Full text data of MDH2
MDH2
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Malate dehydrogenase, mitochondrial; 1.1.1.37; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Malate dehydrogenase, mitochondrial; 1.1.1.37; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00291006
IPI00291006 Malate dehydrogenase, mitochondrial precursor Malate dehydrogenase, mitochondrial precursor membrane n/a n/a n/a n/a n/a n/a n/a n/a 2 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a mitochondrial n/a expected molecular weight found in band > 188 kDa together with ubiquitin
IPI00291006 Malate dehydrogenase, mitochondrial precursor Malate dehydrogenase, mitochondrial precursor membrane n/a n/a n/a n/a n/a n/a n/a n/a 2 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a mitochondrial n/a expected molecular weight found in band > 188 kDa together with ubiquitin
UniProt
P40926
ID MDHM_HUMAN Reviewed; 338 AA.
AC P40926; A8K414; B2RE78; O43682;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 25-NOV-2008, sequence version 3.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Malate dehydrogenase, mitochondrial;
DE EC=1.1.1.37;
DE Flags: Precursor;
GN Name=MDH2;
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], AND VARIANT VAL-9.
RA Hu G.;
RT "Human homolog of mouse and pig MDH mRNA.";
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney, and Tongue;
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 [3]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-9.
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-165; LYS-185; LYS-301;
RP LYS-314; LYS-329 AND LYS-335, 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 [8]
RP ACETYLATION AT LYS-185; LYS-301; LYS-307 AND LYS-314, ENZYME
RP REGULATION, MASS SPECTROMETRY, AND MUTAGENESIS OF LYS-185; LYS-301;
RP LYS-307 AND LYS-314.
RX PubMed=20167786; DOI=10.1126/science.1179689;
RA Zhao S., Xu W., Jiang W., Yu W., Lin Y., Zhang T., Yao J., Zhou L.,
RA Zeng Y., Li H., Li Y., Shi J., An W., Hancock S.M., He F., Qin L.,
RA Chin J., Yang P., Chen X., Lei Q., Xiong Y., Guan K.L.;
RT "Regulation of cellular metabolism by protein lysine acetylation.";
RL Science 327:1000-1004(2010).
RN [9]
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 [10]
RP MALONYLATION AT LYS-307.
RX PubMed=21908771; DOI=10.1074/mcp.M111.012658;
RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y.,
RA He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C.,
RA Dai J., Verdin E., Ye Y., Zhao Y.;
RT "The first identification of lysine malonylation substrates and its
RT regulatory enzyme.";
RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 20-338 IN COMPLEX WITH NAD
RP AND SUBSTRATE, AND SUBUNIT.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human malate dehydrogenase type 2.";
RL Submitted (MAR-2006) to the PDB data bank.
CC -!- CATALYTIC ACTIVITY: (S)-malate + NAD(+) = oxaloacetate + NADH.
CC -!- ENZYME REGULATION: Enzyme activity is enhanced by acetylation.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- PTM: Acetylation is enhanced by up to 67% after treatment either
CC with trichostin A (TSA) or with nicotinamide (NAM) with the
CC appearance of tri-and tetraacetylations. Glucose also increases
CC acetylation by about 60% (By similarity).
CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 1 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; AF047470; AAC03787.1; -; mRNA.
DR EMBL; AK290779; BAF83468.1; -; mRNA.
DR EMBL; AK316587; BAG38175.1; -; mRNA.
DR EMBL; CH471220; EAW71796.1; -; Genomic_DNA.
DR EMBL; BC001917; AAH01917.1; -; mRNA.
DR RefSeq; NP_001269332.1; NM_001282403.1.
DR RefSeq; NP_001269333.1; NM_001282404.1.
DR RefSeq; NP_005909.2; NM_005918.3.
DR UniGene; Hs.520967; -.
DR PDB; 2DFD; X-ray; 1.90 A; A/B/C/D=20-338.
DR PDBsum; 2DFD; -.
DR ProteinModelPortal; P40926; -.
