ODP2_HUMAN
ID ODP2_HUMAN Reviewed; 647 AA.
AC P10515; Q16783; Q53EP3;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 3.
DT 03-AUG-2022, entry version 242.
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=M2 antigen complex 70 kDa subunit;
DE AltName: Full=Pyruvate dehydrogenase complex component E2;
DE Short=PDC-E2;
DE Short=PDCE2;
DE Flags: Precursor;
GN Name=DLAT; Synonyms=DLTA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-43; ALA-318 AND
RP ASN-451.
RC TISSUE=Kidney;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 33-647.
RC TISSUE=Placenta;
RX PubMed=3174635; DOI=10.1073/pnas.85.19.7317;
RA Coppel R.L., McNeilage L.J., Surh C.D., van de Water J., Spithill T.W.,
RA Whittingham S., Gershwin M.E.;
RT "Primary structure of the human M2 mitochondrial autoantigen of primary
RT biliary cirrhosis: dihydrolipoamide acetyltransferase.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:7317-7321(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 73-647, AND LIPOYLATION AT LYS-132 AND
RP LYS-259.
RC TISSUE=Liver;
RX PubMed=3191998; DOI=10.1016/0014-5793(88)80337-5;
RA Thekkumkara T.J., Ho L., Wexler I.D., Pon G., Liu T., Patel M.S.;
RT "Nucleotide sequence of a cDNA for the dihydrolipoamide acetyltransferase
RT component of human pyruvate dehydrogenase complex.";
RL FEBS Lett. 240:45-48(1988).
RN [5]
RP SUBUNIT.
RX PubMed=14638692; DOI=10.1074/jbc.m308172200;
RA Hiromasa Y., Fujisawa T., Aso Y., Roche T.E.;
RT "Organization of the cores of the mammalian pyruvate dehydrogenase complex
RT formed by E2 and E2 plus the E3-binding protein and their capacities to
RT bind the E1 and E3 components.";
RL J. Biol. Chem. 279:6921-6933(2004).
RN [6]
RP INTERACTION WITH PDHB.
RX PubMed=20160912; DOI=10.1016/j.molcatb.2009.05.001;
RA Patel M.S., Korotchkina L.G., Sidhu S.;
RT "Interaction of E1 and E3 components with the core proteins of the human
RT pyruvate dehydrogenase complex.";
RL J. Mol. Catal., B Enzym. 61:2-6(2009).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-466, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-100, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP INTERACTION WITH SIRT4, LIPOYLATION AT LYS-132 AND LYS-259, AND
RP DELIPOYLATION AT LYS-132 AND LYS-259.
RX PubMed=25525879; DOI=10.1016/j.cell.2014.11.046;
RA Mathias R.A., Greco T.M., Oberstein A., Budayeva H.G., Chakrabarti R.,
RA Rowland E.A., Kang Y., Shenk T., Cristea I.M.;
RT "Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex
RT activity.";
RL Cell 159:1615-1625(2014).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12]
RP STRUCTURE BY NMR OF 214-315.
RX PubMed=9649469; DOI=10.1016/s0016-5085(98)70375-0;
RA Howard M.J., Fuller C., Broadhurst R.W., Perham R.N., Tang J.G., Quinn J.,
RA Diamond A.G., Yeaman S.J.;
RT "Three-dimensional structure of the major autoantigen in primary biliary
RT cirrhosis.";
RL Gastroenterology 115:139-146(1998).
RN [13]
RP INVOLVEMENT IN PDHE2 DEFICIENCY.
RX PubMed=16049940; DOI=10.1002/ana.20550;
RA Head R.A., Brown R.M., Zolkipli Z., Shahdadpuri R., King M.D.,
RA Clayton P.T., Brown G.K.;
RT "Clinical and genetic spectrum of pyruvate dehydrogenase deficiency:
RT dihydrolipoamide acetyltransferase (E2) deficiency.";
RL Ann. Neurol. 58:234-241(2005).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 212-319 IN COMPLEX WITH PDK3.
RX PubMed=15861126; DOI=10.1038/sj.emboj.7600663;
RA Kato M., Chuang J.L., Tso S.C., Wynn R.M., Chuang D.T.;
RT "Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl
RT domain 2 of human pyruvate dehydrogenase complex.";
RL EMBO J. 24:1763-1774(2005).
RN [15]
RP STRUCTURE BY NMR OF 92-186.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RSGI RUH-058, a lipoyl domain of human 2-oxoacid
RT dehydrogenase.";
RL Submitted (OCT-2006) to the PDB data bank.
