ID   ODPA_SMIMA              Reviewed;         363 AA.
AC   P52900;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   24-JAN-2024, entry version 104.
DE   RecName: Full=Pyruvate dehydrogenase E1 component subunit alpha, mitochondrial;
DE            Short=PDHE1-A;
DE            EC=1.2.4.1;
DE   Flags: Precursor; Fragment;
GN   Name=PDHA;
OS   Sminthopsis macroura (Stripe-faced dunnart).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Metatheria; Dasyuromorphia; Dasyuridae; Sminthopsis.
OX   NCBI_TaxID=9302;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Testis;
RX   PubMed=8307573; DOI=10.1016/s0888-7543(05)80366-0;
RA   Fitzgerald J., Wilcox S.A., Graves J.A., Dahl H.-H.M.;
RT   "A eutherian X-linked gene, PDHA1, is autosomal in marsupials: a model for
RT   the evolution of a second, testis-specific variant in eutherian mammals.";
RL   Genomics 18:636-642(1993).
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-205, Ser-266 and Ser-273 by PDK family
CC       kinases inactivates the enzyme; for this phosphorylation at a single
CC       site is sufficient. Phosphorylation at Ser-266 interferes with access
CC       to active site, and thereby inactivates the enzyme. Dephosphorylation
CC       at all three sites, i.e. at Ser-205, Ser-266 and Ser-273, 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; L20774; AAA31589.1; -; mRNA.
DR   AlphaFoldDB; P52900; -.
DR   SMR; P52900; -.
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:SF60; PYRUVATE DEHYDROGENASE E1 COMPONENT SUBUNIT ALPHA; 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; Thiamine pyrophosphate;
KW   Transit peptide; Tricarboxylic acid cycle.
FT   TRANSIT         <1..2
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250"
FT   CHAIN           3..363
FT                   /note="Pyruvate dehydrogenase E1 component subunit alpha,
FT                   mitochondrial"
FT                   /id="PRO_0000020446"
FT   MOD_RES         36
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P35486"
FT   MOD_RES         36
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P35486"
FT   MOD_RES         205
FT                   /note="Phosphoserine; by PDK1"
FT                   /evidence="ECO:0000250|UniProtKB:P08559"
FT   MOD_RES         217
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P35486"
FT   MOD_RES         217
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P35486"
FT   MOD_RES         240
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P35486"
FT   MOD_RES         250
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P35486"
FT   MOD_RES         266
FT                   /note="Phosphoserine; by PDK1, PDK2, PDK3 and PDK4"
FT                   /evidence="ECO:0000250|UniProtKB:P08559"
FT   MOD_RES         268
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P35486"
FT   MOD_RES         273
FT                   /note="Phosphoserine; by PDK1, PDK2, PDK3 and PDK4"
FT                   /evidence="ECO:0000250|UniProtKB:P08559"
FT   MOD_RES         274
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P35486"
FT   MOD_RES         286
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P35486"
FT   MOD_RES         286
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P35486"
FT   MOD_RES         294
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P08559"
FT   MOD_RES         309
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P35486"
FT   MOD_RES         358
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P35486"
FT   NON_TER         1
SQ   SEQUENCE   363 AA;  40735 MW;  4884E0A17D7A15A8 CRC64;
     RNFANDATFD IKKCDVHRLE EGPPTTAVLT REEGLKYYKI MQTVRRMELK ADQLYKQKII
     RGFCHLYDGQ EACCMGLEAG INPTDHVITA YRAHGFTYTR GLPVREILAE LTGRRGGCAK
     GKGGSMHMYA KNFYGGNGIV GAQVPLGVGI ALACKYNEKD EICLTLYGDG AANQGQIFEA
     YNMAALWKLP CIFICENNRY GMGTSVERAA ASTDYYKRGD FIPGIMVDGM DVLCVREATK
     FAAAYCRSGK GPMLMELQTY RYHGHSMSDP GVSYRTREEI QEVRSKSDPI MLLKDRMVNN
     NLASIEELKE IDVEVRKEIE DAAQFATADP EPPLEELGYH IYSRDPPFEV RGANQWIKYK
     SVS
//