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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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	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.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing 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...

Alternative products

This entry describes 2 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.

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.11

Natural variations

Alternative sequence

115 – 341

227

Missing in isoform 2.

VSP_045271

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.8
Corresponds to variant rs17850649 [ dbSNP | Ensembl ].

VAR_046621

Experimental info

Mutagenesis

183

1

R → A: Strongly decreased DLD binding. Ref.14

Mutagenesis

185

1

S → A: Strongly decreased DLD binding. Ref.14

Mutagenesis

186

1

P → A: Strongly decreased DLD binding. Ref.14

Mutagenesis

187

1

A → M: Strongly decreased DLD binding. Ref.14

Mutagenesis

189

1

R → A: Strongly decreased DLD binding. Ref.14

Mutagenesis

190

1

N → A: Strongly decreased DLD binding. Ref.14

Mutagenesis

193

1

E → A: Strongly decreased DLD binding. Ref.14

Mutagenesis

208

1

R → A: Strongly decreased DLD binding. Ref.14

Mutagenesis

210

1

I → A: Strongly decreased DLD binding. Ref.14

Mutagenesis

213

1

K → A: Strongly decreased DLD binding. Ref.14

Mutagenesis

214

1

E → A: Strongly decreased DLD binding. Ref.14

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

Sequence conflict

344

1

P → S in BAG62924. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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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

180 – 183

4

Helix

186 – 194

9

Helix

199 – 201

3

Helix

207 – 209

3

Helix

213 – 228

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [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
	Isoform 2 [UniParc]. Checksum: 7657F43CA5F9B61D	FASTA	274	29,906
	10 20 30 40 50 60 MAASWRLGCD PRLLRYLVGF PGRRSVGLVK GALGWSVSRG ANWRWFHSTQ WLRGDPIKIL 70 80 90 100 110 120 MPSLSPTMEE GNIVKWLKKE GEAVSAGDAL CEIETDKAVV TLDASDDGIL AKIVQMPDVN 130 140 150 160 170 180 VSWDGEGPKQ LPFIDISVAV ATDKGLLTPI IKDAAAKGIQ EIADSVKALS KKARDGKLLP 190 200 210 220 230 240 EEYQGGSFSI SNLGMFGIDE FTAVINPPQA CILAVGRFRP VLKLTEDEEG NAKLQQRQLI 250 260 270 TVTMSSDSRV VDDELATRFL KSFKANLENP IRLA

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] [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. , 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. , 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. , 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, MASS SPECTROMETRY.
[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.

IPI

IPI00298423.
IPI00910682.

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.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29026N.

IntAct

O00330. 4 interactions.

MINT

MINT-1482590.

STRING

9606.ENSP00000227868.

PTM databases

PhosphoSite

O00330.

Proteomic databases

PaxDb

O00330.

PeptideAtlas

O00330.

PRIDE

O00330.

Protocols and materials databases

DNASU

8050.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000227868; ENSP00000227868; ENSG00000110435.
ENST00000430469; ENSP00000415695; ENSG00000110435.

GeneID

8050.

KEGG

hsa:8050.

UCSC

uc001mvt.3. human.
uc010req.2. human.

Organism-specific databases

CTD

8050.

GeneCards

GC11P034894.

HGNC

HGNC:21350. PDHX.

HPA

HPA038484.
HPA038485.

MIM

245349. phenotype.
608769. gene.

neXtProt

NX_O00330.

Orphanet

255182. Pyruvate dehydrogenase E3-binding protein deficiency.

PharmGKB

PA134976445.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0508.

HOGENOM

HOG000281566.

HOVERGEN

HBG005063.

InParanoid

O00330.

KO

K13997.

OMA

VGFPGRR.

PhylomeDB

O00330.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000110435-MONOMER.

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

Gene3D

3.30.559.10. 1 hit.
4.10.320.10. 1 hit.

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]

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

EvolutionaryTrace

O00330.

GenomeRNAi

8050.

NextBio

30644.

SOURCE

Search...

Entry information

Entry name

ODPX_HUMAN

Accession

Primary (citable) accession number: O00330
Secondary accession number(s): B4DW62 , D3DR11, E9PBP7, O60221, Q96FV8, Q99783

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 24, 2001
Last modified:	May 29, 2013
This is version 134 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.