ID ODPA_PANTR Reviewed; 390 AA. AC A5A6L0; DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot. DT 12-JUN-2007, sequence version 1. DT 24-JAN-2024, entry version 82. DE RecName: Full=Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial; DE EC=1.2.4.1; DE AltName: Full=PDHE1-A type I; DE Flags: Precursor; GN Name=PDHA1; OS Pan troglodytes (Chimpanzee). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Pan. OX NCBI_TaxID=9598; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RX PubMed=17574350; DOI=10.1016/j.gene.2007.04.013; RA Sakate R., Suto Y., Imanishi T., Tanoue T., Hida M., Hayasaka I., RA Kusuda J., Gojobori T., Hashimoto K., Hirai M.; RT "Mapping of chimpanzee full-length cDNAs onto the human genome unveils RT large potential divergence of the transcriptome."; RL Gene 399:1-10(2007). CC -!- FUNCTION: The pyruvate dehydrogenase complex catalyzes the overall CC conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the CC glycolytic pathway to the tricarboxylic cycle. {ECO:0000250}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + N(6)-[(R)-lipoyl]-L-lysyl-[dihydrolipoyllysine-residue CC acetyltransferase] + pyruvate = CO2 + N(6)-[(R)-S(8)- CC acetyldihydrolipoyl]-L-lysyl-[dihydrolipoyllysine-residue CC acetyltransferase]; Xref=Rhea:RHEA:19189, Rhea:RHEA-COMP:10480, CC Rhea:RHEA-COMP:10481, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16526, ChEBI:CHEBI:83099, ChEBI:CHEBI:83111; EC=1.2.4.1; CC -!- COFACTOR: CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937; CC Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Pyruvate dehydrogenase activity is inhibited by CC phosphorylation of PDHA1; it is reactivated by dephosphorylation. CC {ECO:0000250}. CC -!- SUBUNIT: Heterotetramer of two PDHA1 and two PDHB subunits. The CC heterotetramer interacts with DLAT, and is part of the multimeric CC pyruvate dehydrogenase complex that contains multiple copies of CC pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, CC E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to CC an inner core composed of about 48 DLAT and 12 PDHX molecules (By CC similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250}. CC -!- PTM: Phosphorylation at Ser-232, Ser-293 and Ser-300 by PDK family CC kinases inactivates the enzyme; for this phosphorylation at a single CC site is sufficient. Phosphorylation at Ser-293 interferes with access CC to active site, and thereby inactivates the enzyme. Dephosphorylation CC at all three sites, i.e. at Ser-232, Ser-293 and Ser-300, is required CC for reactivation (By similarity). {ECO:0000250}. CC -!- PTM: Acetylation alters the phosphorylation pattern. Deacetylated by CC SIRT3 (By similarity). {ECO:0000250}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB222138; BAF62383.1; -; mRNA. DR RefSeq; NP_001104283.1; NM_001110813.1. DR AlphaFoldDB; A5A6L0; -. DR SMR; A5A6L0; -. DR STRING; 9598.ENSPTRP00000088760; -. DR PaxDb; 9598-ENSPTRP00000037227; -. DR GeneID; 465525; -. DR KEGG; ptr:465525; -. DR CTD; 5160; -. DR eggNOG; KOG0225; Eukaryota. DR InParanoid; A5A6L0; -. DR OrthoDB; 166915at2759; -. DR Proteomes; UP000002277; Unplaced. DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell. DR GO; GO:0045254; C:pyruvate dehydrogenase complex; ISS:UniProtKB. DR GO; GO:0004739; F:pyruvate dehydrogenase (acetyl-transferring) activity; ISS:UniProtKB. DR GO; GO:0006086; P:acetyl-CoA biosynthetic process from pyruvate; ISS:UniProtKB. DR GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW. DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW. DR CDD; cd02000; TPP_E1_PDC_ADC_BCADC; 1. DR Gene3D; 3.40.50.970; -; 1. DR InterPro; IPR001017; DH_E1. DR InterPro; IPR017597; Pyrv_DH_E1_asu_subgrp-y. DR InterPro; IPR029061; THDP-binding. DR NCBIfam; TIGR03182; PDH_E1_alph_y; 1. DR PANTHER; PTHR11516:SF52; PYRUVATE DEHYDROGENASE E1 COMPONENT SUBUNIT ALPHA, SOMATIC FORM, MITOCHONDRIAL; 1. DR PANTHER; PTHR11516; PYRUVATE DEHYDROGENASE E1 COMPONENT, ALPHA SUBUNIT BACTERIAL AND ORGANELLAR; 1. DR Pfam; PF00676; E1_dh; 1. DR SUPFAM; SSF52518; Thiamin diphosphate-binding fold (THDP-binding); 1. PE 2: Evidence at transcript level; KW Acetylation; Carbohydrate metabolism; Glucose metabolism; Mitochondrion; KW Oxidoreductase; Phosphoprotein; Pyruvate; Reference proteome; KW Thiamine pyrophosphate; Transit peptide; Tricarboxylic acid cycle. FT TRANSIT 1..29 FT /note="Mitochondrion" FT /evidence="ECO:0000250" FT CHAIN 30..390 FT /note="Pyruvate dehydrogenase E1 component subunit alpha, FT somatic form, mitochondrial" FT /id="PRO_0000297491" FT MOD_RES 63 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P35486" FT MOD_RES 63 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P35486" FT MOD_RES 232 FT /note="Phosphoserine; by PDK1" FT /evidence="ECO:0000250|UniProtKB:P08559" FT MOD_RES 244 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P35486" FT MOD_RES 244 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P35486" FT MOD_RES 277 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P35486" FT MOD_RES 293 FT /note="Phosphoserine; by PDK1, PDK2, PDK3 and PDK4" FT /evidence="ECO:0000250|UniProtKB:P08559" FT MOD_RES 295 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P35486" FT MOD_RES 300 FT /note="Phosphoserine; by PDK1, PDK2, PDK3 and PDK4" FT /evidence="ECO:0000250|UniProtKB:P08559" FT MOD_RES 301 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P35486" FT MOD_RES 313 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P35486" FT MOD_RES 313 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P35486" FT MOD_RES 321 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P08559" FT MOD_RES 336 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P35486" FT MOD_RES 385 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P35486" SQ SEQUENCE 390 AA; 43238 MW; 4F95746CBB792E78 CRC64; MRKMLAAVSR VLSGASQKPA SRVLVASRNF ANDATFEIKK CDLHRLEEGP PVTTVLTRED GLKYYRMMQT VRRMELKADQ LYKQKIIRGF CHLCDGQEAC CVGLEAGINP TDHLITAYRA HGFTFTRGLS VREILAELTG RKGGCAKGKG GSMHMYAKNF YGGNGIVGAQ VPLGAGIALA CKYNGKDEVC LTLYGDGAAN QGQIFEAYNM AALWKLPCIF ICENNRYGMG TSVERAAAST DYYKRGDFIP GLRVDGMDIL CVREATRFAA AYCRSGKGPI LMELQTYRYH GHSMSGPGVS YRTREEIQEV RSKSDPIMLL KDRMVNSNLA SVEELKEIDV EVRKEIEDAA QFATADPEPP LEELGYHIYS SDPPFEVRGA NQWIKFKSVS //