ID LDHA_RAT Reviewed; 332 AA. AC P04642; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 13-AUG-1987, sequence version 1. DT 27-MAR-2024, entry version 195. DE RecName: Full=L-lactate dehydrogenase A chain; DE Short=LDH-A; DE EC=1.1.1.27 {ECO:0000250|UniProtKB:P00338}; DE AltName: Full=LDH muscle subunit; DE Short=LDH-M; GN Name=Ldha; Synonyms=Ldh-1, Ldh1; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3873645; DOI=10.1093/nar/13.3.711; RA Matrisian L.M., Rautmann G., Magun B.E., Breathnach R.; RT "Epidermal growth factor or serum stimulation of rat fibroblasts induces an RT elevation in mRNA levels for lactate dehydrogenase and other glycolytic RT enzymes."; RL Nucleic Acids Res. 13:711-726(1985). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP PROTEIN SEQUENCE OF 2-14; 43-57; 91-99; 107-112; 119-126; 233-243; 306-315 RP AND 319-328, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Fibroblast, and Pheochromocytoma; RA Bienvenut W.V., von Kriegsheim A.F., Kolch W.; RL Submitted (JUN-2009) to UniProtKB. RN [4] RP PROTEIN SEQUENCE OF 82-99; 127-132; 156-157; 170-190; 234-245; 306-315 AND RP 319-328. RX PubMed=2991914; DOI=10.1073/pnas.82.16.5260; RA Williams K.R., Reddigari S., Patel G.L.; RT "Identification of a nucleic acid helix-destabilizing protein from rat RT liver as lactate dehydrogenase-5."; RL Proc. Natl. Acad. Sci. U.S.A. 82:5260-5264(1985). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 274-332. RC TISSUE=Liver; RA Bae S.C., Lee S.K.; RT "Characterization of the folding structure of 3'-end of lactate RT dehydrogenase A-mRNA isolated from hormone stimulated rat C-6 glioma cell RT culture."; RL J. Microbiol. 25:94-102(1987). RN [6] RP PROTEIN SEQUENCE OF 319-328, AND IDENTIFICATION BY MASS SPECTROMETRY. RA Lubec G., Chen W.-Q.; RL Submitted (SEP-2006) to UniProtKB. RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-213; TYR-239; THR-309 AND RP THR-322, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: Interconverts simultaneously and stereospecifically pyruvate CC and lactate with concomitant interconversion of NADH and NAD(+). CC {ECO:0000250|UniProtKB:P00338}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(S)-lactate + NAD(+) = H(+) + NADH + pyruvate; CC Xref=Rhea:RHEA:23444, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16651, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.27; CC Evidence={ECO:0000250|UniProtKB:P00338}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23445; CC Evidence={ECO:0000250|UniProtKB:P00338}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23446; CC Evidence={ECO:0000250|UniProtKB:P00338}; CC -!- PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-lactate CC from pyruvate: step 1/1. {ECO:0000250|UniProtKB:P00338}. CC -!- SUBUNIT: Homotetramer. Interacts with PTEN upstream reading frame CC protein MP31. {ECO:0000250|UniProtKB:P00338}. CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P00338}. CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. LDH family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X01964; CAA26000.1; -; mRNA. DR EMBL; BC084698; AAH84698.1; -; mRNA. DR EMBL; M54926; AAA41508.1; -; mRNA. DR PIR; A23083; A23083. DR RefSeq; NP_058721.1; NM_017025.1. DR PDB; 4AJ1; X-ray; 1.87 A; A/B/C/D=2-332. DR PDB; 4AJ2; X-ray; 1.75 A; A/B/C/D=2-332. DR PDB; 4AJ4; X-ray; 1.90 A; A/B/C/D=1-332. DR PDB; 4AJE; X-ray; 2.35 A; A/B/C/D=2-332. DR PDB; 4AJH; X-ray; 1.93 A; A/B/C/D=2-332. DR PDB; 4AJI; X-ray; 1.93 A; A/B/C/D=2-332. DR PDB; 4AJJ; X-ray; 1.75 A; A/B/C/D=2-332. DR PDB; 4AJK; X-ray; 2.03 A; A/B/C/D=2-332. DR PDB; 4AJL; X-ray; 1.77 A; A/B/C/D=2-332. DR PDB; 4AJN; X-ray; 2.10 A; A/B/C/D=2-332. DR PDB; 4AJO; X-ray; 1.96 A; A/B/C/D=2-332. DR PDB; 4AL4; X-ray; 1.78 A; A/B/C/D=2-332. DR PDB; 5ES3; X-ray; 2.29 A; A/B/C/D/E/F/G/H=2-332. DR PDBsum; 4AJ1; -. DR PDBsum; 4AJ2; -. DR PDBsum; 4AJ4; -. DR PDBsum; 4AJE; -. DR PDBsum; 4AJH; -. DR PDBsum; 4AJI; -. DR PDBsum; 4AJJ; -. DR PDBsum; 4AJK; -. DR PDBsum; 4AJL; -. DR PDBsum; 4AJN; -. DR PDBsum; 4AJO; -. DR PDBsum; 4AL4; -. DR PDBsum; 5ES3; -. DR AlphaFoldDB; P04642; -. DR