
RT defect, resolution of its molecular basis, and evidence for distinct
RT acyl-CoA dehydrogenases in isoleucine and valine metabolism.";
RL Am. J. Hum. Genet. 67:1095-1103(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=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.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-432, AND VARIANTS LYS-13
RP 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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 ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-284, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [9]
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.,
RA Buerckstuemmer T., 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 [10]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 52-432 IN COMPLEX WITH FAD
RP AND SUBSTRATE ANALOG, AND SUBUNIT.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human short-branched chain acyl-CoA
RT dehydrogenase.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [11]
RP VARIANT SBCADD PHE-255.
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.,
RA Linck L., Pohowalla P., Sacks M., Kiss D., Rinaldo P., Vockley J.;
RT "2-methylbutyryl-coenzyme A dehydrogenase deficiency: a new inborn
RT error of L-isoleucine metabolism.";
RL Pediatr. Res. 47:830-833(2000).
RN [12]
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
RT IVS3+3A>G mutation that causes exon skipping.";
RL Hum. Genet. 118:680-690(2006).
CC -!- FUNCTION: Has greatest activity toward short branched chain acyl-
CC CoA derivative such as (s)-2-methylbutyryl-CoA, isobutyryl-CoA,
CC and 2-methylhexanoyl-CoA as well as toward short straight chain
CC acyl-CoAs such as butyryl-CoA and hexanoyl-CoA. Can use valproyl-
CC CoA as substrate and may play a role in controlling the metabolic
CC flux of valproic acid in the development of toxicity of this
CC agent.
CC -!- CATALYTIC ACTIVITY: Acyl-CoA + acceptor = 2,3-dehydroacyl-CoA +
CC reduced acceptor.
CC -!- CATALYTIC ACTIVITY: 2-methylbutanoyl-CoA + electron-transfer
CC flavoprotein = (E)-2-methylbut-2-enoyl-CoA + reduced electron-
CC transfer flavoprotein + H(+).
CC -!- COFACTOR: FAD.
CC -!- PATHWAY: Lipid metabolism; mitochondrial fatty acid beta-
CC oxidation.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DISEASE: Short/branched-chain acyl-CoA dehydrogenase deficiency
CC (SBCADD) [MIM:610006]: Autosomal recessive disorder and consists
CC of a defect in catabolism of L-isoleucine which is characterized
CC by an increase of 2-methylbutyrylglycine and 2-
CC methylbutyrylcarnitine in blood and urine. Affected individuals
CC have seizures and psychomotor delay as the main clinical features.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ACADSB";
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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; AK314241; BAG36909.1; -; mRNA.
DR EMBL; AL731666; CAI10847.1; -; Genomic_DNA.
DR EMBL; AC012391; CAI10847.1; JOINED; Genomic_DNA.
DR EMBL; AC073585; CAI10847.1; JOINED; Genomic_DNA.
DR EMBL; CH471066; EAW49291.1; -; Genomic_DNA.
DR EMBL; BC013756; AAH13756.1; -; mRNA.
DR EMBL; AL831821; CAD38535.2; -; mRNA.
DR IPI; IPI00024623; -.
DR PIR; A55680; A55680.
DR RefSeq; NP_001600.1; NM_001609.3.
DR UniGene; Hs.81934; -.
DR PDB; 2JIF; X-ray; 2.00 A; A/B/C/D=52-432.
DR PDBsum; 2JIF; -.
DR ProteinModelPortal; P45954; -.
DR IntAct; P45954; 1.
DR STRING; 9606.ENSP00000357873; -.
DR PhosphoSite; P45954; -.
DR DMDM; 1168283; -.
DR PaxDb; P45954; -.
DR PeptideAtlas; P45954; -.
DR PRIDE; P45954; -.
DR DNASU; 36; -.
DR Ensembl; ENST00000358776; ENSP00000357873; ENSG00000196177.
DR GeneID; 36; -.
DR KEGG; hsa:36; -.
DR UCSC; uc001lhb.3; human.
DR CTD; 36; -.
DR GeneCards; GC10P124758; -.
DR HGNC; HGNC:91; ACADSB.
DR HPA; HPA041458; -.
DR MIM; 600301; gene.
DR MIM; 610006; phenotype.
DR neXtProt; NX_P45954; -.
DR Orphanet; 79157; 2-methylbutyryl-CoA dehydrogenase deficiency.
DR PharmGKB; PA24427; -.
DR eggNOG; COG1960; -.
DR HOGENOM; HOG000131659; -.
DR HOVERGEN; HBG000224; -.
DR InParanoid; P45954; -.
DR KO; K09478; -.
DR OMA; FIVDRET; -.
DR OrthoDB; EOG4RNB8F; -.
