ODPA_SMIMA
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 03-AUG-2022, entry version 99.
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=(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-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}.
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DR EMBL; L20774; AAA31589.1; -; mRNA.
DR AlphaFoldDB; P52900; -.
DR SMR; P52900; -.
DR PRIDE; 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 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; 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
