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Reviewed, UniProtKB/Swiss-Prot O00330 (ODPX_HUMAN)

Last modified June 16, 2009. Version 94. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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 · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Pyruvate dehydrogenase protein X component, mitochondrial
Alternative name(s):
    Dihydrolipoamide dehydrogenase-binding protein of pyruvate dehydrogenase complex
    Lipoyl-containing pyruvate dehydrogenase complex component X
    E3-binding protein
      Short name=E3BP
    proX
Gene names
Name: PDHX
Synonyms: PDX1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length501 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex.

Subunit structure

Eukaryotic pyruvate dehydrogenase complexes are organized about a core consisting of the oligomeric dihydrolipoamide acetyl-transferase, around which are arranged multiple copies of pyruvate dehydrogenase, dihydrolipoamide dehydrogenase and protein X bound by non-covalent bonds.

Subcellular location

Mitochondrion matrix.

Involvement in disease

Defects in PDHX are a cause of lacticacidemia [MIM:245349].

Sequence similarities

Belongs to the 2-oxoacid dehydrogenase family.

Contains 1 lipoyl-binding domain.

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Ontologies

Keywords
   Cellular componentMitochondrion
   Coding sequence diversityPolymorphism
   DomainLipoyl
Transit peptide
   Technical term3D-structure
Gene Ontology (GO)
   Biological processmetabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular componentmitochondrial matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionacyltransferase activity

Inferred from electronic annotation. Source: InterPro

lipoic acid binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 5353Mitochondrion By similarity
Chain54 – 501448Pyruvate dehydrogenase protein X component, mitochondrial
PRO_0000020484

Regions

Domain57 – 13175Lipoyl-binding
Region183 – 21432Interaction with DLD
Compositional bias149 – 17022Pro-rich

Amino acid modifications

Modified residue971N6-lipoyllysine By similarity

Natural variations

Natural variant231R → C: dbSNP rs1049306. Ref.1
VAR_046619
Natural variant1011T → A: dbSNP rs11539202.
VAR_046620
Natural variant3701D → V: dbSNP rs17850649. Ref.5
VAR_046621

Experimental info

Mutagenesis1831R → A: Strongly decreased DLD binding. Ref.9
Mutagenesis1851S → A: Strongly decreased DLD binding. Ref.9
Mutagenesis1861P → A: Strongly decreased DLD binding. Ref.9
Mutagenesis1871A → M: Strongly decreased DLD binding. Ref.9
Mutagenesis1891R → A: Strongly decreased DLD binding. Ref.9
Mutagenesis1901N → A: Strongly decreased DLD binding. Ref.9
Mutagenesis1931E → A: Strongly decreased DLD binding. Ref.9
Mutagenesis2081R → A: Strongly decreased DLD binding. Ref.9
Mutagenesis2101I → A: Strongly decreased DLD binding. Ref.9
Mutagenesis2131K → A: Strongly decreased DLD binding. Ref.9
Mutagenesis2141E → A: Strongly decreased DLD binding. Ref.9
Sequence conflict411A → R in AAC39661. Ref.3
Sequence conflict2511A → S in AAB66315. Ref.1
Sequence conflict2511A → S in CAA73606. Ref.2

Secondary structure

1 ......................... 501
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
O00330-1 [UniParc].

Last modified January 24, 2001. Version 3.
Checksum: 9CF0C1DAE9E12EF9

FASTA50154,122
        10         20         30         40         50         60 
MAASWRLGCD PRLLRYLVGF PGRRSVGLVK GALGWSVSRG ANWRWFHSTQ WLRGDPIKIL 

        70         80         90        100        110        120 
MPSLSPTMEE GNIVKWLKKE GEAVSAGDAL CEIETDKAVV TLDASDDGIL AKIVVEEGSK 

       130        140        150        160        170        180 
NIRLGSLIGL IVEEGEDWKH VEIPKDVGPP PPVSKPSEPR PSPEPQISIP VKKEHIPGTL 

       190        200        210        220        230        240 
RFRLSPAARN ILEKHSLDAS QGTATGPRGI FTKEDALKLV QLKQTGKITE SRPTPAPTAT 

       250        260        270        280        290        300 
PTAPSPLQAT AGPSYPRPVI PPVSTPGQPN AVGTFTEIPA SNIRRVIAKR LTESKSTVPH 

       310        320        330        340        350        360 
AYATADCDLG AVLKVRQDLV KDDIKVSVND FIIKAAAVTL KQMPDVNVSW DGEGPKQLPF 

       370        380        390        400        410        420 
IDISVAVATD KGLLTPIIKD AAAKGIQEIA DSVKALSKKA RDGKLLPEEY QGGSFSISNL 

       430        440        450        460        470        480 
GMFGIDEFTA VINPPQACIL AVGRFRPVLK LTEDEEGNAK LQQRQLITVT MSSDSRVVDD 

