Skip Header

 
Contribute Send feedback
Read comments (0) or add your own

Reviewed, UniProtKB/Swiss-Prot P26440 (IVD_HUMAN)

Last modified November 3, 2009. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Isovaleryl-CoA dehydrogenase, mitochondrial
      Short name=IVD
    EC=1.3.99.10
Gene names
Name: IVD
OrganismHomo sapiens (Human) [Complete 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

3-methylbutanoyl-CoA + acceptor = 3-methylbut-2-enoyl-CoA + reduced acceptor.

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

Defects in IVD are the cause of isovaleric acidemia (IVA) [MIM:243500]. IVA is 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. Ref.12 Ref.13

Sequence similarities

Belongs to the acyl-CoA dehydrogenase family.

Ontologies

Keywords
   Cellular componentMitochondrion
   DiseaseDisease mutation
   DomainTransit peptide
   LigandFAD
Flavoprotein
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Gene Ontology (GO)
   Biological processoxidation reduction

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentmitochondrial matrix Ref.12

Non-traceable author statement. Source: ProtInc

   Molecular functionFAD binding

Inferred from electronic annotation. Source: InterPro

electron carrier activity

Inferred from electronic annotation. Source: InterPro

isovaleryl-CoA dehydrogenase activity

Traceable author statement. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2929Mitochondrion Ref.7
Chain30 – 423394Isovaleryl-CoA dehydrogenase, mitochondrial
PRO_0000000531

Sites

Active site2831Proton acceptor Ref.8

Amino acid modifications

Modified residue751N6-acetyllysine Ref.10

Natural variations

Natural variant421L → P in IVA. Ref.12
VAR_000423
Natural variant501R → P in IVA. Ref.13
VAR_015960
Natural variant691D → N in IVA. Ref.13
VAR_015961
Natural variant1991G → V in IVA. Ref.12
VAR_000424
Natural variant3111A → V in IVA. Ref.13
VAR_015962
Natural variant3571C → R in IVA. Ref.13
VAR_015963
Natural variant3711V → A in IVA. Ref.13
VAR_015964
Natural variant3921R → C in IVA. Ref.13
VAR_015965
Natural variant4111R → L in IVA. Ref.13
VAR_015966

Experimental info

Mutagenesis2831E → D: Residual activity. Ref.8
Mutagenesis2831E → G or Q: Loss of activity. Ref.8
Sequence conflict101W → C in AAH17202. Ref.4

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
P26440-1 [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

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: 2318964] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 10677295] [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: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pericardium.
[4]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"Structural organization of the human isovaleryl-CoA dehydrogenase gene."
Parimoo B., Tanaka K.
Genomics 15:582-590(1993) [PubMed: 8468053] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 381-423.
[6]"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: 1310317] [Abstract]
Cited for: PROTEIN SEQUENCE OF N-TERMINUS.
[7]"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: 12665801] [Abstract]
Cited for: PROTEIN SEQUENCE OF 30-47.
Tissue: Platelet.
[8]"Identification of the active site catalytic residue in human isovaleryl-CoA dehydrogenase."
Mohsen A.W., Vockley J.
Biochemistry 34:10146-10152(1995) [PubMed: 7640268] [Abstract]
Cited for: ACTIVE SITE, MUTAGENESIS OF GLU-283.
[9]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed: 19608861] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-75, MASS SPECTROMETRY.
[11]"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: 9214289] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 35-421.
[12]"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: 2063866] [Abstract]
Cited for: VARIANTS IVA PRO-42 AND VAL-199.
[13]"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: 9665741] [Abstract]
Cited for: VARIANTS IVA PRO-50; ASN-69; VAL-311; ARG-357; ALA-371; CYS-392 AND LEU-411.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

M34192 mRNA. Translation: AAA52711.1.
AF191218 expand/collapse EMBL AC list , AF191214, AF191215, AF191216, AF191217 Genomic DNA. Translation: AAF20182.1.
AK315296 mRNA. Translation: BAG37702.1.
BC017202 mRNA. Translation: AAH17202.1.
AF038318 Genomic DNA. Translation: AAB92584.1.
IPIIPI00645805.
PIRA37033.
RefSeqNP_002216.2.
UniGeneHs.449599
Hs.513646

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1IVHX-ray2.60A/B/C/D30-423[»]
ModBaseSearch...

Protein-protein interaction databases

STRINGP26440.

PTM databases

PhosphoSiteP26440.

2-D gel databases

REPRODUCTION-2DPAGEIPI00645805.

Proteomic databases

PRIDEP26440.

Genome annotation databases

EnsemblENST00000249760; ENSP00000249760; ENSG00000128928; Homo sapiens. [Genome view]
GeneID3712.
KEGGhsa:3712.
NMPDRfig|9606.3.peg.10499.
UCSCuc001zlp.1. human.
uc001zlq.1. human.

Organism-specific databases

GeneCardsGC15P038484.
H-InvDBHIX0012130.
HGNCHGNC:6186. IVD.
MIM243500. phenotype.
607036. gene.
Orphanet33. Isovaleric acidemia.
PharmGKBPA29984.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP26440.
HOVERGENP26440.
OMAELFNETR.

Enzyme and pathway databases

BRENDA1.3.99.10. 247.
ReactomeREACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpressP26440.
BgeeP26440.
CleanExHS_IVD.
GenevestigatorP26440.
GermOnlineENSG00000128928. Homo sapiens.

Family and domain databases

InterProIPR006089. Acyl-CoA_DH_CS.
IPR006092. Acyl-CoA_DH_N.
IPR006090. Acyl-CoA_Oxase/DH_1.
IPR006091. Acyl-CoA_Oxase/DH_M.
IPR013786. AcylCoA_DH/ox_N.
IPR013764. AcylCoA_oxidase/DH_1/2_C.
[Graphical view]
Gene3DG3DSA:2.40.110.10. Acyl_CoA_DH/ox_M. 1 hit.
G3DSA:1.10.540.10. AcylCoA_DH/ox_N. 1 hit.
G3DSA:1.20.140.10. AcylCoA_DH_1/2_C. 1 hit.
PfamPF00441. Acyl-CoA_dh_1. 1 hit.
PF02770. Acyl-CoA_dh_M. 1 hit.
PF02771. Acyl-CoA_dh_N. 1 hit.
[Graphical view]
PROSITEPS00072. ACYL_COA_DH_1. 1 hit.
PS00073. ACYL_COA_DH_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio14547.
SOURCESearch...

Entry information

Entry nameIVD_HUMAN
AccessionPrimary (citable) accession number: P26440
Secondary accession number(s): B2RCV5, Q96AF6
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: November 3, 2009
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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

Human chromosome 15

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents