| Identification |
|---|
| HMDB Protein ID
| HMDBP00055 |
| Secondary Accession Numbers
| |
| Name
| Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial |
| Synonyms
|
- 70 kDa mitochondrial autoantigen of primary biliary cirrhosis
- Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex
- M2 antigen complex 70 kDa subunit
- PBC
- PDC-E2
- PDCE2
- Pyruvate dehydrogenase complex component E2
|
| Gene Name
| DLAT |
| Protein Type
| Enzyme |
| Biological Properties |
|---|
| General Function
| Involved in acyltransferase activity |
| Specific Function
| The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
|
| Pathways
|
- 2-ketoglutarate dehydrogenase complex deficiency
- Citrate cycle (TCA cycle)
- Citric Acid Cycle
- Congenital lactic acidosis
- Fumarase deficiency
- Glutaminolysis and Cancer
- Glycolysis / Gluconeogenesis
- Leigh Syndrome
- Mitochondrial complex II deficiency
- Primary hyperoxaluria II, PH2
- Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency)
- Pyruvate Dehydrogenase Complex Deficiency
- Pyruvate dehydrogenase deficiency (E2)
- Pyruvate dehydrogenase deficiency (E3)
- Pyruvate kinase deficiency
- Pyruvate metabolism
- Pyruvate metabolism
- The oncogenic action of 2-hydroxyglutarate
- The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria
- The Oncogenic Action of Fumarate
- The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria
- The Oncogenic Action of Succinate
- Warburg Effect
|
| Reactions
|
| Acetyl-CoA + enzyme N(6)-(dihydrolipoyl)lysine → Coenzyme A + enzyme N(6)-(S-acetyldihydrolipoyl)lysine |
details
|
| Acetyl-CoA + Enzyme N6-(dihydrolipoyl)lysine → Coenzyme A + [Dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine |
details
|
| Coenzyme A + NAD + Pyruvic acid → Carbon dioxide + Hydrogen Ion + NADH + Acetyl-CoA |
details
|
|
| GO Classification
|
| Biological Process |
| regulation of acetyl-CoA biosynthetic process from pyruvate |
| sleep |
| glycolysis |
| pyruvate metabolic process |
| acetyl-CoA biosynthetic process |
| acetyl-CoA biosynthetic process from pyruvate |
| Cellular Component |
| mitochondrial pyruvate dehydrogenase complex |
| Component |
| macromolecular complex |
| protein complex |
| pyruvate dehydrogenase complex |
| Function |
| binding |
| catalytic activity |
| transferase activity |
| transferase activity, transferring acyl groups |
| transferase activity, transferring acyl groups other than amino-acyl groups |
| acyltransferase activity |
| acetyltransferase activity |
| protein binding |
| s-acetyltransferase activity |
| dihydrolipoyllysine-residue acetyltransferase activity |
| Molecular Function |
| dihydrolipoyllysine-residue acetyltransferase activity |
