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Protein

Isovaleryl-CoA dehydrogenase, mitochondrial

Gene

IVD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 subunit alpha, mitochondrial (MCCC1), Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial (MCCC2)
  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 sitei171Substrate; via carbonyl oxygen1
Binding sitei274Substrate1
Active sitei283Proton acceptor1 Publication1
Binding sitei309FAD1 Publication1
Binding sitei320FAD1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi162 – 171FAD1 Publication10
Nucleotide bindingi195 – 197FAD1 Publication3
Nucleotide bindingi377 – 381FAD1 Publication5
Nucleotide bindingi406 – 408FAD1 Publication3

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

FAD, Flavoprotein

Enzyme and pathway databases

BioCyciZFISH:HS05233-MONOMER.
BRENDAi1.3.8.4. 2681.
ReactomeiR-HSA-70895. Branched-chain amino acid catabolism.
SABIO-RKP26440.
UniPathwayiUPA00363; UER00860.

Chemistry databases

SwissLipidsiSLP:000000936.

Names & Taxonomyi

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

Organism-specific databases

HGNCiHGNC:6186. IVD.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Isovaleric acidemia (IVA)5 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_00042342L → P in IVA. 1 Publication1
Natural variantiVAR_01596050R → P in IVA. 1 Publication1
Natural variantiVAR_01596169D → N in IVA. 1 Publication1
Natural variantiVAR_07006194A → G in IVA. 1 Publication1
Natural variantiVAR_070062120G → R in IVA. 2 PublicationsCorresponds to variant rs142761835dbSNPEnsembl.1
Natural variantiVAR_070063196I → M in IVA. 1 Publication1
Natural variantiVAR_000424199G → V in IVA. 1 Publication1
Natural variantiVAR_070064276L → P in IVA. 1 Publication1
Natural variantiVAR_015962311A → V in IVA. 1 PublicationCorresponds to variant rs28940889dbSNPEnsembl.1
Natural variantiVAR_015963357C → R in IVA. 1 Publication1
Natural variantiVAR_015964371V → A in IVA. 1 Publication1
Natural variantiVAR_015965392R → C in IVA. 1 Publication1
Natural variantiVAR_070065400Y → C in IVA. 1 Publication1
Natural variantiVAR_015966411R → L in IVA. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi283E → D: Residual activity. 1 Publication1
Mutagenesisi283E → 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

DrugBankiDB03147. Flavin adenine dinucleotide.

Polymorphism and mutation databases

BioMutaiIVD.
DMDMi125051.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 29MitochondrionCombined sources2 PublicationsAdd BLAST29
ChainiPRO_000000053130 – 423Isovaleryl-CoA dehydrogenase, mitochondrialAdd BLAST394

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei55N6-acetyllysine; alternateBy similarity1
Modified residuei55N6-succinyllysine; alternateBy similarity1
Modified residuei64N6-acetyllysine; alternateBy similarity1
Modified residuei64N6-succinyllysine; alternateBy similarity1
Modified residuei75N6-acetyllysine; alternateCombined sources1
Modified residuei75N6-succinyllysine; alternateBy similarity1
Modified residuei238N6-acetyllysineBy similarity1
Modified residuei259N6-acetyllysine; alternateBy similarity1
Modified residuei259N6-succinyllysine; alternateBy similarity1
Modified residuei315N6-succinyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP26440.
MaxQBiP26440.
PaxDbiP26440.
PeptideAtlasiP26440.
PRIDEiP26440.

2D gel databases

REPRODUCTION-2DPAGEIPI00645805.
UCD-2DPAGEP26440.

PTM databases

iPTMnetiP26440.
PhosphoSitePlusiP26440.
SwissPalmiP26440.

Expressioni

Gene expression databases

BgeeiENSG00000128928.
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. 2 interactors.
STRINGi9606.ENSP00000418397.

