P08559 (ODPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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 dehydrogenase E1-alpha deficiency (PDHAD) [MIM:312170]. An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis. Ref.27 Ref.28 Ref.29 Ref.30 Ref.32 Ref.33 Ref.34 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.43 Defects in PDHA1 are the cause of X-linked Leigh syndrome (X-LS) [MIM:308930]. X-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.27 Ref.31 Ref.35 Ref.37 Ref.42
Sequence caution	The sequence AAA60055.1 differs from that shown. Reason: Erroneous initiation. 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	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	glycolysis Inferred from electronic annotation. Source: UniProtKB-KW 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	pyruvate dehydrogenase (acetyl-transferring) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

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

77

1

N6-acetyllysine Ref.23

Modified residue

83

1

N6-acetyllysine Ref.23

Modified residue

231

1

Phosphothreonine Ref.20 Ref.21

Modified residue

232

1

Phosphoserine Ref.13 Ref.14 Ref.17 Ref.18 Ref.19

Modified residue

289

1

Phosphotyrosine Ref.15

Modified residue

293

1

Phosphoserine Ref.16 Ref.17 Ref.18 Ref.19 Ref.22

Modified residue

295

1

Phosphoserine Ref.18

Modified residue

300

1

Phosphoserine Ref.18 Ref.22

Modified residue

301

1

Phosphotyrosine Ref.15

Modified residue

321

1

N6-acetyllysine Ref.23

Modified residue

336

1

N6-acetyllysine Ref.23

Natural variations

Natural variant

10

1

R → P in PDHAD; affects mitochondrial import of precursor protein. Ref.38

VAR_010238

Natural variant

72

1

R → C in PDHAD. Ref.37 Ref.40

VAR_004949

Natural variant

113

1

H → D in PDHAD. Ref.40

VAR_004950

Natural variant

162

1

G → R in PDHAD. Ref.40

VAR_004951

Natural variant

167

1

V → M in PDHAD. Ref.32

VAR_004952

Natural variant

199

1

A → T in PDHAD. Ref.32

VAR_004953

Natural variant

205

1

F → L in X-LS; PDHAD. Ref.35 Ref.37

VAR_004954

Natural variant

210

1

M → V in PDHAD. Ref.41

VAR_004955

Natural variant

217

1

P → L in PDHAD. Ref.39

VAR_004956

Natural variant

231

1

T → A in PDHAD. Ref.32

VAR_004957

Natural variant

243

1

Y → N in PDHAD. Ref.33

VAR_021053

Natural variant

258

1

D → A in X-LS; PDHAD. Ref.31

VAR_004958

Natural variant

263

1

R → G in PDHAD and X-LS. Ref.32 Ref.37 Ref.40 Ref.42
Corresponds to variant rs28936081 [ dbSNP | Ensembl ].

VAR_004959

Natural variant

263

1

R → Q in PDHAD. Ref.36

VAR_004960

Natural variant

282

1

M → L. Ref.8 Ref.12 Ref.33
Corresponds to variant rs2229137 [ dbSNP | Ensembl ].

VAR_021054

Natural variant

288

1

R → H in PDHAD. Ref.40

VAR_021055

Natural variant

292

1

H → L in PDHAD. Ref.32

VAR_004961

Natural variant

302

1

R → C in PDHAD; loss of activity; common mutation. Ref.29 Ref.40 Ref.43

VAR_004962

Natural variant

302

1

R → H in PDHAD. Ref.43

VAR_004963

Natural variant

305

1

E → EDSYRTRE in PDHAD.

VAR_020908

Natural variant

307

1

I → IPPHSYRTREEI in PDHAD.

VAR_020909

Natural variant

311

1

Missing in PDHAD.

VAR_004964

Natural variant

313

1

Missing in PDHAD.

VAR_004965

Natural variant

315

1

D → N in PDHAD. Ref.33
Corresponds to variant rs28935187 [ dbSNP | Ensembl ].

VAR_021056

Natural variant

333

1

E → D.
Corresponds to variant rs2228067 [ dbSNP | Ensembl ].

