Full text data of MDH1
MDH1
(MDHA)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Malate dehydrogenase, cytoplasmic; 1.1.1.37 (Cytosolic malate dehydrogenase; Diiodophenylpyruvate reductase; 1.1.1.96)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Malate dehydrogenase, cytoplasmic; 1.1.1.37 (Cytosolic malate dehydrogenase; Diiodophenylpyruvate reductase; 1.1.1.96)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00291005
IPI00291005 Malate dehydrogenase, cytoplasmic Malate dehydrogenase, cytoplasmic membrane n/a n/a n/a n/a n/a n/a n/a n/a 1 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 expected molecular weight found in band between 98-188 kDa
IPI00291005 Malate dehydrogenase, cytoplasmic Malate dehydrogenase, cytoplasmic membrane n/a n/a n/a n/a n/a n/a n/a n/a 1 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 expected molecular weight found in band between 98-188 kDa
UniProt
P40925
ID MDHC_HUMAN Reviewed; 334 AA.
AC P40925; B2R5V5; B4DUN2; B7Z3I7; F5H098; Q6I9V0;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=Malate dehydrogenase, cytoplasmic;
DE EC=1.1.1.37;
DE AltName: Full=Cytosolic malate dehydrogenase;
DE AltName: Full=Diiodophenylpyruvate reductase;
DE EC=1.1.1.96;
GN Name=MDH1; Synonyms=MDHA;
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).
RC TISSUE=Heart;
RX PubMed=8786100; DOI=10.1006/geno.1996.0087;
RA Tanaka T., Inazawa J., Nakamura Y.;
RT "Molecular cloning and mapping of a human cDNA for cytosolic malate
RT dehydrogenase (MDH1).";
RL Genomics 32:128-130(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RA Lo A.S.Y., Waye M.M.Y.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Cerebellum, and Substantia nigra;
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 GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [8]
RP PROTEIN SEQUENCE OF 2-18; 205-213 AND 324-334, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=T-cell;
RA Bienvenut W.V., Kanor S., Tissot J.-D., Quadroni M.;
RL Submitted (MAY-2006) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 168-181.
RC TISSUE=Heart;
RX PubMed=7895732; DOI=10.1002/elps.11501501209;
RA Corbett J.M., Wheeler C.H., Baker C.S., Yacoub M.H., Dunn M.J.;
RT "The human myocardial two-dimensional gel protein database: update
RT 1994.";
RL Electrophoresis 15:1459-1465(1994).
RN [10]
RP PROTEIN SEQUENCE OF 180-201 AND 299-310, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [11]
RP CATALYTIC ACTIVITY.
RX PubMed=3052244; DOI=10.1111/j.1469-1809.1988.tb01075.x;
RA Friedrich C.A., Ferrell R.E., Siciliano M.J., Kitto G.B.;
RT "Biochemical and genetic identity of alpha-keto acid reductase and
RT cytoplasmic malate dehydrogenase from human erythrocytes.";
RL Ann. Hum. Genet. 52:25-37(1988).
RN [12]
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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-118 AND LYS-298, AND MASS
RP 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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 [16]
RP ACETYLATION AT LYS-118; LYS-121 AND LYS-298.
RX PubMed=22693256; DOI=10.1194/jlr.M026567;
RA Kim E.Y., Kim W.K., Kang H.J., Kim J.H., Chung S.J., Seo Y.S.,
RA Park S.G., Lee S.C., Bae K.H.;
RT "Acetylation of malate dehydrogenase 1 promotes adipogenic
RT differentiation via activating its enzymatic activity.";
RL J. Lipid Res. 53:1864-1876(2012).
CC -!- CATALYTIC ACTIVITY: (S)-malate + NAD(+) = oxaloacetate + NADH.
CC -!- CATALYTIC ACTIVITY: 3-(3,5-diiodo-4-hydroxyphenyl)lactate + NAD(+)
CC = 3-(3,5-diiodo-4-hydroxyphenyl)pyruvate + NADH.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P40925-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P40925-2; Sequence=VSP_042661;
CC Name=3;
CC IsoId=P40925-3; Sequence=VSP_045847;
CC Note=No experimental confirmation available;
CC -!- PTM: ISGylated.
CC -!- PTM: Acetylation at Lys-118 dramatically enhances enzymatic
CC activity and promotes adipogenic differentiation.
CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 2 family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Malate dehydrogenase entry;
CC URL="http://en.wikipedia.org/wiki/Malate_dehydrogenase";
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DR EMBL; D55654; BAA09513.1; -; mRNA.
DR EMBL; U20352; AAC16436.1; -; mRNA.
DR EMBL; CR457405; CAG33686.1; -; mRNA.
