Reviewed, UniProtKB/Swiss-Prot P11177 (ODPB_HUMAN)

Names and origin

Protein names

Recommended name:
    Pyruvate dehydrogenase E1 component subunit beta, mitochondrial
      Short name=PDHE1-B
    EC=1.2.4.1

Gene names

Name:	PDHB
Synonyms:	PHE1B

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	359 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	The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2). It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3).
Catalytic activity	Pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO(2).
Cofactor	Thiamine pyrophosphate.
Subunit structure	Tetramer of 2 alpha and 2 beta subunits.
Subcellular location	Mitochondrion matrix.
Involvement in disease	Defects in PDHB are a cause of pyruvate dehydrogenase E1 component deficiency (PDHE1 deficiency) [MIM:312170]. PDHE1 deficiency is the most common enzyme defect in patients with primary lactic acidosis. It is associated with variable clinical phenotypes ranging from neonatal death to prolonged survival complicated by developmental delay, seizures, ataxia, apnea, and in some cases to an X-linked form of Leigh syndrome (LS) (Leigh encephalomyelopathy).

Ontologies

Keywords
Biological process	Glycolysis
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	Pyruvate Thiamine pyrophosphate
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	glycolysis Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW tricarboxylic acid cycle Ref.3 Traceable author statement. Source: ProtInc
Cellular component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	pyruvate dehydrogenase (acetyl-transferring) activity Ref.3 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P11177-1)

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: P11177-2)

The sequence of this isoform differs from the canonical sequence as follows:
     16-33: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 30

30

Mitochondrion

Chain

31 – 359

329

Pyruvate dehydrogenase E1 component subunit beta, mitochondrial

PRO_0000020457

Sites

Binding site

89

1

Thiamine pyrophosphate

Amino acid modifications

Modified residue

67

1

Phosphotyrosine By similarity

Natural variations

Alternative sequence

16 – 33

18

Missing in isoform 2.

VSP_012675

Natural variant

31

1

L → V

VAR_004967

Natural variant

132

1

Y → C in PDHE1 deficiency. dbSNP rs28935769.

VAR_030954

Natural variant

344

1

P → S in PDHE1 deficiency. dbSNP rs28933391.

VAR_021058

Experimental info

Sequence conflict

9 – 13

5

RRPLR → AETPS Ref.5

Sequence conflict

43

1

M → G AA sequence Ref.10

Sequence conflict

160

1

Q → G Ref.5

Sequence conflict

213 – 221

9

PPEAQSKDF → LRKLSQKIL Ref.5

Sequence conflict

213

1

P → L in AAA88097 and BAA14123. Ref.4

Sequence conflict

310 – 312

3

MEG → NGS Ref.5

Secondary structure

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359

Helix Strand Turn

Details...

Beta strand

32 – 34

3

Helix

35 – 49

15

Beta strand

53 – 57

5

Turn

69 – 72

4

Helix

73 – 77

5

Turn

79 – 81

3

Beta strand

82 – 84

3

Helix

89 – 101

13

Beta strand

105 – 109

5

Helix

113 – 119

7

Helix

120 – 125

6

Turn

126 – 128

3

Helix

130 – 133

4

Beta strand

143 – 147

5

Helix

156 – 158

3

Helix

163 – 167

5

Beta strand

173 – 175

3

Helix

180 – 192

13

Beta strand

193 – 195

3

Beta strand

197 – 201

5

Helix

203 – 205

3

Beta strand

209 – 211

3

Helix

214 – 217

4

Beta strand

229 – 232

4

Beta strand

235 – 241

7

Helix

245 – 257

13

Turn

258 – 260

3

Beta strand

263 – 267

5

Beta strand

270 – 272

3

Helix

276 – 286

11

Beta strand

289 – 292

4

Helix

301 – 311

11

Helix

313 – 317

5

Beta strand

323 – 325

3

Helix

336 – 340

5

Helix

346 – 356

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 6, 2007. Version 3. Checksum: AB459B1259FBDBD3	FASTA	359	39,233
	10 20 30 40 50 60 MAAVSGLVRR PLREVSGLLK RRFHWTAPAA LQVTVRDAIN QGMDEELERD EKVFLLGEEV 70 80 90 100 110 120 AQYDGAYKVS RGLWKKYGDK RIIDTPISEM GFAGIAVGAA MAGLRPICEF MTFNFSMQAI 130 140 150 160 170 180 DQVINSAAKT YYMSGGLQPV PIVFRGPNGA SAGVAAQHSQ CFAAWYGHCP GLKVVSPWNS 190 200 210 220 230 240 EDAKGLIKSA IRDNNPVVVL ENELMYGVPF EFPPEAQSKD FLIPIGKAKI ERQGTHITVV 250 260 270 280 290 300 SHSRPVGHCL EAAAVLSKEG VECEVINMRT IRPMDMETIE ASVMKTNHLV TVEGGWPQFG 310 320 330 340 350 VGAEICARIM EGPAFNFLDA PAVRVTGADV PMPYAKILED NSIPQVKDII FAIKKTLNI
	Isoform 2 [UniParc]. Checksum: B4F137127819BB38		341	37,200
	10 20 30 40 50 60 MAAVSGLVRR PLREVTVRDA INQGMDEELE RDEKVFLLGE EVAQYDGAYK VSRGLWKKYG 70 80 90 100 110 120 DKRIIDTPIS EMGFAGIAVG AAMAGLRPIC EFMTFNFSMQ AIDQVINSAA KTYYMSGGLQ 130 140 150 160 170 180 PVPIVFRGPN GASAGVAAQH SQCFAAWYGH CPGLKVVSPW NSEDAKGLIK SAIRDNNPVV 190 200 210 220 230 240 VLENELMYGV PFEFPPEAQS KDFLIPIGKA KIERQGTHIT VVSHSRPVGH CLEAAAVLSK 250 260 270 280 290 300 EGVECEVINM RTIRPMDMET IEASVMKTNH LVTVEGGWPQ FGVGAEICAR IMEGPAFNFL 310 320 330 340 DAPAVRVTGA DVPMPYAKIL EDNSIPQVKD IIFAIKKTLN I

