Reviewed, UniProtKB/Swiss-Prot P08559 (ODPA_HUMAN)

Names and origin

Protein names

Recommended name:
    Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
    EC=1.2.4.1
Alternative name(s):
    PDHE1-A type I

Gene names

Name:	PDHA1
Synonyms:	PHE1A

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	390 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 CO2. 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 + CO2.
Cofactor	Thiamine pyrophosphate.
Enzyme regulation	E1 activity is regulated by phosphorylation (inactivation) and dephosphorylation (activation) of the alpha subunit.
Subunit structure	Tetramer of 2 alpha and 2 beta subunits.
Subcellular location	Mitochondrion matrix.
Tissue specificity	Ubiquitous.
Involvement in disease	Defects in PDHA1 are a cause of pyruvate decarboxylase 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). Defects in PDHA1 are the cause of X-linked Leigh syndrome (LS) [MIM:308930]. LS is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. The lesions are areas of demyelination, gliosis, necrosis, spongiosis, or capillary proliferation. Clinical symptoms depend on which areas of the central nervous system are involved. The most common underlying cause is a defect in oxidative phosphorylation. LS may be a feature of a deficiency of any of the mitochondrial respiratory chain complexes. Ref.21 Ref.25 Ref.29 Ref.31 Ref.36
Sequence caution	The sequence AAB59581.1 differs from that shown. Reason: Frameshift at positions 106 and 175.

Ontologies

Keywords
Biological process	Glycolysis
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation Leigh syndrome
Domain	Transit peptide
Ligand	Pyruvate Thiamine pyrophosphate
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	glycolysis Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct pyruvate dehydrogenase (acetyl-transferring) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DGKE	P52429	1	EBI-715747,EBI-1057499

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 29

29

Mitochondrion

Chain

30 – 390

361

Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial

PRO_0000020440

Amino acid modifications

Modified residue

232

1

Phosphoserine Ref.11 Ref.12 Ref.15 Ref.16 Ref.17

Modified residue

289

1

Phosphotyrosine Ref.13

Modified residue

293

1

Phosphoserine Ref.15 Ref.16 Ref.17 Ref.14

Modified residue

295

1

Phosphoserine Ref.16

Modified residue

300

1

Phosphoserine Ref.16

Modified residue

301

1

Phosphotyrosine Ref.13

Natural variations

Natural variant

10

1

R → P in PDHE1 deficiency; affects mitochondrial import of precursor protein.

VAR_010238

Natural variant

72

1

R → C in PDHE1 deficiency.

VAR_004949

Natural variant

113

1

H → D in PDHE1 deficiency.

VAR_004950

Natural variant

162

1

G → R in PDHE1 deficiency.

VAR_004951

Natural variant

167

1

V → M in PDHE1 deficiency.

VAR_004952

Natural variant

199

1

A → T in PDHE1 deficiency.

VAR_004953

Natural variant

205

1

F → L in LS; PDHE1 deficiency. Ref.29 Ref.31

VAR_004954

Natural variant

210

1

M → V in PDHE1 deficiency.

VAR_004955

Natural variant

217

1

P → L in PDHE1 deficiency.

VAR_004956

Natural variant

231

1

T → A in PDHE1 deficiency.

VAR_004957

Natural variant

243

1

Y → N in PDHE1 deficiency.

VAR_021053

Natural variant

258

1

D → A in LS; PDHE1 deficiency. Ref.25

VAR_004958

Natural variant

263

1

R → G in PDHE1 deficiency and LS.

VAR_004959

Natural variant

263

1

R → Q in PDHE1 deficiency.

VAR_004960

Natural variant

282

1

M → L: dbSNP rs2229137. Ref.8 Ref.10 Ref.27

VAR_021054

Natural variant

288

1

R → H in PDHE1 deficiency.

VAR_021055

Natural variant

292

1

H → L in PDHE1 deficiency.

VAR_004961

Natural variant

302

1

R → C in PDHE1 deficiency; loss of activity; common mutation.

