Full text data of LDHA
LDHA
[Confidence: high (present in two of the MS resources)]
L-lactate dehydrogenase A chain; LDH-A; 1.1.1.27 (Cell proliferation-inducing gene 19 protein; LDH muscle subunit; LDH-M; Renal carcinoma antigen NY-REN-59)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
L-lactate dehydrogenase A chain; LDH-A; 1.1.1.27 (Cell proliferation-inducing gene 19 protein; LDH muscle subunit; LDH-M; Renal carcinoma antigen NY-REN-59)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00217966
IPI00217966 L-lactate dehydrogenase A chain Anaerobic glycolysis; final step, (S)-lactate + NAD+ = pyruvate + NADH, bone marrow soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00217966 L-lactate dehydrogenase A chain Anaerobic glycolysis; final step, (S)-lactate + NAD+ = pyruvate + NADH, bone marrow soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P00338
ID LDHA_HUMAN Reviewed; 332 AA.
AC P00338; B4DKQ2; B7Z5E3; D3DQY3; F8W819; Q53G53; Q6IBM7; Q6ZNV1;
read moreAC Q9UDE8; Q9UDE9;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 173.
DE RecName: Full=L-lactate dehydrogenase A chain;
DE Short=LDH-A;
DE EC=1.1.1.27;
DE AltName: Full=Cell proliferation-inducing gene 19 protein;
DE AltName: Full=LDH muscle subunit;
DE Short=LDH-M;
DE AltName: Full=Renal carcinoma antigen NY-REN-59;
GN Name=LDHA; ORFNames=PIG19;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3838278; DOI=10.1111/j.1432-1033.1985.tb08711.x;
RA Tsujibo H., Tiano H.F., Li S.S.-L.;
RT "Nucleotide sequences of the cDNA and an intronless pseudogene for
RT human lactate dehydrogenase-A isozyme.";
RL Eur. J. Biochem. 147:9-15(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=3000353;
RA Chung F.Z., Tsujibo H., Bhattacharyya U., Sharief F.S., Li S.S.-L.;
RT "Genomic organization of human lactate dehydrogenase-A gene.";
RL Biochem. J. 231:537-541(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kim J.W.;
RT "Identification of a human proliferation-inducing gene.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
RC TISSUE=Umbilical cord;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP GLU-222.
RC TISSUE=Gastric carcinoma;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 2-14; 43-57; 60-73; 77-112; 133-149; 158-169;
RP 233-243; 306-315 AND 319-328, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (MAR-2005) to UniProtKB.
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 112-121 AND 160-175.
RX PubMed=1953713; DOI=10.1016/S0006-291X(05)81177-5;
RA Maekawa M., Sudo K., Li S.S., Kanno T.;
RT "Analysis of genetic mutations in human lactate dehydrogenase-A(M)
RT deficiency using DNA conformation polymorphism in combination with
RT polyacrylamide gradient gel and silver staining.";
RL Biochem. Biophys. Res. Commun. 180:1083-1090(1991).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 250-254.
RX PubMed=1959923; DOI=10.1007/BF00204925;
RA Maekawa M., Sudo K., Li S.S., Kanno T.;
RT "Genotypic analysis of families with lactate dehydrogenase A (M)
RT deficiency by selective DNA amplification.";
RL Hum. Genet. 88:34-38(1991).
RN [13]
RP INVOLVEMENT IN GSD11.
RX PubMed=2334430; DOI=10.1016/0006-291X(90)92374-9;
RA Maekawa M., Sudo K., Kanno T., Li S.S.;
RT "Molecular characterization of genetic mutation in human lactate
RT dehydrogenase-A (M) deficiency.";
RL Biochem. Biophys. Res. Commun. 168:677-682(1990).
RN [14]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [15]
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 [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-10, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2; LYS-5; LYS-14; LYS-57;
RP LYS-81; LYS-118; LYS-126 AND LYS-318, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH NADH AND
RP SUBSTRATE ANALOG, AND HOMOTETRAMERIZATION.
RX PubMed=11276087;
RX DOI=10.1002/1097-0134(20010501)43:2<175::AID-PROT1029>3.0.CO;2-#;
RA Read J.A., Winter V.J., Eszes C.M., Sessions R.B., Brady R.L.;
RT "Structural basis for altered activity of M- and H-isozyme forms of
RT human lactate dehydrogenase.";
RL Proteins 43:175-185(2001).
RN [22]
RP VARIANT CYS-315.
RX PubMed=1445373;
RA Sudo K., Maekawa M., Shioya M., Ikeda K., Takahashi N., Isogai Y.,
RA Li S.S.-L., Kanno T., Machida K., Toriumi J.;
RT "Molecular analysis of genetic mutation in electrophoretic variant of
RT human lactate dehydrogenase-A(M) subunit.";
RL Biochem. Int. 27:1051-1057(1992).
RN [23]
RP VARIANT GLU-222.
RX PubMed=7908613;
RA Maekawa M., Sudo K., Kobayashi A., Sugiyama E., Li S.S.-L., Kanno T.;
RT "Fast-type electrophoretic variant of lactate dehydrogenase M(A) and
RT comparison with other missense mutations in lactate dehydrogenase M(A)
RT and H(B) genes.";
RL Clin. Chem. 40:665-668(1994).
CC -!- CATALYTIC ACTIVITY: (S)-lactate + NAD(+) = pyruvate + NADH.
CC -!- PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-
CC lactate from pyruvate: step 1/1.
CC -!- SUBUNIT: Homotetramer.
CC -!- INTERACTION:
CC P11142:HSPA8; NbExp=4; IntAct=EBI-372327, EBI-351896;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=P00338-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P00338-2; Sequence=VSP_014261, VSP_042787;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=P00338-3; Sequence=VSP_042206;
CC Name=4;
CC IsoId=P00338-4; Sequence=VSP_042786;
CC Name=5;
CC IsoId=P00338-5; Sequence=VSP_042788, VSP_042789;
CC -!- PTM: ISGylated.
CC -!- DISEASE: Glycogen storage disease 11 (GSD11) [MIM:612933]: A
CC metabolic disorder that results in exertional myoglobinuria, pain,
CC cramps and easy fatigue. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. LDH family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/LDHA";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Lactate dehydrogenase entry;
CC URL="http://en.wikipedia.org/wiki/Lactate_dehydrogenase";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Another dark horse -
CC Issue 109 of September 2009;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt109.shtml";
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DR EMBL; X02152; CAA26088.1; -; mRNA.
DR EMBL; X03077; CAA26879.1; -; Genomic_DNA.
DR EMBL; X03078; CAA26879.1; JOINED; Genomic_DNA.
DR EMBL; X03079; CAA26879.1; JOINED; Genomic_DNA.
DR EMBL; X03080; CAA26879.1; JOINED; Genomic_DNA.
DR EMBL; X03081; CAA26879.1; JOINED; Genomic_DNA.
DR EMBL; X03082; CAA26879.1; JOINED; Genomic_DNA.
DR EMBL; X03083; CAA26879.1; JOINED; Genomic_DNA.
DR EMBL; AY423727; AAS00490.1; -; mRNA.
DR EMBL; AK130587; BAC85389.1; -; mRNA.
DR EMBL; AK296667; BAG59264.1; -; mRNA.
DR EMBL; AK298834; BAH12879.1; -; mRNA.
DR EMBL; CR456775; CAG33056.1; -; mRNA.
DR EMBL; CR541714; CAG46515.1; -; mRNA.
DR EMBL; AK223078; BAD96798.1; -; mRNA.
DR EMBL; AC084117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68395.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68396.1; -; Genomic_DNA.
DR EMBL; BC067223; AAH67223.1; -; mRNA.
DR EMBL; S66853; AAB20418.1; -; Genomic_DNA.
DR PIR; A00347; DEHULM.
DR RefSeq; NP_001128711.1; NM_001135239.1.
DR RefSeq; NP_001158886.1; NM_001165414.1.
DR RefSeq; NP_001158887.1; NM_001165415.1.
DR RefSeq; NP_001158888.1; NM_001165416.1.
DR RefSeq; NP_005557.1; NM_005566.3.
DR UniGene; Hs.2795; -.
DR PDB; 1I10; X-ray; 2.30 A; A/B/C/D/E/F/G/H=2-332.
DR PDB; 4AJP; X-ray; 2.38 A; A/B/C/D=2-332.
DR PDB; 4JNK; X-ray; 1.90 A; A/B/C/D=2-332.
DR PDB; 4M49; X-ray; 2.05 A; A/B/C/D=2-332.
DR PDBsum; 1I10; -.
DR PDBsum; 4AJP; -.
DR PDBsum; 4JNK; -.
DR PDBsum; 4M49; -.
DR ProteinModelPortal; P00338; -.
DR SMR; P00338; 2-332.
DR IntAct; P00338; 16.
DR MINT; MINT-4998672; -.
DR STRING; 9606.ENSP00000395337; -.
DR BindingDB; P00338; -.
DR ChEMBL; CHEMBL4835; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; P00338; -.
DR DMDM; 126047; -.
DR DOSAC-COBS-2DPAGE; P00338; -.
DR OGP; P00338; -.
DR REPRODUCTION-2DPAGE; IPI00217966; -.
DR PaxDb; P00338; -.
DR PeptideAtlas; P00338; -.
DR PRIDE; P00338; -.
DR DNASU; 3939; -.
DR Ensembl; ENST00000227157; ENSP00000227157; ENSG00000134333.
DR Ensembl; ENST00000379412; ENSP00000368722; ENSG00000134333.
DR Ensembl; ENST00000396222; ENSP00000379524; ENSG00000134333.
DR Ensembl; ENST00000422447; ENSP00000395337; ENSG00000134333.
DR Ensembl; ENST00000430553; ENSP00000406172; ENSG00000134333.
DR Ensembl; ENST00000540430; ENSP00000445175; ENSG00000134333.
