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Protein

Pyruvate dehydrogenase protein X component, mitochondrial

Gene

PDHX

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000110435-MONOMER.
ZFISH:ENSG00000110435-MONOMER.
ReactomeiR-HSA-204174. Regulation of pyruvate dehydrogenase (PDH) complex.
R-HSA-389661. Glyoxylate metabolism and glycine degradation.
R-HSA-5362517. Signaling by Retinoic Acid.
R-HSA-70268. Pyruvate metabolism.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:PDHX
Synonyms:PDX1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:21350. PDHX.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial matrix Source: Reactome
  • pyruvate dehydrogenase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Pyruvate dehydrogenase E3-binding protein deficiency (PDHXD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:245349

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi183R → A: Strongly decreased DLD binding. 1 Publication1
Mutagenesisi185S → A: Strongly decreased DLD binding. 1 Publication1
Mutagenesisi186P → A: Strongly decreased DLD binding. 1 Publication1
Mutagenesisi187A → M: Strongly decreased DLD binding. 1 Publication1
Mutagenesisi189R → A: Strongly decreased DLD binding. 1 Publication1
Mutagenesisi190N → A: Strongly decreased DLD binding. 1 Publication1
Mutagenesisi193E → A: Strongly decreased DLD binding. 1 Publication1
Mutagenesisi208R → A: Strongly decreased DLD binding. 1 Publication1
Mutagenesisi210I → A: Strongly decreased DLD binding. 1 Publication1
Mutagenesisi213K → A: Strongly decreased DLD binding. 1 Publication1
Mutagenesisi214E → A: Strongly decreased DLD binding. 1 Publication1

Organism-specific databases

DisGeNETi8050.
MalaCardsiPDHX.
MIMi245349. phenotype.
OpenTargetsiENSG00000110435.
Orphaneti255182. Pyruvate dehydrogenase E3-binding protein deficiency.
PharmGKBiPA134976445.

Polymorphism and mutation databases

BioMutaiPDHX.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 53MitochondrionBy similarityAdd BLAST53
ChainiPRO_000002048454 – 501Pyruvate dehydrogenase protein X component, mitochondrialAdd BLAST448

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei97N6-lipoyllysinePROSITE-ProRule annotation1 Publication1
Modified residuei194N6-acetyllysineCombined sources1
Modified residuei196PhosphoserineCombined sources1
Modified residuei394N6-succinyllysineBy similarity1

Post-translational modificationi

Delipoylated at Lys-97 by SIRT4, delipoylation decreases the PHD complex activity.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO00330.
MaxQBiO00330.
PaxDbiO00330.
PeptideAtlasiO00330.
PRIDEiO00330.

PTM databases

iPTMnetiO00330.
PhosphoSitePlusiO00330.
SwissPalmiO00330.

Expressioni

Gene expression databases

BgeeiENSG00000110435.
CleanExiHS_PDHX.
HS_PDX1.
ExpressionAtlasiO00330. baseline and differential.
GenevisibleiO00330. HS.

Organism-specific databases

HPAiHPA038484.
HPA038485.

Interactioni

Subunit structurei

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). Interacts with SIRT4 (PubMed:25525879).4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AGTRAPQ6RW134EBI-751566,EBI-741181
SIRT4Q9Y6E74EBI-751566,EBI-2606540

Protein-protein interaction databases

BioGridi113737. 31 interactors.
DIPiDIP-29026N.
IntActiO00330. 11 interactors.
MINTiMINT-1482590.
STRINGi9606.ENSP00000227868.

Structurei

Secondary structure

1501
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi57 – 60Combined sources4
Beta strandi69 – 71Combined sources3
Beta strandi73 – 78Combined sources6
Beta strandi88 – 94Combined sources7
Beta strandi99 – 103Combined sources5
Beta strandi108 – 112Combined sources5
Beta strandi122 – 125Combined sources4
Beta strandi127 – 132Combined sources6
Helixi180 – 183Combined sources4
Helixi186 – 194Combined sources9
Helixi199 – 201Combined sources3
Helixi207 – 209Combined sources3
Helixi213 – 228Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliO00330.
SMRiO00330.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00330.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini56 – 132Lipoyl-bindingPROSITE-ProRule annotationAdd BLAST77

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni183 – 214Interaction with DLDAdd BLAST32

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi149 – 170Pro-richAdd BLAST22

Sequence similaritiesi

Belongs to the 2-oxoacid dehydrogenase family.Curated
Contains 1 lipoyl-binding domain.PROSITE-ProRule annotationCurated

Keywords - Domaini

Lipoyl, Transit peptide

Phylogenomic databases

eggNOGiKOG0557. Eukaryota.
COG0508. LUCA.
GeneTreeiENSGT00860000133743.
HOGENOMiHOG000281566.
HOVERGENiHBG005063.
InParanoidiO00330.
KOiK13997.
OMAiSWRLGCD.
OrthoDBiEOG091G0CAV.
PhylomeDBiO00330.
TreeFamiTF332256.

Family and domain databases

Gene3Di3.30.559.10. 1 hit.
4.10.320.10. 1 hit.
InterProiIPR003016. 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]
PfamiPF00198. 2-oxoacid_dh. 1 hit.
PF00364. Biotin_lipoyl. 1 hit.
PF02817. E3_binding. 1 hit.
[Graphical view]
SUPFAMiSSF47005. SSF47005. 1 hit.
SSF51230. SSF51230. 1 hit.
PROSITEiPS50968. BIOTINYL_LIPOYL. 1 hit.
PS00189. LIPOYL. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O00330-1) [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
MAASWRLGCD PRLLRYLVGF PGRRSVGLVK GALGWSVSRG ANWRWFHSTQ
60 70 80 90 100
WLRGDPIKIL MPSLSPTMEE GNIVKWLKKE GEAVSAGDAL CEIETDKAVV
110 120 130 140 150
TLDASDDGIL AKIVVEEGSK NIRLGSLIGL IVEEGEDWKH VEIPKDVGPP
160 170 180 190 200
PPVSKPSEPR PSPEPQISIP VKKEHIPGTL RFRLSPAARN ILEKHSLDAS
210 220 230 240 250
QGTATGPRGI FTKEDALKLV QLKQTGKITE SRPTPAPTAT PTAPSPLQAT
260 270 280 290 300
AGPSYPRPVI PPVSTPGQPN AVGTFTEIPA SNIRRVIAKR LTESKSTVPH
310 320 330 340 350
AYATADCDLG AVLKVRQDLV KDDIKVSVND FIIKAAAVTL KQMPDVNVSW
360 370 380 390 400
DGEGPKQLPF IDISVAVATD KGLLTPIIKD AAAKGIQEIA DSVKALSKKA
410 420 430 440 450
RDGKLLPEEY QGGSFSISNL GMFGIDEFTA VINPPQACIL AVGRFRPVLK
460 470 480 490 500
LTEDEEGNAK LQQRQLITVT MSSDSRVVDD ELATRFLKSF KANLENPIRL

A
Length:501
Mass (Da):54,122
Last modified:January 24, 2001 - v3
Checksum:i9CF0C1DAE9E12EF9
GO
Isoform 2 (identifier: O00330-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     115-341: Missing.

Note: No experimental confirmation available.
Show »
Length:274
Mass (Da):29,906
Checksum:i7657F43CA5F9B61D
GO
Isoform 3 (identifier: O00330-3) [UniParc]FASTAAdd to basket

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.
Show »
Length:486
Mass (Da):51,460
Checksum:iC0682D60CAC5BDF5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti41A → R in AAC39661 (PubMed:9467010).Curated1
Sequence conflicti251A → S in AAB66315 (PubMed:9242632).Curated1
Sequence conflicti251A → S in CAA73606 (PubMed:9399911).Curated1
Sequence conflicti344P → S in BAG62924 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04661923R → C.1 PublicationCorresponds to variant rs1049306dbSNPEnsembl.1
Natural variantiVAR_046620101T → A.Corresponds to variant rs11539202dbSNPEnsembl.1
Natural variantiVAR_046621370D → V.1 PublicationCorresponds to variant rs17850649dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0538172 – 53AASWR…TQWLR → QSGGAEGSPGAGRTGRGPGS GKAPPAEISSGAPDFPG in isoform 3. CuratedAdd BLAST52
Alternative sequenceiVSP_045271115 – 341Missing in isoform 2. CuratedAdd BLAST227

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44569.1. [O00330-3]
CCDS53616.1. [O00330-2]
CCDS7896.1. [O00330-1]
RefSeqiNP_001128496.1. NM_001135024.1. [O00330-3]
NP_001159630.1. NM_001166158.1. [O00330-2]
NP_003468.2. NM_003477.2. [O00330-1]
UniGeneiHs.502315.

