Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial

NameDihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
Synonyms
  • 2.3.1.12
  • 70 kDa mitochondrial autoantigen of primary biliary cirrhosis
  • Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex
  • DLTA
  • M2 antigen complex 70 kDa subunit
  • PBC
  • PDC-E2
  • PDCE2
  • Pyruvate dehydrogenase complex component E2
Gene NameDLAT
OrganismHuman
Amino acid sequence
>lcl|BSEQ0036947|Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
MWRVCARRAQNVAPWAGLEARWTALQEVPGTPRVTSRSGPAPARRNSVTTGYGGVRALCG
WTPSSGATPRNRLLLQLLGSPGRRYYSLPPHQKVPLPSLSPTMQAGTIARWEKKEGDKIN
EGDLIAEVETDKATVGFESLEECYMAKILVAEGTRDVPIGAIICITVGKPEDIEAFKNYT
LDSSAAPTPQAAPAPTPAATASPPTPSAQAPGSSYPPHMQVLLPALSPTMTMGTVQRWEK
KVGEKLSEGDLLAEIETDKATIGFEVQEEGYLAKILVPEGTRDVPLGTPLCIIVEKEADI
SAFADYRPTEVTDLKPQVPPPTPPPVAAVPPTPQPLAPTPSAPCPATPAGPKGRVFVSPL
AKKLAVEKGIDLTQVKGTGPDGRITKKDIDSFVPSKVAPAPAAVVPPTGPGMAPVPTGVF
TDIPISNIRRVIAQRLMQSKQTIPHYYLSIDVNMGEVLLVRKELNKILEGRSKISVNDFI
IKASALACLKVPEANSSWMDTVIRQNHVVDVSVAVSTPAGLITPIVFNAHIKGVETIAND
VVSLATKAREGKLQPHEFQGGTFTISNLGMFGIKNFSAIINPPQACILAIGASEDKLVPA
DNEKGFDVASMMSVTLSCDHRVVDGAVGAQWLAEFRKYLEKPITMLL
Number of residues647
Molecular Weight68996.03
Theoretical pI5.95
GO Classification
Functions
  • dihydrolipoyllysine-residue acetyltransferase activity
Processes
  • small molecule metabolic process
  • glucose metabolic process
  • cellular metabolic process
  • acetyl-CoA biosynthetic process from pyruvate
  • pyruvate metabolic process
  • regulation of acetyl-CoA biosynthetic process from pyruvate
  • sleep
  • tricarboxylic acid cycle
Components
  • mitochondrial matrix
  • myelin sheath
  • mitochondrial pyruvate dehydrogenase complex
  • mitochondrion
  • pyruvate dehydrogenase complex
General FunctionDihydrolipoyllysine-residue acetyltransferase activity
Specific FunctionThe 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID35360
UniProtKB IDP10515
UniProtKB Entry NameODP2_HUMAN
Cellular LocationMitochondrion matrix
Gene sequence
>lcl|BSEQ0009912|Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT)
ATGTGGCGCGTCTGTGCGCGACGGGCTCAGAATGTAGCCCCATGGGCGGGACTCGAGGCT
CGGTGGACGGCCTTGCAGGAGGTACCCGGAACTCCACGAGTGACCTCGCGATCTGGCCCG
GCTCCCGCTCGTCGCAACAGCGTGACTACAGGGTATGGCGGGGTCCGGGCACTGTGCGGC
TGGACCCCCAGTTCTGGGGCCACGCCGCGGAACCGCTTACTGCTGCAGCTTTTGGGGTCG
CCCGGCCGCCGCTATTACAGTCTTCCCCCGCATCAGAAGGTTCCATTGCCTTCTCTTTCC
CCCACAATGCAGGCAGGCACCATAGCCCGTTGGGAAAAAAAAGAGGGGGACAAAATCAAT
GAAGGTGACCTAATTGCAGAGGTTGAAACTGATAAAGCCACTGTTGGATTTGAGAGCCTG
GAGGAGTGTTATATGGCAAAGATACTTGTTGCTGAAGGTACCAGGGATGTTCCCATCGGA
GCGATCATCTGTATCACAGTTGGCAAGCCTGAGGATATTGAGGCCTTTAAAAATTATACA
CTGGATTCCTCAGCAGCACCTACCCCACAAGCGGCCCCAGCACCAACCCCTGCTGCCACT
GCTTCGCCACCTACACCTTCTGCTCAGGCTCCTGGTAGCTCATATCCCCCTCACATGCAG
GTACTTCTTCCTGCCCTCTCTCCCACCATGACCATGGGCACAGTTCAGAGATGGGAAAAA
