ODP2_RAT
ID ODP2_RAT Reviewed; 632 AA.
AC P08461; Q3B7V7;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 3.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial;
DE EC=2.3.1.12;
DE AltName: Full=70 kDa mitochondrial autoantigen of primary biliary cirrhosis;
DE Short=PBC;
DE AltName: Full=Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex;
DE AltName: Full=Pyruvate dehydrogenase complex component E2;
DE Short=PDC-E2;
DE Short=PDCE2;
DE Flags: Precursor;
GN Name=Dlat;
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 [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 92-632, PROTEIN SEQUENCE OF 78-91, AND
RP LIPOYLATION AT LYS-123 AND LYS-249.
RC TISSUE=Heart;
RX PubMed=1581353; DOI=10.1016/0167-4781(92)90109-d;
RA Matuda S., Nakano K., Ohta S., Shimura M., Yamanaka T., Nakagawa S.,
RA Titani K., Miyata T.;
RT "Molecular cloning of dihydrolipoamide acetyltransferase of the rat
RT pyruvate dehydrogenase complex: sequence comparison and evolutionary
RT relationship to other dihydrolipoamide acyltransferases.";
RL Biochim. Biophys. Acta 1131:114-118(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 163-632.
RC TISSUE=Liver;
RX PubMed=3571977;
RA Gershwin M.E., McKay I.R., Sturgess A., Coppel R.L.;
RT "Identification and specificity of a cDNA encoding the 70 kd mitochondrial
RT antigen recognized in primary biliary cirrhosis.";
RL J. Immunol. 138:3525-3531(1987).
RN [4]
RP PROTEIN SEQUENCE OF 397-414, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA Lubec G., Chen W.-Q.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE SPECIFICITY.
RX PubMed=19423663; DOI=10.1530/rep-09-0052;
RA Khan S.A., Suryawanshi A.R., Ranpura S.A., Jadhav S.V., Khole V.V.;
RT "Identification of novel immunodominant epididymal sperm proteins using
RT combinatorial approach.";
RL Reproduction 138:81-93(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.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-N(6)-dihydrolipoyl-L-lysyl-[protein] + acetyl-CoA = (R)-
CC N(6)-(S(8)-acetyldihydrolipoyl)-L-lysyl-[protein] + CoA;
CC Xref=Rhea:RHEA:17017, Rhea:RHEA-COMP:10475, Rhea:RHEA-COMP:10478,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:83100,
CC ChEBI:CHEBI:83111; EC=2.3.1.12;
CC -!- COFACTOR:
CC Name=(R)-lipoate; Xref=ChEBI:CHEBI:83088;
CC Note=Binds 1 lipoyl cofactor covalently.;
CC -!- SUBUNIT: Part of the multimeric pyruvate dehydrogenase complex that
CC contains multiple copies of pyruvate dehydrogenase (subunits PDH1A and
CC PDHB, E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide
CC dehydrogenase (DLD, E3). These subunits are bound to an inner core
CC composed of about 48 DLAT and 12 PDHX molecules. Interacts with PDK2
CC and PDK3. Interacts with SIRT4. Interacts with PDHB.
CC {ECO:0000250|UniProtKB:P10515}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- TISSUE SPECIFICITY: Expressed in flagella of epididymal sperm.
CC {ECO:0000269|PubMed:19423663}.
CC -!- PTM: Delipoylated at Lys-123 and Lys-249 by SIRT4, delipoylation
CC decreases the PHD complex activity. {ECO:0000250|UniProtKB:P10515}.
CC -!- DISEASE: Note=Primary biliary cirrhosis (PBC) is an autoimmune disease
CC characterized by inflammatory obliteration of intra-hepatic bile duct,
CC leading to liver cell damage and cirrhosis. The E2 component of
CC pyruvate dehydrogenase complex is the autoantigen for PBC.
CC -!- SIMILARITY: Belongs to the 2-oxoacid dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; BC107440; AAI07441.1; -; mRNA.
DR EMBL; D10655; BAA01504.1; -; mRNA.
DR EMBL; D00092; BAA20956.1; -; mRNA.
DR EMBL; M16075; AAA41813.1; -; mRNA.
DR PIR; S21766; S21766.
DR RefSeq; NP_112287.1; NM_031025.1.
DR AlphaFoldDB; P08461; -.
DR SMR; P08461; -.
DR BioGRID; 249554; 4.
DR IntAct; P08461; 4.
DR MINT; P08461; -.
DR STRING; 10116.ENSRNOP00000032890; -.
DR iPTMnet; P08461; -.
DR PhosphoSitePlus; P08461; -.
DR World-2DPAGE; 0004:P08461; -.
DR jPOST; P08461; -.
DR PaxDb; P08461; -.
DR PRIDE; P08461; -.
DR Ensembl; ENSRNOT00000032152; ENSRNOP00000032890; ENSRNOG00000009994.
DR GeneID; 81654; -.
DR KEGG; rno:81654; -.
DR UCSC; RGD:619859; rat.
DR CTD; 1737; -.
DR RGD; 619859; Dlat.
DR eggNOG; KOG0557; Eukaryota.
DR GeneTree; ENSGT00940000154943; -.
DR HOGENOM; CLU_016733_10_2_1; -.
DR InParanoid; P08461; -.
DR OMA; TMEFESF; -.
DR OrthoDB; 747232at2759; -.
DR PhylomeDB; P08461; -.
DR TreeFam; TF106145; -.
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:P08461; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000009994; Expressed in heart and 18 other tissues.
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:0004742; F:dihydrolipoyllysine-residue acetyltransferase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0000166; F:nucleotide binding; TAS: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:0030431; P:sleep; IEP:RGD.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 4.10.320.10; -; 1.
DR InterPro; IPR003016; 2-oxoA_DH_lipoyl-BS.
DR InterPro; IPR001078; 2-oxoacid_DH_actylTfrase.
DR InterPro; IPR000089; Biotin_lipoyl.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR045257; E2/Pdx1.
DR InterPro; IPR036625; E3-bd_dom_sf.
DR InterPro; IPR006257; LAT1.
DR InterPro; IPR004167; PSBD.
DR InterPro; IPR011053; Single_hybrid_motif.
DR PANTHER; PTHR23151; PTHR23151; 2.
DR Pfam; PF00198; 2-oxoacid_dh; 1.
DR Pfam; PF00364; Biotin_lipoyl; 2.
DR Pfam; PF02817; E3_binding; 1.
DR SUPFAM; SSF47005; SSF47005; 1.
DR SUPFAM; SSF51230; SSF51230; 2.
DR TIGRFAMs; TIGR01349; PDHac_trf_mito; 1.
DR PROSITE; PS50968; BIOTINYL_LIPOYL; 2.
DR PROSITE; PS00189; LIPOYL; 2.
DR PROSITE; PS51826; PSBD; 1.
PE 1: Evidence at protein level;
KW Acetylation; Acyltransferase; Carbohydrate metabolism;
KW Direct protein sequencing; Glucose metabolism; Lipoyl; Mitochondrion;
KW Phosphoprotein; Reference proteome; Repeat; Transferase; Transit peptide;
KW Tricarboxylic acid cycle.
FT TRANSIT 1..77
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:1581353"
FT CHAIN 78..632
FT /note="Dihydrolipoyllysine-residue acetyltransferase
FT component of pyruvate dehydrogenase complex, mitochondrial"
FT /id="PRO_0000162298"
FT DOMAIN 82..158
FT /note="Lipoyl-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT DOMAIN 208..284
FT /note="Lipoyl-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT DOMAIN 342..379
FT /note="Peripheral subunit-binding (PSBD)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01170"
FT REGION 456..632
FT /note="Catalytic"
FT /evidence="ECO:0000250"
FT ACT_SITE 605
FT /evidence="ECO:0000255"
FT ACT_SITE 609
FT /evidence="ECO:0000255"
FT BINDING 600..611
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10515"
FT MOD_RES 123
FT /note="N6-lipoyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066,
FT ECO:0000305|PubMed:1581353"
FT MOD_RES 249
FT /note="N6-lipoyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066,
FT ECO:0000305|PubMed:1581353"
FT MOD_RES 451
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10515"
FT MOD_RES 458
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BMF4"
FT MOD_RES 532
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BMF4"
FT CONFLICT 150..152
FT /note="VGS -> IGC (in Ref. 2; BAA01504)"
FT /evidence="ECO:0000305"
FT CONFLICT 163..164
FT /note="DI -> GP (in Ref. 3; BAA20956/AAA41813)"
FT /evidence="ECO:0000305"
FT CONFLICT 601..632
FT /note="LSCDHRVVDGAVGAQWLAEFKKYLEKPVTMLL -> HSAVIIELWMEQLEPS
FT GLL (in Ref. 3; BAA20956)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 632 AA; 67166 MW; 3F0EDBD44D93EB68 CRC64;
MWRVCARRVQ SAVPRAGFRA RWATLKGPRT GPAAVRCGSG IPSYGVRSLC GWSYGSATVP
RNRILQQLLG SPSRRSYSLP PHQKVPLPSL SPTMQAGTIA RWEKKEGEKI SEGDLIAEVE
TDKATVGFES LEECYMAKIL VPEGTRDVPV GSIICITVEK PQDIEAFKNY TLDSATAATQ
AAPAPAAAPA AAPAAPSASA PGSSYPVHMQ IVLPALSPTM TMGTVQRWEK KVGEKLSEGD
LLAEIETDKA TIGFEVQEEG YLAKILVPEG TRDVPLGTPL CIIVEKQEDI AAFADYRPTE
VTSLKPQAPP PVPPPVAAVP PIPQPLAPTP SAAPAGPKGR VFVSPLAKKL AAEKGIDLTQ
VKGTGPEGRI IKKDIDSFVP TKAAPAAAAA APPGPRVAPT PAGVFIDIPI SNIRRVIAQR
LMQSKQTIPH YYLSVDVNMG EVLLVRKELN KMLEGKGKIS VNDFIIKASA LACLKVPEAN
SSWMDTVIRQ NHVVDVSVAV STPAGLITPI VFNAHIKGLE TIASDVVSLA SKAREGKLQP
HEFQGGTFTI SNLGMFGIKN FSAIINPPQA CILAIGASED KLIPADNEKG FDVASVMSVT
LSCDHRVVDG AVGAQWLAEF KKYLEKPVTM LL