DR EMBL; AK295931; BAH12223.1; -; mRNA.
DR EMBL; AK300719; BAG62394.1; -; mRNA.
DR EMBL; AK312331; BAG35252.1; -; mRNA.
DR EMBL; AC016734; AAY14893.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99959.1; -; Genomic_DNA.
DR EMBL; BC001484; AAH01484.1; -; mRNA.
DR PIR; G01650; G01650.
DR RefSeq; NP_001186040.1; NM_001199111.1.
DR RefSeq; NP_001186041.1; NM_001199112.1.
DR RefSeq; NP_005908.1; NM_005917.3.
DR RefSeq; XP_005264377.1; XM_005264320.1.
DR UniGene; Hs.526521; -.
DR ProteinModelPortal; P40925; -.
DR SMR; P40925; 2-334.
DR IntAct; P40925; 5.
DR MINT; MINT-4999585; -.
DR STRING; 9606.ENSP00000233114; -.
DR BindingDB; P40925; -.
DR ChEMBL; CHEMBL3560; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; P40925; -.
DR DMDM; 1708967; -.
DR REPRODUCTION-2DPAGE; IPI00291005; -.
DR UCD-2DPAGE; P40925; -.
DR PaxDb; P40925; -.
DR PeptideAtlas; P40925; -.
DR PRIDE; P40925; -.
DR Ensembl; ENST00000233114; ENSP00000233114; ENSG00000014641.
DR Ensembl; ENST00000394423; ENSP00000377945; ENSG00000014641.
DR Ensembl; ENST00000539945; ENSP00000438144; ENSG00000014641.
DR Ensembl; ENST00000544381; ENSP00000446395; ENSG00000014641.
DR GeneID; 4190; -.
DR KEGG; hsa:4190; -.
DR UCSC; uc010ypv.2; human.
DR CTD; 4190; -.
DR GeneCards; GC02P063727; -.
DR HGNC; HGNC:6970; MDH1.
DR HPA; CAB047333; -.
DR HPA; HPA027296; -.
DR MIM; 154200; gene.
DR neXtProt; NX_P40925; -.
DR PharmGKB; PA30714; -.
DR eggNOG; COG0039; -.
DR HOVERGEN; HBG006340; -.
DR InParanoid; P40925; -.
DR KO; K00025; -.
DR OMA; NCLIASK; -.
DR OrthoDB; EOG78H3TM; -.
DR PhylomeDB; P40925; -.
DR BioCyc; MetaCyc:HS00361-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P40925; -.
DR ChiTaRS; MDH1; human.
DR GenomeRNAi; 4190; -.
DR NextBio; 16510; -.
DR PRO; PR:P40925; -.
DR ArrayExpress; P40925; -.
DR Bgee; P40925; -.
DR CleanEx; HS_MDH1; -.
DR Genevestigator; P40925; -.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0047860; F:diiodophenylpyruvate reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0030060; F:L-malate dehydrogenase activity; TAS:Reactome.
DR GO; GO:0004470; F:malic enzyme activity; TAS:ProtInc.
DR GO; GO:0051287; F:NAD binding; IEA:Ensembl.
DR GO; GO:0044262; P:cellular carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0006094; P:gluconeogenesis; TAS:Reactome.
DR GO; GO:0006108; P:malate metabolic process; IEA:Ensembl.
DR GO; GO:0006734; P:NADH metabolic process; IEA:Ensembl.
DR GO; GO:0006107; P:oxaloacetate metabolic process; IEA:Ensembl.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.720; -; 1.
DR Gene3D; 3.90.110.10; -; 1.
DR InterPro; IPR001557; L-lactate/malate_DH.
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; IPR001252; Malate_DH_AS.
DR InterPro; IPR011274; Malate_DH_NAD-dep_euk.
DR InterPro; IPR010945; Malate_DH_type2.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR PANTHER; PTHR23382; PTHR23382; 1.
DR Pfam; PF02866; Ldh_1_C; 1.
DR Pfam; PF00056; Ldh_1_N; 1.
DR PIRSF; PIRSF000102; Lac_mal_DH; 1.
DR SUPFAM; SSF56327; SSF56327; 1.
DR TIGRFAMs; TIGR01759; MalateDH-SF1; 1.
DR TIGRFAMs; TIGR01758; MDH_euk_cyt; 1.
DR PROSITE; PS00068; MDH; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Complete proteome; Cytoplasm;
KW Direct protein sequencing; NAD; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Tricarboxylic acid cycle; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 334 Malate dehydrogenase, cytoplasmic.
FT /FTId=PRO_0000113409.
FT NP_BIND 11 17 NAD (By similarity).
