ACAD8_MOUSE
ID ACAD8_MOUSE Reviewed; 413 AA.
AC Q9D7B6; Q8BK36; Q8BKQ8; Q8CFY9; Q9D2L8;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2003, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Isobutyryl-CoA dehydrogenase, mitochondrial;
DE EC=1.3.8.- {ECO:0000250|UniProtKB:Q9UKU7};
DE AltName: Full=Acyl-CoA dehydrogenase family member 8;
DE Short=ACAD-8;
DE Flags: Precursor;
GN Name=Acad8;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, Pituitary, Skin, Testis, and Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; 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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-48; LYS-211 AND LYS-269, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-48 AND LYS-229, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Isobutyryl-CoA dehydrogenase which catalyzes one of the steps
CC of the valine catabolic pathway. To a lesser extent, is also able to
CC catalyze the oxidation of (2S)-2-methylbutanoyl-CoA.
CC {ECO:0000250|UniProtKB:Q9UKU7}.
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:0000250|UniProtKB:Q9UKU7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44181;
CC Evidence={ECO:0000250|UniProtKB:Q9UKU7};
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:0000250|UniProtKB:Q9UKU7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48257;
CC Evidence={ECO:0000250|UniProtKB:Q9UKU7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + oxidized [electron-transfer flavoprotein] + propanoyl-
CC CoA = acryloyl-CoA + reduced [electron-transfer flavoprotein];
CC Xref=Rhea:RHEA:31287, Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57367, ChEBI:CHEBI:57392,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307;
CC Evidence={ECO:0000250|UniProtKB:Q9UKU7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31288;
CC Evidence={ECO:0000250|UniProtKB:Q9UKU7};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q9UKU7};
CC -!- PATHWAY: Amino-acid degradation; L-valine degradation.
CC {ECO:0000250|UniProtKB:Q9UKU7}.
CC -!- SUBUNIT: Homotetramer, formed by a dimer of dimers.
CC {ECO:0000250|UniProtKB:Q9UKU7}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q9UKU7}.
CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC26664.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK009379; BAB26255.2; -; mRNA.
DR EMBL; AK019502; BAB31764.1; -; mRNA.
DR EMBL; AK029897; BAC26664.1; ALT_INIT; mRNA.
DR EMBL; AK051091; BAC34521.1; -; mRNA.
DR EMBL; AK077335; BAC36757.1; -; mRNA.
DR EMBL; BC037644; AAH37644.1; -; mRNA.
DR CCDS; CCDS40567.1; -.
DR RefSeq; NP_080138.2; NM_025862.2.
DR AlphaFoldDB; Q9D7B6; -.
DR SMR; Q9D7B6; -.
DR BioGRID; 211829; 2.
DR STRING; 10090.ENSMUSP00000112908; -.
DR iPTMnet; Q9D7B6; -.
DR PhosphoSitePlus; Q9D7B6; -.
DR SwissPalm; Q9D7B6; -.
DR EPD; Q9D7B6; -.
DR jPOST; Q9D7B6; -.
DR MaxQB; Q9D7B6; -.
DR PaxDb; Q9D7B6; -.
DR PeptideAtlas; Q9D7B6; -.
DR PRIDE; Q9D7B6; -.
DR ProteomicsDB; 285631; -.
DR DNASU; 66948; -.
DR GeneID; 66948; -.
DR KEGG; mmu:66948; -.
DR UCSC; uc009opy.2; mouse.
DR CTD; 27034; -.
DR MGI; MGI:1914198; Acad8.
DR eggNOG; KOG0140; Eukaryota.
DR InParanoid; Q9D7B6; -.
DR OrthoDB; 819314at2759; -.
DR Reactome; R-MMU-70895; Branched-chain amino acid catabolism.
DR UniPathway; UPA00362; -.
DR BioGRID-ORCS; 66948; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Acad8; mouse.
DR PRO; PR:Q9D7B6; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9D7B6; protein.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0003995; F:acyl-CoA dehydrogenase activity; IEA:InterPro.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IEA:UniProt.
DR GO; GO:0006574; P:valine catabolic process; IEA:UniProtKB-UniPathway.
DR CDD; cd01162; IBD; 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; IPR034178; IBD.
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.
PE 1: Evidence at protein level;
KW Acetylation; Branched-chain amino acid catabolism; FAD; Flavoprotein;
KW Mitochondrion; Oxidoreductase; Reference proteome; Transit peptide.
FT TRANSIT 1..20
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 21..413
FT /note="Isobutyryl-CoA dehydrogenase, mitochondrial"
FT /id="PRO_0000000523"
FT ACT_SITE 396
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9UKU7"
FT BINDING 156..165
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:0000250|UniProtKB:Q9UKU7"
FT BINDING 165
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9UKU7"
FT BINDING 189..191
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:0000250|UniProtKB:Q9UKU7"
FT BINDING 272..275
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9UKU7"
FT BINDING 300
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q9UKU7"
FT BINDING 310..311
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q9UKU7"
FT BINDING 369..373
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q9UKU7"
FT BINDING 398..400
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:0000250|UniProtKB:Q9UKU7"
FT BINDING 408
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9UKU7"
FT MOD_RES 48
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 48
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 211
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 229
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 269
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 207
FT /note="G -> E (in Ref. 1; BAB26255/BAB31764/BAC26664/
FT BAC34521/BAC36757)"
FT /evidence="ECO:0000305"
FT CONFLICT 254
FT /note="A -> P (in Ref. 1; BAC34521)"
FT /evidence="ECO:0000305"
FT CONFLICT 413
FT /note="D -> RLAPKLESLAWSLCAAGISLDAPMGCSVQVNHEVDQRAELF (in
FT Ref. 1; BAB31764)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 413 AA; 45020 MW; 13DED42D4BD51231 CRC64;
MAMLRSGYRR FGCLRAALKS LAQTHHRSIT FCIDPSLGLN EEQKGFQKVA FDFAAREMAP
NMAEWDQKEL FPVDVMRKAA QLGFGGVYVR TDVGGSGLSR LDTSVIFEAL ATGCTSTTAY
ISIHNMCAWM IDSFGNEEQR HKFCPPLCTM EKFASYCLTE PGSGSDAASL LTSAKQQGDH
YILNGSKAFI SGGGESDIYV VMCRTGGSGA KGISCIVVEK GTPGLSFGKK EKKVGWNSQP
TRAVIFEDCA VPVANRIGTE GQGFLIAMKG LNGGRINVAS CSLGAAHASV ILTQEHLKVR
KQFGAPLARS QYLQFQLADM ATKLVASRLM IRTAAVALQE EREDAVALCS MAKLFATEEC
FAICNQALQM HGGYGYLKDY AVQQYMRDSR VHQILEGSNE VMRMLISRNL LQD