DR PhylomeDB; P45954; -.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00660; -.
DR ChiTaRS; ACADSB; human.
DR DrugBank; DB00167; L-Isoleucine.
DR EvolutionaryTrace; P45954; -.
DR GenomeRNAi; 36; -.
DR NextBio; 139; -.
DR ArrayExpress; P45954; -.
DR Bgee; P45954; -.
DR CleanEx; HS_ACADSB; -.
DR Genevestigator; P45954; -.
DR GermOnline; ENSG00000196177; Homo sapiens.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0003995; F:acyl-CoA dehydrogenase activity; EXP:Reactome.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0009083; P:branched-chain amino acid catabolic process; TAS:Reactome.
DR GO; GO:0034641; P:cellular nitrogen compound metabolic process; TAS:Reactome.
DR GO; GO:0006631; P:fatty acid metabolic process; TAS:ProtInc.
DR Gene3D; 1.10.540.10; -; 1.
DR Gene3D; 2.40.110.10; -; 1.
DR InterPro; IPR006089; Acyl-CoA_DH_CS.
DR InterPro; IPR006092; Acyl-CoA_DH_N.
DR InterPro; IPR006090; Acyl-CoA_Oxase/DH_1.
DR InterPro; IPR006091; Acyl-CoA_Oxase/DH_cen-dom.
DR InterPro; IPR009075; AcylCo_DH/oxidase_C.
DR InterPro; IPR013786; AcylCoA_DH/ox_N.
DR InterPro; IPR009100; AcylCoA_DH/oxidase.
DR Pfam; PF00441; Acyl-CoA_dh_1; 1.
DR Pfam; PF02770; Acyl-CoA_dh_M; 1.
DR Pfam; PF02771; Acyl-CoA_dh_N; 1.
DR SUPFAM; SSF56645; AcylCoA_dehyd_NM; 1.
DR SUPFAM; SSF47203; AcylCoADH_C_like; 1.
DR PROSITE; PS00072; ACYL_COA_DH_1; 1.
DR PROSITE; PS00073; ACYL_COA_DH_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Disease mutation; FAD;
KW Fatty acid metabolism; Flavoprotein; Lipid metabolism; Mitochondrion;
KW Oxidoreductase; Polymorphism; Reference proteome; Transit peptide.
FT TRANSIT 1 33 Mitochondrion.
FT CHAIN 34 432 Short/branched chain specific acyl-CoA
FT dehydrogenase, mitochondrial.
FT /FTId=PRO_0000000519.
FT NP_BIND 174 183 FAD.
FT NP_BIND 207 209 FAD.
FT NP_BIND 387 391 FAD; shared with dimeric partner.
FT NP_BIND 416 418 FAD.
FT REGION 229 230 Substrate binding.
FT REGION 291 294 Substrate binding.
FT ACT_SITE 414 414 Proton acceptor (By similarity).
FT BINDING 183 183 Substrate; via carbonyl oxygen.
FT BINDING 283 283 Substrate.
FT BINDING 319 319 FAD; shared with dimeric partner.
FT BINDING 330 330 FAD; shared with dimeric partner.
FT BINDING 415 415 Substrate; via amide nitrogen.
FT MOD_RES 284 284 N6-acetyllysine.
FT VARIANT 13 13 R -> K (in dbSNP:rs12263012).
FT /FTId=VAR_048177.
FT VARIANT 209 209 S -> G (in dbSNP:rs1799823).
FT /FTId=VAR_014749.
FT VARIANT 255 255 L -> F (in SBCADD).
FT /FTId=VAR_013010.
FT VARIANT 316 316 I -> V (in dbSNP:rs1131430).
FT /FTId=VAR_048178.
FT VARIANT 376 376 E -> G (in dbSNP:rs12357783).
FT /FTId=VAR_048179.
FT HELIX 59 75
FT HELIX 77 79
FT HELIX 80 86
FT HELIX 91 99
FT TURN 100 103
FT STRAND 104 107
FT HELIX 109 111
FT HELIX 118 129
FT HELIX 133 144
FT HELIX 146 153
FT HELIX 156 168
FT STRAND 172 175
FT STRAND 181 184
FT HELIX 185 187
FT STRAND 191 195
FT STRAND 198 209
FT TURN 210 213
FT STRAND 215 223
FT HELIX 225 231
FT STRAND 232 238
FT STRAND 244 246
FT STRAND 252 254
FT STRAND 260 271
FT HELIX 272 274
FT STRAND 275 278
FT HELIX 282 318
FT HELIX 326 328
FT HELIX 330 358
FT HELIX 364 389
FT HELIX 390 394
FT HELIX 400 407
FT HELIX 408 411
FT TURN 412 414
FT HELIX 417 431
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
//
