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P26440 (IVD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 157. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Isovaleryl-CoA dehydrogenase, mitochondrial

Short name=IVD
EC=1.3.8.4
Gene names
Name:IVD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length423 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

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

Cofactor

FAD.

Pathway

Amino-acid degradation; L-leucine degradation; (S)-3-hydroxy-3-methylglutaryl-CoA from 3-isovaleryl-CoA: step 1/3.

Subunit structure

Homotetramer.

Subcellular location

Mitochondrion matrix.

Involvement in disease

Isovaleric acidemia (IVA) [MIM:243500]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.15 Ref.16 Ref.17 Ref.18

Sequence similarities

Belongs to the acyl-CoA dehydrogenase family.

Sequence caution

The sequence BAG53799.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P26440-1)

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.
Isoform 2 (identifier: P26440-2)

The sequence of this isoform differs from the canonical sequence as follows:
     49-78: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2929Mitochondrion Ref.8 Ref.9
Chain30 – 423394Isovaleryl-CoA dehydrogenase, mitochondrial
PRO_0000000531

Regions

Nucleotide binding162 – 17110FAD
Nucleotide binding195 – 1973FAD
Nucleotide binding377 – 3815FAD
Nucleotide binding406 – 4083FAD
Region219 – 2202Substrate binding
Region281 – 2844Substrate binding
Region404 – 4052Substrate binding

Sites

Active site2831Proton acceptor Ref.10
Binding site1711Substrate; via carbonyl oxygen
Binding site2741Substrate
Binding site3091FAD
Binding site3201FAD

Amino acid modifications

Modified residue551N6-acetyllysine; alternate By similarity
Modified residue551N6-succinyllysine; alternate By similarity
Modified residue641N6-acetyllysine; alternate By similarity
Modified residue641N6-succinyllysine; alternate By similarity
Modified residue751N6-acetyllysine; alternate Ref.11
Modified residue751N6-succinyllysine; alternate By similarity
Modified residue2381N6-acetyllysine By similarity
Modified residue2591N6-acetyllysine; alternate By similarity
Modified residue2591N6-succinyllysine; alternate By similarity
Modified residue3151N6-succinyllysine By similarity

Natural variations

Alternative sequence49 – 7830Missing in isoform 2.
VSP_045193
Natural variant421L → P in IVA. Ref.14
VAR_000423
Natural variant501R → P in IVA. Ref.15
VAR_015960
Natural variant691D → N in IVA. Ref.15
VAR_015961
Natural variant941A → G in IVA. Ref.16
VAR_070061
Natural variant1201G → R in IVA. Ref.16 Ref.17
Corresponds to variant rs142761835 [ dbSNP | Ensembl ].
VAR_070062
Natural variant1961I → M in IVA. Ref.18
VAR_070063
Natural variant1991G → V in IVA. Ref.14
VAR_000424
Natural variant2761L → P in IVA. Ref.16
VAR_070064
Natural variant3111A → V in IVA. Ref.15
Corresponds to variant rs28940889 [ dbSNP | Ensembl ].
VAR_015962
Natural variant3571C → R in IVA. Ref.15
VAR_015963
Natural variant3711V → A in IVA. Ref.15
VAR_015964
Natural variant3921R → C in IVA. Ref.15
VAR_015965
Natural variant4001Y → C in IVA. Ref.16
VAR_070065
Natural variant4111R → L in IVA. Ref.15
VAR_015966

Experimental info

Mutagenesis2831E → D: Residual activity. Ref.10
Mutagenesis2831E → G or Q: Loss of activity. Ref.10
Sequence conflict101W → C in AAH17202. Ref.6

Secondary structure

............................................................. 423
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 1, 1992. Version 1.
Checksum: 121AF14C7F1FA13D

FASTA42346,319
        10         20         30         40         50         60 
MATATRLLGW RVASWRLRPP LAGFVSQRAH SLLPVDDAIN GLSEEQRQLR QTMAKFLQEH 

