ODPA_PIG
ID ODPA_PIG Reviewed; 389 AA.
AC P29804;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 25-MAY-2022, entry version 107.
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; Fragment;
GN Name=PDHA1;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Muscle;
RX PubMed=2395657; DOI=10.1093/nar/18.16.4925;
RA Sermon K., Demeirleir L., Elpers I., Lissens W., Liebaers I.;
RT "Characterisation of a cDNA for porcine PDH-E1 alpha and comparison with
RT the human cDNA.";
RL Nucleic Acids Res. 18:4925-4925(1990).
RN [2]
RP CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP COFACTOR, AND PHOSPHORYLATION AT SER-231; SER-292 AND SER-299.
RX PubMed=227365; DOI=10.1042/bj1810427;
RA Kerbey A.L., Radcliffe P.M., Randle P.J., Sugden P.H.;
RT "Regulation of kinase reactions in pig heart pyruvate dehydrogenase
RT complex.";
RL Biochem. J. 181:427-433(1979).
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.
CC {ECO:0000269|PubMed:227365}.
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 Evidence={ECO:0000269|PubMed:227365};
CC -!- COFACTOR:
CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC Evidence={ECO:0000269|PubMed:227365};
CC -!- ACTIVITY REGULATION: Pyruvate dehydrogenase activity is inhibited by
CC phosphorylation of PDHA1; it is reactivated by dephosphorylation.
CC {ECO:0000269|PubMed:227365}.
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:0000269|PubMed:227365}.
CC -!- PTM: Phosphorylation at Ser-231, Ser-292 and Ser-299 by PDK family
CC kinases inactivates the enzyme; for this phosphorylation at a single
CC site is sufficient. Phosphorylation at Ser-292 interferes with access
CC to active site, and thereby inactivates the enzyme. Dephosphorylation
CC at all three sites, i.e. at Ser-231, Ser-292 and Ser-299, is required
CC for reactivation. {ECO:0000269|PubMed:227365}.
CC -!- PTM: Acetylation alters the phosphorylation pattern. Deacetylated by
CC SIRT3 (By similarity). {ECO:0000250}.
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DR EMBL; X52990; CAA37180.1; -; mRNA.
DR PIR; S20813; DEPGPA.
DR AlphaFoldDB; P29804; -.
DR SMR; P29804; -.
DR STRING; 9823.ENSSSCP00000021757; -.
DR ChEMBL; CHEMBL3774302; -.
DR iPTMnet; P29804; -.
DR PaxDb; P29804; -.
DR PeptideAtlas; P29804; -.
DR PRIDE; P29804; -.
DR eggNOG; KOG0225; Eukaryota.
DR InParanoid; P29804; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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 1: Evidence at protein 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..28
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 29..389
FT /note="Pyruvate dehydrogenase E1 component subunit alpha,
FT somatic form, mitochondrial"
FT /id="PRO_0000020443"
FT MOD_RES 62
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 62
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 231
FT /note="Phosphoserine; by PDK1"
FT /evidence="ECO:0000250|UniProtKB:P08559"
FT MOD_RES 243
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 243
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 276
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 292
FT /note="Phosphoserine; by PDK1, PDK2, PDK3 and PDK4"
FT /evidence="ECO:0000250|UniProtKB:P08559"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 299
FT /note="Phosphoserine; by PDK1, PDK2, PDK3 and PDK4"
FT /evidence="ECO:0000250|UniProtKB:P08559"
FT MOD_RES 300
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 312
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 312
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 320
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P08559"
FT MOD_RES 335
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT MOD_RES 384
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P35486"
FT NON_TER 1
SQ SEQUENCE 389 AA; 43121 MW; E9C7DF85389A9A47 CRC64;
GKMLAAVSRV LSGVAQKPAS RVLVASRTFA NDATFEIKKC DLHRLEEGPP VTTVLTREDG
LKYYRMMQTV RRMELKADQL YKQKIIRGFC HLCDGQEACC VGLEAGINPT DHLITAYRAH
GFTFTRGLSV REILAELTGR RGGCGKGKGG SMHMYAKNFY GGNGIVGAQV PLGAGIALAC
KYNGKDEVCL TLYGDGAANQ GQIFEAYNMA ALWKLPCVFI CENNRYGMGT SVERAAASTD
YYKRGDFIPG LRVDGMDILC VREATRFAAA YCRSGKGPIL MELQTYRYHG HSMSDPGVSY
RTREEIQEVR SKSDPIMLLK DRMVNSNLAS VEELKEIDVE VRKEIEDAAQ FATADPEPPL
EELGYHIYCN DPPFEVRGAN QWIKFKSIS