DR Ensembl; ENST00000542179; ENSP00000445331; ENSG00000134333.
DR GeneID; 3939; -.
DR KEGG; hsa:3939; -.
DR UCSC; uc001mok.3; human.
DR CTD; 3939; -.
DR GeneCards; GC11P018415; -.
DR HGNC; HGNC:6535; LDHA.
DR HPA; CAB015336; -.
DR MIM; 150000; gene.
DR MIM; 612933; phenotype.
DR neXtProt; NX_P00338; -.
DR Orphanet; 284426; Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency.
DR PharmGKB; PA30319; -.
DR eggNOG; COG0039; -.
DR HOGENOM; HOG000213793; -.
DR HOVERGEN; HBG000462; -.
DR InParanoid; P00338; -.
DR KO; K00016; -.
DR OMA; GANSYEA; -.
DR OrthoDB; EOG7X0VH3; -.
DR PhylomeDB; P00338; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P00338; -.
DR UniPathway; UPA00554; UER00611.
DR ChiTaRS; LDHA; human.
DR EvolutionaryTrace; P00338; -.
DR GeneWiki; LDHA; -.
DR GenomeRNAi; 3939; -.
DR NextBio; 15469; -.
DR PRO; PR:P00338; -.
DR ArrayExpress; P00338; -.
DR Bgee; P00338; -.
DR CleanEx; HS_LDHA; -.
DR Genevestigator; P00338; -.
DR GO; GO:0005929; C:cilium; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0004459; F:L-lactate dehydrogenase activity; NAS:UniProtKB.
DR GO; GO:0044262; P:cellular carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IEA:Ensembl.
DR GO; GO:0006096; P:glycolysis; NAS:UniProtKB.
DR GO; GO:0006090; P:pyruvate metabolic process; TAS:Reactome.
DR Gene3D; 3.40.50.720; -; 1.
DR Gene3D; 3.90.110.10; -; 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; IPR016040; NAD(P)-bd_dom.
DR PANTHER; PTHR11540; PTHR11540; 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; 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; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Disease mutation;
KW Glycogen storage disease; Glycolysis; NAD; Oxidoreductase;
KW Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 332 L-lactate dehydrogenase A chain.
FT /FTId=PRO_0000168411.
FT NP_BIND 29 57 NAD.
FT ACT_SITE 193 193 Proton acceptor.
FT BINDING 99 99 NAD.
FT BINDING 106 106 Substrate.
FT BINDING 138 138 NAD or substrate.
FT BINDING 169 169 Substrate.
FT BINDING 248 248 Substrate.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 5 5 N6-acetyllysine.
FT MOD_RES 10 10 Phosphotyrosine.
FT MOD_RES 14 14 N6-acetyllysine.
FT MOD_RES 57 57 N6-acetyllysine.
FT MOD_RES 81 81 N6-acetyllysine.
FT MOD_RES 118 118 N6-acetyllysine.
FT MOD_RES 126 126 N6-acetyllysine.
FT MOD_RES 239 239 Phosphotyrosine (By similarity).
FT MOD_RES 318 318 N6-acetyllysine.
FT VAR_SEQ 1 1 M -> MGEPSGGYTYTQTSIFLFHAKIPFGSKSNM (in
FT isoform 3).
FT /FTId=VSP_042206.
FT VAR_SEQ 82 139 Missing (in isoform 4).
FT /FTId=VSP_042786.
FT VAR_SEQ 230 274 VHKQVVESAYEVIKLKGYTSWAIGLSVADLAESIMKNLRRV
FT HPVS -> CRYTLGDPKGAAILKSSDVISFHCLGYNRILGG
FT GCACCPFYLICD (in isoform 2).
FT /FTId=VSP_014261.
FT VAR_SEQ 237 241 SAYEV -> RVFTE (in isoform 5).
FT /FTId=VSP_042788.
FT VAR_SEQ 242 332 Missing (in isoform 5).
FT /FTId=VSP_042789.
FT VAR_SEQ 275 332 Missing (in isoform 2).
FT /FTId=VSP_042787.
FT VARIANT 161 161 S -> R (in dbSNP:rs5030621).
FT /FTId=VAR_059374.
FT VARIANT 222 222 K -> E.
FT /FTId=VAR_004180.
FT VARIANT 315 315 R -> C.
FT /FTId=VAR_004181.
FT HELIX 4 8
FT STRAND 9 12
FT STRAND 20 26
FT HELIX 30 41
FT STRAND 46 51
FT HELIX 55 67
FT HELIX 68 71
FT STRAND 77 79
FT HELIX 83 86
FT STRAND 90 94
FT HELIX 107 127
FT STRAND 132 135
FT STRAND 137 139
FT HELIX 140 151
FT HELIX 155 157
FT STRAND 158 160
FT HELIX 164 178
FT HELIX 182 184
FT STRAND 189 193
FT HELIX 194 196
FT HELIX 201 203
FT HELIX 211 214
FT TURN 216 219
FT STRAND 220 222
FT HELIX 228 245
FT HELIX 250 264
FT STRAND 269 276
FT STRAND 288 296
FT STRAND 299 304
FT HELIX 310 327
SQ SEQUENCE 332 AA; 36689 MW; 401E8604CEB7F908 CRC64;
MATLKDQLIY NLLKEEQTPQ NKITVVGVGA VGMACAISIL MKDLADELAL VDVIEDKLKG
EMMDLQHGSL FLRTPKIVSG KDYNVTANSK LVIITAGARQ QEGESRLNLV QRNVNIFKFI
IPNVVKYSPN CKLLIVSNPV DILTYVAWKI SGFPKNRVIG SGCNLDSARF RYLMGERLGV
HPLSCHGWVL GEHGDSSVPV WSGMNVAGVS LKTLHPDLGT DKDKEQWKEV HKQVVESAYE
VIKLKGYTSW AIGLSVADLA ESIMKNLRRV HPVSTMIKGL YGIKDDVFLS VPCILGQNGI
SDLVKVTLTS EEEARLKKSA DTLWGIQKEL QF
//
ID LDHA_HUMAN Reviewed; 332 AA.
AC P00338; B4DKQ2; B7Z5E3; D3DQY3; F8W819; Q53G53; Q6IBM7; Q6ZNV1;
read moreAC Q9UDE8; Q9UDE9;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 173.
DE RecName: Full=L-lactate dehydrogenase A chain;
DE Short=LDH-A;
DE EC=1.1.1.27;
DE AltName: Full=Cell proliferation-inducing gene 19 protein;
DE AltName: Full=LDH muscle subunit;
DE Short=LDH-M;
DE AltName: Full=Renal carcinoma antigen NY-REN-59;
GN Name=LDHA; ORFNames=PIG19;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3838278; DOI=10.1111/j.1432-1033.1985.tb08711.x;
RA Tsujibo H., Tiano H.F., Li S.S.-L.;
RT "Nucleotide sequences of the cDNA and an intronless pseudogene for
RT human lactate dehydrogenase-A isozyme.";
RL Eur. J. Biochem. 147:9-15(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=3000353;
RA Chung F.Z., Tsujibo H., Bhattacharyya U., Sharief F.S., Li S.S.-L.;
RT "Genomic organization of human lactate dehydrogenase-A gene.";
RL Biochem. J. 231:537-541(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kim J.W.;
RT "Identification of a human proliferation-inducing gene.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
RC TISSUE=Umbilical cord;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP GLU-222.
RC TISSUE=Gastric carcinoma;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 2-14; 43-57; 60-73; 77-112; 133-149; 158-169;
RP 233-243; 306-315 AND 319-328, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (MAR-2005) to UniProtKB.
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 112-121 AND 160-175.
RX PubMed=1953713; DOI=10.1016/S0006-291X(05)81177-5;
RA Maekawa M., Sudo K., Li S.S., Kanno T.;
RT "Analysis of genetic mutations in human lactate dehydrogenase-A(M)
RT deficiency using DNA conformation polymorphism in combination with
RT polyacrylamide gradient gel and silver staining.";
RL Biochem. Biophys. Res. Commun. 180:1083-1090(1991).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 250-254.
RX PubMed=1959923; DOI=10.1007/BF00204925;
RA Maekawa M., Sudo K., Li S.S., Kanno T.;
RT "Genotypic analysis of families with lactate dehydrogenase A (M)
RT deficiency by selective DNA amplification.";
RL Hum. Genet. 88:34-38(1991).
RN [13]
RP INVOLVEMENT IN GSD11.
RX PubMed=2334430; DOI=10.1016/0006-291X(90)92374-9;
RA Maekawa M., Sudo K., Kanno T., Li S.S.;
RT "Molecular characterization of genetic mutation in human lactate
RT dehydrogenase-A (M) deficiency.";
RL Biochem. Biophys. Res. Commun. 168:677-682(1990).
RN [14]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [15]
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 [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-10, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2; LYS-5; LYS-14; LYS-57;
RP LYS-81; LYS-118; LYS-126 AND LYS-318, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH NADH AND
RP SUBSTRATE ANALOG, AND HOMOTETRAMERIZATION.
RX PubMed=11276087;
RX DOI=10.1002/1097-0134(20010501)43:2<175::AID-PROT1029>3.0.CO;2-#;
RA Read J.A., Winter V.J., Eszes C.M., Sessions R.B., Brady R.L.;
RT "Structural basis for altered activity of M- and H-isozyme forms of
RT human lactate dehydrogenase.";
RL Proteins 43:175-185(2001).
RN [22]
RP VARIANT CYS-315.
RX PubMed=1445373;
RA Sudo K., Maekawa M., Shioya M., Ikeda K., Takahashi N., Isogai Y.,
RA Li S.S.-L., Kanno T., Machida K., Toriumi J.;
RT "Molecular analysis of genetic mutation in electrophoretic variant of
RT human lactate dehydrogenase-A(M) subunit.";
RL Biochem. Int. 27:1051-1057(1992).