SMR; P04642; -. DR BioGRID; 246686; 8. DR IntAct; P04642; 8. DR MINT; P04642; -. DR STRING; 10116.ENSRNOP00000017468; -. DR BindingDB; P04642; -. DR ChEMBL; CHEMBL2176824; -. DR GlyGen; P04642; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P04642; -. DR PhosphoSitePlus; P04642; -. DR SwissPalm; P04642; -. DR jPOST; P04642; -. DR PaxDb; 10116-ENSRNOP00000017468; -. DR Ensembl; ENSRNOT00000017468.3; ENSRNOP00000017468.1; ENSRNOG00000013009.3. DR Ensembl; ENSRNOT00055011345; ENSRNOP00055008913; ENSRNOG00055006882. DR Ensembl; ENSRNOT00060019425; ENSRNOP00060015242; ENSRNOG00060011451. DR Ensembl; ENSRNOT00065014146; ENSRNOP00065010581; ENSRNOG00065008859. DR GeneID; 24533; -. DR KEGG; rno:24533; -. DR AGR; RGD:2996; -. DR CTD; 3939; -. DR RGD; 2996; Ldha. DR eggNOG; KOG1495; Eukaryota. DR GeneTree; ENSGT00940000153201; -. DR HOGENOM; CLU_045401_0_2_1; -. DR InParanoid; P04642; -. DR OrthoDB; 5344346at2759; -. DR PhylomeDB; P04642; -. DR TreeFam; TF314963; -. DR BioCyc; MetaCyc:MONOMER-11604; -. DR Reactome; R-RNO-70268; Pyruvate metabolism. DR UniPathway; UPA00554; UER00611. DR PRO; PR:P04642; -. DR Proteomes; UP000002494; Chromosome 1. DR Bgee; ENSRNOG00000013009; Expressed in skeletal muscle tissue and 20 other cell types or tissues. DR ExpressionAtlas; P04642; baseline and differential. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:1990204; C:oxidoreductase complex; ISO:RGD. DR GO; GO:0035686; C:sperm fibrous sheath; ISO:RGD. DR GO; GO:0042802; F:identical protein binding; IDA:RGD. DR GO; GO:0019900; F:kinase binding; IPI:RGD. DR GO; GO:0004459; F:L-lactate dehydrogenase activity; IDA:RGD. DR GO; GO:0004457; F:lactate dehydrogenase activity; IDA:RGD. DR GO; GO:0051287; F:NAD binding; IDA:RGD. DR GO; GO:0031668; P:cellular response to extracellular stimulus; ISO:RGD. DR GO; GO:0019661; P:glucose catabolic process to lactate via pyruvate; ISO:RGD. DR GO; GO:0006089; P:lactate metabolic process; IDA:RGD. DR GO; GO:0001889; P:liver development; IDA:RGD. DR GO; GO:0019674; P:NAD metabolic process; IDA:RGD. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:RGD. DR GO; GO:0042867; P:pyruvate catabolic process; ISO:RGD. DR GO; GO:0006090; P:pyruvate metabolic process; ISO:RGD. DR GO; GO:0051591; P:response to cAMP; IEP:RGD. DR GO; GO:0043627; P:response to estrogen; IEP:RGD. DR GO; GO:0009749; P:response to glucose; IEP:RGD. DR GO; GO:0042542; P:response to hydrogen peroxide; IEP:RGD. DR GO; GO:0001666; P:response to hypoxia; IEP:RGD. DR GO; GO:0007584; P:response to nutrient; IEP:RGD. DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0007519; P:skeletal muscle tissue development; IDA:RGD. DR CDD; cd05293; LDH_1; 1. DR Gene3D; 3.90.110.10; Lactate dehydrogenase/glycoside hydrolase, family 4, C-terminal; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR HAMAP; MF_00488; Lactate_dehydrog; 1. DR InterPro; IPR001557; L-lactate/malate_DH. DR InterPro; IPR011304; L-lactate_DH. DR InterPro; IPR018177; L-lactate_DH_AS. DR InterPro; IPR022383; Lactate/malate_DH_C. DR InterPro; IPR001236; Lactate/malate_DH_N. DR InterPro; IPR015955; Lactate_DH/Glyco_Ohase_4_C. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR NCBIfam; TIGR01771; L-LDH-NAD; 1. DR PANTHER; PTHR43128; L-2-HYDROXYCARBOXYLATE DEHYDROGENASE (NAD(P)(+)); 1. DR PANTHER; PTHR43128:SF10; L-LACTATE DEHYDROGENASE A CHAIN; 1. DR Pfam; PF02866; Ldh_1_C; 1. DR Pfam; PF00056; Ldh_1_N; 1. DR PIRSF; PIRSF000102; Lac_mal_DH; 1. DR PRINTS; PR00086; LLDHDRGNASE. DR SUPFAM; SSF56327; LDH C-terminal domain-like; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR PROSITE; PS00064; L_LDH; 1. DR Genevisible; P04642; RN. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; KW Isopeptide bond; NAD; Oxidoreductase; Phosphoprotein; Reference proteome; KW Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.3" FT CHAIN 2..332 FT /note="L-lactate dehydrogenase A chain" FT /id="PRO_0000168419" FT ACT_SITE 193 FT /note="Proton acceptor" FT /evidence="ECO:0000250" FT BINDING 29..57 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250" FT BINDING 99 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250" FT BINDING 106 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 138 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250" FT BINDING 138 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 169 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 248 FT /ligand="substrate" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.3" FT MOD_RES 5 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P00338" FT MOD_RES 5 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P06151" FT MOD_RES 14 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P00338" FT MOD_RES 57 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P00338" FT MOD_RES 81 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P00338" FT MOD_RES 118 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P00338" FT MOD_RES 118 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P06151" FT MOD_RES 126 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P00338" FT MOD_RES 213 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 224 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P06151" FT MOD_RES 232 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P06151" FT MOD_RES 239 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 243 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P06151" FT MOD_RES 309 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 318 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P00338" FT MOD_RES 318 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P06151" FT MOD_RES 322 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:22673903" FT CROSSLNK 57 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:P00338" FT CONFLICT 184..191 FT /note="SCHGWVLG -> ADLGEVV (in Ref. 4; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 324 FT /note="W -> G (in Ref. 5; AAA41508)" FT /evidence="ECO:0000305" FT CONFLICT 326 FT /note="I -> T (in Ref. 5; AAA41508)" FT /evidence="ECO:0000305" FT HELIX 4..8 FT /evidence="ECO:0007829|PDB:4AJ2" FT STRAND 9..11 FT /evidence="ECO:0007829|PDB:4AJ2" FT STRAND 20..26 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 30..41 FT /evidence="ECO:0007829|PDB:4AJ2" FT STRAND 46..51 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 55..67 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 68..71 FT /evidence="ECO:0007829|PDB:4AJ2" FT STRAND 76..79 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 83..86 FT /evidence="ECO:0007829|PDB:4AJ2" FT STRAND 89..94 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 106..109 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 110..127 FT /evidence="ECO:0007829|PDB:4AJ2" FT STRAND 132..135 FT /evidence="ECO:0007829|PDB:4AJ2" FT STRAND 137..139 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 140..151 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 155..157 FT /evidence="ECO:0007829|PDB:4AJ2" FT STRAND 158..160 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 164..178 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 182..184 FT /evidence="ECO:0007829|PDB:4AJ2" FT STRAND 189..191 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 201..203 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 211..214 FT /evidence="ECO:0007829|PDB:4AJ2" FT TURN 216..219 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 228..245 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 250..264 FT /evidence="ECO:0007829|PDB:4AJ2" FT STRAND 269..276 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 280..282 FT /evidence="ECO:0007829|PDB:4AJ2" FT STRAND 288..296 FT /evidence="ECO:0007829|PDB:4AJ2" FT STRAND 299..304 FT /evidence="ECO:0007829|PDB:4AJ2" FT HELIX 310..327 FT /evidence="ECO:0007829|PDB:4AJ2" SQ SEQUENCE 332 AA; 36451 MW; 5E432659D032A4D3 CRC64; MAALKDQLIV NLLKEEQVPQ NKITVVGVGA VGMACAISIL MKDLADELAL VDVIEDKLKG EMMDLQHGSL FLKTPKIVSS KDYSVTANSK LVIITAGARQ QEGESRLNLV QRNVNIFKFI IPNVVKYSPQ CKLLIVSNPV DILTYVAWKI SGFPKNRVIG SGCNLDSARF RYLMGERLGV HPLSCHGWVL GEHGDSSVPV WSGVNVAGVS LKSLNPQLGT DADKEQWKDV HKQVVDSAYE VIKLKGYTSW AIGLSVADLA ESIMKNLRRV HPISTMIKGL YGIKEDVFLS VPCILGQNGI SDVVKVTLTP DEEARLKKSA DTLWGIQKEL QF //