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and cDNA sequence of the beta-subunit component of human pyruvate dehydrogenase complex." Ho L., Patel M.S. Gene 86:297-302(1990) [PubMed: 2323578] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Isolation, characterization and chromosomal localization of cDNA clones for the E1 beta subunit of the pyruvate dehydrogenase complex." Chun K., MacKay N., Willard H.F., Robinson B.H. Eur. J. Biochem. 194:587-592(1990) [PubMed: 1702713] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Characterization of two cDNA clones for pyruvate dehydrogenase E1 beta subunit and its regulation in tricarboxylic acid cycle-deficient fibroblast." Huh T.L., Casazza J.P., Huh J.W., Chi Y.T., Song B.J. J. Biol. Chem. 265:13320-13326(1990) [PubMed: 2376596] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT VAL-31.
[4]	"Molecular cloning and characterization of human pyruvate dehydrogenase beta subunit gene." Koike K., Urata Y., Koike M. Proc. Natl. Acad. Sci. U.S.A. 87:5594-5597(1990) [PubMed: 2377599] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[5]	"Cloning and sequencing of cDNAs encoding alpha and beta subunits of human pyruvate dehydrogenase." Koike K., Ohta S., Urata Y., Kagawa Y., Koike M. Proc. Natl. Acad. Sci. U.S.A. 85:41-45(1988) [PubMed: 3422424] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-31.
[6]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[7]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[9]	"Identification of a cDNA clone for the beta-subunit of the pyruvate dehydrogenase component of human pyruvate dehydrogenase complex." Ho L., Javed A.A., Pepin R.A., Thekkumkara T.J., Raefsky C., Mole J.E., Caliendo A.M., Kwon M.S., Kerr D.S., Patel M.S. Biochem. Biophys. Res. Commun. 150:904-908(1988) [PubMed: 2829898] [Abstract] Cited for: PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 23-69.
[10]	"The human myocardial two-dimensional gel protein database: update 1994." Corbett J.M., Wheeler C.H., Baker C.S., Yacoub M.H., Dunn M.J. Electrophoresis 15:1459-1465(1994) [PubMed: 7895732] [Abstract] Cited for: PROTEIN SEQUENCE OF 31-43. Tissue: Heart.
[11]	"Isolation of tryptic fragment of antigen from mitochondrial inner membrane proteins reacting with antimitochondrial antibody in sera of patients with primary biliary cirrhosis." Muno D., Kominami E., Ishii H., Usui K., Saifuku K., Sakakibara Y., Namihisa T. Hepatology 11:16-23(1990) [PubMed: 2295468] [Abstract] Cited for: PROTEIN SEQUENCE OF 31-55.
[12]	"Structural basis for flip-flop action of thiamin pyrophosphate-dependent enzymes revealed by human pyruvate dehydrogenase." Ciszak E.M., Korotchkina L.G., Dominiak P.M., Sidhu S., Patel M.S. J. Biol. Chem. 278:21240-21246(2003) [PubMed: 12651851] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 32-359 IN COMPLEX WITH THIAMINE PYROPHOSPHATE.
[13]	"Mutations in the gene for the E1beta subunit: a novel cause of pyruvate dehydrogenase deficiency." Brown R.M., Head R.A., Boubriak I.I., Leonard J.V., Thomas N.H., Brown G.K. Hum. Genet. 115:123-127(2004) [PubMed: 15138885] [Abstract] Cited for: VARIANTS PDHE1 DEFICIENCY CYS-132 AND SER-344.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M34479 mRNA. Translation: AAA36428.1.
M19123 mRNA. Translation: AAA60052.1. Sequence problems.
M54788 mRNA. Translation: AAA60053.1.
M34055 mRNA. Translation: AAA60233.1.
M34056 mRNA. Translation: AAA60054.1.
D90086 Genomic DNA. Translation: BAA14123.1.
J03576 mRNA. Translation: AAA88097.1.
AL117618 mRNA. Translation: CAB56017.1.
CR541911 mRNA. Translation: CAG46709.1.
BC000439 mRNA. Translation: AAH00439.1.
BC001924 mRNA. Translation: AAH01924.1.
X57778 mRNA. Translation: CAA40924.1.

PIR

DEHUPB. JU0145.

RefSeq

NP_000916.2.

UniGene

Hs.161357

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NI4	X-ray	1.95	B/D	32-359	[»]
2OZL	X-ray	1.90	B/D	31-359	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P11177.

PTM databases

PhosphoSite

P11177.

2-D gel databases

SWISS-2DPAGE

P11177.

HSC-2DPAGE

P11177.

REPRODUCTION-2DPAGE

IPI00549885.

Genome annotation databases

Ensembl

ENSG00000168291. Homo sapiens. [Contig view]

GeneID

5162.

KEGG

hsa:5162.

Organism-specific databases

H-InvDB

HIX0003404.

HGNC