IVD_MOUSE
ID IVD_MOUSE Reviewed; 424 AA.
AC Q9JHI5; Q9CYI3; Q9DBD7;
DT 24-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Isovaleryl-CoA dehydrogenase, mitochondrial;
DE Short=IVD;
DE EC=1.3.8.4 {ECO:0000250|UniProtKB:P26440};
DE AltName: Full=Butyryl-CoA dehydrogenase;
DE EC=1.3.8.1 {ECO:0000250|UniProtKB:P26440};
DE Flags: Precursor;
GN Name=Ivd;
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 [GENOMIC DNA / MRNA].
RC STRAIN=129/Ola;
RX PubMed=11404023; DOI=10.1016/s0378-1119(01)00466-8;
RA Willard J.M., Reinard T., Mohsen A.W., Vockley J.;
RT "Cloning of genomic and cDNA for mouse isovaleryl-CoA dehydrogenase (IVD)
RT and evolutionary comparison to other known IVDs.";
RL Gene 270:253-257(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney, and Salivary 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 [4]
RP PROTEIN SEQUENCE OF 57-76; 154-178; 212-221; 231-239; 273-285; 339-346;
RP 400-411 AND 418-424, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
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 [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-56; LYS-65; LYS-76; LYS-260 AND
RP LYS-316, AND 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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-56; LYS-65; LYS-76; LYS-239 AND
RP LYS-260, AND 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: Catalyzes the conversion of isovaleryl-CoA/3-methylbutanoyl-
CC CoA to 3-methylbut-2-enoyl-CoA as an intermediate step in the leucine
CC (Leu) catabolic pathway. To a lesser extent, is also able to catalyze
CC the oxidation of other saturated short-chain acyl-CoA thioesters as
CC pentanoyl-CoA, hexenoyl-CoA and butenoyl-CoA.
CC {ECO:0000250|UniProtKB:P26440}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-methylbutanoyl-CoA + H(+) + oxidized [electron-transfer
CC flavoprotein] = 3-methyl-(2E)-butenoyl-CoA + reduced [electron-
CC transfer flavoprotein]; Xref=Rhea:RHEA:12276, Rhea:RHEA-COMP:10685,
CC Rhea:RHEA-COMP:10686, ChEBI:CHEBI:15378, ChEBI:CHEBI:57344,
CC ChEBI:CHEBI:57345, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307; EC=1.3.8.4;
CC Evidence={ECO:0000250|UniProtKB:P26440};
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:P26440};
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:0000250|UniProtKB:P26440};
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; EC=1.3.8.1;
CC Evidence={ECO:0000250|UniProtKB:P26440};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P26440};
CC -!- PATHWAY: Amino-acid degradation; L-leucine degradation; (S)-3-hydroxy-
CC 3-methylglutaryl-CoA from 3-isovaleryl-CoA: step 1/3.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P26440}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P12007}.
CC -!- PTM: Acetylation of Lys-76 is observed in liver mitochondria from
CC fasted mice but not from fed mice.
CC -!- SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AF225989; AAF35888.1; -; mRNA.
DR EMBL; AF226043; AAF67667.1; -; Genomic_DNA.
DR EMBL; AF226039; AAF67667.1; JOINED; Genomic_DNA.
DR EMBL; AF226041; AAF67667.1; JOINED; Genomic_DNA.
DR EMBL; AF226040; AAF67667.1; JOINED; Genomic_DNA.
DR EMBL; AF226042; AAF67667.1; JOINED; Genomic_DNA.
DR EMBL; AK005024; BAB23751.1; -; mRNA.
DR EMBL; AK017660; BAB30859.1; -; mRNA.
DR EMBL; BC018325; AAH18325.1; -; mRNA.
DR EMBL; BC027198; AAH27198.1; -; mRNA.
DR CCDS; CCDS16586.1; -.
DR RefSeq; NP_062800.1; NM_019826.3.
DR AlphaFoldDB; Q9JHI5; -.
DR SMR; Q9JHI5; -.
DR BioGRID; 207921; 4.
DR STRING; 10090.ENSMUSP00000028807; -.
DR iPTMnet; Q9JHI5; -.
DR PhosphoSitePlus; Q9JHI5; -.
DR SwissPalm; Q9JHI5; -.
DR REPRODUCTION-2DPAGE; IPI00471246; -.