DR SMR; P40926; 24-337.
DR IntAct; P40926; 12.
DR MINT; MINT-1408946; -.
DR STRING; 9606.ENSP00000327070; -.
DR BindingDB; P40926; -.
DR ChEMBL; CHEMBL5917; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; P40926; -.
DR DMDM; 215274114; -.
DR DOSAC-COBS-2DPAGE; P40926; -.
DR REPRODUCTION-2DPAGE; IPI00291006; -.
DR REPRODUCTION-2DPAGE; P40926; -.
DR UCD-2DPAGE; P40926; -.
DR PaxDb; P40926; -.
DR PRIDE; P40926; -.
DR DNASU; 4191; -.
DR Ensembl; ENST00000315758; ENSP00000327070; ENSG00000146701.
DR Ensembl; ENST00000573193; ENSP00000459911; ENSG00000262847.
DR GeneID; 4191; -.
DR KEGG; hsa:4191; -.
DR UCSC; uc003ueo.3; human.
DR CTD; 4191; -.
DR GeneCards; GC07P075677; -.
DR HGNC; HGNC:6971; MDH2.
DR HPA; HPA019714; -.
DR HPA; HPA019716; -.
DR HPA; HPA019848; -.
DR HPA; HPA026720; -.
DR MIM; 154100; gene.
DR neXtProt; NX_P40926; -.
DR PharmGKB; PA30716; -.
DR eggNOG; COG0039; -.
DR HOGENOM; HOG000213792; -.
DR HOVERGEN; HBG001662; -.
DR InParanoid; P40926; -.
DR KO; K00026; -.
DR OMA; VEVKGFA; -.
DR PhylomeDB; P40926; -.
DR BioCyc; MetaCyc:HS07366-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; Mdh2; human.
DR EvolutionaryTrace; P40926; -.
DR GeneWiki; Malate_dehydrogenase_2; -.
DR GenomeRNAi; 4191; -.
DR NextBio; 16514; -.
DR PRO; PR:P40926; -.
DR ArrayExpress; P40926; -.
DR Bgee; P40926; -.
DR CleanEx; HS_MDH2; -.
DR Genevestigator; P40926; -.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0030060; F:L-malate dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0046554; F:malate dehydrogenase (NADP+) activity; IEA:Ensembl.
DR GO; GO:0044262; P:cellular carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0006094; P:gluconeogenesis; TAS:Reactome.
DR GO; GO:0006475; P:internal protein amino acid acetylation; IDA:UniProtKB.
DR GO; GO:0006108; P:malate metabolic process; IDA:UniProtKB.
DR GO; GO:0006734; P:NADH metabolic process; IEA:Ensembl.
DR GO; GO:0006107; P:oxaloacetate metabolic process; IEA:Ensembl.
DR GO; GO:0006099; P:tricarboxylic acid cycle; 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; 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; IPR010097; Malate_DH_type1.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR PANTHER; PTHR11540; PTHR11540; 1.
DR PANTHER; PTHR11540:SF1; PTHR11540:SF1; 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; TIGR01772; MDH_euk_gproteo; 1.
DR PROSITE; PS00068; MDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Mitochondrion; NAD;
KW Oxidoreductase; Polymorphism; Reference proteome; Transit peptide;
KW Tricarboxylic acid cycle.
FT TRANSIT 1 24 Mitochondrion (By similarity).
FT CHAIN 25 338 Malate dehydrogenase, mitochondrial.
FT /FTId=PRO_0000018628.
FT NP_BIND 31 37 NAD.
FT NP_BIND 140 142 NAD.
FT ACT_SITE 200 200 Proton acceptor (By similarity).
FT BINDING 57 57 NAD.
FT BINDING 104 104 Substrate.
FT BINDING 110 110 Substrate.
FT BINDING 117 117 NAD.
FT BINDING 142 142 Substrate.
FT BINDING 176 176 Substrate.
FT BINDING 251 251 NAD.
FT MOD_RES 78 78 N6-acetyllysine (By similarity).