Structurei

Secondary structure

1423
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi38 – 40Combined sources3
Helixi44 – 60Combined sources17
Turni61 – 64Combined sources4
Helixi65 – 71Combined sources7
Helixi77 – 87Combined sources11
Turni90 – 93Combined sources4
Helixi96 – 98Combined sources3
Helixi105 – 118Combined sources14
Helixi120 – 130Combined sources11
Turni131 – 133Combined sources3
Helixi134 – 140Combined sources7
Helixi143 – 154Combined sources12
Beta strandi160 – 163Combined sources4
Beta strandi169 – 172Combined sources4
Helixi173 – 175Combined sources3
Beta strandi179 – 182Combined sources4
Beta strandi184 – 197Combined sources14
Helixi199 – 201Combined sources3
Beta strandi203 – 211Combined sources9
Helixi218 – 221Combined sources4
Beta strandi222 – 228Combined sources7
Beta strandi234 – 236Combined sources3
Beta strandi242 – 244Combined sources3
Beta strandi250 – 261Combined sources12
Helixi262 – 264Combined sources3
Beta strandi265 – 267Combined sources3
Helixi272 – 287Combined sources16
Helixi289 – 306Combined sources18
Helixi316 – 318Combined sources3
Helixi320 – 348Combined sources29
Helixi354 – 379Combined sources26
Helixi380 – 384Combined sources5
Helixi390 – 399Combined sources10
Turni400 – 404Combined sources5
Helixi407 – 419Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IVHX-ray2.60A/B/C/D30-423[»]
ProteinModelPortaliP26440.
SMRiP26440.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP26440.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni219 – 220Substrate binding2
Regioni281 – 284Substrate binding4
Regioni404 – 405Substrate 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

Gene3Di1.10.540.10. 1 hit.
InterProiIPR006089. Acyl-CoA_DH_CS.
IPR006091. Acyl-CoA_Oxase/DH_cen-dom.
IPR009075. AcylCo_DH/oxidase_C.
IPR013786. AcylCoA_DH/ox_N.
IPR009100. AcylCoA_DH/oxidase_NM_dom.
[Graphical view]
PfamiPF00441. Acyl-CoA_dh_1. 1 hit.
PF02770. Acyl-CoA_dh_M. 1 hit.
PF02771. Acyl-CoA_dh_N. 1 hit.
[Graphical view]
SUPFAMiSSF47203. SSF47203. 1 hit.
SSF56645. SSF56645. 1 hit.
PROSITEiPS00072. ACYL_COA_DH_1. 1 hit.
PS00073. ACYL_COA_DH_2. 1 hit.
[Graphical view]

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

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
MATATRLLGW RVASWRLRPP LAGFVSQRAH SLLPVDDAIN GLSEEQRQLR
60 70 80 90 100
QTMAKFLQEH LAPKAQEIDR SNEFKNLREF WKQLGNLGVL GITAPVQYGG
110 120 130 140 150
SGLGYLEHVL VMEEISRASG AVGLSYGAHS NLCINQLVRN GNEAQKEKYL
160 170 180 190 200
PKLISGEYIG ALAMSEPNAG SDVVSMKLKA EKKGNHYILN GNKFWITNGP
210 220 230 240 250
DADVLIVYAK TDLAAVPASR GITAFIVEKG MPGFSTSKKL DKLGMRGSNT
260 270 280 290 300
CELIFEDCKI PAANILGHEN KGVYVLMSGL DLERLVLAGG PLGLMQAVLD
310 320 330 340 350
HTIPYLHVRE AFGQKIGHFQ LMQGKMADMY TRLMACRQYV YNVAKACDEG
360 370 380 390 400
HCTAKDCAGV ILYSAECATQ VALDGIQCFG GNGYINDFPM GRFLRDAKLY
410 420
EIGAGTSEVR RLVIGRAFNA DFH
Length:423
Mass (Da):46,319
Last modified:August 1, 1992 - v1
Checksum:i121AF14C7F1FA13D
GO
Isoform 2 (identifier: P26440-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     49-78: Missing.