RN [23]
RP VARIANT GLU-222.
RX PubMed=7908613;
RA Maekawa M., Sudo K., Kobayashi A., Sugiyama E., Li S.S.-L., Kanno T.;
RT "Fast-type electrophoretic variant of lactate dehydrogenase M(A) and
RT comparison with other missense mutations in lactate dehydrogenase M(A)
RT and H(B) genes.";
RL Clin. Chem. 40:665-668(1994).
CC -!- CATALYTIC ACTIVITY: (S)-lactate + NAD(+) = pyruvate + NADH.
CC -!- PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-
CC lactate from pyruvate: step 1/1.
CC -!- SUBUNIT: Homotetramer.
CC -!- INTERACTION:
CC P11142:HSPA8; NbExp=4; IntAct=EBI-372327, EBI-351896;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=P00338-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P00338-2; Sequence=VSP_014261, VSP_042787;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=P00338-3; Sequence=VSP_042206;
CC Name=4;
CC IsoId=P00338-4; Sequence=VSP_042786;
CC Name=5;
CC IsoId=P00338-5; Sequence=VSP_042788, VSP_042789;
CC -!- PTM: ISGylated.
CC -!- DISEASE: Glycogen storage disease 11 (GSD11) [MIM:612933]: A
CC metabolic disorder that results in exertional myoglobinuria, pain,
CC cramps and easy fatigue. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. LDH family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/LDHA";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Lactate dehydrogenase entry;
CC URL="http://en.wikipedia.org/wiki/Lactate_dehydrogenase";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Another dark horse -
CC Issue 109 of September 2009;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt109.shtml";
CC -----------------------------------------------------------------------
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DR EMBL; X02152; CAA26088.1; -; mRNA.
DR EMBL; X03077; CAA26879.1; -; Genomic_DNA.
DR EMBL; X03078; CAA26879.1; JOINED; Genomic_DNA.
DR EMBL; X03079; CAA26879.1; JOINED; Genomic_DNA.
DR EMBL; X03080; CAA26879.1; JOINED; Genomic_DNA.
DR EMBL; X03081; CAA26879.1; JOINED; Genomic_DNA.
DR EMBL; X03082; CAA26879.1; JOINED; Genomic_DNA.
DR EMBL; X03083; CAA26879.1; JOINED; Genomic_DNA.
DR EMBL; AY423727; AAS00490.1; -; mRNA.
DR EMBL; AK130587; BAC85389.1; -; mRNA.
DR EMBL; AK296667; BAG59264.1; -; mRNA.
DR EMBL; AK298834; BAH12879.1; -; mRNA.
DR EMBL; CR456775; CAG33056.1; -; mRNA.
DR EMBL; CR541714; CAG46515.1; -; mRNA.
DR EMBL; AK223078; BAD96798.1; -; mRNA.
DR EMBL; AC084117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68395.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68396.1; -; Genomic_DNA.
DR EMBL; BC067223; AAH67223.1; -; mRNA.
DR EMBL; S66853; AAB20418.1; -; Genomic_DNA.
DR PIR; A00347; DEHULM.
DR RefSeq; NP_001128711.1; NM_001135239.1.
DR RefSeq; NP_001158886.1; NM_001165414.1.
DR RefSeq; NP_001158887.1; NM_001165415.1.
DR RefSeq; NP_001158888.1; NM_001165416.1.
DR RefSeq; NP_005557.1; NM_005566.3.
DR UniGene; Hs.2795; -.
DR PDB; 1I10; X-ray; 2.30 A; A/B/C/D/E/F/G/H=2-332.
DR PDB; 4AJP; X-ray; 2.38 A; A/B/C/D=2-332.
DR PDB; 4JNK; X-ray; 1.90 A; A/B/C/D=2-332.
DR PDB; 4M49; X-ray; 2.05 A; A/B/C/D=2-332.
DR PDBsum; 1I10; -.
DR PDBsum; 4AJP; -.
DR PDBsum; 4JNK; -.
DR PDBsum; 4M49; -.
DR ProteinModelPortal; P00338; -.
DR SMR; P00338; 2-332.
DR IntAct; P00338; 16.
DR MINT; MINT-4998672; -.
DR STRING; 9606.ENSP00000395337; -.
DR BindingDB; P00338; -.
DR ChEMBL; CHEMBL4835; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; P00338; -.
DR DMDM; 126047; -.
DR DOSAC-COBS-2DPAGE; P00338; -.
DR OGP; P00338; -.
DR REPRODUCTION-2DPAGE; IPI00217966; -.
DR PaxDb; P00338; -.
DR PeptideAtlas; P00338; -.
DR PRIDE; P00338; -.
DR DNASU; 3939; -.
DR Ensembl; ENST00000227157; ENSP00000227157; ENSG00000134333.
DR Ensembl; ENST00000379412; ENSP00000368722; ENSG00000134333.
DR Ensembl; ENST00000396222; ENSP00000379524; ENSG00000134333.
DR Ensembl; ENST00000422447; ENSP00000395337; ENSG00000134333.
DR Ensembl; ENST00000430553; ENSP00000406172; ENSG00000134333.
DR Ensembl; ENST00000540430; ENSP00000445175; ENSG00000134333.
DR Ensembl; ENST00000542179; ENSP00000445331; ENSG00000134333.
DR GeneID; 3939; -.
DR KEGG; hsa:3939; -.
DR UCSC; uc001mok.3; human.
DR CTD; 3939; -.
DR GeneCards; GC11P018415; -.
DR HGNC; HGNC:6535; LDHA.
DR HPA; CAB015336; -.
DR MIM; 150000; gene.
DR MIM; 612933; phenotype.
DR neXtProt; NX_P00338; -.
DR Orphanet; 284426; Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency.
DR PharmGKB; PA30319; -.
DR eggNOG; COG0039; -.
DR HOGENOM; HOG000213793; -.
DR HOVERGEN; HBG000462; -.
DR InParanoid; P00338; -.
DR KO; K00016; -.
DR OMA; GANSYEA; -.
DR OrthoDB; EOG7X0VH3; -.
DR PhylomeDB; P00338; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P00338; -.
DR UniPathway; UPA00554; UER00611.
DR ChiTaRS; LDHA; human.
DR EvolutionaryTrace; P00338; -.
DR GeneWiki; LDHA; -.
DR GenomeRNAi; 3939; -.
DR NextBio; 15469; -.
DR PRO; PR:P00338; -.
DR ArrayExpress; P00338; -.
DR Bgee; P00338; -.
DR CleanEx; HS_LDHA; -.
DR Genevestigator; P00338; -.
DR GO; GO:0005929; C:cilium; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0004459; F:L-lactate dehydrogenase activity; NAS:UniProtKB.
DR GO; GO:0044262; P:cellular carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IEA:Ensembl.
DR GO; GO:0006096; P:glycolysis; NAS:UniProtKB.
DR GO; GO:0006090; P:pyruvate metabolic process; TAS:Reactome.
DR Gene3D; 3.40.50.720; -; 1.
DR Gene3D; 3.90.110.10; -; 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; IPR016040; NAD(P)-bd_dom.
DR PANTHER; PTHR11540; PTHR11540; 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; 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; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Disease mutation;
KW Glycogen storage disease; Glycolysis; NAD; Oxidoreductase;
KW Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 332 L-lactate dehydrogenase A chain.
FT /FTId=PRO_0000168411.
FT NP_BIND 29 57 NAD.
FT ACT_SITE 193 193 Proton acceptor.
FT BINDING 99 99 NAD.
FT BINDING 106 106 Substrate.
FT BINDING 138 138 NAD or substrate.
FT BINDING 169 169 Substrate.
FT BINDING 248 248 Substrate.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 5 5 N6-acetyllysine.
FT MOD_RES 10 10 Phosphotyrosine.
FT MOD_RES 14 14 N6-acetyllysine.
FT MOD_RES 57 57 N6-acetyllysine.
FT MOD_RES 81 81 N6-acetyllysine.
FT MOD_RES 118 118 N6-acetyllysine.
FT MOD_RES 126 126 N6-acetyllysine.
FT MOD_RES 239 239 Phosphotyrosine (By similarity).
FT MOD_RES 318 318 N6-acetyllysine.
FT VAR_SEQ 1 1 M -> MGEPSGGYTYTQTSIFLFHAKIPFGSKSNM (in
FT isoform 3).
FT /FTId=VSP_042206.
FT VAR_SEQ 82 139 Missing (in isoform 4).
FT /FTId=VSP_042786.
FT VAR_SEQ 230 274 VHKQVVESAYEVIKLKGYTSWAIGLSVADLAESIMKNLRRV
FT HPVS -> CRYTLGDPKGAAILKSSDVISFHCLGYNRILGG
FT GCACCPFYLICD (in isoform 2).
FT /FTId=VSP_014261.
FT VAR_SEQ 237 241 SAYEV -> RVFTE (in isoform 5).
FT /FTId=VSP_042788.
FT VAR_SEQ 242 332 Missing (in isoform 5).
FT /FTId=VSP_042789.
FT VAR_SEQ 275 332 Missing (in isoform 2).
FT /FTId=VSP_042787.
FT VARIANT 161 161 S -> R (in dbSNP:rs5030621).
FT /FTId=VAR_059374.
FT VARIANT 222 222 K -> E.
FT /FTId=VAR_004180.
FT VARIANT 315 315 R -> C.
FT /FTId=VAR_004181.