FT NP_BIND 129 131 NAD (By similarity).
FT ACT_SITE 187 187 Proton acceptor (By similarity).
FT BINDING 92 92 Substrate (By similarity).
FT BINDING 98 98 Substrate (By similarity).
FT BINDING 105 105 NAD (By similarity).
FT BINDING 112 112 NAD (By similarity).
FT BINDING 131 131 Substrate (By similarity).
FT BINDING 162 162 Substrate.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 118 118 N6-acetyllysine.
FT MOD_RES 121 121 N6-acetyllysine.
FT MOD_RES 298 298 N6-acetyllysine.
FT MOD_RES 333 333 Phosphoserine.
FT VAR_SEQ 1 89 Missing (in isoform 2).
FT /FTId=VSP_042661.
FT VAR_SEQ 1 1 M -> MRRCSYFPKDVTVFDKDDK (in isoform 3).
FT /FTId=VSP_045847.
FT CONFLICT 15 15 Q -> R (in Ref. 4; BAH12223).
SQ SEQUENCE 334 AA; 36426 MW; 5F7ED9789CA1DB55 CRC64;
MSEPIRVLVT GAAGQIAYSL LYSIGNGSVF GKDQPIILVL LDITPMMGVL DGVLMELQDC
ALPLLKDVIA TDKEDVAFKD LDVAILVGSM PRREGMERKD LLKANVKIFK SQGAALDKYA
KKSVKVIVVG NPANTNCLTA SKSAPSIPKE NFSCLTRLDH NRAKAQIALK LGVTANDVKN
VIIWGNHSST QYPDVNHAKV KLQGKEVGVY EALKDDSWLK GEFVTTVQQR GAAVIKARKL
SSAMSAAKAI CDHVRDIWFG TPEGEFVSMG VISDGNSYGV PDDLLYSFPV VIKNKTWKFV
EGLPINDFSR EKMDLTAKEL TEEKESAFEF LSSA
//
ID MDHC_HUMAN Reviewed; 334 AA.
AC P40925; B2R5V5; B4DUN2; B7Z3I7; F5H098; Q6I9V0;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=Malate dehydrogenase, cytoplasmic;
DE EC=1.1.1.37;
DE AltName: Full=Cytosolic malate dehydrogenase;
DE AltName: Full=Diiodophenylpyruvate reductase;
DE EC=1.1.1.96;
GN Name=MDH1; Synonyms=MDHA;
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).
RC TISSUE=Heart;
RX PubMed=8786100; DOI=10.1006/geno.1996.0087;
RA Tanaka T., Inazawa J., Nakamura Y.;
RT "Molecular cloning and mapping of a human cDNA for cytosolic malate
RT dehydrogenase (MDH1).";
RL Genomics 32:128-130(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RA Lo A.S.Y., Waye M.M.Y.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Cerebellum, and Substantia nigra;
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 GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [8]
RP PROTEIN SEQUENCE OF 2-18; 205-213 AND 324-334, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=T-cell;
RA Bienvenut W.V., Kanor S., Tissot J.-D., Quadroni M.;
RL Submitted (MAY-2006) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 168-181.
RC TISSUE=Heart;
RX PubMed=7895732; DOI=10.1002/elps.11501501209;
RA Corbett J.M., Wheeler C.H., Baker C.S., Yacoub M.H., Dunn M.J.;
RT "The human myocardial two-dimensional gel protein database: update
RT 1994.";
RL Electrophoresis 15:1459-1465(1994).
RN [10]
RP PROTEIN SEQUENCE OF 180-201 AND 299-310, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [11]
RP CATALYTIC ACTIVITY.
RX PubMed=3052244; DOI=10.1111/j.1469-1809.1988.tb01075.x;
RA Friedrich C.A., Ferrell R.E., Siciliano M.J., Kitto G.B.;
RT "Biochemical and genetic identity of alpha-keto acid reductase and
RT cytoplasmic malate dehydrogenase from human erythrocytes.";
RL Ann. Hum. Genet. 52:25-37(1988).
RN [12]
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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-118 AND LYS-298, AND MASS
RP 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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 [16]
RP ACETYLATION AT LYS-118; LYS-121 AND LYS-298.
RX PubMed=22693256; DOI=10.1194/jlr.M026567;
RA Kim E.Y., Kim W.K., Kang H.J., Kim J.H., Chung S.J., Seo Y.S.,
RA Park S.G., Lee S.C., Bae K.H.;
RT "Acetylation of malate dehydrogenase 1 promotes adipogenic
RT differentiation via activating its enzymatic activity.";
RL J. Lipid Res. 53:1864-1876(2012).
