IVD_HUMAN
ID IVD_HUMAN Reviewed; 426 AA.
AC P26440; B2RCV5; B3KVI7; J3KR54; Q53XZ9; Q96AF6;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 2.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Isovaleryl-CoA dehydrogenase, mitochondrial {ECO:0000305};
DE Short=IVD;
DE EC=1.3.8.4 {ECO:0000269|PubMed:7640268};
DE AltName: Full=Butyryl-CoA dehydrogenase;
DE EC=1.3.8.1 {ECO:0000269|PubMed:7640268};
DE Flags: Precursor;
GN Name=IVD {ECO:0000312|HGNC:HGNC:6186};
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).
RX PubMed=2318964; DOI=10.1172/jci114536;
RA Matsubara Y., Ito M., Glassberg R., Satyabhama S., Ikeda Y., Tanaka K.;
RT "Nucleotide sequence of messenger RNA encoding human isovaleryl-coenzyme A
RT dehydrogenase and its expression in isovaleric acidemia fibroblasts.";
RL J. Clin. Invest. 85:1058-1064(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10677295; DOI=10.1086/302751;
RA Vockley J., Rogan P.K., Anderson B.D., Willard J., Seelan R.S., Smith D.I.,
RA Liu W.;
RT "Exon skipping in IVD RNA processing in isovaleric acidemia caused by point
RT mutations in the coding region of the IVD gene.";
RL Am. J. Hum. Genet. 66:356-367(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Pericardium, and Testis;
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=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 4-426 (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 384-426.
RX PubMed=8468053; DOI=10.1006/geno.1993.1111;
RA Parimoo B., Tanaka K.;
RT "Structural organization of the human isovaleryl-CoA dehydrogenase gene.";
RL Genomics 15:582-590(1993).
RN [9]
RP PROTEIN SEQUENCE OF N-TERMINUS.
RX PubMed=1310317; DOI=10.1016/s0021-9258(18)45906-6;
RA Vockley J., Nagao M., Parimoo B., Tanaka K.;
RT "The variant human isovaleryl-CoA dehydrogenase gene responsible for type
RT II isovaleric acidemia determines an RNA splicing error, leading to the
RT deletion of the entire second coding exon and the production of a truncated
RT precursor protein that interacts poorly with mitochondrial import
RT receptors.";
RL J. Biol. Chem. 267:2494-2501(1992).
RN [10]
RP PROTEIN SEQUENCE OF 33-50.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [11]
RP ACTIVE SITE, MUTAGENESIS OF GLU-286 AND ALA-407, CATALYTIC ACTIVITY,
RP FUNCTION, AND SUBSTRATE SPECIFICITY.
RX PubMed=7640268; DOI=10.1021/bi00032a007;
RA Mohsen A.W., Vockley J.;
RT "Identification of the active site catalytic residue in human isovaleryl-
RT CoA dehydrogenase.";
RL Biochemistry 34:10146-10152(1995).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-78, 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 [13]
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 [14]
RP IDENTIFICATION BY 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 [15]
RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER ALA-32, AND
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 [16]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 33-426 IN COMPLEX WITH FAD AND
RP SUBSTRATE ANALOG, AND COFACTOR.
RX PubMed=9214289; DOI=10.1021/bi970422u;
RA Tiffany K.A., Roberts D.L., Wang M., Paschke R., Mohsen A.W., Vockley J.,
RA Kim J.-J.P.;
RT "Structure of human isovaleryl-CoA dehydrogenase at 2.6-A resolution:
RT structural basis for substrate specificity.";
RL Biochemistry 36:8455-8464(1997).
RN [17]
RP VARIANTS IVA PRO-45 AND VAL-202.
RX PubMed=2063866;
RA Vockley J., Parimoo B., Tanaka K.;
RT "Molecular characterization of four different classes of mutations in the
RT isovaleryl-CoA dehydrogenase gene responsible for isovaleric acidemia.";
RL Am. J. Hum. Genet. 49:147-157(1991).
RN [18]
RP VARIANTS IVA PRO-53; ASN-72; VAL-314; ARG-360; ALA-374; CYS-395 AND
RP LEU-414.
RX PubMed=9665741; DOI=10.1021/bi973096r;
RA Mohsen A.-W.A., Anderson B.D., Volchenboum S.L., Battaile K.P.,
RA Tiffany K.A., Roberts D.L., Kim J.-J.P., Vockley J.;
RT "Characterization of molecular defects in isovaleryl-CoA dehydrogenase in
RT patients with isovaleric acidemia.";
RL Biochemistry 37:10325-10335(1998).