FT HELIX 4 8
FT STRAND 9 12
FT STRAND 20 26
FT HELIX 30 41
FT STRAND 46 51
FT HELIX 55 67
FT HELIX 68 71
FT STRAND 77 79
FT HELIX 83 86
FT STRAND 90 94
FT HELIX 107 127
FT STRAND 132 135
FT STRAND 137 139
FT HELIX 140 151
FT HELIX 155 157
FT STRAND 158 160
FT HELIX 164 178
FT HELIX 182 184
FT STRAND 189 193
FT HELIX 194 196
FT HELIX 201 203
FT HELIX 211 214
FT TURN 216 219
FT STRAND 220 222
FT HELIX 228 245
FT HELIX 250 264
FT STRAND 269 276
FT STRAND 288 296
FT STRAND 299 304
FT HELIX 310 327
SQ SEQUENCE 332 AA; 36689 MW; 401E8604CEB7F908 CRC64;
MATLKDQLIY NLLKEEQTPQ NKITVVGVGA VGMACAISIL MKDLADELAL VDVIEDKLKG
EMMDLQHGSL FLRTPKIVSG KDYNVTANSK LVIITAGARQ QEGESRLNLV QRNVNIFKFI
IPNVVKYSPN CKLLIVSNPV DILTYVAWKI SGFPKNRVIG SGCNLDSARF RYLMGERLGV
HPLSCHGWVL GEHGDSSVPV WSGMNVAGVS LKTLHPDLGT DKDKEQWKEV HKQVVESAYE
VIKLKGYTSW AIGLSVADLA ESIMKNLRRV HPVSTMIKGL YGIKDDVFLS VPCILGQNGI
SDLVKVTLTS EEEARLKKSA DTLWGIQKEL QF
//
MIM
150000
*RECORD*
*FIELD* NO
150000
*FIELD* TI
*150000 LACTATE DEHYDROGENASE A; LDHA
;;LDH, SUBUNIT M
*FIELD* TX
DESCRIPTION
The LDHA gene encodes the A subunit of lactate dehydrogenase (EC
read more1.1.1.27), an enzyme that catalyzes the interconversion of lactate and
pyruvate. The A subunit is expressed in skeletal muscle. Other isoforms
include LDHB (150100), expressed in cardiac muscle, and LDHC (150150),
expressed in testes (Tsujibo et al., 1985; Chung et al., 1985).
CLONING
Tsujibo et al. (1985) isolated cDNA clones corresponding to the human
LDHA gene from a human fibroblast cDNA library. The predicted 332-amino
acid sequence had a molecular mass of 36.7 kD and showed 92% homology to
the porcine Ldha polypeptide. A nonfunctional pseudogene was also
isolated.
GENE STRUCTURE
Chung et al. (1985) determined that the LDHA gene contains 7 exons and
spans about 12 kb.
MAPPING
Studies using human-mouse somatic cell hybrids indicated that the LDHA
and LDHB loci are not linked (Nabholz et al., 1969). By study of cell
hybrids, LDHA was assigned to the short arm of chromosome 11 by Francke
and Busby (1975).
By the study of cells from 4 persons with different interstitial
deletions of 11p, Francke et al. (1977) assigned the LDHA locus to
11p1203-11p1208. At HGM8, controversy arose over the mapping of LDHA
(see Grzeschik and Kazazian, 1985). HGM8 reported the location as
11p14-p12. Lebo et al. (1985) and Lewis et al. (1985) placed the locus
at a more distal position.
Yang-Feng et al. (1986) did in situ hybridization studies in cell lines
from 2 persons with apparently balanced translocations involving 11p13.
Their findings excluded LDHA from any region proximal to 11p13 and
localized the gene to 11p15-p14.
Scrable et al. (1990) demonstrated that LDHA is located in band 11p15.4.
GENE FUNCTION
Centrosomal proteins (e.g., 117139, 117140, 117141, 117143) have been
studied mainly with anticentrosome serum. Using a spontaneously arising
rabbit anticentrosome serum with strong human specificity, Gosti et al.
(1987) identified specific antigens in isolated centrosomes which
reacted with several noncentrosomal proteins, notably, lactate
dehydrogenase.
Anderson and Kovacik (1981) identified an unusual isozyme of lactate
dehydrogenase, which they designated lactate dehydrogenase K (LDHK), in
cells transformed by the Kirsten murine sarcoma virus. They examined 16
different human carcinomas and found that 11 had LDHK activity 10- to
500-fold over the level in adjoining nontumor tissue. Li et al. (1988)
determined that this cancer-associated lactate dehydrogenase is a
tyrosylphosphorylated form of LDHA. The protein was found to be
complexed with 21-kD, 30-kD, and 56-kD proteins.
MOLECULAR GENETICS
Nance et al. (1963) observed a genetically determined variant LDH in the
red cells of 4 members of 2 generations of a Brazilian family. The
mutation involved the A subunit. This was the first instance in which
practical considerations permitted demonstration of the variant in
multiple relatives. Unlike the findings of Shaw and Barto (1963) in
Peromyscus and of Boyer et al. (1963) in man, the findings in the
Brazilian family did not suggest random association between the products
of the mutant and wildtype alleles.
LDH variants, involving either the A or the B subunit, seem to be
unusually frequent in India (Das et al., 1970).
- Glycogen Storage Disease XI
In a patient with LDHA deficiency, or glycogen storage disease XI
(GSD11; 612933), reported by Maekawa et al. (1986), Maekawa et al.
(1990) found homozygosity for a 20-bp deletion in exon 6 of the LDHA
gene (150000.0001). Maekawa et al. (1991) demonstrated the same mutation
in 18 persons from the 4 known affected families in Japan.
EVOLUTION
Markert et al. (1975) suggested that the ancestral vertebrate LDH was an
A4-like enzyme since lampreys have only the A4 isozyme. Sidell and
Beland (1980) presented evidence supporting this view: the hagfish has a
B4 enzyme but it diverges less from A4 enzyme than does the B4 of other
fishes and higher vertebrates. A close phylogenic relative of the
lamprey, the Atlantic hagfish lives under sustained hypoxic conditions
that may have favored evolution of a B4 enzyme. A4 is the muscle
isozyme, B4 is the heart isozyme, and C4 is the testicular isozyme.
Morizot (1984) collated linkage data from lower vertebrates and several
mammalian species. The lower vertebrates included poeciliid fishes
(Xiphophorus and Poeciliopsis), salmonid fishes (trout), and frogs
(Rana). He postulated a 12-locus ancestral synteny group consisting of
isocitrate dehydrogenase (on human 2 and 15), 3 LDH loci (on human 11
and 12), HEXA (on human 15), nucleoside phosphorylase (on human 14),
pyruvate kinase (on human 15), MPI (on human 15), PEPB (on human 12),
citrate synthase (on human 12), TPI (on human 12), and
glyceraldehyde-3-phosphate dehydrogenase (on human 12). If the 3 LDH
loci are part of the primordial synteny group, LDH genes may have
originated by intrachromosomal duplication rather than by
polyploidization as has been thought.
ANIMAL MODEL
In trout, the loci coding for LDH subunits A and B are linked (Morrison
and Wright, 1966). In the mouse, Chang et al. (1979) found that the A
and B subunits are more similar to each other in amino acid sequence
than to the C subunit.
In the mouse, Merkle et al. (1992) found that homozygosity for absent
LDHA subunit led to early postimplantation death. Merkle et al. (1992)
suggested that the fact that human subjects with a complete absence of
LDHA subunits are fully viable may be due to the fact that, in contrast
with the situation in the mouse, LDHB predominates in the human fetus.
*FIELD* AV
.0001
GLYCOGEN STORAGE DISEASE XI
LDHA, 20-BP DEL, EX6
In a patient with lactate dehydrogenase A deficiency, or glycogen
storage disease XI (612933), reported by Maekawa et al. (1986), Maekawa
et al. (1990) found a 20-bp deletion in exon 6 of the LDHA gene,
resulting in a frameshift, premature termination, and complete lack of
the alpha subunits of LDH. The predicted incomplete LDHA subunit
contained only 259 instead of 331 amino acids and appeared to be
degraded rapidly, since no protein was detected immunologically. Maekawa
et al. (1990) stated that 'this female patient with the LDHA deficiency
frequently complained of uterine stiffness during her pregnancy. Uterine
stiffness was a problem in the early stage of delivery and, thus, she
required a Caesarean section.'
In a fragment of the LDHA gene amplified by PCR using 2 primers specific
for the gene, Maekawa et al. (1991) demonstrated the same mutation in 18
persons from the 4 known affected families in Japan.
Miyajima et al. (1993) identified the exon 6 deletion in 2 adult
Japanese sisters that had muscle stiffness following strenuous exercise
since the teens and age 9, respectively. Both had had cesarean sections
because the 'uterus was too stiff in the early stage of delivery.'
.0002
GLYCOGEN STORAGE DISEASE XI
LDHA, GLU328TER
Maekawa et al. (1991) used the ratio of LDHB to LDHA subunits in
erythrocytes as a means of identifying individuals heterozygous for LDHA
deficiency (GSD11; 612933). In one such individual, they identified a
G-to-T transversion in the LDHA gene, resulting in a glu328-to-ter
(E328X) substitution. There were no manifestations in this heterozygous
subject; however, homozygotes would presumably be affected.
*FIELD* SA
Blake et al. (1969); Boone et al. (1972); Davidson et al. (1965);
Maekawa et al. (1984); Shows (1972); Van Someren et al. (1972); Vesell
(1965); Vyas et al. (1977)
*FIELD* RF
1. Anderson, G. R.; Kovacik, W. P., Jr.: LDH(k), an unusual oxygen-sensitive
lactate dehydrogenase expressed in human cancer. Proc. Nat. Acad.
Sci. 78: 3209-3213, 1981.
2. Blake, N. M.; Kirk, R. L.; Pryke, E.; Sinnett, P.: Lactate dehydrogenase
electrophoretic variant in a New Guinea highland population. Science 163:
701-702, 1969.
3. Boone, C. M.; Chen, T. R.; Ruddle, F. H.: Assignment of three
human genes to chromosomes (LDH-A to 11, TK to 17, and IDH to 20)
and evidence for translocation between human and mouse chromosomes
in somatic cell hybrids. Proc. Nat. Acad. Sci. 69: 510-514, 1972.
