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P10515 (ODP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 152. 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·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)
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. It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3).

Catalytic activity

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

Cofactor

Binds 2 lipoyl cofactors covalently.

Subunit structure

20 to 30 alpha(2)-beta2 tetramers of E1 + 6 homodimers of E3 + 60 copies of E2. Interacts with PDK3.

Subcellular location

Mitochondrion matrix.

Involvement in disease

Note=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.

Defects in DLAT are the cause of pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) [MIM:245348]; also known as lactic acidemia due to defect of E2 lipoyl transacetylase of the pyruvate dehydrogenase complex. 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.

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.

Ontologies

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.5

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: 16554811] [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: 3174635] [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: 3191998] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 73-647.
Tissue: Liver.
[5]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed: 19608861] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-466, MASS SPECTROMETRY.
[6]"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: 21269460] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"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: 9649469] [Abstract]
Cited for: STRUCTURE BY NMR OF 214-315.
[8]"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: 16049940] [Abstract]
Cited for: INVOLVEMENT IN PDHE2 DEFICIENCY.
[9]"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: 15861126] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 212-319 IN COMPLEX WITH PDK3.
[10]"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.
[11]"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: 17532006] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 212-319 IN COMPLEX WITH PDK3.
[12]"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: 17683942] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 212-319 IN COMPLEX WITH PDK3.
+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.
IPIIPI00021338.
PIRA40497.
RefSeqNP_001922.2. NM_001931.4.
UniGeneHs.335551.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FYCNMR-A214-315[»]
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, 214-315, 353-395, 409-647.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-29496N.
IntActP10515. 5 interactions.
MINTMINT-3007324.
STRINGP10515.

PTM databases

PhosphoSiteP10515.

Polymorphism databases

DMDM215274207.

Proteomic databases

PRIDEP10515.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000280346; ENSP00000280346; ENSG00000150768.
GeneID1737.
KEGGhsa:1737.

Organism-specific databases

CTD1737.
GeneCardsGC11P111929.
H-InvDBHIX0201624.
HGNCHGNC:2896. DLAT.
HPACAB003782.
MIM245348. phenotype.
608770. gene.
neXtProtNX_P10515.
Orphanet79244. Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex deficiency.
PharmGKBPA27350.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG18935.
HOGENOMHBG630916.
HOVERGENHBG005063.
InParanoidP10515.
OMAYASPMAK.
OrthoDBEOG412M54.
PhylomeDBP10515.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP10515.
BgeeP10515.
CleanExHS_DLAT.
GenevestigatorP10515.

Family and domain databases

InterProIPR003016. 2-oxoA_DH_lipoyl-BS.
IPR001078. 2-oxoacid_DH_actylTfrase.
IPR006257. AcTrfase_Pyrv_DH_cplx_L.
IPR000089. Biotin_lipoyl.
IPR023213. CAT-like_dom.
IPR004167. E3-bd.
IPR011053. Single_hybrid_motif.
[Graphical view]
Gene3DG3DSA:3.30.559.10. CAT-like_dom. 1 hit.
G3DSA:4.10.320.10. E3_bd. 1 hit.
KOK00627.
PfamPF00198. 2-oxoacid_dh. 1 hit.
PF00364. Biotin_lipoyl. 2 hits.
PF02817. E3_binding. 1 hit.
[Graphical view]
SUPFAMSSF47005. E3_bd. 1 hit.
SSF51230. Hybrid_motif. 2 hits.
TIGRFAMsTIGR01349. PDHac_trf_mito. 1 hit.
PROSITEPS50968. BIOTINYL_LIPOYL. 2 hits.
PS00189. LIPOYL. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

DrugBankDB00157. NADH.
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: January 25, 2012
This is version 152 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

Human chromosome 11

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families