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Protein

Isovaleryl-CoA dehydrogenase, mitochondrial

Gene

IVD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalytic activityi

Isovaleryl-CoA + electron-transfer flavoprotein = 3-methylcrotonyl-CoA + reduced electron-transfer flavoprotein.

Cofactori

FAD1 Publication

Pathwayi: L-leucine degradation

This protein is involved in step 1 of the subpathway that synthesizes (S)-3-hydroxy-3-methylglutaryl-CoA from 3-isovaleryl-CoA.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. Isovaleryl-CoA dehydrogenase, mitochondrial (IVD)
  2. Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial (MCCC2), Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial (MCCC1)
  3. Methylglutaconyl-CoA hydratase, mitochondrial (AUH)
This subpathway is part of the pathway L-leucine degradation, which is itself part of Amino-acid degradation.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes (S)-3-hydroxy-3-methylglutaryl-CoA from 3-isovaleryl-CoA, the pathway L-leucine degradation and in Amino-acid degradation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei174Substrate; via carbonyl oxygen1
Binding sitei277Substrate1
Active sitei286Proton acceptor1 Publication1
Binding sitei312FAD1 Publication1
Binding sitei323FAD1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi165 – 174FAD1 Publication10
Nucleotide bindingi198 – 200FAD1 Publication3
Nucleotide bindingi380 – 384FAD1 Publication5
Nucleotide bindingi409 – 411FAD1 Publication3

GO - Molecular functioni

  • flavin adenine dinucleotide binding Source: InterPro
  • isovaleryl-CoA dehydrogenase activity Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
LigandFAD, Flavoprotein

Enzyme and pathway databases

BRENDAi1.3.8.4 2681
ReactomeiR-HSA-70895 Branched-chain amino acid catabolism
SABIO-RKiP26440
UniPathwayi
UPA00363;UER00860

Chemistry databases

SwissLipidsiSLP:000000936

Names & Taxonomyi

Protein namesi
Recommended name:
Isovaleryl-CoA dehydrogenase, mitochondrialCurated (EC:1.3.8.4)
Short name:
IVD
Gene namesi
Name:IVDImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000128928.8
HGNCiHGNC:6186 IVD
MIMi607036 gene
neXtProtiNX_P26440

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Isovaleric acidemia (IVA)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA metabolic disorder characterized by retarded psychomotor development, a peculiar odor resembling sweaty feet, an aversion to dietary protein, and pernicious vomiting, leading to acidosis and coma. The acute neonatal form leads to massive metabolic acidosis from the first days of life and rapid death.
See also OMIM:243500
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00042345L → P in IVA. 1 Publication1
Natural variantiVAR_01596053R → P in IVA. 1 Publication1
Natural variantiVAR_01596172D → N in IVA. 1 Publication1
Natural variantiVAR_07006197A → G in IVA. 1 Publication1
Natural variantiVAR_070062123G → R in IVA. 2 PublicationsCorresponds to variant dbSNP:rs142761835EnsemblClinVar.1
Natural variantiVAR_070063199I → M in IVA. 1 Publication1
Natural variantiVAR_000424202G → V in IVA. 1 Publication1
Natural variantiVAR_079552250G → A in IVA; unknown pathological significance. 1 Publication1
Natural variantiVAR_070064279L → P in IVA. 1 Publication1
Natural variantiVAR_079553291A → V in IVA; unknown pathological significance. 1 Publication1
Natural variantiVAR_015962314A → V in IVA. 1 PublicationCorresponds to variant dbSNP:rs28940889EnsemblClinVar.1
Natural variantiVAR_015963360C → R in IVA. 1 Publication1
Natural variantiVAR_015964374V → A in IVA. 1 Publication1
Natural variantiVAR_079554379I → T in IVA; unknown pathological significance. 1 Publication1
Natural variantiVAR_015965395R → C in IVA. 1 Publication1
Natural variantiVAR_079555398R → Q in IVA; unknown pathological significance. 1 Publication1
Natural variantiVAR_070065403Y → C in IVA. 1 Publication1
Natural variantiVAR_079556403Y → N in IVA; unknown pathological significance. 1 Publication1
Natural variantiVAR_015966414R → L in IVA. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi286E → D: Residual activity. 1 Publication1
Mutagenesisi286E → G or Q: Loss of activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3712
MalaCardsiIVD
MIMi243500 phenotype
Orphaneti33 Isovaleric acidemia
PharmGKBiPA29984

Chemistry databases

DrugBankiDB04036 Coenzyme a Persulfide
DB03147 Flavin adenine dinucleotide

Polymorphism and mutation databases

BioMutaiIVD
DMDMi125051

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 32MitochondrionCombined sources2 PublicationsAdd BLAST32
ChainiPRO_000000053133 – 426Isovaleryl-CoA dehydrogenase, mitochondrialAdd BLAST394