VAR_004962

Natural variant

302

1

R → H in PDHE1 deficiency.

VAR_004963

Natural variant

305

1

E → EDSYRTRE in PDHE1 deficiency.

VAR_020908

Natural variant

307

1

I → IPPHSYRTREEI in PDHE1 deficiency.

VAR_020909

Natural variant

311

1

Missing in PDHE1 deficiency.

VAR_004964

Natural variant

313

1

Missing in PDHE1 deficiency.

VAR_004965

Natural variant

315

1

D → N in PDHE1 deficiency.

VAR_021056

Natural variant

333

1

E → D: dbSNP rs2228067.

VAR_050436

Natural variant

378

1

R → H in LS; PDHE1 deficiency. Ref.21 Ref.31

VAR_004966

Experimental info

Sequence conflict

301

1

Y → S in AAD23857. Ref.10

Sequence conflict

306

1

E → D in AAD23857. Ref.10

Sequence conflict

349

1

A → P in AAA60055. Ref.6

Sequence conflict

354

1

T → A in AAA60055. Ref.6

Secondary structure

1

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390

Helix Strand Turn

Details...

Beta strand

32 – 37

6

Beta strand

42 – 45

4

Beta strand

52 – 57

6

Helix

58 – 83

26

Helix

98 – 107

10

Beta strand

112 – 115

4

Helix

121 – 126

6

Helix

131 – 138

8

Turn

145 – 148

4

Turn

167 – 169

3

Helix

170 – 183

14

Beta strand

190 – 195

6

Helix

198 – 200

3

Helix

202 – 213

12

Beta strand

218 – 224

7

Beta strand

226 – 228

3

Helix

233 – 236

4

Helix

242 – 244

3

Turn

245 – 248

4

Beta strand

251 – 255

5

Helix

259 – 274

16

Beta strand

280 – 285

6

Beta strand

300 – 302

3

Helix

304 – 314

11

Helix

316 – 326

11

Helix

332 – 355

24

Helix

361 – 363

3

Turn

364 – 367

4

Beta strand

368 – 371

4

Beta strand

375 – 378

4

Beta strand

385 – 388

4

Sequences

	Sequence		Length	Mass (Da)
	P08559-1 [UniParc]. Last modified May 1, 1992. Version 3. Checksum: 4D685BBE44A92D4B	FASTA	390	43,296
	10 20 30 40 50 60 MRKMLAAVSR VLSGASQKPA SRVLVASRNF ANDATFEIKK CDLHRLEEGP PVTTVLTRED 70 80 90 100 110 120 GLKYYRMMQT VRRMELKADQ LYKQKIIRGF CHLCDGQEAC CVGLEAGINP TDHLITAYRA 130 140 150 160 170 180 HGFTFTRGLS VREILAELTG RKGGCAKGKG GSMHMYAKNF YGGNGIVGAQ VPLGAGIALA 190 200 210 220 230 240 CKYNGKDEVC LTLYGDGAAN QGQIFEAYNM AALWKLPCIF ICENNRYGMG TSVERAAAST 250 260 270 280 290 300 DYYKRGDFIP GLRVDGMDIL CVREATRFAA AYCRSGKGPI LMELQTYRYH GHSMSDPGVS 310 320 330 340 350 360 YRTREEIQEV RSKSDPIMLL KDRMVNSNLA SVEELKEIDV EVRKEIEDAA QFATADPEPP 370 380 390 LEELGYHIYS SDPPFEVRGA NQWIKFKSVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization and nucleotide sequence of the gene encoding the human pyruvate dehydrogenase alpha-subunit." Koike K., Urata Y., Matsuo S., Koike M. Gene 93:307-311(1990) [PubMed: 2227443] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Leukocyte.
[2]	"Characterization of cDNAs encoding human pyruvate dehydrogenase alpha subunit." Ho L., Wexler I.D., Liu T.C., Thekkumkara T.J., Patel M.S. Proc. Natl. Acad. Sci. U.S.A. 86:5330-5334(1989) [PubMed: 2748588] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	Huh T.L., Chi Y.T., Casazza J.P., Veech R.L., Song B.J. Submitted (APR-1990) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain and Liver.
[4]	"The human pyruvate dehydrogenase complex. Isolation of cDNA clones for the E1 alpha subunit, sequence analysis, and characterization of the mRNA." Dahl H.-H.M., Hunt S.M., Hutchison W.M., Brown G.K. J. Biol. Chem. 262:7398-7403(1987) [PubMed: 3034892] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Structural organization of the gene for the E1 alpha subunit of the human pyruvate dehydrogenase complex." Maragos C., Hutchinson W.M., Hayasaki K., Brown G.K., Dahl H.-H.M. J. Biol. Chem. 264:12294-12298(1989) [PubMed: 2745444] [Abstract] Cited for: SEQUENCE REVISION.