        70         80         90        100        110        120 
LAPKAQEIDR SNEFKNLREF WKQLGNLGVL GITAPVQYGG SGLGYLEHVL VMEEISRASG 

       130        140        150        160        170        180 
AVGLSYGAHS NLCINQLVRN GNEAQKEKYL PKLISGEYIG ALAMSEPNAG SDVVSMKLKA 

       190        200        210        220        230        240 
EKKGNHYILN GNKFWITNGP DADVLIVYAK TDLAAVPASR GITAFIVEKG MPGFSTSKKL 

       250        260        270        280        290        300 
DKLGMRGSNT CELIFEDCKI PAANILGHEN KGVYVLMSGL DLERLVLAGG PLGLMQAVLD 

       310        320        330        340        350        360 
HTIPYLHVRE AFGQKIGHFQ LMQGKMADMY TRLMACRQYV YNVAKACDEG HCTAKDCAGV 

       370        380        390        400        410        420 
ILYSAECATQ VALDGIQCFG GNGYINDFPM GRFLRDAKLY EIGAGTSEVR RLVIGRAFNA 


DFH 

« Hide

Isoform 2 [UniParc].

Checksum: 6C75C436286F2617
Show »

FASTA39342,724

References

« Hide 'large scale' references
[1]"Nucleotide sequence of messenger RNA encoding human isovaleryl-coenzyme A dehydrogenase and its expression in isovaleric acidemia fibroblasts."
Matsubara Y., Ito M., Glassberg R., Satyabhama S., Ikeda Y., Tanaka K.
J. Clin. Invest. 85:1058-1064(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Exon skipping in IVD RNA processing in isovaleric acidemia caused by point mutations in the coding region of the IVD gene."
Vockley J., Rogan P.K., Anderson B.D., Willard J., Seelan R.S., Smith D.I., Liu W.
Am. J. Hum. Genet. 66:356-367(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Pericardium and Testis.
[4]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[7]"Structural organization of the human isovaleryl-CoA dehydrogenase gene."
Parimoo B., Tanaka K.
Genomics 15:582-590(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 381-423.
[8]"The variant human isovaleryl-CoA dehydrogenase gene responsible for type II isovaleric acidemia determines an RNA splicing error, leading to the deletion of the entire second coding exon and the production of a truncated precursor protein that interacts poorly with mitochondrial import receptors."
Vockley J., Nagao M., Parimoo B., Tanaka K.
J. Biol. Chem. 267:2494-2501(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF N-TERMINUS.
[9]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 30-47.
Tissue: Platelet.
[10]"Identification of the active site catalytic residue in human isovaleryl-CoA dehydrogenase."
Mohsen A.W., Vockley J.
Biochemistry 34:10146-10152(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVE SITE, MUTAGENESIS OF GLU-283.
[11]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-75, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Structure of human isovaleryl-CoA dehydrogenase at 2.6-A resolution: structural basis for substrate specificity."
Tiffany K.A., Roberts D.L., Wang M., Paschke R., Mohsen A.W., Vockley J., Kim J.-J.P.
Biochemistry 36:8455-8464(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 30-423 IN COMPLEX WITH FAD AND SUBSTRATE ANALOG.
[14]"Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric acidemia."
Vockley J., Parimoo B., Tanaka K.
Am. J. Hum. Genet. 49:147-157(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IVA PRO-42 AND VAL-199.
[15]"Characterization of molecular defects in isovaleryl-CoA dehydrogenase in patients with isovaleric acidemia."
Mohsen A.-W.A., Anderson B.D., Volchenboum S.L., Battaile K.P., Tiffany K.A., Roberts D.L., Kim J.-J.P., Vockley J.
Biochemistry 37:10325-10335(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IVA PRO-50; ASN-69; VAL-311; ARG-357; ALA-371; CYS-392 AND LEU-411.
[16]"Phenotypic and mutation spectrums of Thai patients with isovaleric acidemia."
Vatanavicharn N., Liammongkolkul S., Sakamoto O., Sathienkijkanchai A., Wasant P.
Pediatr. Int. 53:990-994(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IVA GLY-94; ARG-120; PRO-276 AND CYS-400.
[17]"Clinical variability of isovaleric acidemia in a genetically homogeneous population."
Dercksen M., Duran M., Ijlst L., Mienie L.J., Reinecke C.J., Ruiter J.P., Waterham H.R., Wanders R.J.
J. Inherit. Metab. Dis. 35:1021-1029(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT IVA ARG-120.
[18]"Two novel isovaleryl-CoA dehydrogenase gene mutations in a Chinese infant."
Bei F., Sun J.H., Yu Y.G., Jia J., Zheng Z.J., Fu Q.H., Cai W.
Gene 524:396-400(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT IVA MET-196.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M34192 mRNA. Translation: AAA52711.1.
AF191218 expand/collapse EMBL AC list , AF191214, AF191215, AF191216, AF191217 Genomic DNA. Translation: AAF20182.1.
AK122922 mRNA. Translation: BAG53799.1. Different initiation.
AK315296 mRNA. Translation: BAG37702.1.
AC013356 Genomic DNA. No translation available.
CH471125 Genomic DNA. Translation: EAW92414.1.
BC017202 mRNA. Translation: AAH17202.1.
AF038318 Genomic DNA. Translation: AAB92584.1.
PIRA37033.
RefSeqNP_001152980.1. NM_001159508.1.
NP_002216.2. NM_002225.3.
UniGeneHs.513646.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IVHX-ray2.60A/B/C/D30-423[»]
ProteinModelPortalP26440.
SMRP26440. Positions 35-421.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109916. 2 interactions.
IntActP26440. 1 interaction.
STRING9606.ENSP00000249760.