FT MOD_RES 91 91 N6-acetyllysine (By similarity).
FT MOD_RES 165 165 N6-acetyllysine.
FT MOD_RES 185 185 N6-acetyllysine.
FT MOD_RES 215 215 N6-acetyllysine (By similarity).
FT MOD_RES 239 239 N6-acetyllysine; alternate (By
FT similarity).
FT MOD_RES 239 239 N6-malonyllysine; alternate (By
FT similarity).
FT MOD_RES 239 239 N6-succinyllysine; alternate (By
FT similarity).
FT MOD_RES 296 296 N6-acetyllysine (By similarity).
FT MOD_RES 301 301 N6-acetyllysine; alternate.
FT MOD_RES 301 301 N6-succinyllysine; alternate (By
FT similarity).
FT MOD_RES 307 307 N6-acetyllysine; alternate.
FT MOD_RES 307 307 N6-malonyllysine; alternate.
FT MOD_RES 314 314 N6-acetyllysine.
FT MOD_RES 324 324 N6-acetyllysine (By similarity).
FT MOD_RES 328 328 N6-acetyllysine; alternate (By
FT similarity).
FT MOD_RES 328 328 N6-succinyllysine; alternate (By
FT similarity).
FT MOD_RES 329 329 N6-acetyllysine; alternate.
FT MOD_RES 329 329 N6-malonyllysine; alternate (By
FT similarity).
FT MOD_RES 335 335 N6-acetyllysine.
FT VARIANT 9 9 A -> V (in dbSNP:rs17849553).
FT /FTId=VAR_047787.
FT MUTAGEN 185 185 K->R: No activation of enzyme activity on
FT treatment with TSA or NAM; when
FT associated with R-301; R-307 and R-314.
FT MUTAGEN 301 301 K->R: No activation of enzyme activity on
FT treatment with TSA or NAM; when
FT associated with R-185; R-307 and R-314.
FT MUTAGEN 307 307 K->R: No activation of enzyme activity on
FT treatment with TSA or NAM; when
FT associated with R-185; R-301 and R-314.
FT MUTAGEN 314 314 K->R: No activation of enzyme activity on
FT treatment with TSA or NAM; when
FT associated with R-185; R-301 and R-307.
FT STRAND 25 30
FT TURN 31 33
FT HELIX 37 45
FT STRAND 50 60
FT HELIX 61 69
FT STRAND 71 74
FT STRAND 76 82
FT TURN 83 85
FT HELIX 86 90
FT STRAND 94 98
FT HELIX 110 113
FT HELIX 114 131
FT STRAND 135 139
FT HELIX 144 157
FT STRAND 165 168
FT HELIX 171 185
FT HELIX 189 191
FT STRAND 196 198
FT HELIX 202 204
FT STRAND 205 207
FT HELIX 209 211
FT HELIX 220 241
FT HELIX 249 266
FT STRAND 273 279
FT STRAND 282 295
FT STRAND 298 302
FT HELIX 310 335
SQ SEQUENCE 338 AA; 35503 MW; AAB9F5E5B2FBC8CA CRC64;
MLSALARPAS AALRRSFSTS AQNNAKVAVL GASGGIGQPL SLLLKNSPLV SRLTLYDIAH
TPGVAADLSH IETKAAVKGY LGPEQLPDCL KGCDVVVIPA GVPRKPGMTR DDLFNTNATI
VATLTAACAQ HCPEAMICVI ANPVNSTIPI TAEVFKKHGV YNPNKIFGVT TLDIVRANTF
VAELKGLDPA RVNVPVIGGH AGKTIIPLIS QCTPKVDFPQ DQLTALTGRI QEAGTEVVKA
KAGAGSATLS MAYAGARFVF SLVDAMNGKE GVVECSFVKS QETECTYFST PLLLGKKGIE
KNLGIGKVSS FEEKMISDAI PELKASIKKG EDFVKTLK
//
ID MDHM_HUMAN Reviewed; 338 AA.