[6]	"Isolation of a full-length complementary DNA coding for human E1 alpha subunit of the pyruvate dehydrogenase complex." de Meirleir L., MacKay N., Wah A.M.L.H., Robinson B.H. J. Biol. Chem. 263:1991-1995(1988) [PubMed: 2828359] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]	"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].
[8]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-282. Tissue: Dermoid cancer.
[9]	"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]. Tissue: Muscle.
[10]	"X chromosome evidence for ancient human histories." Harris E.E., Hey J. Proc. Natl. Acad. Sci. U.S.A. 96:3320-3324(1999) [PubMed: 10077682] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 202-336, VARIANT LEU-282.
[11]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232, MASS SPECTROMETRY. Tissue: Epithelium.
[12]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-289 AND TYR-301, MASS SPECTROMETRY.
[14]	"Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line." Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S. Electrophoresis 28:2027-2034(2007) [PubMed: 17487921] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293, MASS SPECTROMETRY.
[15]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232 AND SER-293, MASS SPECTROMETRY. Tissue: Platelet.
[16]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232; SER-293; SER-295 AND SER-300, MASS SPECTROMETRY.
[17]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232 AND SER-293, MASS SPECTROMETRY.
[18]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[19]	"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) IN COMPLEX WITH THIAMINE PYROPHOSPHATE.
[20]	"Mutations and polymorphisms in the pyruvate dehydrogenase E1 alpha gene." Dahl H.-H.M., Brown G.K., Brown R.M., Hansen L.L., Kerr D.S., Wexler I.D., Patel M.S., de Meirleir L., Lissens W., Chun K., McKay N., Robinson B.H. Hum. Mutat. 1:97-102(1992) [PubMed: 1301207] [Abstract] Cited for: REVIEW ON VARIANTS.
[21]	"Characterization of the mutations in three patients with pyruvate dehydrogenase E1 alpha deficiency." Hansen L.L., Brown G.K., Kirby D.M., Dahl H.-H.M. J. Inherit. Metab. Dis. 14:140-151(1991) [PubMed: 1909401] [Abstract] Cited for: VARIANT PDHE1 DEFICIENCY LYS-313 DEL, VARIANT LS HIS-378.
[22]	"Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair insertion mutation in the E1 alpha subunit." De Meirleir L., Lissens W., Vamos E., Liebaers I. Hum. Genet. 88:649-652(1992) [PubMed: 1551669] [Abstract] Cited for: VARIANT PDHE1 DEFICIENCY ASP-SER-TYR-ARG-THR-ARG-GLU-305 INS.
[23]	"X-linked pyruvate dehydrogenase E1 alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation." Dahl H.-H.M., Hansen L.L., Brown R.M., Danks D.M., Rogers J.G., Brown G.K. J. Inherit. Metab. Dis. 15:835-847(1992) [PubMed: 1293379] [Abstract] Cited for: VARIANT PDHE1 DEFICIENCY CYS-302.
[24]	"Mutation of E1 alpha gene in a female patient with pyruvate dehydrogenase deficiency due to rapid degradation of E1 protein." Ito M., Huq A.H., Naito E., Saijo T., Takeda E., Kuroda Y. J. Inherit. Metab. Dis. 15:848-856(1992) [PubMed: 1338114] [Abstract] Cited for: INVOLVEMENT IN PDHE1 DEFICIENCY.
[25]	"Molecular genetic characterization of an X-linked form of Leigh's syndrome." Matthews P.M., Marchington D.R., Squier M., Land J., Brown R.M., Brown G.K. Ann. Neurol. 33:652-655(1993) [PubMed: 8498846] [Abstract] Cited for: VARIANT LS ALA-258.
[26]	"Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase leading to deficiency of the pyruvate dehydrogenase complex." Chun K., McKay N., Petrova-Benedict R., Robinson B.H. Hum. Mol. Genet. 2:449-454(1993) [PubMed: 8504306] [Abstract] Cited for: VARIANTS PDHE1 DEFICIENCY MET-167; THR-199; ALA-231; GLY-263 AND LEU-292.