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei58N6-acetyllysine; alternateBy similarity1
Modified residuei58N6-succinyllysine; alternateBy similarity1
Modified residuei67N6-acetyllysine; alternateBy similarity1
Modified residuei67N6-succinyllysine; alternateBy similarity1
Modified residuei78N6-acetyllysine; alternateCombined sources1
Modified residuei78N6-succinyllysine; alternateBy similarity1
Modified residuei241N6-acetyllysineBy similarity1
Modified residuei262N6-acetyllysine; alternateBy similarity1
Modified residuei262N6-succinyllysine; alternateBy similarity1
Modified residuei318N6-succinyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP26440
MaxQBiP26440
PaxDbiP26440
PeptideAtlasiP26440
PRIDEiP26440
ProteomicsDBi54348

2D gel databases

REPRODUCTION-2DPAGEiIPI00645805
UCD-2DPAGEiP26440

PTM databases

iPTMnetiP26440
PhosphoSitePlusiP26440
SwissPalmiP26440

Expressioni

Gene expression databases

BgeeiENSG00000128928 Expressed in 207 organ(s), highest expression level in left lobe of thyroid gland
CleanExiHS_IVD
ExpressionAtlasiP26440 baseline and differential
GenevisibleiP26440 HS

Organism-specific databases

HPAiHPA041391
HPA044250

Interactioni

Subunit structurei

Homotetramer.1 Publication

Protein-protein interaction databases

BioGridi109916, 10 interactors
IntActiP26440, 6 interactors
STRINGi9606.ENSP00000418397

Structurei

Secondary structure

1426
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP26440
SMRiP26440
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP26440

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni222 – 223Substrate binding2
Regioni284 – 287Substrate binding4
Regioni407 – 408Substrate binding2

Sequence similaritiesi

Belongs to the acyl-CoA dehydrogenase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0141 Eukaryota
ENOG410XNMY LUCA
HOGENOMiHOG000131659
HOVERGENiHBG000224
InParanoidiP26440
KOiK00253
PhylomeDBiP26440
TreeFamiTF105050

Family and domain databases

CDDicd01156 IVD, 1 hit
Gene3Di1.10.540.10, 1 hit
InterProiView protein in InterPro
IPR006089 Acyl-CoA_DH_CS
IPR006091 Acyl-CoA_Oxase/DH_cen-dom
IPR036250 AcylCo_DH-like_C
IPR009075 AcylCo_DH/oxidase_C
IPR013786 AcylCoA_DH/ox_N
IPR037069 AcylCoA_DH/ox_N_sf
IPR009100 AcylCoA_DH/oxidase_NM_dom
IPR034183 IVD
PfamiView protein in Pfam
PF00441 Acyl-CoA_dh_1, 1 hit
PF02770 Acyl-CoA_dh_M, 1 hit
PF02771 Acyl-CoA_dh_N, 1 hit
SUPFAMiSSF47203 SSF47203, 1 hit
SSF56645 SSF56645, 1 hit
PROSITEiView protein in PROSITE
PS00072 ACYL_COA_DH_1, 1 hit
PS00073 ACYL_COA_DH_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 8 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: P26440-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAEMATATRL LGWRVASWRL RPPLAGFVSQ RAHSLLPVDD AINGLSEEQR
60 70 80 90 100
QLRQTMAKFL QEHLAPKAQE IDRSNEFKNL REFWKQLGNL GVLGITAPVQ
110 120 130 140 150
YGGSGLGYLE HVLVMEEISR ASGAVGLSYG AHSNLCINQL VRNGNEAQKE
160 170 180 190 200
KYLPKLISGE YIGALAMSEP NAGSDVVSMK LKAEKKGNHY ILNGNKFWIT
210 220 230 240 250
NGPDADVLIV YAKTDLAAVP ASRGITAFIV EKGMPGFSTS KKLDKLGMRG
260 270 280 290 300
SNTCELIFED CKIPAANILG HENKGVYVLM SGLDLERLVL AGGPLGLMQA
310 320 330 340 350
VLDHTIPYLH VREAFGQKIG HFQLMQGKMA DMYTRLMACR QYVYNVAKAC
360 370 380 390 400
DEGHCTAKDC AGVILYSAEC ATQVALDGIQ CFGGNGYIND FPMGRFLRDA
410 420
KLYEIGAGTS EVRRLVIGRA FNADFH
Length:426
Mass (Da):46,651
Last modified:September 12, 2018 - v2
Checksum:iD744DA85752BF307
GO
Isoform 2 (identifier: P26440-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     52-81: Missing.