4. Boyer, S. H.; Fainer, D. C.; Watson-Williams, E. J.: Lactate dehydrogenase
variant from human blood: evidence for molecular subunits. Science 141:
642-643, 1963.
5. Chang, S.-M. T.; Lee, C.-Y.; Li, S. S.-L.: Structural relatedness
of mouse lactate dehydrogenase isozymes, A4 (muscle), B4 (heart),
and C4 (testis). Biochem. Genet. 17: 715-729, 1979.
6. Chung, F.-Z.; Tsujibo, H.; Bhattacharyya, U.; Sharief, F. S.; Li,
S. S.-L: Genomic organization of human lactate dehydrogenase-A gene. Biochem.
J. 231: 537-541, 1985.
7. Das, S. R.; Mukherjee, B. N.; Das, S. K.; Ananthakrishnan, R.;
Blake, N. M.; Kirk, R. L.: LDH variants in India. Humangenetik 9:
107-109, 1970.
8. Davidson, R. G.; Fildes, R. A.; Glen-Bott, A. M.; Harris, H.; Robson,
E. B.; Cleghorn, T. E.: Genetical studies on a variant of human lactate
dehydrogenase (subunit A). Ann. Hum. Genet. 29: 5-17, 1965.
9. Francke, U.; Busby, N.: Assignments of the human genes for lactate
dehydrogenase-A and thymidine kinase to specific chromosomal regions. Birth
Defects Orig. Art. Ser. XI(3): 143-149, 1975. Note: Alternate: Cytogenet.
Cell Genet. 14: 313-319, 1975.
10. Francke, U.; George, D. L.; Brown, M. G.; Riccardi, V. M.: Gene
dose effect: intraband mapping of LDHA locus using cells from four
individuals with different interstitial deletions of 11p. Cytogenet.
Cell Genet. 19: 197-207, 1977.
11. Gosti, F.; Marty, M.-C.; Courvalin, J. C.; Maunoury, R.; Bornens,
M.: Centrosomal proteins and lactate dehydrogenase possess a common
epitope in human cell lines. Proc. Nat. Acad. Sci. 84: 1000-1004,
1987.
12. Grzeschik, K.-H.; Kazazian, H. H.: Report of the committee on
the genetic constitution of chromosomes 10, 11, and 12. Cytogenet.
Cell Genet. 40: 177-205, 1985.
13. Lebo, R. V.; Cheung, M. C.; Bruce, B. D.; Riccardi, V. M.; Kao,
F. T.; Kan, Y. W.: Mapping parathyroid hormone, beta-globin, insulin,
and LDH-A genes within the human chromosome 11 short arm by spot blotting
sorted chromosomes. Hum. Genet. 69: 316-320, 1985.
14. Lewis, W. H.; Goguen, J. M.; Powers, V. E.; Willard, H. F.; Michaloparilan,
E. E.: Gene order on the short arm of human chromosome 11: regional
assignment of LDHA distal to catalase. Hum. Genet. 71: 249-253,
1985.
15. Li, S. S.-L.; Pan, Y.-C. E.; Sharief, F. S.; Evans, M. J.; Lin,
M.-F.; Clinton, G. M.; Holbrook, J. J.: Cancer-associated lactate
dehydrogenase is a tyrosylphosphorylated form of human LDH-A, skeletal
muscle isoenzyme. Cancer Invest. 6: 93-101, 1988.
16. Maekawa, M.; Kanda, S.; Sudo, K.; Kanno, T.: Estimation of the
gene frequency of lactate dehydrogenase subunit deficiencies. Am.
J. Hum. Genet. 36: 1204-1214, 1984.
17. Maekawa, M.; Sudo, K.; Kanno, T.: Immunochemical studies on lactate
dehydrogenase A subunit deficiencies. Am. J. Hum. Genet. 39: 232-238,
1986.
18. Maekawa, M.; Sudo, K.; Kanno, T.; Li, S. S.-L.: Molecular characterization
of genetic mutation in human lactate dehydrogenase-A (M) deficiency. Biochem.
Biophys. Res. Commun. 168: 677-682, 1990.
19. Maekawa, M.; Sudo, K.; Li, S. S.-L.; Kanno, T.: Analysis of genetic
mutations in human lactate dehydrogenase-A(M) deficiency using DNA
conformation polymorphism in combination with polyacrylamide gradient
gel and silver staining. Biochem. Biophys. Res. Commun. 180: 1083-1090,
1991.
20. Maekawa, M.; Sudo, K.; Li, S. S.-L.; Kanno, T.: Genotypic analysis
of families with lactate dehydrogenase A(M) deficiency by selective
DNA amplification. Hum. Genet. 88: 34-38, 1991.
21. Markert, C. L.; Shaklee, J. B.; Whitt, G. S.: Evolution of a
gene: multiple genes for LDH isozymes provide a model of the evolution
of gene structure, function, and regulation. Science 189: 102-114,
1975.
22. Merkle, S.; Favor, J.; Graw, J.; Hornhardt, S.; Pretsch, W.:
Hereditary lactate dehydrogenase A-subunit deficiency as cause of
early postimplantation death of homozygotes in Mus musculus. Genetics 131:
413-421, 1992.
23. Miyajima, H.; Takahashi, Y.; Suzuki, M.; Shimizu, T.; Kaneko,
E.: Molecular characterization of gene expression in human lactate
dehydrogenase-A deficiency. Neurology 43: 1414-1419, 1993.
24. Morizot, D. C.: Tracing linkage groups from fishes to mammals.
(Abstract) Cytogenet. Cell Genet. 37: 543 only, 1984.
25. Morrison, W. J.; Wright, J. E.: Genetic analysis of three lactate
dehydrogenase isozyme systems in trout: evidence for linkage of genes
coding subunits A and B. J. Exp. Zool. 163: 259-270, 1966.
26. Nabholz, M.; Miggiano, V.; Bodmer, W. F.: Genetic analysis with
human-mouse somatic cell hybrids. Nature 223: 358-363, 1969.
27. Nance, W. E.; Claflin, A.; Smithies, O.: Lactic dehydrogenase:
genetic control in man. Science 142: 1075-1077, 1963.
28. Scrable, H. J.; Johnson, D. K.; Rinchik, E. M.; Cavenee, W. K.
: Rhabdomyosarcoma-associated locus and MYOD1 are syntenic but separate
loci on the short arm of human chromosome 11. Proc. Nat. Acad. Sci. 87:
2182-2186, 1990.
29. Shaw, C. R.; Barto, E.: Genetic evidence for the subunit structure
of lactate dehydrogenase isozymes. Proc. Nat. Acad. Sci. 50: 211-214,
1963.
30. Shows, T. B.: Genetics of human-mouse somatic cell hybrids: linkage
of human genes for lactate dehydrogenase-A and esterase-A4. Proc.
Nat. Acad. Sci. 69: 348-352, 1972.
31. Sidell, B. D.; Beland, K. F.: Lactate dehydrogenases of Atlantic
hagfish: physiological and evolutionary implications of a primitive
heart isozyme. Science 207: 769-770, 1980.
32. Tsujibo, H.; Tiano, H. F.; Li, S. S.-L.: Nucleotide sequences
of the cDNA and an intronless pseudogene for human lactate dehydrogenase-A
isozyme. Europ. J. Biochem. 147: 9-15, 1985.
33. Van Someren, H.; Meera Khan, P.; Westerveld, A.; Bootsma, D.:
Two new linkage groups carrying different loci for LDH and glutamic-pyruvic
transaminase found. Nature 240: 221-222, 1972.
34. Vesell, E. S.: Genetic control of isozyme patterns in human tissue. Prog.
Med. Genet. 4: 128-175, 1965.
35. Vyas, G. N.; Peterson, D. L.; Townsend, R. M.: Hepatitis B 'e'
antigens: an apparent association with lactate dehydrogenase isozyme-5. Science 198:
1068-1070, 1977.
36. Yang-Feng, T. L.; Bruns, G. A. P.; Carroll, A. J.; Simola, K.
O. J.; Francke, U.: Localization of the LDHA gene to 11p14-11p15
by in situ hybridization of an LDHA cDNA probe to two translocations
with breakpoints in 11p13. Hum. Genet. 74: 331-334, 1986.
*FIELD* CN
Carol A. Bocchini - updated: 7/27/2011
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
terry: 08/01/2011
carol: 7/27/2011
terry: 8/3/2010
carol: 7/31/2009
carol: 7/30/2009
ckniffin: 7/28/2009
mgross: 3/17/2004
mcapotos: 12/15/1999
mark: 1/12/1998
alopez: 6/2/1997
terry: 7/15/1994
davew: 7/13/1994
warfield: 4/21/1994
pfoster: 4/5/1994
carol: 3/14/1994
carol: 7/23/1992
*RECORD*
*FIELD* NO
150000
*FIELD* TI
*150000 LACTATE DEHYDROGENASE A; LDHA
;;LDH, SUBUNIT M
*FIELD* TX
DESCRIPTION
The LDHA gene encodes the A subunit of lactate dehydrogenase (EC
read more1.1.1.27), an enzyme that catalyzes the interconversion of lactate and
pyruvate. The A subunit is expressed in skeletal muscle. Other isoforms
include LDHB (150100), expressed in cardiac muscle, and LDHC (150150),
expressed in testes (Tsujibo et al., 1985; Chung et al., 1985).
CLONING
Tsujibo et al. (1985) isolated cDNA clones corresponding to the human
LDHA gene from a human fibroblast cDNA library. The predicted 332-amino
acid sequence had a molecular mass of 36.7 kD and showed 92% homology to
the porcine Ldha polypeptide. A nonfunctional pseudogene was also
isolated.
GENE STRUCTURE
Chung et al. (1985) determined that the LDHA gene contains 7 exons and
spans about 12 kb.