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 212-319 IN COMPLEX WITH PDK3.
RX PubMed=17532006; DOI=10.1016/j.jmb.2007.04.083;
RA Devedjiev Y., Steussy C.N., Vassylyev D.G.;
RT "Crystal structure of an asymmetric complex of pyruvate dehydrogenase
RT kinase 3 with lipoyl domain 2 and its biological implications.";
RL J. Mol. Biol. 370:407-416(2007).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 212-319 IN COMPLEX WITH PDK3.
RX PubMed=17683942; DOI=10.1016/j.str.2007.07.001;
RA Kato M., Li J., Chuang J.L., Chuang D.T.;
RT "Distinct structural mechanisms for inhibition of pyruvate dehydrogenase
RT kinase isoforms by AZD7545, dichloroacetate, and radicicol.";
RL Structure 15:992-1004(2007).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 214-300 IN COMPLEX WITH PDK2.
RX PubMed=18387944; DOI=10.1074/jbc.m800311200;
RA Green T., Grigorian A., Klyuyeva A., Tuganova A., Luo M., Popov K.M.;
RT "Structural and functional insights into the molecular mechanisms
RT responsible for the regulation of pyruvate dehydrogenase kinase 2.";
RL J. Biol. Chem. 283:15789-15798(2008).
RN [19]
RP STRUCTURE BY ELECTRON MICROSCOPY (18.3 ANGSTROMS) OF INNER CORE OF THE
RP COMPLEX, AND SUBUNIT.
RX PubMed=20361979; DOI=10.1016/j.jmb.2010.03.043;
RA Vijayakrishnan S., Kelly S.M., Gilbert R.J., Callow P., Bhella D.,
RA Forsyth T., Lindsay J.G., Byron O.;
RT "Solution structure and characterisation of the human pyruvate
RT dehydrogenase complex core assembly.";
RL J. Mol. Biol. 399:71-93(2010).
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 2 lipoyl cofactors 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) (PubMed:14638692). These subunits are bound to
CC an inner core composed of about 48 DLAT and 12 PDHX molecules
CC (PubMed:14638692, PubMed:20361979). Interacts with PDK2 and PDK3
CC (PubMed:15861126, PubMed:17532006, PubMed:17683942, PubMed:18387944).
CC Interacts with SIRT4 (PubMed:25525879). Interacts with PDHB
CC (PubMed:20160912). {ECO:0000269|PubMed:14638692,
CC ECO:0000269|PubMed:15861126, ECO:0000269|PubMed:17532006,
CC ECO:0000269|PubMed:17683942, ECO:0000269|PubMed:18387944,
CC ECO:0000269|PubMed:20160912, ECO:0000269|PubMed:20361979,
CC ECO:0000269|PubMed:25525879}.
CC -!- INTERACTION:
CC P10515; P10515: DLAT; NbExp=2; IntAct=EBI-2959723, EBI-2959723;
CC P10515; P11177: PDHB; NbExp=7; IntAct=EBI-2959723, EBI-1035872;
CC P10515; Q15120: PDK3; NbExp=2; IntAct=EBI-2959723, EBI-1383915;
CC P10515; Q9Y6E7: SIRT4; NbExp=6; IntAct=EBI-2959723, EBI-2606540;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- PTM: Delipoylated at Lys-132 and Lys-259 by SIRT4, delipoylation
CC decreases the PHD complex activity. {ECO:0000269|PubMed:25525879}.
CC -!- DISEASE: Note=Primary biliary cirrhosis is a chronic, progressive
CC cholestatic liver disease characterized by the presence of
CC antimitochondrial autoantibodies in patients' serum. It manifests with
CC inflammatory obliteration of intra-hepatic bile duct, leading to liver
CC cell damage and cirrhosis. Patients with primary biliary cirrhosis show
CC autoantibodies against the E2 component of pyruvate dehydrogenase
CC complex.
CC -!- DISEASE: Pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency)
CC [MIM:245348]: Pyruvate dehydrogenase (PDH) deficiency is a major cause
CC of primary lactic acidosis and neurological dysfunction in infancy and
CC early childhood. In this form of PDH deficiency episodic dystonia is
CC the major neurological manifestation, with other more common features
CC of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia,
CC being less prominent. {ECO:0000269|PubMed:16049940}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the 2-oxoacid dehydrogenase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA62253.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAA62253.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK223596; BAD97316.1; -; mRNA.