CC -!- CATALYTIC ACTIVITY: (S)-malate + NAD(+) = oxaloacetate + NADH.
CC -!- CATALYTIC ACTIVITY: 3-(3,5-diiodo-4-hydroxyphenyl)lactate + NAD(+)
CC = 3-(3,5-diiodo-4-hydroxyphenyl)pyruvate + NADH.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P40925-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P40925-2; Sequence=VSP_042661;
CC Name=3;
CC IsoId=P40925-3; Sequence=VSP_045847;
CC Note=No experimental confirmation available;
CC -!- PTM: ISGylated.
CC -!- PTM: Acetylation at Lys-118 dramatically enhances enzymatic
CC activity and promotes adipogenic differentiation.
CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 2 family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Malate dehydrogenase entry;
CC URL="http://en.wikipedia.org/wiki/Malate_dehydrogenase";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; D55654; BAA09513.1; -; mRNA.
DR EMBL; U20352; AAC16436.1; -; mRNA.
DR EMBL; CR457405; CAG33686.1; -; mRNA.
DR EMBL; AK295931; BAH12223.1; -; mRNA.
DR EMBL; AK300719; BAG62394.1; -; mRNA.
DR EMBL; AK312331; BAG35252.1; -; mRNA.
DR EMBL; AC016734; AAY14893.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99959.1; -; Genomic_DNA.
DR EMBL; BC001484; AAH01484.1; -; mRNA.
DR PIR; G01650; G01650.
DR RefSeq; NP_001186040.1; NM_001199111.1.
DR RefSeq; NP_001186041.1; NM_001199112.1.
DR RefSeq; NP_005908.1; NM_005917.3.
DR RefSeq; XP_005264377.1; XM_005264320.1.
DR UniGene; Hs.526521; -.
DR ProteinModelPortal; P40925; -.
DR SMR; P40925; 2-334.
DR IntAct; P40925; 5.
DR MINT; MINT-4999585; -.
DR STRING; 9606.ENSP00000233114; -.
DR BindingDB; P40925; -.
DR ChEMBL; CHEMBL3560; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; P40925; -.
DR DMDM; 1708967; -.
DR REPRODUCTION-2DPAGE; IPI00291005; -.
DR UCD-2DPAGE; P40925; -.
DR PaxDb; P40925; -.
DR PeptideAtlas; P40925; -.
DR PRIDE; P40925; -.
DR Ensembl; ENST00000233114; ENSP00000233114; ENSG00000014641.
DR Ensembl; ENST00000394423; ENSP00000377945; ENSG00000014641.
DR Ensembl; ENST00000539945; ENSP00000438144; ENSG00000014641.
DR Ensembl; ENST00000544381; ENSP00000446395; ENSG00000014641.
DR GeneID; 4190; -.
DR KEGG; hsa:4190; -.
DR UCSC; uc010ypv.2; human.
DR CTD; 4190; -.
DR GeneCards; GC02P063727; -.
DR HGNC; HGNC:6970; MDH1.
DR HPA; CAB047333; -.
DR HPA; HPA027296; -.
DR MIM; 154200; gene.
DR neXtProt; NX_P40925; -.
DR PharmGKB; PA30714; -.
DR eggNOG; COG0039; -.
DR HOVERGEN; HBG006340; -.
DR InParanoid; P40925; -.
DR KO; K00025; -.
DR OMA; NCLIASK; -.
DR OrthoDB; EOG78H3TM; -.
DR PhylomeDB; P40925; -.
DR BioCyc; MetaCyc:HS00361-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P40925; -.
DR ChiTaRS; MDH1; human.
DR GenomeRNAi; 4190; -.
DR NextBio; 16510; -.
DR PRO; PR:P40925; -.
DR ArrayExpress; P40925; -.
DR Bgee; P40925; -.
DR CleanEx; HS_MDH1; -.
DR Genevestigator; P40925; -.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0047860; F:diiodophenylpyruvate reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0030060; F:L-malate dehydrogenase activity; TAS:Reactome.
DR GO; GO:0004470; F:malic enzyme activity; TAS:ProtInc.
DR GO; GO:0051287; F:NAD binding; IEA:Ensembl.
DR GO; GO:0044262; P:cellular carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0006094; P:gluconeogenesis; TAS:Reactome.
DR GO; GO:0006108; P:malate metabolic process; IEA:Ensembl.
DR GO; GO:0006734; P:NADH metabolic process; IEA:Ensembl.
DR GO; GO:0006107; P:oxaloacetate metabolic process; IEA:Ensembl.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.720; -; 1.
DR Gene3D; 3.90.110.10; -; 1.
DR InterPro; IPR001557; L-lactate/malate_DH.
