Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P10515 (ODP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 176. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial

EC=2.3.1.12
Alternative name(s):
70 kDa mitochondrial autoantigen of primary biliary cirrhosis
Short name=PBC
Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex
M2 antigen complex 70 kDa subunit
Pyruvate dehydrogenase complex component E2
Short name=PDC-E2
Short name=PDCE2
Gene names
Name:DLAT
Synonyms:DLTA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length647 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2, and thereby links the glycolytic pathway to the tricarboxylic cycle.

Catalytic activity

Acetyl-CoA + enzyme N(6)-(dihydrolipoyl)lysine = CoA + enzyme N(6)-(S-acetyldihydrolipoyl)lysine.

Cofactor

Binds 2 lipoyl cofactors covalently.

Subunit structure

Part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules. Interacts with PDK2 and PDK3. Ref.5

Subcellular location

Mitochondrion matrix.

Involvement in disease

Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex.

Pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) [MIM:245348]: Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Sequence similarities

Belongs to the 2-oxoacid dehydrogenase family.

Contains 2 lipoyl-binding domains.

Sequence caution

The sequence AAA62253.1 differs from that shown. Reason: Frameshift at positions 449, 451 and 455.

The sequence AAA62253.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PDHBP111777EBI-2959723,EBI-1035872

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 8686Mitochondrion
Chain87 – 647561Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
PRO_0000020479

Regions

Domain92 – 16675Lipoyl-binding 1
Domain219 – 29375Lipoyl-binding 2
Region358 – 38932E3-binding site By similarity
Region417 – 647231Catalytic By similarity

Sites

Active site6201 Potential
Active site6241 Potential

Amino acid modifications

Modified residue1321N6-lipoyllysine
Modified residue2591N6-lipoyllysine
Modified residue4661N6-acetyllysine Ref.6
Modified residue4731N6-succinyllysine By similarity
Modified residue5471N6-succinyllysine By similarity

Natural variations

Natural variant431A → V. Ref.1
Corresponds to variant rs2303436 [ dbSNP | Ensembl ].
VAR_047410
Natural variant981S → F.
Corresponds to variant rs537057 [ dbSNP | Ensembl ].
VAR_047411
Natural variant991L → F.
Corresponds to variant rs537060 [ dbSNP | Ensembl ].
VAR_047412
Natural variant2091Q → R.
Corresponds to variant rs11553595 [ dbSNP | Ensembl ].
VAR_047413
Natural variant3131D → V.
Corresponds to variant rs11553592 [ dbSNP | Ensembl ].
VAR_047414
Natural variant3181V → A. Ref.1
Corresponds to variant rs627441 [ dbSNP | Ensembl ].
VAR_047415
Natural variant4511D → N. Ref.1
Corresponds to variant rs10891314 [ dbSNP | Ensembl ].
VAR_047416

Experimental info

Sequence conflict1121E → K in CAA68787. Ref.4
Sequence conflict3421A → T in AAA62253. Ref.3
Sequence conflict3581S → D in AAA62253. Ref.3

Secondary structure

...................................... 647
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P10515 [UniParc].

Last modified November 25, 2008. Version 3.
Checksum: DD93A8E666E377C2

FASTA64768,997
        10         20         30         40         50         60 
MWRVCARRAQ NVAPWAGLEA RWTALQEVPG TPRVTSRSGP APARRNSVTT GYGGVRALCG 

        70         80         90        100        110        120 
WTPSSGATPR NRLLLQLLGS PGRRYYSLPP HQKVPLPSLS PTMQAGTIAR WEKKEGDKIN 

       130        140        150        160        170        180 
EGDLIAEVET DKATVGFESL EECYMAKILV AEGTRDVPIG AIICITVGKP EDIEAFKNYT 

       190        200        210        220        230        240 
LDSSAAPTPQ AAPAPTPAAT ASPPTPSAQA PGSSYPPHMQ VLLPALSPTM TMGTVQRWEK 

