CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-001738
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 L-lactate dehydrogenase A chain 
Protein Synonyms/Alias
 LDH-A; Cell proliferation-inducing gene 19 protein; LDH muscle subunit; LDH-M; Renal carcinoma antigen NY-REN-59 
Gene Name
 LDHA 
Gene Synonyms/Alias
 PIG19 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
5***MATLKDQLIYNLacetylation[1]
5***MATLKDQLIYNLubiquitination[2, 3, 4]
14QLIYNLLKEEQTPQNacetylation[1, 5]
14QLIYNLLKEEQTPQNubiquitination[3, 4, 6, 7, 8, 9]
57LVDVIEDKLKGEMMDacetylation[1]
57LVDVIEDKLKGEMMDubiquitination[2, 7, 9]
59DVIEDKLKGEMMDLQubiquitination[2, 3, 7, 9]
76SLFLRTPKIVSGKDYubiquitination[2, 3, 4, 7, 9]
81TPKIVSGKDYNVTANacetylation[1]
81TPKIVSGKDYNVTANubiquitination[3, 4, 6, 7, 9]
90YNVTANSKLVIITAGubiquitination[7]
118QRNVNIFKFIIPNVVacetylation[1]
118QRNVNIFKFIIPNVVubiquitination[2, 3, 4, 6, 7, 8, 9]
126FIIPNVVKYSPNCKLacetylation[1]
126FIIPNVVKYSPNCKLubiquitination[3, 8, 9]
132VKYSPNCKLLIVSNPubiquitination[7, 8]
155WKISGFPKNRVIGSGubiquitination[3, 4, 7, 10]
222HPDLGTDKDKEQWKEacetylation[1, 11, 12, 13]
222HPDLGTDKDKEQWKEubiquitination[4, 7, 10, 13, 14]
224DLGTDKDKEQWKEVHacetylation[13]
224DLGTDKDKEQWKEVHubiquitination[13, 14]
228DKDKEQWKEVHKQVVacetylation[11]
228DKDKEQWKEVHKQVVubiquitination[10]
232EQWKEVHKQVVESAYacetylation[11, 12, 13]
232EQWKEVHKQVVESAYubiquitination[3, 7, 9, 13, 14, 15]
243ESAYEVIKLKGYTSWacetylation[12, 13]
243ESAYEVIKLKGYTSWubiquitination[3, 6, 7, 8, 9, 10, 13, 14, 15]
245AYEVIKLKGYTSWAIubiquitination[14]
278HPVSTMIKGLYGIKDacetylation[1, 11]
278HPVSTMIKGLYGIKDubiquitination[3, 7, 10]
284IKGLYGIKDDVFLSVubiquitination[7]
317SEEEARLKKSADTLWubiquitination[4, 14]
318EEEARLKKSADTLWGacetylation[1, 11, 13]
318EEEARLKKSADTLWGubiquitination[4, 7, 13, 14]
328DTLWGIQKELQF***acetylation[11]
328DTLWGIQKELQF***ubiquitination[3, 4, 7, 8, 9, 10, 13, 14]
Reference
 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [5] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [6] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [7] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [8] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [9] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [10] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [11] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [12] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [13] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [14] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [15] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931
Functional Description
  
Sequence Annotation
 NP_BIND 29 57 NAD.
 ACT_SITE 193 193 Proton acceptor.
 BINDING 99 99 NAD.
 BINDING 106 106 Substrate.
 BINDING 138 138 NAD or substrate.
 BINDING 169 169 Substrate.
 BINDING 248 248 Substrate.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 5 5 N6-acetyllysine.
 MOD_RES 10 10 Phosphotyrosine.
 MOD_RES 14 14 N6-acetyllysine.
 MOD_RES 57 57 N6-acetyllysine.
 MOD_RES 81 81 N6-acetyllysine.
 MOD_RES 118 118 N6-acetyllysine.
 MOD_RES 126 126 N6-acetyllysine.
 MOD_RES 239 239 Phosphotyrosine (By similarity).
 MOD_RES 318 318 N6-acetyllysine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Glycogen storage disease; Glycolysis; NAD; Oxidoreductase; Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 332 AA 
Protein Sequence
MATLKDQLIY NLLKEEQTPQ NKITVVGVGA VGMACAISIL MKDLADELAL VDVIEDKLKG 60
EMMDLQHGSL FLRTPKIVSG KDYNVTANSK LVIITAGARQ QEGESRLNLV QRNVNIFKFI 120
IPNVVKYSPN CKLLIVSNPV DILTYVAWKI SGFPKNRVIG SGCNLDSARF RYLMGERLGV 180
HPLSCHGWVL GEHGDSSVPV WSGMNVAGVS LKTLHPDLGT DKDKEQWKEV HKQVVESAYE 240
VIKLKGYTSW AIGLSVADLA ESIMKNLRRV HPVSTMIKGL YGIKDDVFLS VPCILGQNGI 300
SDLVKVTLTS EEEARLKKSA DTLWGIQKEL QF 332 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005739; C:mitochondrion; IEA:Compara.
 GO:0004459; F:L-lactate dehydrogenase activity; NAS:UniProtKB.
 GO:0044262; P:cellular carbohydrate metabolic process; IEA:InterPro.
 GO:0031668; P:cellular response to extracellular stimulus; IEA:Compara.
 GO:0006096; P:glycolysis; NAS:UniProtKB.
 GO:0006090; P:pyruvate metabolic process; TAS:Reactome. 
Interpro
 IPR001557; L-lactate/malate_DH.
 IPR011304; L-lactate_DH.
 IPR018177; L-lactate_DH_AS.
 IPR022383; Lactate/malate_DH_C.
 IPR001236; Lactate/malate_DH_N.
 IPR015955; Lactate_DH/Glyco_Ohase_4_C.
 IPR016040; NAD(P)-bd_dom. 
Pfam
 PF02866; Ldh_1_C
 PF00056; Ldh_1_N 
SMART
  
PROSITE
 PS00064; L_LDH 
PRINTS
 PR00086; LLDHDRGNASE.