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; IPR001252; Malate_DH_AS.
DR InterPro; IPR011274; Malate_DH_NAD-dep_euk.
DR InterPro; IPR010945; Malate_DH_type2.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR PANTHER; PTHR23382; PTHR23382; 1.
DR Pfam; PF02866; Ldh_1_C; 1.
DR Pfam; PF00056; Ldh_1_N; 1.
DR PIRSF; PIRSF000102; Lac_mal_DH; 1.
DR SUPFAM; SSF56327; SSF56327; 1.
DR TIGRFAMs; TIGR01759; MalateDH-SF1; 1.
DR TIGRFAMs; TIGR01758; MDH_euk_cyt; 1.
DR PROSITE; PS00068; MDH; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Complete proteome; Cytoplasm;
KW Direct protein sequencing; NAD; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Tricarboxylic acid cycle; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 334 Malate dehydrogenase, cytoplasmic.
FT /FTId=PRO_0000113409.
FT NP_BIND 11 17 NAD (By similarity).
FT NP_BIND 129 131 NAD (By similarity).
FT ACT_SITE 187 187 Proton acceptor (By similarity).
FT BINDING 92 92 Substrate (By similarity).
FT BINDING 98 98 Substrate (By similarity).
FT BINDING 105 105 NAD (By similarity).
FT BINDING 112 112 NAD (By similarity).
FT BINDING 131 131 Substrate (By similarity).
FT BINDING 162 162 Substrate.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 118 118 N6-acetyllysine.
FT MOD_RES 121 121 N6-acetyllysine.
FT MOD_RES 298 298 N6-acetyllysine.
FT MOD_RES 333 333 Phosphoserine.
FT VAR_SEQ 1 89 Missing (in isoform 2).
FT /FTId=VSP_042661.
FT VAR_SEQ 1 1 M -> MRRCSYFPKDVTVFDKDDK (in isoform 3).
FT /FTId=VSP_045847.
FT CONFLICT 15 15 Q -> R (in Ref. 4; BAH12223).
SQ SEQUENCE 334 AA; 36426 MW; 5F7ED9789CA1DB55 CRC64;
MSEPIRVLVT GAAGQIAYSL LYSIGNGSVF GKDQPIILVL LDITPMMGVL DGVLMELQDC
ALPLLKDVIA TDKEDVAFKD LDVAILVGSM PRREGMERKD LLKANVKIFK SQGAALDKYA
KKSVKVIVVG NPANTNCLTA SKSAPSIPKE NFSCLTRLDH NRAKAQIALK LGVTANDVKN
VIIWGNHSST QYPDVNHAKV KLQGKEVGVY EALKDDSWLK GEFVTTVQQR GAAVIKARKL
SSAMSAAKAI CDHVRDIWFG TPEGEFVSMG VISDGNSYGV PDDLLYSFPV VIKNKTWKFV
EGLPINDFSR EKMDLTAKEL TEEKESAFEF LSSA
//
MIM
154200
*RECORD*
*FIELD* NO
154200
*FIELD* TI
*154200 MALATE DEHYDROGENASE, SOLUBLE; MDH1
;;MALATE DEHYDROGENASE, CYTOPLASMIC
*FIELD* TX
read more
DESCRIPTION
Malate dehydrogenase (EC 1.1.1.37) catalyzes the reversible oxidation of
malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the
citric acid cycle. Two isozymes are known, one in the cytosol (MDH1) and
the other in the mitochondria (MDH2; 154100) (summary by Tanaka et al.,
1996).
CLONING
Tanaka et al. (1996) isolated a human cDNA encoding a protein of 334
amino acids that showed 96% identity in amino acid sequence to murine
cytosolic malate dehydrogenase. Among the adult human tissues examined
by Northern blot analysis, heart and skeletal muscle expressed this gene
most highly.
MAPPING
MDH is syntenic with isocitrate dehydrogenase (147700) (Shows, 1972).
Chu et al. (1975) presented cell-hybrid evidence for synteny of
gal-1-PT, acid phosphatase, MDH1 and gal-plus-activator and for
assignment to chromosome 2.
By fluorescence in situ hybridization, Tanaka et al. (1996) mapped the
MDH1 gene to chromosome 2p16. This localization was somewhat different
from that earlier determined by less precise methods, i.e., analysis of
enzyme activity in somatic cell hybrids and deletion mapping.
In the mouse, the cytosolic form of malate dehydrogenase is determined
by a gene symbolized Mor2 and the mitochondrial form by a gene
symbolized Mor1 (the opposite numbering system from that used with the
mitochondrial and cytosolic isozymes in the human). Ball et al. (1994)
induced a mutant Mor2 allele and used it to map the gene to mouse
chromosome 11 in a region of homology with human chromosome 2 by linkage
analysis.