       250        260        270        280        290        300 
KVGEKLSEGD LLAEIETDKA TIGFEVQEEG YLAKILVPEG TRDVPLGTPL CIIVEKEADI 

       310        320        330        340        350        360 
SAFADYRPTE VTDLKPQVPP PTPPPVAAVP PTPQPLAPTP SAPCPATPAG PKGRVFVSPL 

       370        380        390        400        410        420 
AKKLAVEKGI DLTQVKGTGP DGRITKKDID SFVPSKVAPA PAAVVPPTGP GMAPVPTGVF 

       430        440        450        460        470        480 
TDIPISNIRR VIAQRLMQSK QTIPHYYLSI DVNMGEVLLV RKELNKILEG RSKISVNDFI 

       490        500        510        520        530        540 
IKASALACLK VPEANSSWMD TVIRQNHVVD VSVAVSTPAG LITPIVFNAH IKGVETIAND 

       550        560        570        580        590        600 
VVSLATKARE GKLQPHEFQG GTFTISNLGM FGIKNFSAII NPPQACILAI GASEDKLVPA 

       610        620        630        640 
DNEKGFDVAS MMSVTLSCDH RVVDGAVGAQ WLAEFRKYLE KPITMLL 

« Hide

References

« Hide 'large scale' references
[1]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS VAL-43; ALA-318 AND ASN-451.
Tissue: Kidney.
[2]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: dihydrolipoamide acetyltransferase."
Coppel R.L., McNeilage L.J., Surh C.D., van de Water J., Spithill T.W., Whittingham S., Gershwin M.E.
Proc. Natl. Acad. Sci. U.S.A. 85:7317-7321(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 33-647.
Tissue: Placenta.
[4]"Nucleotide sequence of a cDNA for the dihydrolipoamide acetyltransferase component of human pyruvate dehydrogenase complex."
Thekkumkara T.J., Ho L., Wexler I.D., Pon G., Liu T., Patel M.S.
FEBS Lett. 240:45-48(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 73-647.
Tissue: Liver.
[5]"Organization of the cores of the mammalian pyruvate dehydrogenase complex formed by E2 and E2 plus the E3-binding protein and their capacities to bind the E1 and E3 components."
Hiromasa Y., Fujisawa T., Aso Y., Roche T.E.
J. Biol. Chem. 279:6921-6933(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[6]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-466, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Three-dimensional structure of the major autoantigen in primary biliary cirrhosis."
Howard M.J., Fuller C., Broadhurst R.W., Perham R.N., Tang J.G., Quinn J., Diamond A.G., Yeaman S.J.
Gastroenterology 115:139-146(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 214-315.
[9]"Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency."
Head R.A., Brown R.M., Zolkipli Z., Shahdadpuri R., King M.D., Clayton P.T., Brown G.K.
Ann. Neurol. 58:234-241(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PDHE2 DEFICIENCY.
[10]"Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complex."
Kato M., Chuang J.L., Tso S.C., Wynn R.M., Chuang D.T.
EMBO J. 24:1763-1774(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 212-319 IN COMPLEX WITH PDK3.
[11]"Solution structure of RSGI RUH-058, a lipoyl domain of human 2-oxoacid dehydrogenase."
RIKEN structural genomics initiative (RSGI)
Submitted (OCT-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 92-186.
[12]"Crystal structure of an asymmetric complex of pyruvate dehydrogenase kinase 3 with lipoyl domain 2 and its biological implications."
Devedjiev Y., Steussy C.N., Vassylyev D.G.
J. Mol. Biol. 370:407-416(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 212-319 IN COMPLEX WITH PDK3.
[13]"Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol."
Kato M., Li J., Chuang J.L., Chuang D.T.
Structure 15:992-1004(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 212-319 IN COMPLEX WITH PDK3.
[14]"Structural and functional insights into the molecular mechanisms responsible for the regulation of pyruvate dehydrogenase kinase 2."
Green T., Grigorian A., Klyuyeva A., Tuganova A., Luo M., Popov K.M.
J. Biol. Chem. 283:15789-15798(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 214-300 IN COMPLEX WITH PDK2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK223596 mRNA. Translation: BAD97316.1.
AP000907 Genomic DNA. No translation available.
J03866 mRNA. Translation: AAA62253.1. Sequence problems.
Y00978 mRNA. Translation: CAA68787.1.
CCDSCCDS8354.1.
PIRA40497.
RefSeqNP_001922.2. NM_001931.4.
UniGeneHs.335551.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FYCNMR-A212-315[»]
1Y8NX-ray2.60B212-319[»]
1Y8OX-ray2.48B212-319[»]
1Y8PX-ray2.63B212-319[»]
2DNENMR-A92-186[»]
2PNRX-ray2.50C/G212-319[»]
2Q8IX-ray2.60B212-319[»]
3B8Kelectron microscopy8.80A409-647[»]
3CRKX-ray2.30C/D214-300[»]
3CRLX-ray2.61C/D214-300[»]
ProteinModelPortalP10515.
SMRP10515. Positions 92-182, 214-306, 409-647.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108081. 25 interactions.
DIPDIP-29496N.
IntActP10515. 8 interactions.
MINTMINT-3007324.
STRING9606.ENSP00000280346.

