ODPA_RAT
ID ODPA_RAT Reviewed; 390 AA.
AC P26284;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 2.
DT 25-MAY-2022, entry version 144.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2025639; DOI=10.1016/0167-4781(91)90076-x;
RA Matuda S., Nakano K., Ohta S., Saheki T., Kawanishi Y., Miyata T.;
RT "The alpha-ketoacid dehydrogenase complexes. Sequence similarity of rat
RT pyruvate dehydrogenase with Escherichia coli and Azotobacter vinelandii
RT alpha-ketoglutarate dehydrogenase.";
RL Biochim. Biophys. Acta 1089:1-7(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=8158120; DOI=10.1046/j.1471-4159.1994.62051682.x;
RA Cullingford T.E., Clark J.B., Phillips I.R.;
RT "The pyruvate dehydrogenase complex: cloning of the rat somatic E1 alpha
RT subunit and its coordinate expression with the mRNAs for the E1 beta, E2,
RT and E3 catalytic subunits in developing rat brain.";
RL J. Neurochem. 62:1682-1690(1994).
RN [3]
RP PROTEIN SEQUENCE OF 133-141; 216-226; 245-253; 289-302 AND 324-343, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA Lubec G., Diao W., Chen W.-Q.;
RL Submitted (APR-2007) to UniProtKB.
RN [4]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-232; SER-293 AND SER-300.
RX PubMed=19341700; DOI=10.1016/j.ab.2009.03.040;
RA Rardin M.J., Wiley S.E., Naviaux R.K., Murphy A.N., Dixon J.E.;
RT "Monitoring phosphorylation of the pyruvate dehydrogenase complex.";
RL Anal. Biochem. 389:157-164(2009).
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
CC {ECO:0000269|PubMed:19341700}.
CC -!- TISSUE SPECIFICITY: In all tissues, but in very low amount in testis.
CC {ECO:0000269|PubMed:8158120}.
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. {ECO:0000269|PubMed:19341700}.
CC -!- PTM: Acetylation alters the phosphorylation pattern. Deacetylated by
CC SIRT3 (By similarity). {ECO:0000250}.
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DR EMBL; Z12158; CAA78146.1; -; mRNA.
DR PIR; S15891; DERTPA.
DR PIR; S21553; DERTP1.
DR AlphaFoldDB; P26284; -.
DR SMR; P26284; -.
DR ComplexPortal; CPX-378; Pyruvate dehydrogenase E1 heterotetramer.
DR IntAct; P26284; 1.
DR MINT; P26284; -.
DR STRING; 10116.ENSRNOP00000030279; -.
DR ChEMBL; CHEMBL2176823; -.
DR CarbonylDB; P26284; -.
DR iPTMnet; P26284; -.
DR PhosphoSitePlus; P26284; -.
DR World-2DPAGE; 0004:P26284; -.
DR jPOST; P26284; -.
DR PaxDb; P26284; -.
DR PRIDE; P26284; -.
DR RGD; 3286; Pdha1.
DR eggNOG; KOG0225; Eukaryota.
DR InParanoid; P26284; -.
DR PhylomeDB; P26284; -.
DR Reactome; R-RNO-204174; Regulation of pyruvate dehydrogenase (PDH) complex.
DR Reactome; R-RNO-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-RNO-5362517; Signaling by Retinoic Acid.
DR Reactome; R-RNO-70268; Pyruvate metabolism.
DR PRO; PR:P26284; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005967; C:mitochondrial pyruvate dehydrogenase complex; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0045254; C:pyruvate dehydrogenase complex; IDA:RGD.
DR GO; GO:0004739; F:pyruvate dehydrogenase (acetyl-transferring) activity; IDA:RGD.
DR GO; GO:0034604; F:pyruvate dehydrogenase (NAD+) activity; ISO:RGD.
DR GO; GO:0004738; F:pyruvate dehydrogenase activity; ISO:RGD.
DR GO; GO:0006086; P:acetyl-CoA biosynthetic process from pyruvate; IDA:RGD.
DR GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0061732; P:mitochondrial acetyl-CoA biosynthetic process from pyruvate; ISO:RGD.
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; Direct protein sequencing;
KW Glucose metabolism; Mitochondrion; Oxidoreductase; Phosphoprotein;
KW Pyruvate; Reference proteome; Thiamine pyrophosphate; Transit peptide;
KW 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_0000020445"
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:0000269|PubMed:19341700"
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 267
FT /note="N6-acetyllysine"
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:0000269|PubMed:19341700"
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:0000269|PubMed:19341700"
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"
FT CONFLICT 10
FT /note="R -> H (in Ref. 2; CAA78146)"
FT /evidence="ECO:0000305"
FT CONFLICT 126
FT /note="N -> T (in Ref. 2; CAA78146)"
FT /evidence="ECO:0000305"
FT CONFLICT 129..130
FT /note="HA -> LP (in Ref. 2; CAA78146)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="I -> V (in Ref. 1)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 390 AA; 43227 MW; 254B5A801E750DC0 CRC64;
MRKMLAAVSR VLAGAAQKPA SRVLVASRNF ANDATFEIKK CDLHRLEEGP PVTTVLTRED
GLKYYRMMQT VRRMELKADQ LYKQKIIRGF CHLCDGQEAC CVGLEAGINP TDHLITAYRA
HGFTFNRGHA VRAILAELTG RRGGCAKGKG GSMHMYAKNF YGGNGIVGAQ VPLGAGIALA
CKYNGKDEVC LTLYGDGAAN QGQIFEAYNM AALWKLPCIF ICENNRYGMG TSVERAAAST
DYYKRGDFIP GLRVDGMDIL CVREATKFAA AYCRSGKGPI LMELQTYRYH GHSMSDPGVS
YRTREEIQEV RSKSDPIMLL KDRMVNSNLA SVEELKEIDV EVRKEIEDAA QFATADPEPP
LEELGYHIYS SDPPFEVRGA NQWIKFKSVS
