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O00330 (ODPX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pyruvate dehydrogenase protein X component, mitochondrial
Alternative name(s):
Dihydrolipoamide dehydrogenase-binding protein of pyruvate dehydrogenase complex
E3-binding protein
Short name=E3BP
Lipoyl-containing pyruvate dehydrogenase complex component X
proX
Gene names
Name:PDHX
Synonyms:PDX1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

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

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

Part of the inner core of the multimeric pyruvate dehydrogenase complex that is composed of about 48 DLAT and 12 PDHX molecules. This core binds multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). Ref.10

Subcellular location

Mitochondrion matrix.

Involvement in disease

Pyruvate dehydrogenase E3-binding protein deficiency (PDHXD) [MIM:245349]: A metabolic disorder characterized by decreased activity of the pyruvate dehydrogenase complex without observable reduction in the activities of enzymes E1, E2, or E3. Clinical features include hypotonia and psychomotor retardation.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2

Sequence similarities

Belongs to the 2-oxoacid dehydrogenase family.

Contains 1 lipoyl-binding domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O00330-1)

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: O00330-2)

The sequence of this isoform differs from the canonical sequence as follows:
     115-341: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: O00330-3)

The sequence of this isoform differs from the canonical sequence as follows:
     2-53: AASWRLGCDP...RWFHSTQWLR → QSGGAEGSPG...ISSGAPDFPG
Note: No experimental confirmation available. Gene prediction based on EST data.

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
Modified residue1941N6-acetyllysine Ref.11
Modified residue3941N6-succinyllysine By similarity

Natural variations

Alternative sequence2 – 5352AASWR…TQWLR → QSGGAEGSPGAGRTGRGPGS GKAPPAEISSGAPDFPG in isoform 3.
VSP_053817
Alternative sequence115 – 341227Missing in isoform 2.
VSP_045271
Natural variant231R → C. Ref.1
Corresponds to variant rs1049306 [ dbSNP | Ensembl ].
VAR_046619
Natural variant1011T → A.
Corresponds to variant rs11539202 [ dbSNP | Ensembl ].
VAR_046620
Natural variant3701D → V. Ref.8
Corresponds to variant rs17850649 [ dbSNP | Ensembl ].
VAR_046621

Experimental info

Mutagenesis1831R → A: Strongly decreased DLD binding. Ref.14
Mutagenesis1851S → A: Strongly decreased DLD binding. Ref.14
Mutagenesis1861P → A: Strongly decreased DLD binding. Ref.14
Mutagenesis1871A → M: Strongly decreased DLD binding. Ref.14
Mutagenesis1891R → A: Strongly decreased DLD binding. Ref.14
Mutagenesis1901N → A: Strongly decreased DLD binding. Ref.14
Mutagenesis1931E → A: Strongly decreased DLD binding. Ref.14
Mutagenesis2081R → A: Strongly decreased DLD binding. Ref.14
Mutagenesis2101I → A: Strongly decreased DLD binding. Ref.14
Mutagenesis2131K → A: Strongly decreased DLD binding. Ref.14
Mutagenesis2141E → A: Strongly decreased DLD binding. Ref.14
Sequence conflict411A → R in AAC39661. Ref.3
Sequence conflict2511A → S in AAB66315. Ref.1
Sequence conflict2511A → S in CAA73606. Ref.2
Sequence conflict3441P → S in BAG62924. Ref.5

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 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

Isoform 2 [UniParc].

Checksum: 7657F43CA5F9B61D
Show »

FASTA27429,906
Isoform 3 [UniParc].

Checksum: C0682D60CAC5BDF5
Show »

