LDHA_MOUSE
ID LDHA_MOUSE Reviewed; 332 AA.
AC P06151;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 203.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C57BL/10; TISSUE=Liver;
RX PubMed=3036647; DOI=10.1093/genetics/116.1.99;
RA Fukasawa K.M., Li S.S.-L.;
RT "Complete nucleotide sequence of the mouse lactate dehydrogenase-A
RT functional gene: comparison of the exon-intron organization of
RT dehydrogenase genes.";
RL Genetics 116:99-105(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3996406; DOI=10.1111/j.1432-1033.1985.tb08914.x;
RA Li S.S.-L., Tiano H.F., Fukasawa K.M., Yagi K., Shimizu M., Sharief F.S.,
RA Nakashima Y., Pan Y.E.;
RT "Protein structure and gene organization of mouse lactate dehydrogenase-A
RT isozyme.";
RL Eur. J. Biochem. 149:215-225(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=DBA/2J;
RA Hiraoka Y., Li S.S.-L.;
RT "Lactate dehydrogenase-A mRNAs in mouse testis and somatic tissues
RT containing different 5' noncoding sequences.";
RL J. Genet. Mol. Biol. 1:1-6(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-42.
RX PubMed=3017306; DOI=10.1042/bj2350435;
RA Fukasawa K.M., Li S.S.-L.;
RT "Nucleotide sequence of the putative regulatory region of mouse lactate
RT dehydrogenase-A gene.";
RL Biochem. J. 235:435-439(1986).
RN [5]
RP PROTEIN SEQUENCE OF 6-14; 23-73; 82-99; 107-126; 133-149; 158-169; 172-177;
RP 213-228; 233-243; 246-265; 269-315 AND 319-328, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=C57BL/6J, and OF1; TISSUE=Brain, and Hippocampus;
RA Lubec G., Kang S.U., Klug S., Yang J.W., Zigmond M., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 202-332.
RX PubMed=2993055; DOI=10.1016/0020-711x(85)90298-8;
RA Akai K., Yagi K., Tiano H.F., Pan Y.-C.E., Shimizu M., Fong K.,
RA Jungmann R.A., Li S.S.-L.;
RT "Isolation and characterization of a cDNA and a pseudogene for mouse
RT lactate dehydrogenase-A isozyme.";
RL Int. J. Biochem. 17:645-648(1985).
RN [7]
RP ISGYLATION.
RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132;
RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J.,
RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.;
RT "Proteomic identification of proteins conjugated to ISG15 in mouse and
RT human cells.";
RL Biochem. Biophys. Res. Commun. 336:496-506(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-239, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2; LYS-5; LYS-81; LYS-118;
RP LYS-126; LYS-224; LYS-232; LYS-243 AND LYS-318, SUCCINYLATION [LARGE SCALE
RP ANALYSIS] AT LYS-5; LYS-118 AND LYS-318, CLEAVAGE OF INITIATOR METHIONINE
RP [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast, and Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
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 -!- INTERACTION:
CC P06151; Q60668: Hnrnpd; NbExp=2; IntAct=EBI-444940, EBI-299932;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- PTM: ISGylated. {ECO:0000269|PubMed:16139798}.
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; Y00309; CAA68410.1; -; Genomic_DNA.
DR EMBL; X02520; CAA26360.1; -; Genomic_DNA.
DR EMBL; X02521; CAA26360.1; JOINED; Genomic_DNA.
DR EMBL; X02522; CAA26360.1; JOINED; Genomic_DNA.
DR EMBL; X02523; CAA26360.1; JOINED; Genomic_DNA.
DR EMBL; X02524; CAA26360.1; JOINED; Genomic_DNA.
DR EMBL; X02525; CAA26360.1; JOINED; Genomic_DNA.
DR EMBL; X02526; CAA26360.1; JOINED; Genomic_DNA.
DR EMBL; U13687; AAA21466.1; -; mRNA.
DR EMBL; X03753; CAA27387.1; -; Genomic_DNA.
DR EMBL; M17516; AAA39424.1; -; mRNA.
DR CCDS; CCDS21289.1; -.
DR PIR; A25205; DEMSLM.
DR PIR; I48240; I48240.
DR RefSeq; NP_034829.1; NM_010699.2.
DR AlphaFoldDB; P06151; -.
DR SMR; P06151; -.
DR BioGRID; 201127; 22.
DR IntAct; P06151; 20.