[27]	"Pyruvate dehydrogenase deficiency. Clinical presentation and molecular genetic characterization of five new patients." Matthews P.M., Brown R.M., Otero L.J., Marchington D.R., LeGris M., Howes R., Meadows L.S., Shevell M., Scriver C.R., Brown G.K. Brain 117:435-443(1994) [PubMed: 8032855] [Abstract] Cited for: VARIANTS PDHE1 DEFICIENCY ASN-243; ASN-315 AND HIS-378, VARIANT LEU-282.
[28]	"Pyruvate dehydrogenase deficiency caused by a 33 base pair duplication in the PDH E1 alpha subunit." Hansen L.L., Horn N., Dahl H.-H.M., Kruse T.A. Hum. Mol. Genet. 3:1021-1022(1994) [PubMed: 7545958] [Abstract] Cited for: VARIANT PDHE1 DEFICIENCY PRO-PRO-HIS-SER-TYR-ARG-THR-ARG-GLU-GLU-ILE-307 INS.
[29]	"Pyruvate dehydrogenase deficiency in a male caused by a point mutation (F205L) in the E1 alpha subunit." Dahl H.-H.M., Brown G.K. Hum. Mutat. 3:152-155(1994) [PubMed: 8199595] [Abstract] Cited for: VARIANT LS LEU-205.
[30]	"Characterization of a point mutation in the pyruvate dehydrogenase E1 alpha gene from two boys with primary lactic acidaemia." Awata H., Endo F., Tanoue A., Kitano A., Matsuda I. J. Inherit. Metab. Dis. 17:189-195(1994) [PubMed: 7967473] [Abstract] Cited for: VARIANT PDHE1 DEFICIENCY GLN-263.
[31]	"Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase: exon skipping, insertion of duplicate sequence, and missense mutations leading to the deficiency of the pyruvate dehydrogenase complex." Chun K., MacKay N., Petrova-Benedict R., Federico A., Fois A., Cole D.E.C., Robertson E., Robinson B.H. Am. J. Hum. Genet. 56:558-569(1995) [PubMed: 7887409] [Abstract] Cited for: VARIANTS PDHE1 DEFICIENCY CYS-72; GLY-263 AND ARG-311 DEL, VARIANTS LS LEU-205 AND HIS-378.
[32]	"An amino acid substitution in the pyruvate dehydrogenase E1 alpha gene, affecting mitochondrial import of the precursor protein." Takakubo F., Cartwright P., Hoogenraad N., Thorburn D.R., Collins F., Lithgow T., Dahl H.-H.M. Am. J. Hum. Genet. 57:772-780(1995) [PubMed: 7573035] [Abstract] Cited for: VARIANT PDHE1 DEFICIENCY PRO-10.
[33]	"Pyruvate dehydrogenase complex deficiency due to a point mutation (P188L) within the thiamine pyrophosphate binding loop of the E1 alpha subunit." Hemalatha S.G., Kerr D.S., Wexler I.D., Lusk M.M., Kaung M., Du Y., Kolli M., Schelper R.L., Patel M.S. Hum. Mol. Genet. 4:315-318(1995) [PubMed: 7757088] [Abstract] Cited for: VARIANT PDHE1 DEFICIENCY LEU-217.
[34]	"Mutation analysis of the pyruvate dehydrogenase E1 alpha gene in eight patients with a pyruvate dehydrogenase complex deficiency." Lissens W., de Meirleir L., Seneca S., Benelli C., Marsac C., Poll-The B.T., Briones P., Ruitenbeek W., van Diggelen O., Chaigne D., Ramaekers V., Liebaers I. Hum. Mutat. 7:46-51(1996) [PubMed: 8664900] [Abstract] Cited for: VARIANTS PDHE1 DEFICIENCY CYS-72; ASP-113; ARG-162; GLY-263; HIS-288 AND CYS-302.
[35]	"Three new mutations of the pyruvate dehydrogenase alpha subunit: a point mutation (M181V), 3 bp deletion (-R282), and 16 bp insertion/frameshift (K358SVS-->TVDQS)." Tripatara A., Kerr D.S., Lusk M.M., Kolli M., Tan J., Patel M.S. Hum. Mutat. 8:180-182(1996) [PubMed: 8844217] [Abstract] Cited for: VARIANTS PDHE1 DEFICIENCY VAL-210 AND ARG-311 DEL.
[36]	"Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency." Naito E., Ito M., Yokota I., Saijo T., Matsuda J., Osaka H., Kimura S., Kuroda Y. J. Inherit. Metab. Dis. 20:539-548(1997) [PubMed: 9266390] [Abstract] Cited for: VARIANT LS GLY-263.
[37]	"Arginine 302 mutations in the pyruvate dehydrogenase E1alpha subunit gene: identification of further patients and in vitro demonstration of pathogenicity." Otero L.J., Brown R.M., Brown G.K. Hum. Mutat. 12:114-121(1998) [PubMed: 9671272] [Abstract] Cited for: VARIANTS PDHE1 DEFICIENCY CYS-302 AND HIS-302.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