GENE FUNCTION
Zhao et al. (2010) showed that lysine acetylation is a prevalent
modification in enzymes that catalyze intermediate metabolism in the
human liver. Virtually every enzyme in glycolysis, gluconeogenesis, the
tricarboxylic acid (TCA) cycle, the urea cycle, fatty acid metabolism,
and glycogen metabolism was found to be acetylated in human liver
tissue. The concentration of metabolic fuels, such as glucose, amino
acids, and fatty acids, influenced the acetylation status of metabolic
enzymes. Acetylation activated enoyl-coenzyme A
hydratase/3-hydroxyacyl-coenzyme A dehydrogenase (607037) in fatty acid
oxidation and malate dehydrogenase in the TCA cycle, inhibited
argininosuccinate lyase (608310) in the urea cycle, and destabilized
phosphoenolpyruvate carboxykinase (261680) in gluconeogenesis. Zhao et
al. (2010) concluded that acetylation plays a major role in metabolic
regulation.
EVOLUTION
Mitochondrial and soluble MDHs agree with the rule that the 2 forms of
enzymes are coded by different chromosomes. However, Birktoft et al.
(1982) found close structural homology of the 2 (as well as lactate
dehydrogenase, see 150000) and concluded that they were derived from a
common ancestral gene.
MOLECULAR GENETICS
Davidson and Cortner (1967) observed an inherited variant of supernatant
malate dehydrogenase of erythrocytes. The variant was found in a black
woman and her 2 sons during a survey of 1470 blacks and 1440 whites. The
electrophoretic nature of the variant suggested that the molecule is a
dimer with mutation in the gene controlling one of the elements and that
this gene is autosomal.
HISTORY
Larson et al. (1982) mapped MDH1 to 2p23 by gene dosage.
Friedrich et al. (1988) presented evidence from several nonhuman species
and from humans that alpha-keto acid reductase (107920) and cytoplasmic
malate dehydrogenase are identical. Friedrich et al. (1988) questioned
the assignment of KAR to chromosome 12.
*FIELD* SA
Blake et al. (1970); Leakey et al. (1972); Weil et al. (1977)
*FIELD* RF
1. Ball, S. T.; Moseley, H. J.; Peters, J.: Mor2, supernatant malate
dehydrogenase, is linked to wa2 and Hba on mouse chromosome 11 in
a region of homology with human chromosome 2p. Genomics 24: 399-400,
1994.
2. Birktoft, J. J.; Fernley, R. T.; Bradshaw, R. A.; Banaszak, L.
J.: Amino acid sequence homology among the 2-hydroxy acid dehydrogenases:
mitochondrial and cytoplasmic malate dehydrogenases form a homologous
system with lactate dehydrogenase. Proc. Nat. Acad. Sci. 79: 6166-6170,
1982.
3. Blake, N. M.; Kirk, R. L.; Simons, M. J.; Alpers, M. P.: Genetic
variants of soluble malate dehydrogenase in New Guinea populations. Humangenetik 11:
72-74, 1970.
4. Chu, E. H. Y.; Chang, C. C.; Sun, N. C.: Synteny of the human
genes for GAL-1-PT, ACP-1, MDH-1, and GAL+-ACT and assignment to chromosome
2. Birth Defects Orig. Art. Ser. XI(3): 103-106, 1975. Note: Alternate:
Cytogenet. Cell Genet. 14: 273-276, 1975.
5. Davidson, R. G.; Cortner, J. A.: Genetic variant of human erythrocyte
malate dehydrogenase. Nature 215: 761-762, 1967.
6. Friedrich, C. A.; Ferrell, R. E.; Siciliano, M. J.; Kitto, G. B.
: Biochemical and genetic identity of alpha-keto acid reductase and
cytoplasmic malate dehydrogenase from human erythrocytes. Ann. Hum.
Genet. 52: 25-37, 1988.
7. Larson, L. M.; Bruce, A. W.; Saumur, J. H.; Wasdahl, W. A.: Further
evidence by gene dosage for the regional assignment of erythrocyte
acid phosphatase (ACP1) and malate dehydrogenase (MDH1) loci on chromosome
2p. Clin. Genet. 22: 220-225, 1982.
8. Leakey, T. E. B.; Coward, A. R.; Warlow, A.; Mourant, A. E.: The
distribution in human populations of electrophoretic variants of cytoplasmic
malate dehydrogenase. Hum. Hered. 22: 542-551, 1972.
9. Shows, T. B.: Genetics of human-mouse somatic cell hybrids: linkage
of human genes for isocitrate dehydrogenase and malate dehydrogenase. Biochem.