| Process |
| metabolic process |
| cellular metabolic process |
| organic acid metabolic process |
| oxoacid metabolic process |
| carboxylic acid metabolic process |
| monocarboxylic acid metabolic process |
| pyruvate metabolic process |
|
| Cellular Location
|
- Mitochondrion matrix
|
| Gene Properties |
|---|
| Chromosome Location
| 11 |
| Locus
| 11q23.1 |
| SNPs
| DLAT |
| Gene Sequence
|
>1944 bp
ATGTGGCGCGTCTGTGCGCGACGGGCTCAGAATGTAGCCCCATGGGCGGGACTCGAGGCT
CGGTGGACGGCCTTGCAGGAGGTACCCGGAACTCCACGAGTGACCTCGCGATCTGGCCCG
GCTCCCGTTCGTCGCAACAGCGTGACTACAGGGTATGGCGGGGTCCGGGCACTGTGCGGC
TGGACCCCCAGTTCTGGGGCCACGCCGCGGAACCGCTTACTGCTGCAGCTTTTGGGGTCG
CCCGGCCGCCGCTATTACAGTCTTCCCCCGCATCAGAAGGTTCCATTGCCTTCTCTTTCC
CCCACAATGCAGGCAGGCACCATAGCCCGTTGGGAAAAAAAAGAGGGAGACAAAATCAAT
GAAGGTGACCTAATTGCAGAGGTTGAAACTGATAAAGCCACTGTTGGATTTGAGAGCCTG
GAGGAGTGTTATATGGCAAAGATACTTGTTGCTGAAGGTACCAGGGATGTTCCCATCGGA
GCGATCATCTGTATCACAGTTGGCAAGCCTGAGGATATTGAGGCCTTTAAAAATTATACA
CTGGATTCCTCAGCAGCACCTACCCCACAAGCGGCCCCAGCACCAACCCCTGCTGCCACT
GCTTCGCCACCTACACCTTCTGCTCAGGCTCCTGGTAGCTCATATCCCCCTCACATGCAG
GTACTTCTTCCTGCCCTCTCTCCCACCATGACCATGGGCACAGTTCAGAGATGGGAAAAA
AAAGTGGGTGAGAAGCTAAGTGAAGGAGACTTACTGGCAGAGATAGAAACTGACAAAGCC
ACTATAGGTTTTGAAGTACAGGAAGAAGGTTATCTGGCAAAAATCCTGGTCCCTGAAGGC
ACAAGAGATGTCCCTCTAGGAACCCCACTCTGTATCATTGTAGAAAAAGAGGCAGATATA
TCAGCATTTGCTGACTATAGGCCAACCGAAGTAACAGATTTAAAACCACAAGCGCCACCA
CCTACCCCACCCCCGGTGGCCGCTGTTCCTCCAACTCCCCAGCCTTTAGCTCCTACACCT
TCAGCACCCTGCCCAGCTACTCCTGCTGGACCAAAGGGAAGGGTGTTTGTTAGCCCTCTT
GCAAAGAAGTTGGCAGTAGAGAAAGGGATTGATCTTACACAAGTAAAAGGGACAGGACCA
GATGGTAGAATCACCAAGAAGGATATCGACTCTTTTGTGCCTAGTAAAGTTGCTCCTGCT
CCGGCAGCTGTTGTGCCTCCCACAGGTCCTGGAATGGCACCAGTTCCTACAGGTGTCTTC
ACAGATATCCCAATCAGCAACATTCGTCGGGTTATTGCACAGCGATTAATGCAATCAAAG
CAAACCATACCTCATTATTACCTTTCTATCAATGTAAATATGGGAGAAGTTTTGTTGGTA
CGGAAAGAACTTAATAAGATATTAGAAGGGAGAAGCAAAATTTCTGTCAATGACTTCATC
ATAAAAGCTTCAGCTTTGGCATGTTTAAAAGTTCCCGAAGCAAATTCTTCTTGGATGGAC
ACAGTTATAAGACAAAATCATGTTGTTGATGTCAGTGTTGCGGTCAGTACTCCTGCAGGA
CTCATCACACCTATTGTGTTTAATGCACATATAAAAGGAGTGGAAACCATTGCTAATGAT
GTTGTTTCTTTAGCAACCAAAGCAAGAGAGGGTAAACTACAGCCACATGAATTCCAGGGT
GGCACTTTTACGATCTCCAATTTAGGAATGTTTGGAATTAAGAATTTCTCTGCTATTATT
AACCCACCTCAAGCATGTATTTTGGCAATTGGTGCTTCAGAGGATAAACTGGTCCCTGCA
GATAATGAAAAAGGGTTTGATGTGGCTAGCATGATGTCTGTTACACTCAGTTGTGATCAC
CGGGTGGTGGATGGAGCAGTTGGAGCCCAGTGGCTTGCTGAGTTTAGAAAGTACCTTGAA
AAACCTATCACTATGTTGTTGTAA
|
| Protein Properties |
|---|
| Number of Residues
| 647 |
| Molecular Weight
| 68996.03 |
| Theoretical pI
| 7.835 |
| Pfam Domain Function
|
|
| Signals
|
Not Available
|
|
Transmembrane Regions
|
Not Available
|
| Protein Sequence
|
>Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