DR REPRODUCTION-2DPAGE; Q9JHI5; -.
DR UCD-2DPAGE; Q9JHI5; -.
DR EPD; Q9JHI5; -.
DR jPOST; Q9JHI5; -.
DR MaxQB; Q9JHI5; -.
DR PaxDb; Q9JHI5; -.
DR PeptideAtlas; Q9JHI5; -.
DR PRIDE; Q9JHI5; -.
DR ProteomicsDB; 269417; -.
DR Antibodypedia; 23079; 234 antibodies from 27 providers.
DR DNASU; 56357; -.
DR Ensembl; ENSMUST00000028807; ENSMUSP00000028807; ENSMUSG00000027332.
DR GeneID; 56357; -.
DR KEGG; mmu:56357; -.
DR UCSC; uc008lsv.1; mouse.
DR CTD; 3712; -.
DR MGI; MGI:1929242; Ivd.
DR VEuPathDB; HostDB:ENSMUSG00000027332; -.
DR eggNOG; KOG0141; Eukaryota.
DR GeneTree; ENSGT00940000158100; -.
DR HOGENOM; CLU_018204_0_1_1; -.
DR InParanoid; Q9JHI5; -.
DR OMA; CFITNSG; -.
DR OrthoDB; 589058at2759; -.
DR PhylomeDB; Q9JHI5; -.
DR TreeFam; TF105050; -.
DR BRENDA; 1.3.8.4; 3474.
DR Reactome; R-MMU-70895; Branched-chain amino acid catabolism.
DR UniPathway; UPA00363; UER00860.
DR BioGRID-ORCS; 56357; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Ivd; mouse.
DR PRO; PR:Q9JHI5; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9JHI5; protein.
DR Bgee; ENSMUSG00000027332; Expressed in retinal neural layer and 267 other tissues.
DR Genevisible; Q9JHI5; MM.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0003995; F:acyl-CoA dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0004085; F:butyryl-CoA dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0008470; F:isovaleryl-CoA dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0009083; P:branched-chain amino acid catabolic process; ISS:UniProtKB.
DR GO; GO:0033539; P:fatty acid beta-oxidation using acyl-CoA dehydrogenase; ISO:MGI.
DR GO; GO:0006552; P:leucine catabolic process; ISS:UniProtKB.
DR CDD; cd01156; IVD; 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; IPR034183; IVD.
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 Acetylation; Direct protein sequencing; FAD; Flavoprotein; Mitochondrion;
KW Oxidoreductase; Reference proteome; Transit peptide.
FT TRANSIT 1..30
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT CHAIN 31..424
FT /note="Isovaleryl-CoA dehydrogenase, mitochondrial"
FT /id="PRO_0000000532"
FT ACT_SITE 284
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 163..172
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 172
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 196..198
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 220..221
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 275
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 282..285
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 310
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 321
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 378..382
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 405..406
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT BINDING 407..409
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P26440"
FT MOD_RES 56
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 56
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 65
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 65
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 76
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 76
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 239
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 260
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 260
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 316
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 29
FT /note="R -> G (in Ref. 2; BAB23751)"
FT /evidence="ECO:0000305"
FT CONFLICT 41
FT /note="N -> K (in Ref. 2; BAB30859)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 424 AA; 46325 MW; 7B8A556A9E73B0B6 CRC64;
MATAIRLLGR RVSSWRLRPS PSPLAVPRRA HSILPVDDDI NGLNEEQKQL RHTISKFLQE
NLAPKAQEID QTNDFKNLRE FWKQLGSLGV LGITAPVQYG GSGLGYLEHV LVMEEISRAS
GAVGLSYGAH SNLCVNQIVR NGNEAQKEKY LPKLISGEFI GALAMSEPNA GSDVVSMKLK
AEKKGDHYVL NGNKFWITNG PDADILVVYA KTDLTAVPAS RGITAFIVEK GMPGFSTSKK
LDKLGMRGSN TCELVFEDCK VPAANVLSQE SKGVYVLMSG LDLERLVLAG GPLGIMQAVL
DHTIPYLHVR EAFGQKIGQF QLMQGKMADM YTRLMASRQY VYNVAKACDE GHIIPKDCAG
VILYAAECAT QVALDGIQCL GGNGYINDFP MGRFLRDAKL YEIGAGTSEV RRLVIGRAFN
ADFR