Genome annotation databases

EnsembliENST00000227868; ENSP00000227868; ENSG00000110435. [O00330-1]
ENST00000430469; ENSP00000415695; ENSG00000110435. [O00330-2]
ENST00000448838; ENSP00000389404; ENSG00000110435. [O00330-3]
GeneIDi8050.
KEGGihsa:8050.
UCSCiuc001mvt.4. human. [O00330-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44569.1. [O00330-3]
CCDS53616.1. [O00330-2]
CCDS7896.1. [O00330-1]
RefSeqiNP_001128496.1. NM_001135024.1. [O00330-3]
NP_001159630.1. NM_001166158.1. [O00330-2]
NP_003468.2. NM_003477.2. [O00330-1]
UniGeneiHs.502315.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliO00330.
SMRiO00330.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113737. 31 interactors.
DIPiDIP-29026N.
IntActiO00330. 11 interactors.
MINTiMINT-1482590.
STRINGi9606.ENSP00000227868.

PTM databases

iPTMnetiO00330.
PhosphoSitePlusiO00330.
SwissPalmiO00330.

Polymorphism and mutation databases

BioMutaiPDHX.

Proteomic databases

EPDiO00330.
MaxQBiO00330.
PaxDbiO00330.
PeptideAtlasiO00330.
PRIDEiO00330.

Protocols and materials databases

DNASUi8050.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000227868; ENSP00000227868; ENSG00000110435. [O00330-1]
ENST00000430469; ENSP00000415695; ENSG00000110435. [O00330-2]
ENST00000448838; ENSP00000389404; ENSG00000110435. [O00330-3]
GeneIDi8050.
KEGGihsa:8050.
UCSCiuc001mvt.4. human. [O00330-1]

Organism-specific databases

CTDi8050.
DisGeNETi8050.
GeneCardsiPDHX.
HGNCiHGNC:21350. PDHX.
HPAiHPA038484.
HPA038485.
MalaCardsiPDHX.
MIMi245349. phenotype.
608769. gene.
neXtProtiNX_O00330.
OpenTargetsiENSG00000110435.
Orphaneti255182. Pyruvate dehydrogenase E3-binding protein deficiency.
PharmGKBiPA134976445.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0557. Eukaryota.
COG0508. LUCA.
GeneTreeiENSGT00860000133743.
HOGENOMiHOG000281566.
HOVERGENiHBG005063.
InParanoidiO00330.
KOiK13997.
OMAiSWRLGCD.
OrthoDBiEOG091G0CAV.
PhylomeDBiO00330.
TreeFamiTF332256.

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000110435-MONOMER.
ZFISH:ENSG00000110435-MONOMER.
ReactomeiR-HSA-204174. Regulation of pyruvate dehydrogenase (PDH) complex.
R-HSA-389661. Glyoxylate metabolism and glycine degradation.
R-HSA-5362517. Signaling by Retinoic Acid.
R-HSA-70268. Pyruvate metabolism.

Miscellaneous databases

ChiTaRSiPDHX. human.
EvolutionaryTraceiO00330.
GeneWikiiE3_binding_protein.
GenomeRNAii8050.
PROiO00330.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000110435.
CleanExiHS_PDHX.
HS_PDX1.
ExpressionAtlasiO00330. baseline and differential.
GenevisibleiO00330. HS.

Family and domain databases

Gene3Di3.30.559.10. 1 hit.
4.10.320.10. 1 hit.
InterProiIPR003016. 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]
PfamiPF00198. 2-oxoacid_dh. 1 hit.
PF00364. Biotin_lipoyl. 1 hit.
PF02817. E3_binding. 1 hit.
[Graphical view]
SUPFAMiSSF47005. SSF47005. 1 hit.
SSF51230. SSF51230. 1 hit.
PROSITEiPS50968. BIOTINYL_LIPOYL. 1 hit.
PS00189. LIPOYL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiODPX_HUMAN
AccessioniPrimary (citable) accession number: O00330
Secondary accession number(s): B4DW62
, D3DR11, E9PB14, E9PBP7, O60221, Q96FV8, Q99783
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 24, 2001
Last modified: November 30, 2016
This is version 170 of the entry and version 3 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, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.