AAAGTGGGTGAGAAGCTAAGTGAAGGAGACTTACTGGCAGAGATAGAAACTGACAAAGCC
ACTATAGGTTTTGAAGTACAGGAAGAAGGTTATCTGGCAAAAATCCTGGTCCCTGAAGGC
ACAAGAGATGTCCCTCTAGGAACCCCACTCTGTATCATTGTAGAAAAAGAGGCAGATATA
TCAGCATTTGCTGACTATAGGCCAACCGAAGTAACAGATTTAAAACCACAAGTGCCACCA
CCTACCCCACCCCCGGTGGCCGCTGTTCCTCCAACTCCCCAGCCTTTAGCTCCTACACCT
TCAGCACCCTGCCCAGCTACTCCTGCTGGACCAAAGGGAAGGGTGTTTGTTAGCCCTCTT
GCAAAGAAGTTGGCAGTAGAGAAAGGGATTGATCTTACACAAGTAAAAGGGACAGGACCA
GATGGTAGAATCACCAAGAAGGATATCGACTCTTTTGTGCCTAGTAAAGTTGCTCCTGCT
CCGGCAGCTGTTGTGCCTCCCACAGGTCCTGGAATGGCACCAGTTCCTACAGGTGTCTTC
ACAGATATCCCAATCAGCAACATTCGTCGGGTTATTGCACAGCGATTAATGCAATCAAAG
CAAACCATACCTCATTATTACCTTTCTATCGATGTAAATATGGGAGAAGTTTTGTTGGTA
CGGAAAGAACTTAATAAGATATTAGAAGGGAGAAGCAAAATTTCTGTCAATGACTTCATC
ATAAAAGCTTCAGCTTTGGCATGTTTAAAAGTTCCCGAAGCAAATTCTTCTTGGATGGAC
ACAGTTATAAGACAAAATCATGTTGTTGATGTCAGTGTTGCGGTCAGTACTCCTGCAGGA
CTCATCACACCTATTGTGTTTAATGCACATATAAAAGGAGTGGAAACCATTGCTAATGAT
GTTGTTTCTTTAGCAACCAAAGCAAGAGAGGGTAAACTACAGCCACATGAATTCCAGGGT
GGCACTTTTACGATCTCCAATTTAGGAATGTTTGGAATTAAGAATTTCTCTGCTATTATT
AACCCACCTCAAGCATGTATTTTGGCAATTGGTGCTTCAGAGGATAAACTGGTCCCTGCA
GATAATGAAAAAGGGTTTGATGTGGCTAGCATGATGTCTGTTACACTCAGTTGTGATCAC
CGGGTGGTGGATGGAGCAGTTGGAGCCCAGTGGCTTGCTGAGTTTAGAAAGTACCTTGAA
AAACCTATCACTATGTTGTTGTAA
GenBank Gene IDY00978
GeneCard IDNot Available
GenAtlas IDDLAT
HGNC IDHGNC:2896
Chromosome Location11
Locus11q23.1
References
  1. 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. 16554811
  2. 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. 3174635
  3. 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. 3191998
  4. Hiromasa Y, Fujisawa T, Aso Y, Roche TE: 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. J Biol Chem. 2004 Feb 20;279(8):6921-33. Epub 2003 Nov 24. 14638692
  5. 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. 19608861
  6. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  7. Mathias RA, Greco TM, Oberstein A, Budayeva HG, Chakrabarti R, Rowland EA, Kang Y, Shenk T, Cristea IM: Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity. Cell. 2014 Dec 18;159(7):1615-25. doi: 10.1016/j.cell.2014.11.046. 25525879
  8. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  9. 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. 9649469
  10. 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. 16049940
  11. 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. 15861126
  12. 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. 17532006
  13. 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. 17683942
  14. Green T, Grigorian A, Klyuyeva A, Tuganova A, Luo M, Popov KM: Structural and functional insights into the molecular mechanisms responsible for the regulation of pyruvate dehydrogenase kinase 2. J Biol Chem. 2008 Jun 6;283(23):15789-98. doi: 10.1074/jbc.M800311200. Epub 2008 Apr 3. 18387944