MWRVCARRAQNVAPWAGLEARWTALQEVPGTPRVTSRSGPAPARRNSVTTGYGGVRALCG
WTPSSGATPRNRLLLQLLGSPGRRYYSLPPHQKVPLPSLSPTMQAGTIARWEKKEGDKIN
EGDLIAEVETDKATVGFESLEECYMAKILVAEGTRDVPIGAIICITVGKPEDIEAFKNYT
LDSSAAPTPQAAPAPTPAATASPPTPSAQAPGSSYPPHMQVLLPALSPTMTMGTVQRWEK
KVGEKLSEGDLLAEIETDKATIGFEVQEEGYLAKILVPEGTRDVPLGTPLCIIVEKEADI
SAFADYRPTEVTDLKPQVPPPTPPPVAAVPPTPQPLAPTPSAPCPATPAGPKGRVFVSPL
AKKLAVEKGIDLTQVKGTGPDGRITKKDIDSFVPSKVAPAPAAVVPPTGPGMAPVPTGVF
TDIPISNIRRVIAQRLMQSKQTIPHYYLSIDVNMGEVLLVRKELNKILEGRSKISVNDFI
IKASALACLKVPEANSSWMDTVIRQNHVVDVSVAVSTPAGLITPIVFNAHIKGVETIAND
VVSLATKAREGKLQPHEFQGGTFTISNLGMFGIKNFSAIINPPQACILAIGASEDKLVPA
DNEKGFDVASMMSVTLSCDHRVVDGAVGAQWLAEFRKYLEKPITMLL
|
| External Links |
|---|
| GenBank ID Protein
| 62898924 |
| UniProtKB/Swiss-Prot ID
| P10515 |
| UniProtKB/Swiss-Prot Entry Name
| ODP2_HUMAN |
| PDB IDs
|
|
| GenBank Gene ID
| AK223596 |
| GeneCard ID
| DLAT |
| GenAtlas ID
| DLAT |
| HGNC ID
| HGNC:2896 |
| References |
|---|
| General References
| - Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
- Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [PubMed:16554811 ]
- Coppel RL, McNeilage LJ, Surh CD, Van de Water J, Spithill TW, Whittingham S, Gershwin ME: Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: dihydrolipoamide acetyltransferase. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7317-21. [PubMed:3174635 ]
- Thekkumkara TJ, Ho L, Wexler ID, Pons G, Liu TC, Patel MS: Nucleotide sequence of a cDNA for the dihydrolipoamide acetyltransferase component of human pyruvate dehydrogenase complex. FEBS Lett. 1988 Nov 21;240(1-2):45-8. [PubMed:3191998 ]
- Howard MJ, Fuller C, Broadhurst RW, Perham RN, Tang JG, Quinn J, Diamond AG, Yeaman SJ: Three-dimensional structure of the major autoantigen in primary biliary cirrhosis. Gastroenterology. 1998 Jul;115(1):139-46. [PubMed:9649469 ]
- Head RA, Brown RM, Zolkipli Z, Shahdadpuri R, King MD, Clayton PT, Brown GK: Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency. Ann Neurol. 2005 Aug;58(2):234-41. [PubMed:16049940 ]
- Kato M, Chuang JL, Tso SC, Wynn RM, Chuang DT: Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complex. EMBO J. 2005 May 18;24(10):1763-74. Epub 2005 Apr 28. [PubMed:15861126 ]
- Devedjiev Y, Steussy CN, Vassylyev DG: Crystal structure of an asymmetric complex of pyruvate dehydrogenase kinase 3 with lipoyl domain 2 and its biological implications. J Mol Biol. 2007 Jul 13;370(3):407-16. Epub 2007 May 10. [PubMed:17532006 ]
- Kato M, Li J, Chuang JL, Chuang DT: Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol. Structure. 2007 Aug;15(8):992-1004. Epub 2007 Aug 2. [PubMed:17683942 ]
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