       490        500 
ELATRFLKSF KANLENPIRL A

« Hide

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References

« Hide 'large scale' references
[1]"Dihydrolipoamide dehydrogenase-binding protein of the human pyruvate dehydrogenase complex. DNA-derived amino acid sequence, expression, and reconstitution of the pyruvate dehydrogenase complex."
Harris R.A., Bowker-Kinley M.M., Wu P., Jeng J., Popov K.M.
J. Biol. Chem. 272:19746-19751(1997) [PubMed: 9242632] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CYS-23.
[2]"Mutations in PDX1, the human lipoyl-containing component X of the pyruvate dehydrogenase-complex gene on chromosome 11p1, in congenital lactic acidosis."
Aral B., Benelli C., Ait-Ghezala G., Amessou M., Fouque F., Maunoury C., Creau N., Kamoun P., Marsac C.
Am. J. Hum. Genet. 61:1318-1326(1997) [PubMed: 9399911] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[3]"Detection of a homozygous four base pair deletion in the protein X gene in a case of pyruvate dehydrogenase complex deficiency."
Ling M., McEachern G., Seyda A., Mackay N., Scherer S.W., Bratinova S., Beatty B., Giovannucci-Uzielli M.L., Robinson B.H.
Hum. Mol. Genet. 7:501-505(1998) [PubMed: 9467010] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Human gene sequence for PDX1, the human lipoyl-containing component X of the pyruvate dehydrogenase complex."
Aral B., Dey R., Marsac C.
Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"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], VARIANT VAL-370.
Tissue: Brain.
[6]"Large-scale concatenation cDNA sequencing."
Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W., Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.
Genome Res. 7:353-358(1997) [PubMed: 9110174] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 127-501.
Tissue: Brain.
[7]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]"How dihydrolipoamide dehydrogenase-binding protein binds dihydrolipoamide dehydrogenase in the human pyruvate dehydrogenase complex."
Ciszak E.M., Makal A., Hong Y.S., Vettaikkorumakankauv A.K., Korotchkina L.G., Patel M.S.
J. Biol. Chem. 281:648-655(2006) [PubMed: 16263718] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 54-274 IN COMPLEX WITH DLD.
[9]"Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex."
Brautigam C.A., Wynn R.M., Chuang J.L., Machius M., Tomchick D.R., Chuang D.T.
Structure 14:611-621(2006) [PubMed: 16442803] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 174-230 IN COMPLEX WITH DLD, MUTAGENESIS OF ARG-183; SER-185; PRO-186; ALA-187; ARG-189; ASN-190; GLU-193; ARG-208; ILE-210; LYS-213 AND GLU-214.
[10]"Solution structure of RSGI RUH-054, a lipoyl domain from human 2-oxoacid dehydrogenase."
RIKEN structural genomics initiative (RSGI)
Submitted (OCT-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 57-141.
+Additional computationally mapped references.

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Cross-references

Sequence databases

AF001437 mRNA. Translation: AAB66315.1.
Y13145 mRNA. Translation: CAA73606.1.
U82328 mRNA. Translation: AAC39661.1.
AJ298105 Genomic DNA. Translation: CAC18649.1.
BC010389 mRNA. Translation: AAH10389.1.
U79296 mRNA. Translation: AAB50223.1.
IPIIPI00298423.
RefSeqNP_001128496.1.
NP_003468.2.
UniGeneHs.502315

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1ZY8X-ray2.59K/L/M/N/O54-274[»]
2DNCNMR-A57-141[»]
2F5ZX-ray2.18K/L/M/N/O174-228[»]
2F60X-ray1.55K174-228[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:29026N.
IntActO00330. 2 interactions.

PTM databases

PhosphoSiteO00330.

Proteomic databases

PeptideAtlasO00330.
PRIDEO00330.

Genome annotation databases

EnsemblENSG00000110435. Homo sapiens. [Contig view]
GeneID8050.
NMPDRfig|9606.3.peg.5459.

Organism-specific databases

GeneCardsGC11P034894.
H-InvDBHIX0009554.
HGNCHGNC:21350. PDHX.
MIM245349. phenotype.
608769. gene.
Orphanet765. Pyruvate dehydrogenase deficiency.
PharmGKBPA134976445.
GenAtlasSearch...

Phylogenomic databases

HOGENOMO00330.
HOVERGENO00330.
OMAO00330. ADPIKIL.

Enzyme and pathway databases

ReactomeREACT_1505. Integration of energy metabolism.

Gene expression databases

ArrayExpressO00330.
BgeeO00330.
CleanExHS_PDHX.
HS_PDX1.
GermOnlineENSG00000110435. Homo sapiens.

Family and domain databases

InterProIPR003016. 2-oxoA_DH_lipoyl-BS.
IPR001078. 2-oxoacid_DH_actylTfrase.
IPR000089. Biotin_lipoyl.
IPR004167. E3_bd.
[Graphical view]
PfamPF00198. 2-oxoacid_dh. 1 hit.
PF00364. Biotin_lipoyl. 1 hit.
PF02817. E3_binding. 1 hit.
[Graphical view]
ProDomPD001115. 2Oxoacid_dh. 1 hit.
[Graphical view] [Entries sharing at least one domain]
PROSITEPS50968. BIOTINYL_LIPOYL. 1 hit.
PS00189. LIPOYL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio30644.
SOURCESearch...

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Entry information

Entry nameODPX_HUMAN
AccessionPrimary (citable) accession number: O00330
Secondary accession number(s): O60221, Q96FV8, Q99783
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 24, 2001
Last modified: June 16, 2009
This is version 94 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 11

Human chromosome 11: 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

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 · Cross-references · Entry information · Relevant documents