Chemistry

DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP10515.

Polymorphism databases

DMDM215274207.

Proteomic databases

MaxQBP10515.
PaxDbP10515.
PRIDEP10515.

Protocols and materials databases

DNASU1737.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000280346; ENSP00000280346; ENSG00000150768.
ENST00000574572; ENSP00000461764; ENSG00000263032.
GeneID1737.
KEGGhsa:1737.
UCSCuc001pmo.3. human.

Organism-specific databases

CTD1737.
GeneCardsGC11P111895.
HGNCHGNC:2896. DLAT.
HPACAB003782.
HPA040786.
MIM245348. phenotype.
608770. gene.
neXtProtNX_P10515.
Orphanet79244. Pyruvate dehydrogenase E2 deficiency.
PharmGKBPA27350.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0508.
HOGENOMHOG000281566.
HOVERGENHBG005063.
InParanoidP10515.
KOK00627.
OMAPISNIRK.
PhylomeDBP10515.
TreeFamTF106145.

Enzyme and pathway databases

BioCycMetaCyc:HS07688-MONOMER.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP10515.
BgeeP10515.
CleanExHS_DLAT.
GenevestigatorP10515.

Family and domain databases

Gene3D3.30.559.10. 1 hit.
4.10.320.10. 1 hit.
InterProIPR003016. 2-oxoA_DH_lipoyl-BS.
IPR001078. 2-oxoacid_DH_actylTfrase.
IPR000089. Biotin_lipoyl.
IPR023213. CAT-like_dom.
IPR004167. E3-bd.
IPR006257. LAT1.
IPR011053. Single_hybrid_motif.
[Graphical view]
PfamPF00198. 2-oxoacid_dh. 1 hit.
PF00364. Biotin_lipoyl. 2 hits.
PF02817. E3_binding. 1 hit.
[Graphical view]
SUPFAMSSF47005. SSF47005. 1 hit.
SSF51230. SSF51230. 2 hits.
TIGRFAMsTIGR01349. PDHac_trf_mito. 1 hit.
PROSITEPS50968. BIOTINYL_LIPOYL. 2 hits.
PS00189. LIPOYL. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP10515.
GeneWikiDihydrolipoyl_transacetylase.
GenomeRNAi1737.
NextBio7043.
PROP10515.
SOURCESearch...

Entry information

Entry nameODP2_HUMAN
AccessionPrimary (citable) accession number: P10515
Secondary accession number(s): Q16783, Q53EP3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: November 25, 2008
Last modified: July 9, 2014
This is version 176 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM