ID   ODPA_PONAB              Reviewed;         390 AA.
AC   Q5R490;
DT   12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   25-MAY-2022, entry version 88.
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   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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=(R)-N(6)-lipoyl-L-lysyl-[dihydrolipoyllysine-residue
CC         acetyltransferase] + H(+) + pyruvate = (R)-N(6)-(S(8)-
CC         acetyldihydrolipoyl)-L-lysyl-[dihydrolipoyllysine-residue
CC         acetyltransferase] + CO2; 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; CR861366; CAH93426.1; -; mRNA.
DR   RefSeq; NP_001127663.1; NM_001134191.1.
DR   AlphaFoldDB; Q5R490; -.
DR   SMR; Q5R490; -.
DR   STRING; 9601.ENSPPYP00000022568; -.
DR   GeneID; 100174745; -.
DR   KEGG; pon:100174745; -.
DR   CTD; 5160; -.
DR   eggNOG; KOG0225; Eukaryota.
DR   InParanoid; Q5R490; -.
DR   OrthoDB; 871160at2759; -.
DR   Proteomes; UP000001595; 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   InterPro; IPR001017; DH_E1.
DR   InterPro; IPR017597; Pyrv_DH_E1_asu_subgrp-y.
DR   InterPro; IPR029061; THDP-binding.
DR   Pfam; PF00676; E1_dh; 1.
DR   SUPFAM; SSF52518; SSF52518; 1.
DR   TIGRFAMs; TIGR03182; PDH_E1_alph_y; 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_0000020444"
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;  43224 MW;  4C0A5ADD25CB2D49 CRC64;
     MRKMLAAVSR VLSGASQKPA SRVLVASRNF ANDATFEIKK CDLHRLEEGP PVTTVLTRED
     GLKYYRMMQT VRRMELKADQ LYKQKIIRGF CHLCDGQEAC CVGLEAGINP TDHLITAYRA
     HGFTFTRGLS VREILAELTG RKGGCAKGKG GSMHMYAKNF YGGNGIVGAQ VPLGAGIALA
     CKYNGKDEVC LTLYGDGAAN QGQIFGAYNM AALWKLPCIF ICENNRYGMG TSVERAAAST
     DYYKRGDFIP GLRVDGMDIL CVREATRFAA AYCRSGKGPI LMELQTYRYH GHSMSDPGVS
     YRTREEIQEV RSKSDPIMLL KDRMVNSNLA SVEELKEIDV EVRKEIEDAA QFATADPEPP
     LEELGYHIYS SDPPFEVRGA NQWIKFKSVS