DR EMBL; AP000907; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; J03866; AAA62253.1; ALT_SEQ; mRNA.
DR EMBL; Y00978; CAA68787.1; -; mRNA.
DR CCDS; CCDS8354.1; -.
DR PIR; A40497; A40497.
DR RefSeq; NP_001922.2; NM_001931.4.
DR PDB; 1FYC; NMR; -; A=212-315.
DR PDB; 1Y8N; X-ray; 2.60 A; B=212-319.
DR PDB; 1Y8O; X-ray; 2.48 A; B=212-319.
DR PDB; 1Y8P; X-ray; 2.63 A; B=212-319.
DR PDB; 2DNE; NMR; -; A=92-186.
DR PDB; 2PNR; X-ray; 2.50 A; C/G=212-319.
DR PDB; 2Q8I; X-ray; 2.60 A; B=212-319.
DR PDB; 3B8K; EM; 8.80 A; A=409-647.
DR PDB; 3CRK; X-ray; 2.30 A; C/D=214-300.
DR PDB; 3CRL; X-ray; 2.61 A; C/D=214-300.
DR PDB; 6CT0; EM; 3.10 A; 0=1-647.
DR PDB; 6H55; EM; 6.00 A; A=1-647.
DR PDBsum; 1FYC; -.
DR PDBsum; 1Y8N; -.
DR PDBsum; 1Y8O; -.
DR PDBsum; 1Y8P; -.
DR PDBsum; 2DNE; -.
DR PDBsum; 2PNR; -.
DR PDBsum; 2Q8I; -.
DR PDBsum; 3B8K; -.
DR PDBsum; 3CRK; -.
DR PDBsum; 3CRL; -.
DR PDBsum; 6CT0; -.
DR PDBsum; 6H55; -.
DR AlphaFoldDB; P10515; -.
DR SMR; P10515; -.
DR BioGRID; 108081; 194.
DR ComplexPortal; CPX-6233; Mitochondrial pyruvate dehydrogenase complex, somatic variant.
DR ComplexPortal; CPX-6242; Mitochondrial pyruvate dehydrogenase complex, testis-specific variant.
DR DIP; DIP-29496N; -.
DR IntAct; P10515; 46.
DR MINT; P10515; -.
DR STRING; 9606.ENSP00000280346; -.
DR ChEMBL; CHEMBL4523180; -.
DR DrugBank; DB03760; Dihydrolipoic Acid.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB03758; Radicicol.
DR CarbonylDB; P10515; -.
DR GlyGen; P10515; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P10515; -.
DR PhosphoSitePlus; P10515; -.
DR SwissPalm; P10515; -.
DR BioMuta; DLAT; -.
DR DMDM; 215274207; -.
DR EPD; P10515; -.
DR jPOST; P10515; -.
DR MassIVE; P10515; -.
DR PaxDb; P10515; -.
DR PeptideAtlas; P10515; -.
DR PRIDE; P10515; -.
DR ProteomicsDB; 52610; -.
DR ABCD; P10515; 1 sequenced antibody.
DR Antibodypedia; 18282; 325 antibodies from 30 providers.
DR DNASU; 1737; -.
DR Ensembl; ENST00000280346.11; ENSP00000280346.7; ENSG00000150768.17.
DR GeneID; 1737; -.
DR KEGG; hsa:1737; -.
DR MANE-Select; ENST00000280346.11; ENSP00000280346.7; NM_001931.5; NP_001922.2.
DR CTD; 1737; -.
DR DisGeNET; 1737; -.
DR GeneCards; DLAT; -.
DR GeneReviews; DLAT; -.
DR HGNC; HGNC:2896; DLAT.
DR HPA; ENSG00000150768; Tissue enhanced (tongue).
DR MalaCards; DLAT; -.
DR MIM; 245348; phenotype.
DR MIM; 608770; gene.
DR neXtProt; NX_P10515; -.
DR OpenTargets; ENSG00000150768; -.
DR Orphanet; 79244; Pyruvate dehydrogenase E2 deficiency.
DR PharmGKB; PA27350; -.
DR VEuPathDB; HostDB:ENSG00000150768; -.
DR eggNOG; KOG0557; Eukaryota.
DR GeneTree; ENSGT00940000154943; -.
DR InParanoid; P10515; -.
DR OMA; TMEFESF; -.
DR OrthoDB; 747232at2759; -.
DR PhylomeDB; P10515; -.