AC P40926; A8K414; B2RE78; O43682;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 25-NOV-2008, sequence version 3.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Malate dehydrogenase, mitochondrial;
DE EC=1.1.1.37;
DE Flags: Precursor;
GN Name=MDH2;
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], AND VARIANT VAL-9.
RA Hu G.;
RT "Human homolog of mouse and pig MDH mRNA.";
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney, and Tongue;
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 [3]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-9.
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-165; LYS-185; LYS-301;
RP LYS-314; LYS-329 AND LYS-335, 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 [8]
RP ACETYLATION AT LYS-185; LYS-301; LYS-307 AND LYS-314, ENZYME
RP REGULATION, MASS SPECTROMETRY, AND MUTAGENESIS OF LYS-185; LYS-301;
RP LYS-307 AND LYS-314.
RX PubMed=20167786; DOI=10.1126/science.1179689;
RA Zhao S., Xu W., Jiang W., Yu W., Lin Y., Zhang T., Yao J., Zhou L.,
RA Zeng Y., Li H., Li Y., Shi J., An W., Hancock S.M., He F., Qin L.,
RA Chin J., Yang P., Chen X., Lei Q., Xiong Y., Guan K.L.;
RT "Regulation of cellular metabolism by protein lysine acetylation.";
RL Science 327:1000-1004(2010).
RN [9]
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 [10]
RP MALONYLATION AT LYS-307.
RX PubMed=21908771; DOI=10.1074/mcp.M111.012658;
RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y.,
RA He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C.,
RA Dai J., Verdin E., Ye Y., Zhao Y.;
RT "The first identification of lysine malonylation substrates and its
RT regulatory enzyme.";
RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 20-338 IN COMPLEX WITH NAD
RP AND SUBSTRATE, AND SUBUNIT.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human malate dehydrogenase type 2.";
RL Submitted (MAR-2006) to the PDB data bank.
CC -!- CATALYTIC ACTIVITY: (S)-malate + NAD(+) = oxaloacetate + NADH.
CC -!- ENZYME REGULATION: Enzyme activity is enhanced by acetylation.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- PTM: Acetylation is enhanced by up to 67% after treatment either
CC with trichostin A (TSA) or with nicotinamide (NAM) with the
CC appearance of tri-and tetraacetylations. Glucose also increases
CC acetylation by about 60% (By similarity).
CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 1 family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Malate dehydrogenase entry;
CC URL="http://en.wikipedia.org/wiki/Malate_dehydrogenase";
CC -----------------------------------------------------------------------
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DR EMBL; AF047470; AAC03787.1; -; mRNA.
DR EMBL; AK290779; BAF83468.1; -; mRNA.
DR EMBL; AK316587; BAG38175.1; -; mRNA.
DR EMBL; CH471220; EAW71796.1; -; Genomic_DNA.
DR EMBL; BC001917; AAH01917.1; -; mRNA.
DR RefSeq; NP_001269332.1; NM_001282403.1.
DR RefSeq; NP_001269333.1; NM_001282404.1.
DR RefSeq; NP_005909.2; NM_005918.3.
DR UniGene; Hs.520967; -.
DR PDB; 2DFD; X-ray; 1.90 A; A/B/C/D=20-338.
DR PDBsum; 2DFD; -.
DR ProteinModelPortal; P40926; -.
DR SMR; P40926; 24-337.
DR IntAct; P40926; 12.
DR MINT; MINT-1408946; -.
DR STRING; 9606.ENSP00000327070; -.
DR BindingDB; P40926; -.
DR ChEMBL; CHEMBL5917; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; P40926; -.
DR DMDM; 215274114; -.
DR DOSAC-COBS-2DPAGE; P40926; -.
DR REPRODUCTION-2DPAGE; IPI00291006; -.
DR REPRODUCTION-2DPAGE; P40926; -.
DR UCD-2DPAGE; P40926; -.
DR PaxDb; P40926; -.
DR PRIDE; P40926; -.