RN [19]
RP VARIANTS IVA GLY-97; ARG-123; PRO-279 AND CYS-403.
RX PubMed=22004070; DOI=10.1111/j.1442-200x.2011.03488.x;
RA Vatanavicharn N., Liammongkolkul S., Sakamoto O., Sathienkijkanchai A.,
RA Wasant P.;
RT "Phenotypic and mutation spectrums of Thai patients with isovaleric
RT acidemia.";
RL Pediatr. Int. 53:990-994(2011).
RN [20]
RP VARIANT IVA ARG-123.
RX PubMed=22350545; DOI=10.1007/s10545-012-9457-2;
RA Dercksen M., Duran M., Ijlst L., Mienie L.J., Reinecke C.J., Ruiter J.P.,
RA Waterham H.R., Wanders R.J.;
RT "Clinical variability of isovaleric acidemia in a genetically homogeneous
RT population.";
RL J. Inherit. Metab. Dis. 35:1021-1029(2012).
RN [21]
RP VARIANT IVA MET-199.
RX PubMed=23587913; DOI=10.1016/j.gene.2013.03.139;
RA Bei F., Sun J.H., Yu Y.G., Jia J., Zheng Z.J., Fu Q.H., Cai W.;
RT "Two novel isovaleryl-CoA dehydrogenase gene mutations in a Chinese
RT infant.";
RL Gene 524:396-400(2013).
RN [22]
RP VARIANTS IVA ALA-250; VAL-291; THR-379; GLN-398 AND ASN-403.
RX PubMed=28535199; DOI=10.1093/hmg/ddx195;
RA Zaki O.K., Priya Doss C.G., Ali S.A., Murad G.G., Elashi S.A.,
RA Ebnou M.S.A., Kumar D T., Khalifa O., Gamal R., El Abd H.S.A., Nasr B.N.,
RA Zayed H.;
RT "Genotype-phenotype correlation in patients with isovaleric acidaemia:
RT comparative structural modelling and computational analysis of novel
RT variants.";
RL Hum. Mol. Genet. 26:3105-3115(2017).
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 (PubMed:7640268). To a lesser extent, is also
CC able to catalyze the oxidation of other saturated short-chain acyl-CoA
CC thioesters as pentanoyl-CoA, hexenoyl-CoA and butenoyl-CoA
CC (PubMed:7640268). {ECO:0000269|PubMed:7640268}.
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:0000269|PubMed:7640268};
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:0000269|PubMed:7640268};
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:7640268};
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:0000269|PubMed:7640268};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:9214289};
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:0000269|PubMed:9214289}.
CC -!- INTERACTION:
CC P26440; Q08043: ACTN3; NbExp=3; IntAct=EBI-2866408, EBI-2880652;
CC P26440; Q9Y4H4: GPSM3; NbExp=3; IntAct=EBI-2866408, EBI-347538;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P12007}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P26440-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P26440-2; Sequence=VSP_045193;
CC -!- DISEASE: Isovaleric acidemia (IVA) [MIM:243500]: A metabolic disorder
CC characterized by retarded psychomotor development, a peculiar odor
CC resembling sweaty feet, an aversion to dietary protein, and pernicious
CC vomiting, leading to acidosis and coma. The acute neonatal form leads
CC to massive metabolic acidosis from the first days of life and rapid
CC death. {ECO:0000269|PubMed:2063866, ECO:0000269|PubMed:22004070,
CC ECO:0000269|PubMed:22350545, ECO:0000269|PubMed:23587913,
CC ECO:0000269|PubMed:28535199, ECO:0000269|PubMed:9665741}. 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 -!- CAUTION: It is uncertain whether Met-1 or Met-4 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA52711.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAB92584.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH17202.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG37702.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; M34192; AAA52711.1; ALT_INIT; mRNA.
DR EMBL; AF191218; AAF20182.1; -; Genomic_DNA.
DR EMBL; AF191214; AAF20182.1; JOINED; Genomic_DNA.
DR EMBL; AF191215; AAF20182.1; JOINED; Genomic_DNA.
DR EMBL; AF191216; AAF20182.1; JOINED; Genomic_DNA.
DR EMBL; AF191217; AAF20182.1; JOINED; Genomic_DNA.
DR EMBL; AK122922; BAG53799.1; -; mRNA.