MAPPING
Studies using human-mouse somatic cell hybrids indicated that the LDHA
and LDHB loci are not linked (Nabholz et al., 1969). By study of cell
hybrids, LDHA was assigned to the short arm of chromosome 11 by Francke
and Busby (1975).
By the study of cells from 4 persons with different interstitial
deletions of 11p, Francke et al. (1977) assigned the LDHA locus to
11p1203-11p1208. At HGM8, controversy arose over the mapping of LDHA
(see Grzeschik and Kazazian, 1985). HGM8 reported the location as
11p14-p12. Lebo et al. (1985) and Lewis et al. (1985) placed the locus
at a more distal position.
Yang-Feng et al. (1986) did in situ hybridization studies in cell lines
from 2 persons with apparently balanced translocations involving 11p13.
Their findings excluded LDHA from any region proximal to 11p13 and
localized the gene to 11p15-p14.
Scrable et al. (1990) demonstrated that LDHA is located in band 11p15.4.
GENE FUNCTION
Centrosomal proteins (e.g., 117139, 117140, 117141, 117143) have been
studied mainly with anticentrosome serum. Using a spontaneously arising
rabbit anticentrosome serum with strong human specificity, Gosti et al.
(1987) identified specific antigens in isolated centrosomes which
reacted with several noncentrosomal proteins, notably, lactate
dehydrogenase.
Anderson and Kovacik (1981) identified an unusual isozyme of lactate
dehydrogenase, which they designated lactate dehydrogenase K (LDHK), in
cells transformed by the Kirsten murine sarcoma virus. They examined 16
different human carcinomas and found that 11 had LDHK activity 10- to
500-fold over the level in adjoining nontumor tissue. Li et al. (1988)
determined that this cancer-associated lactate dehydrogenase is a
tyrosylphosphorylated form of LDHA. The protein was found to be
complexed with 21-kD, 30-kD, and 56-kD proteins.
MOLECULAR GENETICS
Nance et al. (1963) observed a genetically determined variant LDH in the
red cells of 4 members of 2 generations of a Brazilian family. The
mutation involved the A subunit. This was the first instance in which
practical considerations permitted demonstration of the variant in
multiple relatives. Unlike the findings of Shaw and Barto (1963) in
Peromyscus and of Boyer et al. (1963) in man, the findings in the
Brazilian family did not suggest random association between the products
of the mutant and wildtype alleles.
LDH variants, involving either the A or the B subunit, seem to be
unusually frequent in India (Das et al., 1970).
- Glycogen Storage Disease XI
In a patient with LDHA deficiency, or glycogen storage disease XI
(GSD11; 612933), reported by Maekawa et al. (1986), Maekawa et al.
(1990) found homozygosity for a 20-bp deletion in exon 6 of the LDHA
gene (150000.0001). Maekawa et al. (1991) demonstrated the same mutation
in 18 persons from the 4 known affected families in Japan.
EVOLUTION
Markert et al. (1975) suggested that the ancestral vertebrate LDH was an
A4-like enzyme since lampreys have only the A4 isozyme. Sidell and
Beland (1980) presented evidence supporting this view: the hagfish has a
B4 enzyme but it diverges less from A4 enzyme than does the B4 of other
fishes and higher vertebrates. A close phylogenic relative of the
lamprey, the Atlantic hagfish lives under sustained hypoxic conditions
that may have favored evolution of a B4 enzyme. A4 is the muscle
isozyme, B4 is the heart isozyme, and C4 is the testicular isozyme.
Morizot (1984) collated linkage data from lower vertebrates and several
mammalian species. The lower vertebrates included poeciliid fishes
(Xiphophorus and Poeciliopsis), salmonid fishes (trout), and frogs
(Rana). He postulated a 12-locus ancestral synteny group consisting of
isocitrate dehydrogenase (on human 2 and 15), 3 LDH loci (on human 11
and 12), HEXA (on human 15), nucleoside phosphorylase (on human 14),
pyruvate kinase (on human 15), MPI (on human 15), PEPB (on human 12),
citrate synthase (on human 12), TPI (on human 12), and
glyceraldehyde-3-phosphate dehydrogenase (on human 12). If the 3 LDH
loci are part of the primordial synteny group, LDH genes may have
originated by intrachromosomal duplication rather than by
polyploidization as has been thought.
ANIMAL MODEL
In trout, the loci coding for LDH subunits A and B are linked (Morrison
and Wright, 1966). In the mouse, Chang et al. (1979) found that the A
and B subunits are more similar to each other in amino acid sequence
than to the C subunit.
In the mouse, Merkle et al. (1992) found that homozygosity for absent
LDHA subunit led to early postimplantation death. Merkle et al. (1992)
suggested that the fact that human subjects with a complete absence of
LDHA subunits are fully viable may be due to the fact that, in contrast
with the situation in the mouse, LDHB predominates in the human fetus.
*FIELD* AV
.0001
GLYCOGEN STORAGE DISEASE XI
LDHA, 20-BP DEL, EX6
In a patient with lactate dehydrogenase A deficiency, or glycogen
storage disease XI (612933), reported by Maekawa et al. (1986), Maekawa
et al. (1990) found a 20-bp deletion in exon 6 of the LDHA gene,
resulting in a frameshift, premature termination, and complete lack of
the alpha subunits of LDH. The predicted incomplete LDHA subunit
contained only 259 instead of 331 amino acids and appeared to be
degraded rapidly, since no protein was detected immunologically. Maekawa
et al. (1990) stated that 'this female patient with the LDHA deficiency
frequently complained of uterine stiffness during her pregnancy. Uterine
stiffness was a problem in the early stage of delivery and, thus, she
required a Caesarean section.'
In a fragment of the LDHA gene amplified by PCR using 2 primers specific
for the gene, Maekawa et al. (1991) demonstrated the same mutation in 18
persons from the 4 known affected families in Japan.
Miyajima et al. (1993) identified the exon 6 deletion in 2 adult
Japanese sisters that had muscle stiffness following strenuous exercise
since the teens and age 9, respectively. Both had had cesarean sections
because the 'uterus was too stiff in the early stage of delivery.'
.0002
GLYCOGEN STORAGE DISEASE XI
LDHA, GLU328TER
Maekawa et al. (1991) used the ratio of LDHB to LDHA subunits in
erythrocytes as a means of identifying individuals heterozygous for LDHA
deficiency (GSD11; 612933). In one such individual, they identified a
G-to-T transversion in the LDHA gene, resulting in a glu328-to-ter
(E328X) substitution. There were no manifestations in this heterozygous
subject; however, homozygotes would presumably be affected.
*FIELD* SA
Blake et al. (1969); Boone et al. (1972); Davidson et al. (1965);
Maekawa et al. (1984); Shows (1972); Van Someren et al. (1972); Vesell
(1965); Vyas et al. (1977)
*FIELD* RF
1. Anderson, G. R.; Kovacik, W. P., Jr.: LDH(k), an unusual oxygen-sensitive
lactate dehydrogenase expressed in human cancer. Proc. Nat. Acad.
Sci. 78: 3209-3213, 1981.
2. Blake, N. M.; Kirk, R. L.; Pryke, E.; Sinnett, P.: Lactate dehydrogenase
electrophoretic variant in a New Guinea highland population. Science 163:
701-702, 1969.
3. Boone, C. M.; Chen, T. R.; Ruddle, F. H.: Assignment of three
human genes to chromosomes (LDH-A to 11, TK to 17, and IDH to 20)
and evidence for translocation between human and mouse chromosomes
in somatic cell hybrids. Proc. Nat. Acad. Sci. 69: 510-514, 1972.
4. Boyer, S. H.; Fainer, D. C.; Watson-Williams, E. J.: Lactate dehydrogenase
variant from human blood: evidence for molecular subunits. Science 141:
642-643, 1963.
5. Chang, S.-M. T.; Lee, C.-Y.; Li, S. S.-L.: Structural relatedness
of mouse lactate dehydrogenase isozymes, A4 (muscle), B4 (heart),
and C4 (testis). Biochem. Genet. 17: 715-729, 1979.
6. Chung, F.-Z.; Tsujibo, H.; Bhattacharyya, U.; Sharief, F. S.; Li,
S. S.-L: Genomic organization of human lactate dehydrogenase-A gene. Biochem.
J. 231: 537-541, 1985.
7. Das, S. R.; Mukherjee, B. N.; Das, S. K.; Ananthakrishnan, R.;
Blake, N. M.; Kirk, R. L.: LDH variants in India. Humangenetik 9:
107-109, 1970.
8. Davidson, R. G.; Fildes, R. A.; Glen-Bott, A. M.; Harris, H.; Robson,
E. B.; Cleghorn, T. E.: Genetical studies on a variant of human lactate
dehydrogenase (subunit A). Ann. Hum. Genet. 29: 5-17, 1965.
9. Francke, U.; Busby, N.: Assignments of the human genes for lactate
dehydrogenase-A and thymidine kinase to specific chromosomal regions. Birth
Defects Orig. Art. Ser. XI(3): 143-149, 1975. Note: Alternate: Cytogenet.
Cell Genet. 14: 313-319, 1975.
10. Francke, U.; George, D. L.; Brown, M. G.; Riccardi, V. M.: Gene
dose effect: intraband mapping of LDHA locus using cells from four
individuals with different interstitial deletions of 11p. Cytogenet.
Cell Genet. 19: 197-207, 1977.
11. Gosti, F.; Marty, M.-C.; Courvalin, J. C.; Maunoury, R.; Bornens,
M.: Centrosomal proteins and lactate dehydrogenase possess a common
epitope in human cell lines. Proc. Nat. Acad. Sci. 84: 1000-1004,
1987.
12. Grzeschik, K.-H.; Kazazian, H. H.: Report of the committee on
the genetic constitution of chromosomes 10, 11, and 12. Cytogenet.
Cell Genet. 40: 177-205, 1985.