PTM databases

PhosphoSiteP26440.

Polymorphism databases

DMDM125051.

2D gel databases

REPRODUCTION-2DPAGEIPI00645805.
UCD-2DPAGEP26440.

Proteomic databases

PaxDbP26440.
PRIDEP26440.

Protocols and materials databases

DNASU3712.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000249760; ENSP00000249760; ENSG00000128928. [P26440-1]
ENST00000479013; ENSP00000417990; ENSG00000128928.
GeneID3712.
KEGGhsa:3712.
UCSCuc001zlq.2. human.

Organism-specific databases

CTD3712.
GeneCardsGC15P040697.
HGNCHGNC:6186. IVD.
HPAHPA041391.
HPA044250.
MIM243500. phenotype.
607036. gene.
neXtProtNX_P26440.
Orphanet33. Isovaleric acidemia.
PharmGKBPA29984.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1960.
HOGENOMHOG000131659.
HOVERGENHBG000224.
InParanoidP26440.
KOK00253.
PhylomeDBP26440.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
SABIO-RKP26440.
UniPathwayUPA00363; UER00860.

Gene expression databases

ArrayExpressP26440.
BgeeP26440.
CleanExHS_IVD.
GenevestigatorP26440.

Family and domain databases

Gene3D1.10.540.10. 1 hit.
2.40.110.10. 1 hit.
InterProIPR006089. 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]
PfamPF00441. Acyl-CoA_dh_1. 1 hit.
PF02770. Acyl-CoA_dh_M. 1 hit.
PF02771. Acyl-CoA_dh_N. 1 hit.
[Graphical view]
SUPFAMSSF47203. SSF47203. 1 hit.
SSF56645. SSF56645. 1 hit.
PROSITEPS00072. ACYL_COA_DH_1. 1 hit.
PS00073. ACYL_COA_DH_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSIVD. human.
EvolutionaryTraceP26440.
GenomeRNAi3712.
NextBio14547.
PROP26440.
SOURCESearch...

Entry information

Entry nameIVD_HUMAN
AccessionPrimary (citable) accession number: P26440
Secondary accession number(s): B2RCV5, B3KVI7, Q96AF6
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: April 16, 2014
This is version 157 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM