ODP2_MOUSE
ID ODP2_MOUSE Reviewed; 642 AA.
AC Q8BMF4; Q8K2G8; Q8R339; Q91ZB1;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial;
DE EC=2.3.1.12;
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II, FVB/N-3, and NMRI; TISSUE=Mammary tumor;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 84-642.
RC TISSUE=Hepatoma;
RX PubMed=12108679; DOI=10.1007/s005350200065;
RA Wang L., Kaneko S., Kagaya M., Ohno H., Honda M., Kobayashi K.;
RT "Molecular cloning, and characterization and expression of dihydrolipoamide
RT acetyltransferase component of murine pyruvate dehydrogenase complex in
RT bile duct cancer cells.";
RL J. Gastroenterol. 37:449-454(2002).
RN [4]
RP PROTEIN SEQUENCE OF 93-109; 147-176; 282-295; 383-424; 469-477; 486-499;
RP 528-542; 548-569; 600-631 AND 633-642, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Klug S., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-468 AND LYS-542, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
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)-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; Evidence={ECO:0000250};
CC Note=Binds 1 lipoyl cofactor covalently. {ECO:0000250};
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 -!- PTM: Delipoylated at Lys-131 and Lys-258 by SIRT4, delipoylation
CC decreases the PHD complex activity. {ECO:0000250|UniProtKB:P10515}.
CC -!- SIMILARITY: Belongs to the 2-oxoacid dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AK032124; BAC27715.1; -; mRNA.
DR EMBL; BC026680; AAH26680.1; -; mRNA.
DR EMBL; BC031495; AAH31495.1; -; mRNA.
DR EMBL; BC069862; AAH69862.1; -; mRNA.
DR EMBL; AY044265; AAL02400.1; -; mRNA.
DR CCDS; CCDS23168.1; -.
DR RefSeq; NP_663589.3; NM_145614.4.
DR AlphaFoldDB; Q8BMF4; -.
DR SMR; Q8BMF4; -.
DR BioGRID; 231646; 57.
DR IntAct; Q8BMF4; 7.
DR MINT; Q8BMF4; -.
DR STRING; 10090.ENSMUSP00000034567; -.
DR iPTMnet; Q8BMF4; -.
DR PhosphoSitePlus; Q8BMF4; -.
DR SwissPalm; Q8BMF4; -.
DR REPRODUCTION-2DPAGE; IPI00153660; -.
DR UCD-2DPAGE; Q8BMF4; -.
DR EPD; Q8BMF4; -.
DR jPOST; Q8BMF4; -.
DR MaxQB; Q8BMF4; -.
DR PaxDb; Q8BMF4; -.
DR PeptideAtlas; Q8BMF4; -.
DR PRIDE; Q8BMF4; -.
DR ProteomicsDB; 293495; -.
DR Antibodypedia; 18282; 325 antibodies from 30 providers.
DR DNASU; 235339; -.
DR Ensembl; ENSMUST00000034567; ENSMUSP00000034567; ENSMUSG00000000168.
DR GeneID; 235339; -.
DR KEGG; mmu:235339; -.
DR UCSC; uc009pka.2; mouse.
DR CTD; 1737; -.
DR MGI; MGI:2385311; Dlat.
DR VEuPathDB; HostDB:ENSMUSG00000000168; -.
DR eggNOG; KOG0557; Eukaryota.
DR GeneTree; ENSGT00940000154943; -.
DR HOGENOM; CLU_016733_10_2_1; -.
DR InParanoid; Q8BMF4; -.
DR OMA; TMEFESF; -.
DR OrthoDB; 747232at2759; -.
DR PhylomeDB; Q8BMF4; -.
DR TreeFam; TF106145; -.
DR Reactome; R-MMU-204174; Regulation of pyruvate dehydrogenase (PDH) complex.
DR Reactome; R-MMU-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-MMU-5362517; Signaling by Retinoic Acid.
DR Reactome; R-MMU-70268; Pyruvate metabolism.
DR BioGRID-ORCS; 235339; 5 hits in 76 CRISPR screens.
DR ChiTaRS; Dlat; mouse.
DR PRO; PR:Q8BMF4; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8BMF4; protein.
DR Bgee; ENSMUSG00000000168; Expressed in digastric muscle group and 267 other tissues.
DR Genevisible; Q8BMF4; MM.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005967; C:mitochondrial pyruvate dehydrogenase complex; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0045254; C:pyruvate dehydrogenase complex; ISO:MGI.
DR GO; GO:0004742; F:dihydrolipoyllysine-residue acetyltransferase activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0034604; F:pyruvate dehydrogenase (NAD+) activity; ISO:MGI.
DR GO; GO:0006086; P:acetyl-CoA biosynthetic process from pyruvate; ISO:MGI.
DR GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0061732; P:mitochondrial acetyl-CoA biosynthetic process from pyruvate; ISO:MGI.
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..85
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 86..642
FT /note="Dihydrolipoyllysine-residue acetyltransferase
FT component of pyruvate dehydrogenase complex, mitochondrial"
FT /id="PRO_0000285717"
FT DOMAIN 90..166
FT /note="Lipoyl-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT DOMAIN 217..293
FT /note="Lipoyl-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT DOMAIN 351..388
FT /note="Peripheral subunit-binding (PSBD)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01170"
FT REGION 80..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 313..346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 466..642
FT /note="Catalytic"
FT /evidence="ECO:0000250"
FT COMPBIAS 316..341
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 615
FT /evidence="ECO:0000255"
FT ACT_SITE 619
FT /evidence="ECO:0000255"
FT BINDING 610..621
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10515"
FT MOD_RES 131
FT /note="N6-lipoyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT MOD_RES 258
FT /note="N6-lipoyllysine"
FT /evidence="ECO:0000250, ECO:0000255|PROSITE-
FT ProRule:PRU01066"
FT MOD_RES 461
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10515"
FT MOD_RES 468
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 542
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 84
FT /note="S -> Y (in Ref. 3; AAL02400)"
FT /evidence="ECO:0000305"
FT CONFLICT 198
FT /note="P -> T (in Ref. 1; BAC27715)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="L -> P (in Ref. 3; AAL02400)"
FT /evidence="ECO:0000305"
FT CONFLICT 393
FT /note="A -> V (in Ref. 2; AAH31495)"
FT /evidence="ECO:0000305"
FT CONFLICT 604
FT /note="A -> V (in Ref. 2; AAH31495)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 642 AA; 67942 MW; 1294FAC4857FC29C CRC64;
MWRVCARRAR SAVPRDGFRA RWAALKEGPG APCGSPRIGP AAVRCGSGIP RYGVRSLCGW
SSGSGTVPRN RLLRQLLGSP SRRSYSLPPH QKVPLPSLSP TMQAGTIARW EKKEGEKISE
GDLIAEVETD KATVGFESLE ECYMAKILVP EGTRDVPVGS IICITVEKPQ DIEAFKNYTL
DLAAAAAPQA APAAAPAPAA APAAPSASAP GSSYPTHMQI VLPALSPTMT MGTVQRWEKK
VGEKLSEGDL LAEIETDKAT IGFEVQEEGY LAKILVPEGT RDVPLGAPLC IIVEKQEDIA
AFADYRPTEV TSLKPQAAPP APPPVAAVPP TPQPVAPTPS AAPAGPKGRV FVSPLAKKLA
AEKGIDLTQV KGTGPEGRII KKDIDSFVPS KAAPAAAAAM APPGPRVAPA PAGVFTDIPI
SNIRRVIAQR LMQSKQTIPH YYLSVDVNMG EVLLVRKELN KMLEGKGKIS VNDFIIKASA
LACLKVPEAN SSWMDTVIRQ NHVVDVSVAV STPAGLITPI VFNAHIKGLE TIASDVVSLA
SKAREGKLQP HEFQGGTFTI SNLGMFGIKN FSAIINPPQA CILAIGASED KLIPADNEKG
FDVASVMSVT LSCDHRVVDG AVGAQWLAEF KKYLEKPITM LL