DR EMBL; AK315296; BAG37702.1; ALT_INIT; mRNA.
DR EMBL; AC013356; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471125; EAW92413.1; -; Genomic_DNA.
DR EMBL; CH471125; EAW92414.1; -; Genomic_DNA.
DR EMBL; CH471125; EAW92415.1; -; Genomic_DNA.
DR EMBL; BC017202; AAH17202.1; ALT_INIT; mRNA.
DR EMBL; AF038318; AAB92584.1; ALT_INIT; Genomic_DNA.
DR EMBL; BT007145; AAP35809.1; -; mRNA.
DR PIR; A37033; A37033.
DR RefSeq; NP_001152980.1; NM_001159508.1.
DR RefSeq; NP_002216.2; NM_002225.3.
DR PDB; 1IVH; X-ray; 2.60 A; A/B/C/D=33-426.
DR PDBsum; 1IVH; -.
DR AlphaFoldDB; P26440; -.
DR SMR; P26440; -.
DR BioGRID; 109916; 78.
DR IntAct; P26440; 19.
DR STRING; 9606.ENSP00000418397; -.
DR DrugBank; DB04036; Coenzyme A persulfide.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR SwissLipids; SLP:000000936; -.
DR iPTMnet; P26440; -.
DR PhosphoSitePlus; P26440; -.
DR SwissPalm; P26440; -.
DR BioMuta; IVD; -.
DR DMDM; 125051; -.
DR REPRODUCTION-2DPAGE; IPI00645805; -.
DR UCD-2DPAGE; P26440; -.
DR EPD; P26440; -.
DR jPOST; P26440; -.
DR MassIVE; P26440; -.
DR MaxQB; P26440; -.
DR PaxDb; P26440; -.
DR PeptideAtlas; P26440; -.
DR PRIDE; P26440; -.
DR ProteomicsDB; 3759; -.
DR ProteomicsDB; 54348; -. [P26440-1]
DR Antibodypedia; 23079; 234 antibodies from 27 providers.
DR DNASU; 3712; -.
DR Ensembl; ENST00000650656.1; ENSP00000498731.1; ENSG00000128928.10. [P26440-2]
DR Ensembl; ENST00000651168.1; ENSP00000499074.1; ENSG00000128928.10. [P26440-1]
DR GeneID; 3712; -.
DR KEGG; hsa:3712; -.
DR UCSC; uc001zlq.3; human. [P26440-1]
DR CTD; 3712; -.
DR DisGeNET; 3712; -.
DR GeneCards; IVD; -.
DR HGNC; HGNC:6186; IVD.
DR HPA; ENSG00000128928; Low tissue specificity.
DR MalaCards; IVD; -.
DR MIM; 243500; phenotype.
DR MIM; 607036; gene.
DR neXtProt; NX_P26440; -.
DR OpenTargets; ENSG00000128928; -.
DR Orphanet; 33; Isovaleric acidemia.
DR PharmGKB; PA29984; -.
DR VEuPathDB; HostDB:ENSG00000128928; -.
DR eggNOG; KOG0141; Eukaryota.
DR GeneTree; ENSGT00940000158100; -.
DR HOGENOM; CLU_018204_3_5_1; -.
DR InParanoid; P26440; -.
DR OrthoDB; 589058at2759; -.
DR PhylomeDB; P26440; -.
DR TreeFam; TF105050; -.
DR BRENDA; 1.3.8.4; 2681.
DR PathwayCommons; P26440; -.
DR Reactome; R-HSA-70895; Branched-chain amino acid catabolism.
DR SABIO-RK; P26440; -.
DR SignaLink; P26440; -.
DR UniPathway; UPA00363; UER00860.
DR BioGRID-ORCS; 3712; 9 hits in 1082 CRISPR screens.
DR ChiTaRS; IVD; human.
DR EvolutionaryTrace; P26440; -.
DR GenomeRNAi; 3712; -.
DR Pharos; P26440; Tbio.
DR PRO; PR:P26440; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P26440; protein.
DR Bgee; ENSG00000128928; Expressed in right lobe of thyroid gland and 184 other tissues.
DR ExpressionAtlas; P26440; baseline and differential.
DR Genevisible; P26440; HS.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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; IDA:UniProtKB.
DR GO; GO:0009083; P:branched-chain amino acid catabolic process; IDA:UniProtKB.
DR GO; GO:0033539; P:fatty acid beta-oxidation using acyl-CoA dehydrogenase; IDA:BHF-UCL.