VAR_050436

Natural variant

378

1

R → H in X-LS; PDHAD. Ref.27 Ref.33 Ref.37

VAR_004966

Experimental info

Sequence conflict

301

1

Y → S in AAD23857. Ref.12

Sequence conflict

306

1

E → D in AAD23857. Ref.12

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 [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 DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	"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.
[12]	"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.
[13]	"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: Cervix carcinoma.
[14]	"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: Cervix carcinoma.
[15]	"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. Tissue: Lung carcinoma.
[16]	"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. Tissue: Prostate cancer.
[17]	"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.
[18]	"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. Tissue: Cervix carcinoma.
[19]	"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. Tissue: Cervix carcinoma.
[20]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-231, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[21]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-231, MASS SPECTROMETRY.
[22]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293 AND SER-300, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[23]	"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-77; LYS-83; LYS-321 AND LYS-336, MASS SPECTROMETRY.
[24]	"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].
[25]	"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.
[26]	"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.
[27]	"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 PDHAD LYS-313 DEL, VARIANT X-LS HIS-378.
[28]	"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 PDHAD ASP-SER-TYR-ARG-THR-ARG-GLU-305 INS.
[29]	"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 PDHAD CYS-302.
[30]	"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 PDHAD.
[31]	"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 X-LS ALA-258.
[32]	"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 PDHAD MET-167; THR-199; ALA-231; GLY-263 AND LEU-292.
[33]	"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 PDHAD ASN-243; ASN-315 AND HIS-378, VARIANT LEU-282.
[34]	"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 PDHAD PRO-PRO-HIS-SER-TYR-ARG-THR-ARG-GLU-GLU-ILE-307 INS.
[35]	"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 X-LS LEU-205.
[36]	"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 PDHAD GLN-263.
[37]	"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 PDHAD CYS-72; GLY-263 AND ARG-311 DEL, VARIANTS X-LS LEU-205 AND HIS-378.
[38]	"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 PDHAD PRO-10.
[39]	"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 PDHAD LEU-217.
[40]	"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 PDHAD CYS-72; ASP-113; ARG-162; GLY-263; HIS-288 AND CYS-302.
[41]	"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 PDHAD VAL-210 AND ARG-311 DEL.
[42]	"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 X-LS GLY-263.
[43]	"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 PDHAD CYS-302 AND HIS-302.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
AL732326 Genomic DNA. Translation: CAI41291.1.
CH471074 Genomic DNA. Translation: EAW98960.1.
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. NM_000284.3.

UniGene

Hs.530331.

3D structure databases

PDBe
RCSB PDB
PDBj

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/C/E/G	30-390	[»]
3EXI	X-ray	2.20	A	30-390	[»]

ProteinModelPortal

P08559.

SMR

P08559. Positions 29-390.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-37652N.

IntAct

P08559. 5 interactions.

STRING

P08559.

PTM databases

PhosphoSite

P08559.

Polymorphism databases

DMDM

129063.

2D gel databases

REPRODUCTION-2DPAGE

IPI00306301.

UCD-2DPAGE

P08559.

Proteomic databases

PeptideAtlas

P08559.

PRIDE

P08559.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000422285; ENSP00000394382; ENSG00000131828.

GeneID

5160.

KEGG

hsa:5160.

UCSC

uc004czg.2. human.

Organism-specific databases

CTD

5160.

GeneCards

GC0XP019271.

H-InvDB

HIX0016687.

HGNC

HGNC:8806. PDHA1.

MIM

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

neXtProt

NX_P08559.

Orphanet

70474. Leigh syndrome with myopathy.
79243. Pyruvate dehydrogenase complex E1 component subunit alpha deficiency.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12224.

HOVERGEN

HBG001863.

InParanoid

P08559.

OrthoDB

EOG4W0XD6.

PhylomeDB

P08559.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P08559.

Bgee

P08559.

CleanEx

HS_PDHA1.

Genevestigator

P08559.

GermOnline

ENSG00000131828. Homo sapiens.

Family and domain databases

InterPro

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

KO

K00161.

Pfam

PF00676. E1_dh. 1 hit.
[Graphical view]

TIGRFAMs

TIGR03182. PDH_E1_alph_y. 1 hit.

ProtoNet

Search...

Other

DrugBank

DB00157. NADH.

NextBio

19962.

SOURCE

Search...

Entry information

Entry name

ODPA_HUMAN

Accession

Primary (citable) accession number: P08559
Secondary accession number(s): Q53H41 , Q5JPT8, Q9NP12, Q9UBJ8, Q9UBU0, Q9UNG4, Q9UNG5

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	May 1, 1992
Last modified:	January 25, 2012
This is version 154 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.