DR TreeFam; TF106145; -.
DR BioCyc; MetaCyc:HS07688-MON; -.
DR BRENDA; 1.2.1.104; 2681.
DR BRENDA; 2.3.1.12; 2681.
DR PathwayCommons; P10515; -.
DR Reactome; R-HSA-204174; Regulation of pyruvate dehydrogenase (PDH) complex.
DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-HSA-5362517; Signaling by Retinoic Acid.
DR Reactome; R-HSA-70268; Pyruvate metabolism.
DR SABIO-RK; P10515; -.
DR SignaLink; P10515; -.
DR SIGNOR; P10515; -.
DR BioGRID-ORCS; 1737; 28 hits in 1079 CRISPR screens.
DR ChiTaRS; DLAT; human.
DR EvolutionaryTrace; P10515; -.
DR GeneWiki; Dihydrolipoyl_transacetylase; -.
DR GenomeRNAi; 1737; -.
DR Pharos; P10515; Tbio.
DR PRO; PR:P10515; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P10515; protein.
DR Bgee; ENSG00000150768; Expressed in heart right ventricle and 213 other tissues.
DR ExpressionAtlas; P10515; baseline and differential.
DR Genevisible; P10515; HS.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005967; C:mitochondrial pyruvate dehydrogenase complex; IPI:ComplexPortal.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0045254; C:pyruvate dehydrogenase complex; IDA:UniProtKB.
DR GO; GO:0004742; F:dihydrolipoyllysine-residue acetyltransferase activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0006086; P:acetyl-CoA biosynthetic process from pyruvate; IDA:ComplexPortal.
DR GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
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 3D-structure; Acetylation; Acyltransferase; Carbohydrate metabolism;
KW Glucose metabolism; Lipoyl; Mitochondrion; Phosphoprotein;
KW Reference proteome; Repeat; Transferase; Transit peptide;
KW Tricarboxylic acid cycle.
FT TRANSIT 1..86
FT /note="Mitochondrion"
FT CHAIN 87..647
FT /note="Dihydrolipoyllysine-residue acetyltransferase
FT component of pyruvate dehydrogenase complex, mitochondrial"
FT /id="PRO_0000020479"
FT DOMAIN 91..167
FT /note="Lipoyl-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT DOMAIN 218..294
FT /note="Lipoyl-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT DOMAIN 356..393
FT /note="Peripheral subunit-binding (PSBD)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01170"
FT REGION 29..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 184..219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 312..346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 417..647
FT /note="Catalytic"
FT /evidence="ECO:0000250"
FT COMPBIAS 190..204
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 314..346
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 620
FT /evidence="ECO:0000255"
FT ACT_SITE 624
FT /evidence="ECO:0000255"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 132
FT /note="N6-lipoyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066,
FT ECO:0000269|PubMed:25525879, ECO:0000269|PubMed:3191998"
FT MOD_RES 259
FT /note="N6-lipoyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066,
FT ECO:0000269|PubMed:25525879, ECO:0000269|PubMed:3191998"
FT MOD_RES 466
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 473
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BMF4"
FT MOD_RES 547
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BMF4"
FT VARIANT 43
FT /note="A -> V (in dbSNP:rs2303436)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_047410"
FT VARIANT 98
FT /note="S -> F (in dbSNP:rs537057)"
FT /id="VAR_047411"
FT VARIANT 99
FT /note="L -> F (in dbSNP:rs537060)"
FT /id="VAR_047412"
FT VARIANT 209