13. Lebo, R. V.; Cheung, M. C.; Bruce, B. D.; Riccardi, V. M.; Kao,
F. T.; Kan, Y. W.: Mapping parathyroid hormone, beta-globin, insulin,
and LDH-A genes within the human chromosome 11 short arm by spot blotting
sorted chromosomes. Hum. Genet. 69: 316-320, 1985.
14. Lewis, W. H.; Goguen, J. M.; Powers, V. E.; Willard, H. F.; Michaloparilan,
E. E.: Gene order on the short arm of human chromosome 11: regional
assignment of LDHA distal to catalase. Hum. Genet. 71: 249-253,
1985.
15. Li, S. S.-L.; Pan, Y.-C. E.; Sharief, F. S.; Evans, M. J.; Lin,
M.-F.; Clinton, G. M.; Holbrook, J. J.: Cancer-associated lactate
dehydrogenase is a tyrosylphosphorylated form of human LDH-A, skeletal
muscle isoenzyme. Cancer Invest. 6: 93-101, 1988.
16. Maekawa, M.; Kanda, S.; Sudo, K.; Kanno, T.: Estimation of the
gene frequency of lactate dehydrogenase subunit deficiencies. Am.
J. Hum. Genet. 36: 1204-1214, 1984.
17. Maekawa, M.; Sudo, K.; Kanno, T.: Immunochemical studies on lactate
dehydrogenase A subunit deficiencies. Am. J. Hum. Genet. 39: 232-238,
1986.
18. Maekawa, M.; Sudo, K.; Kanno, T.; Li, S. S.-L.: Molecular characterization
of genetic mutation in human lactate dehydrogenase-A (M) deficiency. Biochem.
Biophys. Res. Commun. 168: 677-682, 1990.
19. Maekawa, M.; Sudo, K.; Li, S. S.-L.; Kanno, T.: Analysis of genetic
mutations in human lactate dehydrogenase-A(M) deficiency using DNA
conformation polymorphism in combination with polyacrylamide gradient
gel and silver staining. Biochem. Biophys. Res. Commun. 180: 1083-1090,
1991.
20. Maekawa, M.; Sudo, K.; Li, S. S.-L.; Kanno, T.: Genotypic analysis
of families with lactate dehydrogenase A(M) deficiency by selective
DNA amplification. Hum. Genet. 88: 34-38, 1991.
21. Markert, C. L.; Shaklee, J. B.; Whitt, G. S.: Evolution of a
gene: multiple genes for LDH isozymes provide a model of the evolution
of gene structure, function, and regulation. Science 189: 102-114,
1975.
22. Merkle, S.; Favor, J.; Graw, J.; Hornhardt, S.; Pretsch, W.:
Hereditary lactate dehydrogenase A-subunit deficiency as cause of
early postimplantation death of homozygotes in Mus musculus. Genetics 131:
413-421, 1992.
23. Miyajima, H.; Takahashi, Y.; Suzuki, M.; Shimizu, T.; Kaneko,
E.: Molecular characterization of gene expression in human lactate
dehydrogenase-A deficiency. Neurology 43: 1414-1419, 1993.
24. Morizot, D. C.: Tracing linkage groups from fishes to mammals.
(Abstract) Cytogenet. Cell Genet. 37: 543 only, 1984.
25. Morrison, W. J.; Wright, J. E.: Genetic analysis of three lactate
dehydrogenase isozyme systems in trout: evidence for linkage of genes
coding subunits A and B. J. Exp. Zool. 163: 259-270, 1966.
26. Nabholz, M.; Miggiano, V.; Bodmer, W. F.: Genetic analysis with
human-mouse somatic cell hybrids. Nature 223: 358-363, 1969.
27. Nance, W. E.; Claflin, A.; Smithies, O.: Lactic dehydrogenase:
genetic control in man. Science 142: 1075-1077, 1963.
28. Scrable, H. J.; Johnson, D. K.; Rinchik, E. M.; Cavenee, W. K.
: Rhabdomyosarcoma-associated locus and MYOD1 are syntenic but separate
loci on the short arm of human chromosome 11. Proc. Nat. Acad. Sci. 87:
2182-2186, 1990.
29. Shaw, C. R.; Barto, E.: Genetic evidence for the subunit structure
of lactate dehydrogenase isozymes. Proc. Nat. Acad. Sci. 50: 211-214,
1963.
30. Shows, T. B.: Genetics of human-mouse somatic cell hybrids: linkage
of human genes for lactate dehydrogenase-A and esterase-A4. Proc.
Nat. Acad. Sci. 69: 348-352, 1972.
31. Sidell, B. D.; Beland, K. F.: Lactate dehydrogenases of Atlantic
hagfish: physiological and evolutionary implications of a primitive
heart isozyme. Science 207: 769-770, 1980.
32. Tsujibo, H.; Tiano, H. F.; Li, S. S.-L.: Nucleotide sequences
of the cDNA and an intronless pseudogene for human lactate dehydrogenase-A
isozyme. Europ. J. Biochem. 147: 9-15, 1985.
33. Van Someren, H.; Meera Khan, P.; Westerveld, A.; Bootsma, D.:
Two new linkage groups carrying different loci for LDH and glutamic-pyruvic
transaminase found. Nature 240: 221-222, 1972.
34. Vesell, E. S.: Genetic control of isozyme patterns in human tissue. Prog.
Med. Genet. 4: 128-175, 1965.
35. Vyas, G. N.; Peterson, D. L.; Townsend, R. M.: Hepatitis B 'e'
antigens: an apparent association with lactate dehydrogenase isozyme-5. Science 198:
1068-1070, 1977.
36. Yang-Feng, T. L.; Bruns, G. A. P.; Carroll, A. J.; Simola, K.
O. J.; Francke, U.: Localization of the LDHA gene to 11p14-11p15
by in situ hybridization of an LDHA cDNA probe to two translocations
with breakpoints in 11p13. Hum. Genet. 74: 331-334, 1986.
*FIELD* CN
Carol A. Bocchini - updated: 7/27/2011
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
terry: 08/01/2011
carol: 7/27/2011
terry: 8/3/2010
carol: 7/31/2009
carol: 7/30/2009
ckniffin: 7/28/2009
mgross: 3/17/2004
mcapotos: 12/15/1999
mark: 1/12/1998
alopez: 6/2/1997
terry: 7/15/1994
davew: 7/13/1994
warfield: 4/21/1994
pfoster: 4/5/1994
carol: 3/14/1994
carol: 7/23/1992
MIM
612933
*RECORD*
*FIELD* NO
612933
*FIELD* TI
#612933 GLYCOGEN STORAGE DISEASE XI; GSD11
;;GSD XI;;
LACTATE DEHYDROGENASE A DEFICIENCY
read more*FIELD* TX
A number sign (#) is used with this entry because glycogen storage
disease XI (GSD11), or lactate dehydrogenase A deficiency, is caused by
mutation in the LDHA gene (150000).
CLINICAL FEATURES
Kanno et al. (1980) described a family with deficiency of the muscle (M)
isoform of LDH (LDHA). The proband was an 18-year-old male who
complained of exertional myoglobinuria and easy fatigue. Ischemic work
of the forearm was accompanied by increased blood lactate, pyruvate, and
serum creatine kinase, with myoglobinuria. Maekawa et al. (1984)
reported 2 Japanese daughters, born of first cousins, with homozygous
LDHA deficiency.
Kanno et al. (1988) studied carbohydrate metabolism in 3 Japanese
families with LDHA deficiency. A total of 8 individuals (4 male, 4
female) were affected. In 1 family, which had not previously been
reported, the proband was a 23-year-old male who was easily fatigued and
had renal failure dating from the age of 13 years. Painful muscle
stiffness and cramps had first been noted at age 9 during a 100-meter
dash. A sister likewise had complete absence of LDHA.
Yoshikuni et al. (1986) reported 2 adult Japanese patients with
myoglobinuria and easy fatigability after strenuous exercise due to
deficiency of LDHA. They also had characteristic nonpruritic
erythematosquamous skin lesions on the extensor surfaces of the
extremities since childhood, showing some improvement after puberty.
Takayasu et al. (1991) reported a 16-year-old Japanese girl who had
desquamating erythematosquamous lesions mostly on the extensor surface
of the extremities, mild muscle pain after strenuous exercise, and
complete lack of LDHA in red cells. The epidermis of the diseased skin
and scalp hair follicles were virtually devoid of LDH activity. Both
parents, who were related as second cousins, had decreased red cell
LDHA.
MOLECULAR GENETICS
In a woman with glycogen storage disease XI reported by Maekawa et al.
(1986), Maekawa et al. (1990) found homozygosity for a 20-bp deletion in
exon 6 of the LDHA gene (150000.0001). Maekawa et al. (1990) noted the
that woman 'frequently complained of uterine stiffness during her
pregnancy. Uterine stiffness was a problem in the early stage of
delivery and, thus, she required a Caesarean section.'
Maekawa et al. (1991) demonstrated the same LDHA mutation in 18 persons
from the 4 known affected families in Japan.
Miyajima et al. (1993) identified the exon 6 deletion in 2 adult
Japanese sisters that had muscle stiffness following strenuous exercise
since the teens and age 9, respectively. Both had had cesarean sections
because the 'uterus was too stiff in the early stage of delivery.'
POPULATION GENETICS
In a survey of 3,776 healthy persons in Shizuoka Prefecture in Japan,
Maekawa et al. (1984) found the frequency of heterozygous LDHA and LDHB
subunit deficiencies to be 0.185% (about 1 in 540) and 0.159% (about 1
in 630), respectively. These frequencies were probably higher than in
most other populations.
*FIELD* RF
1. Kanno, T.; Sudo, K.; Maekawa, M.; Nishimura, Y.; Ukita, M.; Fukutake,
K.: Lactate dehydrogenase M-subunit deficiency: a new type of hereditary
exertional myopathy. Clin. Chim. Acta 173: 89-98, 1988.