Note: No experimental confirmation available.
Show »
Length:396
Mass (Da):43,056
Checksum:i996C093DA6FC7E04
GO

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A0MT83A0A0A0MT83_HUMAN
Isovaleryl-CoA dehydrogenase, mitoc...
IVD
426Annotation score:
H0YN10H0YN10_HUMAN
Isovaleryl-CoA dehydrogenase, mitoc...
IVD
212Annotation score:
H7C4G6H7C4G6_HUMAN
Isovaleryl-CoA dehydrogenase, mitoc...
IVD
307Annotation score:
H0YLC3H0YLC3_HUMAN
Isovaleryl-CoA dehydrogenase, mitoc...
IVD
243Annotation score:
A0A087WVD3A0A087WVD3_HUMAN
Isovaleryl-CoA dehydrogenase, mitoc...
IVD
214Annotation score:
H0YKV0H0YKV0_HUMAN
Isovaleryl-CoA dehydrogenase, mitoc...
IVD
145Annotation score:
H0YNT5H0YNT5_HUMAN
Isovaleryl-CoA dehydrogenase, mitoc...
IVD
58Annotation score:
H0YNA4H0YNA4_HUMAN
Isovaleryl-CoA dehydrogenase, mitoc...
IVD
41Annotation score:

Sequence cautioni

The sequence AAA52711 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAB92584 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH17202 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAG37702 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti13W → C in AAP35809 (Ref. 7) Curated1
Sequence conflicti13W → C in AAH17202 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00042345L → P in IVA. 1 Publication1
Natural variantiVAR_01596053R → P in IVA. 1 Publication1
Natural variantiVAR_01596172D → N in IVA. 1 Publication1
Natural variantiVAR_07006197A → G in IVA. 1 Publication1
Natural variantiVAR_070062123G → R in IVA. 2 PublicationsCorresponds to variant dbSNP:rs142761835EnsemblClinVar.1
Natural variantiVAR_070063199I → M in IVA. 1 Publication1
Natural variantiVAR_000424202G → V in IVA. 1 Publication1
Natural variantiVAR_079552250G → A in IVA; unknown pathological significance. 1 Publication1
Natural variantiVAR_070064279L → P in IVA. 1 Publication1
Natural variantiVAR_079553291A → V in IVA; unknown pathological significance. 1 Publication1
Natural variantiVAR_015962314A → V in IVA. 1 PublicationCorresponds to variant dbSNP:rs28940889EnsemblClinVar.1
Natural variantiVAR_015963360C → R in IVA. 1 Publication1
Natural variantiVAR_015964374V → A in IVA. 1 Publication1
Natural variantiVAR_079554379I → T in IVA; unknown pathological significance. 1 Publication1
Natural variantiVAR_015965395R → C in IVA. 1 Publication1
Natural variantiVAR_079555398R → Q in IVA; unknown pathological significance. 1 Publication1
Natural variantiVAR_070065403Y → C in IVA. 1 Publication1
Natural variantiVAR_079556403Y → N in IVA; unknown pathological significance. 1 Publication1
Natural variantiVAR_015966414R → L in IVA. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04519352 – 81Missing in isoform 2. 1 PublicationAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34192 mRNA Translation: AAA52711.1 Different initiation.
AF191218
, AF191214, AF191215, AF191216, AF191217 Genomic DNA Translation: AAF20182.1
AK122922 mRNA Translation: BAG53799.1
AK315296 mRNA Translation: BAG37702.1 Different initiation.
AC013356 Genomic DNA No translation available.
CH471125 Genomic DNA Translation: EAW92413.1
CH471125 Genomic DNA Translation: EAW92414.1
CH471125 Genomic DNA Translation: EAW92415.1
BC017202 mRNA Translation: AAH17202.1 Different initiation.
AF038318 Genomic DNA Translation: AAB92584.1 Different initiation.
BT007145 mRNA Translation: AAP35809.1
PIRiA37033
RefSeqiNP_001152980.1, NM_001159508.1
NP_002216.2, NM_002225.3
UniGeneiHs.513646

Genome annotation databases

EnsembliENST00000479013; ENSP00000417990; ENSG00000128928
GeneIDi3712
KEGGihsa:3712
UCSCiuc001zlq.3 human [P26440-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiIVD_HUMAN
AccessioniPrimary (citable) accession number: P26440
Secondary accession number(s): B2RCV5
, B3KVI7, J3KR54, Q53XZ9, Q96AF6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: September 12, 2018
Last modified: September 12, 2018
This is version 191 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health

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