DR DNASU; 4191; -.
DR Ensembl; ENST00000315758; ENSP00000327070; ENSG00000146701.
DR Ensembl; ENST00000573193; ENSP00000459911; ENSG00000262847.
DR GeneID; 4191; -.
DR KEGG; hsa:4191; -.
DR UCSC; uc003ueo.3; human.
DR CTD; 4191; -.
DR GeneCards; GC07P075677; -.
DR HGNC; HGNC:6971; MDH2.
DR HPA; HPA019714; -.
DR HPA; HPA019716; -.
DR HPA; HPA019848; -.
DR HPA; HPA026720; -.
DR MIM; 154100; gene.
DR neXtProt; NX_P40926; -.
DR PharmGKB; PA30716; -.
DR eggNOG; COG0039; -.
DR HOGENOM; HOG000213792; -.
DR HOVERGEN; HBG001662; -.
DR InParanoid; P40926; -.
DR KO; K00026; -.
DR OMA; VEVKGFA; -.
DR PhylomeDB; P40926; -.
DR BioCyc; MetaCyc:HS07366-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; Mdh2; human.
DR EvolutionaryTrace; P40926; -.
DR GeneWiki; Malate_dehydrogenase_2; -.
DR GenomeRNAi; 4191; -.
DR NextBio; 16514; -.
DR PRO; PR:P40926; -.
DR ArrayExpress; P40926; -.
DR Bgee; P40926; -.
DR CleanEx; HS_MDH2; -.
DR Genevestigator; P40926; -.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0030060; F:L-malate dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0046554; F:malate dehydrogenase (NADP+) activity; IEA:Ensembl.
DR GO; GO:0044262; P:cellular carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0006094; P:gluconeogenesis; TAS:Reactome.
DR GO; GO:0006475; P:internal protein amino acid acetylation; IDA:UniProtKB.
DR GO; GO:0006108; P:malate metabolic process; IDA:UniProtKB.
DR GO; GO:0006734; P:NADH metabolic process; IEA:Ensembl.
DR GO; GO:0006107; P:oxaloacetate metabolic process; IEA:Ensembl.
DR GO; GO:0006099; P:tricarboxylic acid cycle; 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; 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; IPR010097; Malate_DH_type1.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR PANTHER; PTHR11540; PTHR11540; 1.
DR PANTHER; PTHR11540:SF1; PTHR11540:SF1; 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; TIGR01772; MDH_euk_gproteo; 1.
DR PROSITE; PS00068; MDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Mitochondrion; NAD;
KW Oxidoreductase; Polymorphism; Reference proteome; Transit peptide;
KW Tricarboxylic acid cycle.
FT TRANSIT 1 24 Mitochondrion (By similarity).
FT CHAIN 25 338 Malate dehydrogenase, mitochondrial.
FT /FTId=PRO_0000018628.
FT NP_BIND 31 37 NAD.
FT NP_BIND 140 142 NAD.
FT ACT_SITE 200 200 Proton acceptor (By similarity).
FT BINDING 57 57 NAD.
FT BINDING 104 104 Substrate.
FT BINDING 110 110 Substrate.
FT BINDING 117 117 NAD.
FT BINDING 142 142 Substrate.
FT BINDING 176 176 Substrate.
FT BINDING 251 251 NAD.
FT MOD_RES 78 78 N6-acetyllysine (By similarity).
FT MOD_RES 91 91 N6-acetyllysine (By similarity).
FT MOD_RES 165 165 N6-acetyllysine.
FT MOD_RES 185 185 N6-acetyllysine.
FT MOD_RES 215 215 N6-acetyllysine (By similarity).
FT MOD_RES 239 239 N6-acetyllysine; alternate (By
FT similarity).
FT MOD_RES 239 239 N6-malonyllysine; alternate (By
FT similarity).
FT MOD_RES 239 239 N6-succinyllysine; alternate (By
FT similarity).
FT MOD_RES 296 296 N6-acetyllysine (By similarity).