2. Kanno, T.; Sudo, K.; Takeuchi, I.; Kanda, S.; Honda, N.; Nishimura,
Y.; Oyama, K.: Hereditary deficiency of lactate dehydrogenase M-subunit. Clin.
Chim. Acta 108: 267-276, 1980.
3. Maekawa, M.; Kanda, S.; Sudo, K.; Kanno, T.: Estimation of the
gene frequency of lactate dehydrogenase subunit deficiencies. Am.
J. Hum. Genet. 36: 1204-1214, 1984.
4. Maekawa, M.; Sudo, K.; Kanno, T.: Immunochemical studies on lactate
dehydrogenase A subunit deficiencies. Am. J. Hum. Genet. 39: 232-238,
1986.
5. Maekawa, M.; Sudo, K.; Kanno, T.; Li, S. S.-L.: Molecular characterization
of genetic mutation in human lactate dehydrogenase-A (M) deficiency. Biochem.
Biophys. Res. Commun. 168: 677-682, 1990.
6. Maekawa, M.; Sudo, K.; Li, S. S.-L.; Kanno, T.: Genotypic analysis
of families with lactate dehydrogenase A(M) deficiency by selective
DNA amplification. Hum. Genet. 88: 34-38, 1991.
7. Miyajima, H.; Takahashi, Y.; Suzuki, M.; Shimizu, T.; Kaneko, E.
: Molecular characterization of gene expression in human lactate dehydrogenase-A
deficiency. Neurology 43: 1414-1419, 1993.
8. Takayasu, S.; Fujiwara, S.; Waki, T.: Hereditary lactate dehydrogenase
M-subunit deficiency: lactate dehydrogenase activity in skin lesions
and in hair follicles. J. Am. Acad. Derm. 24: 339-342, 1991.
9. Yoshikuni, K.; Tagami, H.; Yamada, M.; Sudo, K.; Kanno, T.: Erythematosquamous
skin lesions in hereditary lactate dehydrogenase M-subunit deficiency. Arch.
Derm. 122: 1420-1424, 1986.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GENITOURINARY:
[Kidneys];
Myoglobinuria;
Renal failure may occur
SKIN, NAILS, HAIR:
[Skin];
Erythematous squamous skin lesions
MUSCLE, SOFT TISSUE:
Muscle cramps;
Muscle pain;
Exercise intolerance;
Muscle rigidity;
Muscle stiffness;
Rhabdomyolysis;
Uterine muscle may be stiff during pregnancy
LABORATORY ABNORMALITIES:
Increased serum creatine kinase;
Increased serum lactate;
Increased serum pyruvate
MISCELLANEOUS:
Onset in childhood;
Symptoms induced by strenuous exercise
MOLECULAR BASIS:
Caused by mutation in the lactate dehydrogenase A gene (LDHA, 150000.0001)
*FIELD* CD
Cassandra L. Kniffin: 7/28/2009
*FIELD* ED
joanna: 01/07/2010
ckniffin: 7/28/2009
*FIELD* CD
Cassandra L. Kniffin: 7/27/2009
*FIELD* ED
terry: 04/28/2011
carol: 7/31/2009
carol: 7/30/2009
ckniffin: 7/28/2009
*RECORD*
*FIELD* NO
612933
*FIELD* TI
#612933 GLYCOGEN STORAGE DISEASE XI; GSD11
;;GSD XI;;
LACTATE DEHYDROGENASE A DEFICIENCY
read more*FIELD* TX
A number sign (#) is used with this entry because glycogen storage
disease XI (GSD11), or lactate dehydrogenase A deficiency, is caused by
mutation in the LDHA gene (150000).
CLINICAL FEATURES
Kanno et al. (1980) described a family with deficiency of the muscle (M)
isoform of LDH (LDHA). The proband was an 18-year-old male who
complained of exertional myoglobinuria and easy fatigue. Ischemic work
of the forearm was accompanied by increased blood lactate, pyruvate, and
serum creatine kinase, with myoglobinuria. Maekawa et al. (1984)
reported 2 Japanese daughters, born of first cousins, with homozygous
LDHA deficiency.
Kanno et al. (1988) studied carbohydrate metabolism in 3 Japanese
families with LDHA deficiency. A total of 8 individuals (4 male, 4
female) were affected. In 1 family, which had not previously been
reported, the proband was a 23-year-old male who was easily fatigued and
had renal failure dating from the age of 13 years. Painful muscle
stiffness and cramps had first been noted at age 9 during a 100-meter
dash. A sister likewise had complete absence of LDHA.
Yoshikuni et al. (1986) reported 2 adult Japanese patients with
myoglobinuria and easy fatigability after strenuous exercise due to
deficiency of LDHA. They also had characteristic nonpruritic
erythematosquamous skin lesions on the extensor surfaces of the
extremities since childhood, showing some improvement after puberty.
Takayasu et al. (1991) reported a 16-year-old Japanese girl who had
desquamating erythematosquamous lesions mostly on the extensor surface
of the extremities, mild muscle pain after strenuous exercise, and
complete lack of LDHA in red cells. The epidermis of the diseased skin
and scalp hair follicles were virtually devoid of LDH activity. Both
parents, who were related as second cousins, had decreased red cell
LDHA.
MOLECULAR GENETICS
In a woman with glycogen storage disease XI reported by Maekawa et al.
(1986), Maekawa et al. (1990) found homozygosity for a 20-bp deletion in
exon 6 of the LDHA gene (150000.0001). Maekawa et al. (1990) noted the
that woman 'frequently complained of uterine stiffness during her
pregnancy. Uterine stiffness was a problem in the early stage of
delivery and, thus, she required a Caesarean section.'
Maekawa et al. (1991) demonstrated the same LDHA mutation in 18 persons
from the 4 known affected families in Japan.
Miyajima et al. (1993) identified the exon 6 deletion in 2 adult
Japanese sisters that had muscle stiffness following strenuous exercise
since the teens and age 9, respectively. Both had had cesarean sections
because the 'uterus was too stiff in the early stage of delivery.'
POPULATION GENETICS
In a survey of 3,776 healthy persons in Shizuoka Prefecture in Japan,
Maekawa et al. (1984) found the frequency of heterozygous LDHA and LDHB
subunit deficiencies to be 0.185% (about 1 in 540) and 0.159% (about 1
in 630), respectively. These frequencies were probably higher than in
most other populations.
*FIELD* RF
1. Kanno, T.; Sudo, K.; Maekawa, M.; Nishimura, Y.; Ukita, M.; Fukutake,
K.: Lactate dehydrogenase M-subunit deficiency: a new type of hereditary
exertional myopathy. Clin. Chim. Acta 173: 89-98, 1988.
2. Kanno, T.; Sudo, K.; Takeuchi, I.; Kanda, S.; Honda, N.; Nishimura,
Y.; Oyama, K.: Hereditary deficiency of lactate dehydrogenase M-subunit. Clin.
Chim. Acta 108: 267-276, 1980.
3. Maekawa, M.; Kanda, S.; Sudo, K.; Kanno, T.: Estimation of the
gene frequency of lactate dehydrogenase subunit deficiencies. Am.
J. Hum. Genet. 36: 1204-1214, 1984.
4. Maekawa, M.; Sudo, K.; Kanno, T.: Immunochemical studies on lactate
dehydrogenase A subunit deficiencies. Am. J. Hum. Genet. 39: 232-238,
1986.
5. Maekawa, M.; Sudo, K.; Kanno, T.; Li, S. S.-L.: Molecular characterization
of genetic mutation in human lactate dehydrogenase-A (M) deficiency. Biochem.
Biophys. Res. Commun. 168: 677-682, 1990.
6. Maekawa, M.; Sudo, K.; Li, S. S.-L.; Kanno, T.: Genotypic analysis
of families with lactate dehydrogenase A(M) deficiency by selective
DNA amplification. Hum. Genet. 88: 34-38, 1991.
7. Miyajima, H.; Takahashi, Y.; Suzuki, M.; Shimizu, T.; Kaneko, E.
: Molecular characterization of gene expression in human lactate dehydrogenase-A
deficiency. Neurology 43: 1414-1419, 1993.
8. Takayasu, S.; Fujiwara, S.; Waki, T.: Hereditary lactate dehydrogenase
M-subunit deficiency: lactate dehydrogenase activity in skin lesions
and in hair follicles. J. Am. Acad. Derm. 24: 339-342, 1991.
9. Yoshikuni, K.; Tagami, H.; Yamada, M.; Sudo, K.; Kanno, T.: Erythematosquamous
skin lesions in hereditary lactate dehydrogenase M-subunit deficiency. Arch.
Derm. 122: 1420-1424, 1986.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GENITOURINARY:
[Kidneys];
Myoglobinuria;
Renal failure may occur
SKIN, NAILS, HAIR:
[Skin];
Erythematous squamous skin lesions
MUSCLE, SOFT TISSUE:
Muscle cramps;
Muscle pain;
Exercise intolerance;
Muscle rigidity;
Muscle stiffness;
Rhabdomyolysis;
Uterine muscle may be stiff during pregnancy
LABORATORY ABNORMALITIES:
Increased serum creatine kinase;
Increased serum lactate;
Increased serum pyruvate
MISCELLANEOUS:
Onset in childhood;
Symptoms induced by strenuous exercise
MOLECULAR BASIS:
Caused by mutation in the lactate dehydrogenase A gene (LDHA, 150000.0001)
*FIELD* CD
Cassandra L. Kniffin: 7/28/2009
*FIELD* ED
joanna: 01/07/2010
ckniffin: 7/28/2009
*FIELD* CD
Cassandra L. Kniffin: 7/27/2009
*FIELD* ED
terry: 04/28/2011
carol: 7/31/2009
carol: 7/30/2009
ckniffin: 7/28/2009