Genet. 7: 193-204, 1972.
10. Tanaka, T.; Inazawa, J.; Nakamura, Y.: Molecular cloning and
mapping of a human cDNA for cytosolic malate dehydrogenase (MDH1). Genomics 32:
128-130, 1996.
11. Weil, D.; Van Cong, N.; Finaz, C.; Rebourcet, R.; Cochet, C.;
de Grouchy, J.; Frezal, J.: Localisation regionale des genes humains
IDH-S, MDH-S, PGK, alpha-GAL, G6PD par l'hybridation cellulaire interspecifique. Hum.
Genet. 36: 205-211, 1977.
12. Zhao, S.; Xu, W.; Jiang, W.; Yu, W.; Lin, Y.; Zhang, T.; Yao,
J.; Zhou, L.; Zeng, Y.; Li, H.; Li, Y.; Shi, J.; and 10 others:
Regulation of cellular metabolism by protein lysine acetylation. Science 327:
1000-1004, 2010.
*FIELD* CN
Ada Hamosh - updated: 3/9/2010
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
alopez: 03/05/2012
alopez: 3/11/2010
terry: 3/9/2010
carol: 4/14/1999
mark: 3/13/1996
mark: 3/11/1996
terry: 3/7/1996
mark: 7/26/1995
carol: 1/9/1995
terry: 5/16/1994
warfield: 3/28/1994
supermim: 3/16/1992
supermim: 3/20/1990
*RECORD*
*FIELD* NO
154200
*FIELD* TI
*154200 MALATE DEHYDROGENASE, SOLUBLE; MDH1
;;MALATE DEHYDROGENASE, CYTOPLASMIC
*FIELD* TX
read more
DESCRIPTION
Malate dehydrogenase (EC 1.1.1.37) catalyzes the reversible oxidation of
malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the
citric acid cycle. Two isozymes are known, one in the cytosol (MDH1) and
the other in the mitochondria (MDH2; 154100) (summary by Tanaka et al.,
1996).
CLONING
Tanaka et al. (1996) isolated a human cDNA encoding a protein of 334
amino acids that showed 96% identity in amino acid sequence to murine
cytosolic malate dehydrogenase. Among the adult human tissues examined
by Northern blot analysis, heart and skeletal muscle expressed this gene
most highly.
MAPPING
MDH is syntenic with isocitrate dehydrogenase (147700) (Shows, 1972).
Chu et al. (1975) presented cell-hybrid evidence for synteny of
gal-1-PT, acid phosphatase, MDH1 and gal-plus-activator and for
assignment to chromosome 2.
By fluorescence in situ hybridization, Tanaka et al. (1996) mapped the
MDH1 gene to chromosome 2p16. This localization was somewhat different
from that earlier determined by less precise methods, i.e., analysis of
enzyme activity in somatic cell hybrids and deletion mapping.
In the mouse, the cytosolic form of malate dehydrogenase is determined
by a gene symbolized Mor2 and the mitochondrial form by a gene
symbolized Mor1 (the opposite numbering system from that used with the
mitochondrial and cytosolic isozymes in the human). Ball et al. (1994)
induced a mutant Mor2 allele and used it to map the gene to mouse
chromosome 11 in a region of homology with human chromosome 2 by linkage
analysis.
GENE FUNCTION
Zhao et al. (2010) showed that lysine acetylation is a prevalent
modification in enzymes that catalyze intermediate metabolism in the
human liver. Virtually every enzyme in glycolysis, gluconeogenesis, the
tricarboxylic acid (TCA) cycle, the urea cycle, fatty acid metabolism,
and glycogen metabolism was found to be acetylated in human liver
tissue. The concentration of metabolic fuels, such as glucose, amino
acids, and fatty acids, influenced the acetylation status of metabolic
enzymes. Acetylation activated enoyl-coenzyme A
hydratase/3-hydroxyacyl-coenzyme A dehydrogenase (607037) in fatty acid
oxidation and malate dehydrogenase in the TCA cycle, inhibited
argininosuccinate lyase (608310) in the urea cycle, and destabilized
phosphoenolpyruvate carboxykinase (261680) in gluconeogenesis. Zhao et
al. (2010) concluded that acetylation plays a major role in metabolic
regulation.
EVOLUTION
Mitochondrial and soluble MDHs agree with the rule that the 2 forms of
enzymes are coded by different chromosomes. However, Birktoft et al.
(1982) found close structural homology of the 2 (as well as lactate
dehydrogenase, see 150000) and concluded that they were derived from a
common ancestral gene.