DR MINT; P06151; -.
DR STRING; 10090.ENSMUSP00000103267; -.
DR BindingDB; P06151; -.
DR MoonProt; P06151; -.
DR iPTMnet; P06151; -.
DR PhosphoSitePlus; P06151; -.
DR SwissPalm; P06151; -.
DR REPRODUCTION-2DPAGE; P06151; -.
DR SWISS-2DPAGE; P06151; -.
DR UCD-2DPAGE; P06151; -.
DR EPD; P06151; -.
DR jPOST; P06151; -.
DR PaxDb; P06151; -.
DR PeptideAtlas; P06151; -.
DR PRIDE; P06151; -.
DR ProteomicsDB; 265055; -.
DR TopDownProteomics; P06151; -.
DR Antibodypedia; 4200; 911 antibodies from 40 providers.
DR DNASU; 16828; -.
DR Ensembl; ENSMUST00000005051; ENSMUSP00000103267; ENSMUSG00000063229.
DR Ensembl; ENSMUST00000048209; ENSMUSP00000036386; ENSMUSG00000063229.
DR GeneID; 16828; -.
DR KEGG; mmu:16828; -.
DR UCSC; uc009gzm.2; mouse.
DR CTD; 3939; -.
DR MGI; MGI:96759; Ldha.
DR VEuPathDB; HostDB:ENSMUSG00000063229; -.
DR eggNOG; KOG1495; Eukaryota.
DR GeneTree; ENSGT00940000153201; -.
DR HOGENOM; CLU_045401_0_2_1; -.
DR InParanoid; P06151; -.
DR OMA; ASCAEYI; -.
DR PhylomeDB; P06151; -.
DR Reactome; R-MMU-70268; Pyruvate metabolism.
DR UniPathway; UPA00554; UER00611.
DR BioGRID-ORCS; 16828; 23 hits in 70 CRISPR screens.
DR ChiTaRS; Ldha; mouse.
DR PRO; PR:P06151; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P06151; protein.
DR Bgee; ENSMUSG00000063229; Expressed in otic placode and 269 other tissues.
DR ExpressionAtlas; P06151; baseline and differential.
DR Genevisible; P06151; MM.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:1990204; C:oxidoreductase complex; ISO:MGI.
DR GO; GO:0035686; C:sperm fibrous sheath; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0004459; F:L-lactate dehydrogenase activity; IDA:MGI.
DR GO; GO:0004457; F:lactate dehydrogenase activity; IMP:MGI.
DR GO; GO:0051287; F:NAD binding; ISO:MGI.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IDA:MGI.
DR GO; GO:0019661; P:glucose catabolic process to lactate via pyruvate; IMP:MGI.
DR GO; GO:0019244; P:lactate biosynthetic process from pyruvate; IC:MGI.
DR GO; GO:0006089; P:lactate metabolic process; ISO:MGI.
DR GO; GO:0019674; P:NAD metabolic process; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0006090; P:pyruvate metabolic process; ISO:MGI.
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 Acetylation; Cytoplasm; Direct protein sequencing; Isopeptide bond; NAD;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CHAIN 2..332
FT /note="L-lactate dehydrogenase A chain"
FT /id="PRO_0000168414"
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:0007744|PubMed:23806337"
FT MOD_RES 5
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 5
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
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:0007744|PubMed:23806337"
FT MOD_RES 118
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 118
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 126
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 224
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 232
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 239
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 243
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 309
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04642"
FT MOD_RES 318
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 318
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 322
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04642"
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 11
FT /note="N -> I (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 332 AA; 36499 MW; 5AEB41E1E0B95100 CRC64;
MATLKDQLIV NLLKEEQAPQ NKITVVGVGA VGMACAISIL MKDLADELAL VDVMEDKLKG
EMMDLQHGSL FLKTPKIVSS KDYCVTANSK LVIITAGARQ QEGESRLNLV QRNVNIFKFI
IPNIVKYSPH CKLLIVSNPV DILTYVAWKI SGFPKNRVIG SGCNLDSARF RYLMGERLGV
HALSCHGWVL GEHGDSSVPV WSGVNVAGVS LKSLNPELGT DADKEQWKEV HKQVVDSAYE
VIKLKGYTSW AIGLSVADLA ESIMKNLRRV HPISTMIKGL YGINEDVFLS VPCILGQNGI
SDVVKVTLTP EEEARLKKSA DTLWGIQKEL QF