FT /note="Q -> R (in dbSNP:rs11553595)"
FT /id="VAR_047413"
FT VARIANT 313
FT /note="D -> V (in dbSNP:rs11553592)"
FT /id="VAR_047414"
FT VARIANT 318
FT /note="V -> A (in dbSNP:rs627441)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_047415"
FT VARIANT 451
FT /note="D -> N (in dbSNP:rs10891314)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_047416"
FT CONFLICT 112
FT /note="E -> K (in Ref. 4; CAA68787)"
FT /evidence="ECO:0000305"
FT CONFLICT 342
FT /note="A -> T (in Ref. 3; AAA62253)"
FT /evidence="ECO:0000305"
FT CONFLICT 358
FT /note="S -> D (in Ref. 3; AAA62253)"
FT /evidence="ECO:0000305"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:2DNE"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:2DNE"
FT STRAND 105..110
FT /evidence="ECO:0007829|PDB:2DNE"
FT STRAND 123..129
FT /evidence="ECO:0007829|PDB:2DNE"
FT STRAND 134..138
FT /evidence="ECO:0007829|PDB:2DNE"
FT STRAND 140..147
FT /evidence="ECO:0007829|PDB:2DNE"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:2DNE"
FT STRAND 162..168
FT /evidence="ECO:0007829|PDB:2DNE"
FT HELIX 170..177
FT /evidence="ECO:0007829|PDB:2DNE"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:2DNE"
FT STRAND 218..222
FT /evidence="ECO:0007829|PDB:3CRK"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:1FYC"
FT STRAND 232..238
FT /evidence="ECO:0007829|PDB:3CRK"
FT STRAND 251..256
FT /evidence="ECO:0007829|PDB:3CRK"
FT STRAND 261..265
FT /evidence="ECO:0007829|PDB:3CRK"
FT STRAND 270..277
FT /evidence="ECO:0007829|PDB:3CRK"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:1Y8O"
FT STRAND 289..297
FT /evidence="ECO:0007829|PDB:3CRK"
FT HELIX 301..303
FT /evidence="ECO:0007829|PDB:2Q8I"
FT HELIX 427..440
FT /evidence="ECO:0007829|PDB:6CT0"
FT STRAND 446..453
FT /evidence="ECO:0007829|PDB:6CT0"
FT HELIX 455..467
FT /evidence="ECO:0007829|PDB:6CT0"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:6CT0"
FT HELIX 476..490
FT /evidence="ECO:0007829|PDB:6CT0"
FT HELIX 492..495
FT /evidence="ECO:0007829|PDB:6CT0"
FT STRAND 496..498
FT /evidence="ECO:0007829|PDB:6CT0"
FT STRAND 500..505
FT /evidence="ECO:0007829|PDB:6CT0"
FT STRAND 511..513
FT /evidence="ECO:0007829|PDB:6CT0"
FT TURN 527..531
FT /evidence="ECO:0007829|PDB:6CT0"
FT HELIX 534..549
FT /evidence="ECO:0007829|PDB:6CT0"
FT HELIX 555..558
FT /evidence="ECO:0007829|PDB:6CT0"
FT STRAND 564..567
FT /evidence="ECO:0007829|PDB:6CT0"
FT TURN 569..572
FT /evidence="ECO:0007829|PDB:6CT0"
FT STRAND 584..599
FT /evidence="ECO:0007829|PDB:6CT0"
FT STRAND 601..618
FT /evidence="ECO:0007829|PDB:6CT0"
FT STRAND 620..622
FT /evidence="ECO:0007829|PDB:6CT0"
FT HELIX 625..640
FT /evidence="ECO:0007829|PDB:6CT0"
FT HELIX 642..646
FT /evidence="ECO:0007829|PDB:6CT0"
SQ SEQUENCE 647 AA; 68997 MW; DD93A8E666E377C2 CRC64;
MWRVCARRAQ NVAPWAGLEA RWTALQEVPG TPRVTSRSGP APARRNSVTT GYGGVRALCG
WTPSSGATPR NRLLLQLLGS PGRRYYSLPP HQKVPLPSLS PTMQAGTIAR WEKKEGDKIN
EGDLIAEVET DKATVGFESL EECYMAKILV AEGTRDVPIG AIICITVGKP EDIEAFKNYT
LDSSAAPTPQ AAPAPTPAAT ASPPTPSAQA PGSSYPPHMQ VLLPALSPTM TMGTVQRWEK
KVGEKLSEGD LLAEIETDKA TIGFEVQEEG YLAKILVPEG TRDVPLGTPL CIIVEKEADI
SAFADYRPTE VTDLKPQVPP PTPPPVAAVP PTPQPLAPTP SAPCPATPAG PKGRVFVSPL
AKKLAVEKGI DLTQVKGTGP DGRITKKDID SFVPSKVAPA PAAVVPPTGP GMAPVPTGVF
TDIPISNIRR VIAQRLMQSK QTIPHYYLSI DVNMGEVLLV RKELNKILEG RSKISVNDFI
IKASALACLK VPEANSSWMD TVIRQNHVVD VSVAVSTPAG LITPIVFNAH IKGVETIAND
VVSLATKARE GKLQPHEFQG GTFTISNLGM FGIKNFSAII NPPQACILAI GASEDKLVPA
DNEKGFDVAS MMSVTLSCDH RVVDGAVGAQ WLAEFRKYLE KPITMLL