MOLECULAR GENETICS
Davidson and Cortner (1967) observed an inherited variant of supernatant
malate dehydrogenase of erythrocytes. The variant was found in a black
woman and her 2 sons during a survey of 1470 blacks and 1440 whites. The
electrophoretic nature of the variant suggested that the molecule is a
dimer with mutation in the gene controlling one of the elements and that
this gene is autosomal.
HISTORY
Larson et al. (1982) mapped MDH1 to 2p23 by gene dosage.
Friedrich et al. (1988) presented evidence from several nonhuman species
and from humans that alpha-keto acid reductase (107920) and cytoplasmic
malate dehydrogenase are identical. Friedrich et al. (1988) questioned
the assignment of KAR to chromosome 12.
*FIELD* SA
Blake et al. (1970); Leakey et al. (1972); Weil et al. (1977)
*FIELD* RF
1. Ball, S. T.; Moseley, H. J.; Peters, J.: Mor2, supernatant malate
dehydrogenase, is linked to wa2 and Hba on mouse chromosome 11 in
a region of homology with human chromosome 2p. Genomics 24: 399-400,
1994.
2. Birktoft, J. J.; Fernley, R. T.; Bradshaw, R. A.; Banaszak, L.
J.: Amino acid sequence homology among the 2-hydroxy acid dehydrogenases:
mitochondrial and cytoplasmic malate dehydrogenases form a homologous
system with lactate dehydrogenase. Proc. Nat. Acad. Sci. 79: 6166-6170,
1982.
3. Blake, N. M.; Kirk, R. L.; Simons, M. J.; Alpers, M. P.: Genetic
variants of soluble malate dehydrogenase in New Guinea populations. Humangenetik 11:
72-74, 1970.
4. Chu, E. H. Y.; Chang, C. C.; Sun, N. C.: Synteny of the human
genes for GAL-1-PT, ACP-1, MDH-1, and GAL+-ACT and assignment to chromosome
2. Birth Defects Orig. Art. Ser. XI(3): 103-106, 1975. Note: Alternate:
Cytogenet. Cell Genet. 14: 273-276, 1975.
5. Davidson, R. G.; Cortner, J. A.: Genetic variant of human erythrocyte
malate dehydrogenase. Nature 215: 761-762, 1967.
6. Friedrich, C. A.; Ferrell, R. E.; Siciliano, M. J.; Kitto, G. B.
: Biochemical and genetic identity of alpha-keto acid reductase and
cytoplasmic malate dehydrogenase from human erythrocytes. Ann. Hum.
Genet. 52: 25-37, 1988.
7. Larson, L. M.; Bruce, A. W.; Saumur, J. H.; Wasdahl, W. A.: Further
evidence by gene dosage for the regional assignment of erythrocyte
acid phosphatase (ACP1) and malate dehydrogenase (MDH1) loci on chromosome
2p. Clin. Genet. 22: 220-225, 1982.
8. Leakey, T. E. B.; Coward, A. R.; Warlow, A.; Mourant, A. E.: The
distribution in human populations of electrophoretic variants of cytoplasmic
malate dehydrogenase. Hum. Hered. 22: 542-551, 1972.
9. Shows, T. B.: Genetics of human-mouse somatic cell hybrids: linkage
of human genes for isocitrate dehydrogenase and malate dehydrogenase. Biochem.
Genet. 7: 193-204, 1972.
10. Tanaka, T.; Inazawa, J.; Nakamura, Y.: Molecular cloning and
mapping of a human cDNA for cytosolic malate dehydrogenase (MDH1). Genomics 32:
128-130, 1996.
11. Weil, D.; Van Cong, N.; Finaz, C.; Rebourcet, R.; Cochet, C.;
de Grouchy, J.; Frezal, J.: Localisation regionale des genes humains
IDH-S, MDH-S, PGK, alpha-GAL, G6PD par l'hybridation cellulaire interspecifique. Hum.
Genet. 36: 205-211, 1977.
12. Zhao, S.; Xu, W.; Jiang, W.; Yu, W.; Lin, Y.; Zhang, T.; Yao,
J.; Zhou, L.; Zeng, Y.; Li, H.; Li, Y.; Shi, J.; and 10 others:
Regulation of cellular metabolism by protein lysine acetylation. Science 327:
1000-1004, 2010.
*FIELD* CN
Ada Hamosh - updated: 3/9/2010
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
alopez: 03/05/2012
alopez: 3/11/2010
terry: 3/9/2010
carol: 4/14/1999
mark: 3/13/1996
mark: 3/11/1996
terry: 3/7/1996
mark: 7/26/1995
carol: 1/9/1995
terry: 5/16/1994
warfield: 3/28/1994
supermim: 3/16/1992
supermim: 3/20/1990