FASTA48651,460

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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN PDHXD.
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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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]"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].
Tissue: Synovium.
[6]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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), VARIANT VAL-370.
Tissue: Brain.
[9]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 127-501 (ISOFORM 1).
Tissue: Brain.
[10]"Organization of the cores of the mammalian pyruvate dehydrogenase complex formed by E2 and E2 plus the E3-binding protein and their capacities to bind the E1 and E3 components."
Hiromasa Y., Fujisawa T., Aso Y., Roche T.E.
J. Biol. Chem. 279:6921-6933(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[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-194, 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]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 54-274 IN COMPLEX WITH DLD.
[14]"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] [Europe PMC] [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.
[15]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF001437 mRNA. Translation: AAB66315.1.
Y13145 mRNA. Translation: CAA73606.1.
U82328 mRNA. Translation: AAC39661.1.
AJ298105 Genomic DNA. Translation: CAC18649.1.
AK301384 mRNA. Translation: BAG62924.1.
AC107928 Genomic DNA. No translation available.
AL138810 Genomic DNA. No translation available.
AL356215 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68158.1.
CH471064 Genomic DNA. Translation: EAW68160.1.
BC010389 mRNA. Translation: AAH10389.1.
U79296 mRNA. Translation: AAB50223.1.
CCDSCCDS53616.1. [O00330-2]
CCDS7896.1. [O00330-1]
RefSeqNP_001128496.1. NM_001135024.1. [O00330-3]
NP_001159630.1. NM_001166158.1. [O00330-2]
NP_003468.2. NM_003477.2. [O00330-1]
UniGeneHs.502315.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZY8X-ray2.59K/L/M/N/O54-274[»]
2DNCNMR-A57-141[»]
2F5ZX-ray2.18K/L/M/N/O173-228[»]
2F60X-ray1.55K173-228[»]
ProteinModelPortalO00330.
SMRO00330. Positions 57-144, 183-225, 266-500.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113737. 12 interactions.
DIPDIP-29026N.
IntActO00330. 5 interactions.
MINTMINT-1482590.
STRING9606.ENSP00000227868.

PTM databases

PhosphoSiteO00330.

Proteomic databases

MaxQBO00330.
PaxDbO00330.
PeptideAtlasO00330.
PRIDEO00330.

Protocols and materials databases

DNASU8050.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000227868; ENSP00000227868; ENSG00000110435. [O00330-1]
ENST00000430469; ENSP00000415695; ENSG00000110435. [O00330-2]
ENST00000448838; ENSP00000389404; ENSG00000110435.
GeneID8050.
KEGGhsa:8050.
UCSCuc001mvt.3. human. [O00330-1]

Organism-specific databases

CTD8050.
GeneCardsGC11P034894.
HGNCHGNC:21350. PDHX.
HPAHPA038484.
HPA038485.
MIM245349. phenotype.
608769. gene.
neXtProtNX_O00330.
Orphanet255182. Pyruvate dehydrogenase E3-binding protein deficiency.
PharmGKBPA134976445.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0508.
HOGENOMHOG000281566.
HOVERGENHBG005063.
InParanoidO00330.
KOK13997.
OMASWRLGCD.
PhylomeDBO00330.
TreeFamTF332256.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000110435-MONOMER.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressO00330.
BgeeO00330.
CleanExHS_PDHX.
HS_PDX1.
GenevestigatorO00330.

Family and domain databases

Gene3D3.30.559.10. 1 hit.
4.10.320.10. 1 hit.
InterProIPR003016. 2-oxoA_DH_lipoyl-BS.
IPR001078. 2-oxoacid_DH_actylTfrase.
IPR000089. Biotin_lipoyl.
IPR023213. CAT-like_dom.
IPR004167. E3-bd.
IPR011053. Single_hybrid_motif.
[Graphical view]
PfamPF00198. 2-oxoacid_dh. 1 hit.
PF00364. Biotin_lipoyl. 1 hit.
PF02817. E3_binding. 1 hit.
[Graphical view]
SUPFAMSSF47005. SSF47005. 1 hit.
SSF51230. SSF51230. 1 hit.
PROSITEPS50968. BIOTINYL_LIPOYL. 1 hit.
PS00189. LIPOYL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO00330.
GeneWikiE3_binding_protein.
GenomeRNAi8050.
NextBio30644.
PROO00330.
SOURCESearch...

Entry information

Entry nameODPX_HUMAN
AccessionPrimary (citable) accession number: O00330
Secondary accession number(s): B4DW62 expand/collapse secondary AC list , D3DR11, E9PB14, E9PBP7, O60221, Q96FV8, Q99783
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 24, 2001
Last modified: July 9, 2014
This is version 144 of the entry and version 3 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

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 11

Human chromosome 11: entries, gene names and cross-references to MIM