DR GO; GO:0006552; P:leucine catabolic process; IDA: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 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing;
KW Disease variant; FAD; Fatty acid metabolism; Flavoprotein;
KW Lipid metabolism; Mitochondrion; Oxidoreductase; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..32
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0000269|PubMed:1310317, ECO:0007744|PubMed:25944712"
FT CHAIN 33..426
FT /note="Isovaleryl-CoA dehydrogenase, mitochondrial"
FT /id="PRO_0000000531"
FT ACT_SITE 286
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:7640268,
FT ECO:0007744|PDB:1IVH"
FT BINDING 165..174
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:9214289,
FT ECO:0007744|PDB:1IVH"
FT BINDING 174
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:9214289,
FT ECO:0007744|PDB:1IVH"
FT BINDING 198..200
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:9214289,
FT ECO:0007744|PDB:1IVH"
FT BINDING 222..223
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:9214289,
FT ECO:0007744|PDB:1IVH"
FT BINDING 277
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:9214289,
FT ECO:0007744|PDB:1IVH"
FT BINDING 284..287
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:9214289,
FT ECO:0007744|PDB:1IVH"
FT BINDING 312
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:9214289,
FT ECO:0007744|PDB:1IVH"
FT BINDING 323
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:9214289,
FT ECO:0007744|PDB:1IVH"
FT BINDING 380..384
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:9214289,
FT ECO:0007744|PDB:1IVH"
FT BINDING 407..408
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:9214289,
FT ECO:0007744|PDB:1IVH"
FT BINDING 409..411
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:9214289,
FT ECO:0007744|PDB:1IVH"
FT MOD_RES 58
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JHI5"
FT MOD_RES 58
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JHI5"
FT MOD_RES 67
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JHI5"
FT MOD_RES 67
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JHI5"
FT MOD_RES 78
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 78
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JHI5"
FT MOD_RES 241
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9JHI5"
FT MOD_RES 262
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JHI5"
FT MOD_RES 262
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JHI5"
FT MOD_RES 318
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9JHI5"
FT VAR_SEQ 52..81
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045193"
FT VARIANT 45
FT /note="L -> P (in IVA; dbSNP:rs121434284)"
FT /evidence="ECO:0000269|PubMed:2063866"
FT /id="VAR_000423"
FT VARIANT 53
FT /note="R -> P (in IVA; dbSNP:rs2229311)"
FT /evidence="ECO:0000269|PubMed:9665741"
FT /id="VAR_015960"
FT VARIANT 72
FT /note="D -> N (in IVA; dbSNP:rs747273828)"
FT /evidence="ECO:0000269|PubMed:9665741"
FT /id="VAR_015961"
FT VARIANT 97
FT /note="A -> G (in IVA)"
FT /evidence="ECO:0000269|PubMed:22004070"
FT /id="VAR_070061"
FT VARIANT 123
FT /note="G -> R (in IVA; dbSNP:rs142761835)"
FT /evidence="ECO:0000269|PubMed:22004070,
FT ECO:0000269|PubMed:22350545"
FT /id="VAR_070062"
FT VARIANT 199
FT /note="I -> M (in IVA)"
FT /evidence="ECO:0000269|PubMed:23587913"
FT /id="VAR_070063"
FT VARIANT 202
FT /note="G -> V (in IVA; dbSNP:rs121434285)"
FT /evidence="ECO:0000269|PubMed:2063866"
FT /id="VAR_000424"
FT VARIANT 250
FT /note="G -> A (in IVA; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28535199"
FT /id="VAR_079552"
FT VARIANT 279
FT /note="L -> P (in IVA)"
FT /evidence="ECO:0000269|PubMed:22004070"
FT /id="VAR_070064"
FT VARIANT 291
FT /note="A -> V (in IVA; unknown pathological significance;
FT dbSNP:rs886042098)"
FT /evidence="ECO:0000269|PubMed:28535199"
FT /id="VAR_079553"
FT VARIANT 314
FT /note="A -> V (in IVA; dbSNP:rs28940889)"
FT /evidence="ECO:0000269|PubMed:9665741"
FT /id="VAR_015962"
FT VARIANT 360
FT /note="C -> R (in IVA; dbSNP:rs760822119)"
FT /evidence="ECO:0000269|PubMed:9665741"
FT /id="VAR_015963"
FT VARIANT 374
FT /note="V -> A (in IVA; dbSNP:rs754600862)"
FT /evidence="ECO:0000269|PubMed:9665741"
FT /id="VAR_015964"
FT VARIANT 379
FT /note="I -> T (in IVA; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28535199"
FT /id="VAR_079554"
FT VARIANT 395
FT /note="R -> C (in IVA; dbSNP:rs371427844)"
FT /evidence="ECO:0000269|PubMed:9665741"
FT /id="VAR_015965"
FT VARIANT 398
FT /note="R -> Q (in IVA; unknown pathological significance;
FT dbSNP:rs1477527791)"
FT /evidence="ECO:0000269|PubMed:28535199"
FT /id="VAR_079555"
FT VARIANT 403
FT /note="Y -> C (in IVA; dbSNP:rs773560012)"
FT /evidence="ECO:0000269|PubMed:22004070"
FT /id="VAR_070065"
FT VARIANT 403
FT /note="Y -> N (in IVA; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28535199"
FT /id="VAR_079556"
FT VARIANT 414
FT /note="R -> L (in IVA)"
FT /evidence="ECO:0000269|PubMed:9665741"
FT /id="VAR_015966"
FT MUTAGEN 286
FT /note="E->D: Residual isovaleryl-CoA dehydrogenase
FT activity."