D90084 Genomic DNA. Translation: BAA14121.1.
M24848 mRNA. Translation: AAA36533.1.
X52709 mRNA. Translation: CAA36933.1.
X52710 mRNA. Translation: CAA36934.1.
M27257 , M29155, M29156, M29157, M29158, M29159, M29160, M29161, M29162, M29163, M29164 Genomic DNA. Translation: AAA60051.1.
L13318 mRNA. Translation: AAA60227.1.
J03503 mRNA. Translation: AAA60055.1. Different initiation.
J03575 mRNA. Translation: AAA60050.1.
L48690 mRNA. Translation: AAB59581.1. Frameshift.
AK222740 mRNA. Translation: BAD96460.1.
BC002406 mRNA. Translation: AAH02406.1.
AF125053 Genomic DNA. Translation: AAD23841.1.
AF125054 Genomic DNA. Translation: AAD23842.1.
AF125055 Genomic DNA. Translation: AAD23843.1.
AF125056 Genomic DNA. Translation: AAD23844.1.
AF125057 Genomic DNA. Translation: AAD23845.1.
AF125058 Genomic DNA. Translation: AAD23846.1.
AF125059 Genomic DNA. Translation: AAD23847.1.
AF125060 Genomic DNA. Translation: AAD23848.1.
AF125061 Genomic DNA. Translation: AAD23849.1.
AF125062 Genomic DNA. Translation: AAD23850.1.
AF125063 Genomic DNA. Translation: AAD23851.1.
AF125064 Genomic DNA. Translation: AAD23852.1.
AF125065 Genomic DNA. Translation: AAD23853.1.
AF125066 Genomic DNA. Translation: AAD23854.1.
AF125067 Genomic DNA. Translation: AAD23855.1.
AF125068 Genomic DNA. Translation: AAD23856.1.
AF125069 Genomic DNA. Translation: AAD23857.1.
AF125070 Genomic DNA. Translation: AAD23858.1.
AF125071 Genomic DNA. Translation: AAD23859.1.
AF125072 Genomic DNA. Translation: AAD23860.1.
AF125073 Genomic DNA. Translation: AAD23861.1.
AF125074 Genomic DNA. Translation: AAD23862.1.
AF125075 Genomic DNA. Translation: AAD23863.1.
AF125076 Genomic DNA. Translation: AAD23864.1.
AF125078 Genomic DNA. Translation: AAD23866.1.
AF125079 Genomic DNA. Translation: AAD23867.1.
AF125080 Genomic DNA. Translation: AAD23868.1.
AF125081 Genomic DNA. Translation: AAD23869.1.
AF125082 Genomic DNA. Translation: AAD23870.1.
AF125083 Genomic DNA. Translation: AAD23871.1.
AF125084 Genomic DNA. Translation: AAD23872.1.
AF125085 Genomic DNA. Translation: AAD23873.1.
AF125086 Genomic DNA. Translation: AAD23874.1.
AF125087 Genomic DNA. Translation: AAD23875.1.
AF125088 Genomic DNA. Translation: AAD23876.1.

