O00330 (ODPX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	PDHX
Synonyms:	PDX1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	501 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	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 the cause of pyruvate dehydrogenase E3-binding protein deficiency (PDHE3BPD) [MIM:245349].
Sequence similarities	Belongs to the 2-oxoacid dehydrogenase family. Contains 1 lipoyl-binding domain.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Lipoyl Transit peptide
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	pyruvate metabolic process Traceable author statement. Source: Reactome regulation of acetyl-CoA biosynthetic process from pyruvate Traceable author statement. Source: Reactome
Cellular component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular function	transferase activity, transferring acyl groups Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 53

53

Mitochondrion By similarity

Chain

54 – 501

448

Pyruvate dehydrogenase protein X component, mitochondrial

PRO_0000020484

Regions

Domain

57 – 131

75

Lipoyl-binding

Region

183 – 214

32

Interaction with DLD

Compositional bias

149 – 170

22

Pro-rich

Amino acid modifications

Modified residue

97

1

N6-lipoyllysine By similarity

Modified residue

194

1

N6-acetyllysine Ref.8

Natural variations

Natural variant

23

1

R → C. Ref.1
Corresponds to variant rs1049306 [ dbSNP | Ensembl ].

VAR_046619

Natural variant

101

1

T → A.
Corresponds to variant rs11539202 [ dbSNP | Ensembl ].

VAR_046620

Natural variant

370

1

D → V. Ref.6
Corresponds to variant rs17850649 [ dbSNP | Ensembl ].

VAR_046621

Experimental info

Mutagenesis

183

1

R → A: Strongly decreased DLD binding. Ref.11

Mutagenesis

185

1

S → A: Strongly decreased DLD binding. Ref.11

Mutagenesis

186

1

P → A: Strongly decreased DLD binding. Ref.11

Mutagenesis

187

1

A → M: Strongly decreased DLD binding. Ref.11

Mutagenesis

189

1

R → A: Strongly decreased DLD binding. Ref.11

Mutagenesis

190

1

N → A: Strongly decreased DLD binding. Ref.11

Mutagenesis

193

1

E → A: Strongly decreased DLD binding. Ref.11

Mutagenesis

208

1

R → A: Strongly decreased DLD binding. Ref.11

Mutagenesis

210

1

I → A: Strongly decreased DLD binding. Ref.11

Mutagenesis

213

1

K → A: Strongly decreased DLD binding. Ref.11

Mutagenesis

214

1

E → A: Strongly decreased DLD binding. Ref.11

Sequence conflict

41

1

A → R in AAC39661. Ref.3

Sequence conflict

251

1

A → S in AAB66315. Ref.1

Sequence conflict

251

1

A → S in CAA73606. Ref.2

Secondary structure

1

.

.

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.

.

.

.

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.

.

.

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.

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.

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501

Helix Strand Turn

Details...

Beta strand

57 – 60

4

Beta strand

69 – 71

3

Beta strand

73 – 78

6

Beta strand

88 – 94

7

Beta strand

99 – 103

5

Beta strand

108 – 112

5

Beta strand

122 – 125

4

Beta strand

127 – 132

6

Helix

188 – 194

7

Helix

199 – 201

3

Helix

207 – 209

3

Helix

213 – 224

12

Sequences

	Sequence		Length	Mass (Da)
	O00330 [UniParc]. Last modified January 24, 2001. Version 3. Checksum: 9CF0C1DAE9E12EF9	FASTA	501	54,122
	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

References

	« Hide 'large scale' referencesShow '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]	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. , 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].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-370. Tissue: Brain.
[7]	"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.
[8]	"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-194, MASS SPECTROMETRY.
[9]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"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.
[11]	"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.
[12]	"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.
CH471064 Genomic DNA. Translation: EAW68158.1.
CH471064 Genomic DNA. Translation: EAW68160.1.
BC010389 mRNA. Translation: AAH10389.1.
U79296 mRNA. Translation: AAB50223.1.

IPI

IPI00298423.

RefSeq

NP_001128496.1. NM_001135024.1.
NP_001159630.1. NM_001166158.1.
NP_003468.2. NM_003477.2.

UniGene

Hs.502315.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ZY8	X-ray	2.59	K/L/M/N/O	54-274	[»]
2DNC	NMR	-	A	57-141	[»]
2F5Z	X-ray	2.18	K/L/M/N/O	174-228	[»]
2F60	X-ray	1.55	K	174-228	[»]

ProteinModelPortal

O00330.

SMR

O00330. Positions 57-144, 183-225, 272-500.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29026N.

IntAct

O00330. 4 interactions.

MINT

MINT-1482590.

STRING

O00330.

PTM databases

PhosphoSite

O00330.

Proteomic databases

PeptideAtlas

O00330.

PRIDE

O00330.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000227868; ENSP00000227868; ENSG00000110435.

GeneID

8050.

KEGG

hsa:8050.

NMPDR

fig|9606.3.peg.5459.

UCSC

uc001mvt.1. human.

Organism-specific databases

CTD

8050.

GeneCards

GC11P034894.

H-InvDB

HIX0009554.

HGNC

HGNC:21350. PDHX.

HPA

HPA038484.
HPA038485.

MIM

245349. phenotype.
608769. gene.

neXtProt

NX_O00330.

Orphanet

255182. Pyruvate dehydrogenase protein X component deficiency.

PharmGKB

PA134976445.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05180.

GeneTree

ENSGT00560000077144.

HOGENOM

HBG630916.

HOVERGEN

HBG005063.

InParanoid

O00330.

OMA

ADPIKIL.

PhylomeDB

O00330.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

O00330.

Bgee

O00330.

CleanEx

HS_PDHX.
HS_PDX1.

Genevestigator

O00330.

GermOnline

ENSG00000110435. Homo sapiens.

Family and domain databases

InterPro

IPR003016. 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]

Gene3D

G3DSA:3.30.559.10. CAT-like_dom. 1 hit.
G3DSA:4.10.320.10. E3_bd. 1 hit.

KO

K13997.

Pfam

PF00198. 2-oxoacid_dh. 1 hit.
PF00364. Biotin_lipoyl. 1 hit.
PF02817. E3_binding. 1 hit.
[Graphical view]

SUPFAM

SSF47005. E3_bd. 1 hit.
SSF51230. Hybrid_motif. 1 hit.

PROSITE

PS50968. BIOTINYL_LIPOYL. 1 hit.
PS00189. LIPOYL. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

30644.

SOURCE

Search...

Entry information

Entry name

ODPX_HUMAN

Accession

Primary (citable) accession number: O00330
Secondary accession number(s): D3DR11 , O60221, Q96FV8, Q99783

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 24, 2001
Last modified:	January 25, 2012
This is version 120 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.