PDHA1
entrez
5160
canonical
uniprot
P08559
canonical
ensembl
ENSG00000131828
resolver
ensp
ENSP00000348062
resolver
ensp
ENSP00000394382
resolver
ensp
ENSP00000406473
resolver
ensp
ENSP00000440761
resolver
ensp
ENSP00000551177
resolver
genesymbol
PDHA1
resolver
genesymbol_syn
PHE1A
resolver
hgnc
HGNC:8806
resolver
uniprot
A5YVE9
resolver
uniprot
B2R5P7
resolver
uniprot
B7Z3T7
resolver
uniprot
B7Z3X5
resolver
uniprot
Q53H41
resolver
uniprot
Q5JPT8
resolver
uniprot
Q9NP12
resolver
uniprot
Q9UBJ8
resolver
uniprot
Q9UBU0
resolver
uniprot
Q9UNG4
resolver
uniprot
Q9UNG5
resolver
uniprot_entry
ODPA_HUMAN
resolver
uniprot_sec
A5YVE9
resolver
uniprot_sec
B2R5P7
resolver
uniprot_sec
B7Z3T7
resolver
uniprot_sec
B7Z3X5
resolver
uniprot_sec
Q53H41
resolver
uniprot_sec
Q5JPT8
resolver
uniprot_sec
Q9NP12
resolver
uniprot_sec
Q9UBJ8
resolver
uniprot_sec
Q9UBU0
resolver
uniprot_sec
Q9UNG4
resolver
uniprot_sec
Q9UNG5
resolver
activity_regulation
ACTIVITY REGULATION: Pyruvate dehydrogenase activity is inhibited by phosphorylation of PDHA1; it is reactivated by dephosphorylation. {ECO:0000269|PubMed:17474719, ECO:0000269|PubMed:19081061, ECO:0000269|PubMed:7782287}.
uniprot
proteins
amino_acid_sequence
MRKMLAAVSRVLSGASQKPASRVLVASRNFANDATFEIKKCDLHRLEEGPPVTTVLTREDGLKYYRMMQTVRRMELKADQLYKQKIIRGFCHLCDGQEACCVGLEAGINPTDHLITAYRAHGFTFTRGLSVREILAELTGRKGGCAKGKGGSMHMYAKNFYGGNGIVGAQVPLGAGIALACKYNGKDEVCLTLYGDGAANQGQIFEAYNMAALWKLPCIFICENNRYGMGTSVERAAASTDYYKRGDFIPGLRVDGMDILCVREATRFAAAYCRSGKGPILMELQTYRYHGHSMSDPGVSYRTREEIQEVRSKSDPIMLLKDRMVNSNLASVEELKEIDVEVRKEIEDAAQFATADPEPPLEELGYHIYSSDPPFEVRGANQWIKFKSVS
uniprot
proteins
disease_involvement
DISEASE: 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. {ECO:0000269|PubMed:1293379, ECO:0000269|PubMed:1338114, ECO:0000269|PubMed:1551669, ECO:0000269|PubMed:1909401, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:29970614, ECO:0000269|PubMed:7545958, ECO:0000269|PubMed:7573035, ECO:0000269|PubMed:7757088, ECO:0000269|PubMed:7887409, ECO:0000269|PubMed:7967473, ECO:0000269|PubMed:8032855, ECO:0000269|PubMed:8199595, ECO:0000269|PubMed:8498846, ECO:0000269|PubMed:8504306, ECO:0000269|PubMed:8664900, ECO:0000269|PubMed:8844217, ECO:0000269|PubMed:9266390, ECO:0000269|PubMed:9671272}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
1.2.4.1
uniprot
proteins
function
FUNCTION: Together with PDHB forms the heterotetrameric E1 subunit of the pyruvate dehydrogenase (PDH) complex (PubMed:17474719, PubMed:19081061). The PDH complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links cytoplasmic glycolysis and the mitochondrial tricarboxylic acid (TCA) cycle (PubMed:19081061, PubMed:7782287). It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and dihydrolipoamide dehydrogenase (E3) (Probable). The E1 subunit catalyzes both the thiamine pyrophosphate (TPP)-dependent decarboxylation of pyruvate and the reductive acetylation of a lipoyl group covalently linked to the lipoyl-bearing domains of E2 (PubMed:17474719, PubMed:19081061, PubMed:7782287). {ECO:0000269|PubMed:17474719, ECO:0000269|PubMed:19081061, ECO:0000269|PubMed:7782287, ECO:0000305|PubMed:17474719, ECO:0000305|PubMed:19081061, ECO:0000305|PubMed:7782287}.
uniprot
proteins
mass_dalton
43296
uniprot
proteins
mutagenesis
MUTAGEN 232; /note="S->A: Abolishes inactivation by phosphorylation; when associated with A-293 and A-300."; /evidence="ECO:0000269|PubMed:7782287"; MUTAGEN 293; /note="S->A: Reduces enzyme activity. Abolishes inactivation by phosphorylation; when associated with A-232 and A-300."; /evidence="ECO:0000269|PubMed:17474719, ECO:0000269|PubMed:7782287"; MUTAGEN 293; /note="S->E: Interferes with substrate binding."; /evidence="ECO:0000269|PubMed:17474719, ECO:0000269|PubMed:7782287"; MUTAGEN 300; /note="S->A: Abolishes inactivation by phosphorylation; when associated with A-232 and A-293."; /evidence="ECO:0000269|PubMed:7782287
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-232, Ser-293 and Ser-300 by PDK family kinases inactivates the enzyme; for this phosphorylation at a single site is sufficient. Dephosphorylation at all three sites, i.e. at Ser-232, Ser-293 and Ser-300, is required for reactivation. {ECO:0000269|PubMed:11486000, ECO:0000269|PubMed:17474719, ECO:0000269|PubMed:19081061}.; PTM: Acetylation alters the phosphorylation pattern. Deacetylated by SIRT3 (By similarity). {ECO:0000250|UniProtKB:P35486}.
uniprot
proteins
pubmed
10077682
uniprot
proteins
pubmed
11486000
uniprot
proteins
pubmed
12651851
uniprot
proteins
pubmed
1293379
uniprot
proteins
pubmed
1301207
uniprot
proteins
pubmed
1338114
uniprot
proteins
pubmed
14638692
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1551669
uniprot
proteins
pubmed
15772651
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17474719
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19081061
uniprot
proteins
pubmed
1909401
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
2227443
uniprot
proteins
pubmed
23033978
uniprot
proteins
pubmed
23146587
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
2745444
uniprot
proteins
pubmed
2748588
uniprot
proteins
pubmed
27864847
uniprot
proteins
pubmed
2828359
uniprot
proteins
pubmed
29970614
uniprot
proteins
pubmed
3034892
uniprot
proteins
pubmed
3422424
uniprot
proteins
pubmed
7545958
uniprot
proteins
pubmed
7573035
uniprot
proteins
pubmed
7757088
uniprot
proteins
pubmed
7782287
uniprot
proteins
pubmed
7887409
uniprot
proteins
pubmed
7967473
uniprot
proteins
pubmed
8032855
uniprot
proteins
pubmed
8199595
uniprot
proteins
pubmed
8498846
uniprot
proteins
pubmed
8504306
uniprot
proteins
pubmed
8664900
uniprot
proteins
pubmed
8844217
uniprot
proteins
pubmed
9266390
uniprot
proteins
pubmed
9671272
uniprot
proteins
sequence_length
390
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250|UniProtKB:P26284}.
uniprot
proteins