Note: No experimental confirmation available.
Show »
Length:393
Mass (Da):42,724
Checksum:i6C75C436286F2617
GO

Sequence cautioni

The sequence BAG53799 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence EAW92413 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAW92414 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAW92415 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti10W → C in AAP35809 (Ref. 3) Curated1
Sequence conflicti10W → C in AAH17202 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00042342L → P in IVA. 1 Publication1
Natural variantiVAR_01596050R → P in IVA. 1 Publication1
Natural variantiVAR_01596169D → N in IVA. 1 Publication1
Natural variantiVAR_07006194A → G in IVA. 1 Publication1
Natural variantiVAR_070062120G → R in IVA. 2 PublicationsCorresponds to variant rs142761835dbSNPEnsembl.1
Natural variantiVAR_070063196I → M in IVA. 1 Publication1
Natural variantiVAR_000424199G → V in IVA. 1 Publication1
Natural variantiVAR_070064276L → P in IVA. 1 Publication1
Natural variantiVAR_015962311A → V in IVA. 1 PublicationCorresponds to variant rs28940889dbSNPEnsembl.1
Natural variantiVAR_015963357C → R in IVA. 1 Publication1
Natural variantiVAR_015964371V → A in IVA. 1 Publication1
Natural variantiVAR_015965392R → C in IVA. 1 Publication1
Natural variantiVAR_070065400Y → C in IVA. 1 Publication1
Natural variantiVAR_015966411R → L in IVA. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04519349 – 78Missing in isoform 2. 1 PublicationAdd BLAST30

Sequence databases

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

Cross-referencesi

Sequence databases

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IVHX-ray2.60A/B/C/D30-423[»]
ProteinModelPortaliP26440.
SMRiP26440.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109916. 10 interactors.
IntActiP26440. 2 interactors.
STRINGi9606.ENSP00000418397.

Chemistry databases

DrugBankiDB03147. Flavin adenine dinucleotide.
SwissLipidsiSLP:000000936.

PTM databases

iPTMnetiP26440.
PhosphoSitePlusiP26440.
SwissPalmiP26440.

Polymorphism and mutation databases

BioMutaiIVD.
DMDMi125051.

2D gel databases

REPRODUCTION-2DPAGEIPI00645805.
UCD-2DPAGEP26440.

Proteomic databases

EPDiP26440.
MaxQBiP26440.
PaxDbiP26440.
PeptideAtlasiP26440.
PRIDEiP26440.

Protocols and materials databases

DNASUi3712.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3712.
DisGeNETi3712.
GeneCardsiIVD.
HGNCiHGNC:6186. IVD.
HPAiHPA041391.
HPA044250.
MalaCardsiIVD.
MIMi243500. phenotype.
607036. gene.
neXtProtiNX_P26440.
Orphaneti33. Isovaleric acidemia.
PharmGKBiPA29984.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0141. Eukaryota.
ENOG410XNMY. LUCA.
HOGENOMiHOG000131659.
HOVERGENiHBG000224.
InParanoidiP26440.
KOiK00253.
PhylomeDBiP26440.
TreeFamiTF105050.

Enzyme and pathway databases

UniPathwayiUPA00363; UER00860.
BioCyciZFISH:HS05233-MONOMER.
BRENDAi1.3.8.4. 2681.
ReactomeiR-HSA-70895. Branched-chain amino acid catabolism.
SABIO-RKP26440.

Miscellaneous databases

ChiTaRSiIVD. human.
EvolutionaryTraceiP26440.
GenomeRNAii3712.
PROiP26440.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000128928.
CleanExiHS_IVD.
ExpressionAtlasiP26440. baseline and differential.
GenevisibleiP26440. HS.

Family and domain databases

Gene3Di1.10.540.10. 1 hit.
InterProiIPR006089. Acyl-CoA_DH_CS.
IPR006091. Acyl-CoA_Oxase/DH_cen-dom.
IPR009075. AcylCo_DH/oxidase_C.
IPR013786. AcylCoA_DH/ox_N.
IPR009100. AcylCoA_DH/oxidase_NM_dom.
[Graphical view]
PfamiPF00441. Acyl-CoA_dh_1. 1 hit.
PF02770. Acyl-CoA_dh_M. 1 hit.
PF02771. Acyl-CoA_dh_N. 1 hit.
[Graphical view]
SUPFAMiSSF47203. SSF47203. 1 hit.
SSF56645. SSF56645. 1 hit.
PROSITEiPS00072. ACYL_COA_DH_1. 1 hit.
PS00073. ACYL_COA_DH_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIVD_HUMAN
AccessioniPrimary (citable) accession number: P26440
Secondary accession number(s): B2RCV5
, B3KVI7, J3KR54, Q53XZ9, Q96AF6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: November 2, 2016
This is version 181 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.