LDHA_RAT
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 03-AUG-2022, entry version 187.
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}.
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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 iPTMnet; P04642; -.
DR PhosphoSitePlus; P04642; -.
DR SwissPalm; P04642; -.
DR jPOST; P04642; -.
DR PaxDb; P04642; -.
DR PRIDE; P04642; -.
DR Ensembl; ENSRNOT00000017468; ENSRNOP00000017468; ENSRNOG00000013009.
DR GeneID; 24533; -.
DR KEGG; rno:24533; -.
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 OMA; ASCAEYI; -.
DR OrthoDB; 1204514at2759; -.
DR PhylomeDB; P04642; -.
DR TreeFam; TF314963; -.
DR BioCyc; MetaCyc:MON-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 tissues.
DR ExpressionAtlas; P04642; baseline and differential.
DR Genevisible; P04642; RN.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
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:0019674; P:NAD metabolic process; IDA:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:RGD.
DR GO; GO:0048569; P:post-embryonic animal organ development; IEP: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 Gene3D; 3.90.110.10; -; 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 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; SSF51735; SSF51735; 1.
DR SUPFAM; SSF56327; SSF56327; 1.
DR TIGRFAMs; TIGR01771; L-LDH-NAD; 1.
DR PROSITE; PS00064; L_LDH; 1.
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