FT /evidence="ECO:0000269|PubMed:7640268"
FT MUTAGEN 286
FT /note="E->G: Loss of isovaleryl-CoA dehydrogenase activity.
FT Does not affect isovaleryl-CoA dehydrogenase activity; when
FT associated with 407-E."
FT /evidence="ECO:0000269|PubMed:7640268"
FT MUTAGEN 286
FT /note="E->Q: Loss of isovaleryl-CoA dehydrogenase
FT activity."
FT /evidence="ECO:0000269|PubMed:7640268"
FT MUTAGEN 407
FT /note="A->E: Does not affect isovaleryl-CoA dehydrogenase
FT activity; when associated with 286-D."
FT /evidence="ECO:0000269|PubMed:7640268"
FT CONFLICT 13
FT /note="W -> C (in Ref. 7; AAP35809 and 6; AAH17202)"
FT /evidence="ECO:0000305"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 47..63
FT /evidence="ECO:0007829|PDB:1IVH"
FT TURN 64..67
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 68..74
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 80..90
FT /evidence="ECO:0007829|PDB:1IVH"
FT TURN 93..96
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 108..121
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 123..133
FT /evidence="ECO:0007829|PDB:1IVH"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 137..143
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 146..157
FT /evidence="ECO:0007829|PDB:1IVH"
FT STRAND 163..166
FT /evidence="ECO:0007829|PDB:1IVH"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:1IVH"
FT STRAND 182..185
FT /evidence="ECO:0007829|PDB:1IVH"
FT STRAND 187..200
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:1IVH"
FT STRAND 206..214
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 221..224
FT /evidence="ECO:0007829|PDB:1IVH"
FT STRAND 225..231
FT /evidence="ECO:0007829|PDB:1IVH"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:1IVH"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:1IVH"
FT STRAND 253..264
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:1IVH"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 275..290
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 292..309
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 323..351
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 357..382
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 383..387
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 393..402
FT /evidence="ECO:0007829|PDB:1IVH"
FT TURN 403..407
FT /evidence="ECO:0007829|PDB:1IVH"
FT HELIX 410..422
FT /evidence="ECO:0007829|PDB:1IVH"
SQ SEQUENCE 426 AA; 46651 MW; D744DA85752BF307 CRC64;
MAEMATATRL LGWRVASWRL RPPLAGFVSQ RAHSLLPVDD AINGLSEEQR QLRQTMAKFL
QEHLAPKAQE IDRSNEFKNL REFWKQLGNL GVLGITAPVQ YGGSGLGYLE HVLVMEEISR
ASGAVGLSYG AHSNLCINQL VRNGNEAQKE KYLPKLISGE YIGALAMSEP NAGSDVVSMK
LKAEKKGNHY ILNGNKFWIT NGPDADVLIV YAKTDLAAVP ASRGITAFIV EKGMPGFSTS
KKLDKLGMRG SNTCELIFED CKIPAANILG HENKGVYVLM SGLDLERLVL AGGPLGLMQA
VLDHTIPYLH VREAFGQKIG HFQLMQGKMA DMYTRLMACR QYVYNVAKAC DEGHCTAKDC
AGVILYSAEC ATQVALDGIQ CFGGNGYIND FPMGRFLRDA KLYEIGAGTS EVRRLVIGRA
FNADFH