FT MOD_RES 301 301 N6-acetyllysine; alternate.
FT MOD_RES 301 301 N6-succinyllysine; alternate (By
FT similarity).
FT MOD_RES 307 307 N6-acetyllysine; alternate.
FT MOD_RES 307 307 N6-malonyllysine; alternate.
FT MOD_RES 314 314 N6-acetyllysine.
FT MOD_RES 324 324 N6-acetyllysine (By similarity).
FT MOD_RES 328 328 N6-acetyllysine; alternate (By
FT similarity).
FT MOD_RES 328 328 N6-succinyllysine; alternate (By
FT similarity).
FT MOD_RES 329 329 N6-acetyllysine; alternate.
FT MOD_RES 329 329 N6-malonyllysine; alternate (By
FT similarity).
FT MOD_RES 335 335 N6-acetyllysine.
FT VARIANT 9 9 A -> V (in dbSNP:rs17849553).
FT /FTId=VAR_047787.
FT MUTAGEN 185 185 K->R: No activation of enzyme activity on
FT treatment with TSA or NAM; when
FT associated with R-301; R-307 and R-314.
FT MUTAGEN 301 301 K->R: No activation of enzyme activity on
FT treatment with TSA or NAM; when
FT associated with R-185; R-307 and R-314.
FT MUTAGEN 307 307 K->R: No activation of enzyme activity on
FT treatment with TSA or NAM; when
FT associated with R-185; R-301 and R-314.
FT MUTAGEN 314 314 K->R: No activation of enzyme activity on
FT treatment with TSA or NAM; when
FT associated with R-185; R-301 and R-307.
FT STRAND 25 30
FT TURN 31 33
FT HELIX 37 45
FT STRAND 50 60
FT HELIX 61 69
FT STRAND 71 74
FT STRAND 76 82
FT TURN 83 85
FT HELIX 86 90
FT STRAND 94 98
FT HELIX 110 113
FT HELIX 114 131
FT STRAND 135 139
FT HELIX 144 157
FT STRAND 165 168
FT HELIX 171 185
FT HELIX 189 191
FT STRAND 196 198
FT HELIX 202 204
FT STRAND 205 207
FT HELIX 209 211
FT HELIX 220 241
FT HELIX 249 266
FT STRAND 273 279
FT STRAND 282 295
FT STRAND 298 302
FT HELIX 310 335
SQ SEQUENCE 338 AA; 35503 MW; AAB9F5E5B2FBC8CA CRC64;
MLSALARPAS AALRRSFSTS AQNNAKVAVL GASGGIGQPL SLLLKNSPLV SRLTLYDIAH
TPGVAADLSH IETKAAVKGY LGPEQLPDCL KGCDVVVIPA GVPRKPGMTR DDLFNTNATI
VATLTAACAQ HCPEAMICVI ANPVNSTIPI TAEVFKKHGV YNPNKIFGVT TLDIVRANTF
VAELKGLDPA RVNVPVIGGH AGKTIIPLIS QCTPKVDFPQ DQLTALTGRI QEAGTEVVKA
KAGAGSATLS MAYAGARFVF SLVDAMNGKE GVVECSFVKS QETECTYFST PLLLGKKGIE
KNLGIGKVSS FEEKMISDAI PELKASIKKG EDFVKTLK
//
MIM
154100
*RECORD*
*FIELD* NO
154100
*FIELD* TI
*154100 MALATE DEHYDROGENASE, MITOCHONDRIAL; MDH2
*FIELD* TX
In both leukocytes and placentas, Davidson and Cortner (1967) found
read morepolymorphism of the malate dehydrogenase that is bound to mitochondria,
called M-MDH originally and now symbolized MDH2. The fact that
mitochondrial malate dehydrogenase was indistinguishable from normal in
persons with variation in the supernatant MDH indicates that a separate
locus is involved in its genetic determination. Mendelian segregation
rather than maternal inheritance of MDH2 suggests that not all
mitochondrial proteins are coded by mitochondrial DNA. Mitochondrial
glutamic oxaloacetic transaminase (138150) is also determined by nuclear
genes. From study of hybrid cells, Van Heyningen et al. (1975) mapped
the locus for MDH2 to chromosome 7. Habets et al. (1992) subsequently
mapped the locus to 7cen-q22.