IPI

IPI00922697.

PIR

DEHUPA. JQ0770.

RefSeq

NP_000275.1.

UniGene

Hs.530331

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NI4	X-ray	1.95	A/C	30-390	[»]
2OZL	X-ray	1.90	A/C	30-390	[»]
3EXE	X-ray	1.98	A/C/E/G	30-390	[»]
3EXF	X-ray	3.00	A/C/E/G	30-390	[»]
3EXG	X-ray	3.01	1/3/5/A/C/E/G/I/K/M/O/Q/S/U/W/Y	30-390	[»]
3EXH	X-ray	2.44	A/E	30-390	[»]
			C/G	30-390	[»]
3EXI	X-ray	2.20	A	30-390	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P08559. 6 interactions.

PTM databases

PhosphoSite

P08559.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00306301.

Proteomic databases

PeptideAtlas

P08559.

PRIDE

P08559.

Genome annotation databases

Ensembl

ENSG00000131828. Homo sapiens. [Contig view]

GeneID

5160.

KEGG

hsa:5160.

Organism-specific databases

GeneCards

GC0XP019271.

H-InvDB

HIX0016687.

HGNC

HGNC:8806. PDHA1.

MIM

300502. gene.
308930. phenotype.
312170. phenotype.

Orphanet

506. Leigh syndrome.
765. Pyruvate dehydrogenase deficiency.

PharmGKB

PA33150.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P08559.

HOVERGEN

P08559.

OMA

P08559. YAMGTST.

Enzyme and pathway databases

BRENDA

1.2.4.1. 247.

Reactome

REACT_1505. Integration of energy metabolism.

Gene expression databases

ArrayExpress

P08559.

Bgee

P08559.

CleanEx

HS_PDHA1.

GermOnline

ENSG00000131828. Homo sapiens.

Family and domain databases

InterPro

IPR001017. DH_E1.
IPR017597. Pyrv_DH_E1_asu_subgrp-y.
[Graphical view]

Pfam

PF00676. E1_dh. 1 hit.
[Graphical view]

TIGRFAMs

TIGR03182. PDH_E1_alph_y. 1 hit.

ProtoNet

Search...

Other Resources

DrugBank

DB00157. NADH.

NextBio

19962.

SOURCE

Search...

Entry information

Entry name

ODPA_HUMAN

Accession

Primary (citable) accession number: P08559
Secondary accession number(s): Q53H41 , Q9NP12, Q9UBJ8, Q9UBU0, Q9UNG4, Q9UNG5

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	May 1, 1992
Last modified:	June 16, 2009
This is version 125 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)