*FIELD* SA
Benn et al. (1977); Blake (1978); Shimizu et al. (1978); Shows (1972)
*FIELD* RF
1. Benn, P.; Chern, C. J.; Bruns, G.; Craig, I. W.; Croce, C. M.:
Assignment of the genes for human beta-glucuronidase and mitochondrial
malate dehydrogenase to the region pter-q22 of chromosome 7. Cytogenet.
Cell Genet. 19: 273-280, 1977.
2. Blake, N. M.: Malate dehydrogenase types in the Asian-Pacific
area, and a description of new phenotypes. Hum. Genet. 43: 69-80,
1978.
3. Davidson, R. G.; Cortner, J. A.: Mitochondrial malate dehydrogenase:
a new genetic polymorphism in man. Science 157: 1569-1571, 1967.
4. Habets, G. G. M.; van der Kammen, R. A.; Willemsen, V.; Balemans,
M.; Wiegant, J.; Collard, J. G.: Sublocalization of an invasion-inducing
locus and other genes on human chromosome 7. Cytogenet. Cell Genet. 60:
200-205, 1992.
5. Shimizu, N.; Shimizu, Y.; Ruddle, F. H.: Assignment of the human
mitochondrial NAD-linked malate dehydrogenase gene to the p22-qter
region of chromosome 7. Cytogenet. Cell Genet. 22: 441-445, 1978.
6. 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.
7. Van Heyningen, V.; Bobrow, M.; Bodmer, W. F.; Gardiner, S. E.;
Povey, S.; Hopkinson, D. A.: Chromosome assignment of some human
enzyme loci: mitochondrial malate dehydrogenase to 7, mannosephosphate
isomerase and pyruvate kinase to 15 and probably, esterase D to 13. Ann.
Hum. Genet. 38: 295-303, 1975.
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
carol: 12/13/2001
carol: 6/8/1999
carol: 1/9/1995
terry: 5/16/1994
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
*RECORD*
*FIELD* NO
154100
*FIELD* TI
*154100 MALATE DEHYDROGENASE, MITOCHONDRIAL; MDH2
*FIELD* TX
In both leukocytes and placentas, Davidson and Cortner (1967) found
read morepolymorphism of the malate dehydrogenase that is bound to mitochondria,
called M-MDH originally and now symbolized MDH2. The fact that
mitochondrial malate dehydrogenase was indistinguishable from normal in
persons with variation in the supernatant MDH indicates that a separate
locus is involved in its genetic determination. Mendelian segregation
rather than maternal inheritance of MDH2 suggests that not all
mitochondrial proteins are coded by mitochondrial DNA. Mitochondrial
glutamic oxaloacetic transaminase (138150) is also determined by nuclear
genes. From study of hybrid cells, Van Heyningen et al. (1975) mapped
the locus for MDH2 to chromosome 7. Habets et al. (1992) subsequently
mapped the locus to 7cen-q22.
*FIELD* SA
Benn et al. (1977); Blake (1978); Shimizu et al. (1978); Shows (1972)
*FIELD* RF
1. Benn, P.; Chern, C. J.; Bruns, G.; Craig, I. W.; Croce, C. M.:
Assignment of the genes for human beta-glucuronidase and mitochondrial
malate dehydrogenase to the region pter-q22 of chromosome 7. Cytogenet.
Cell Genet. 19: 273-280, 1977.
2. Blake, N. M.: Malate dehydrogenase types in the Asian-Pacific
area, and a description of new phenotypes. Hum. Genet. 43: 69-80,
1978.
3. Davidson, R. G.; Cortner, J. A.: Mitochondrial malate dehydrogenase:
a new genetic polymorphism in man. Science 157: 1569-1571, 1967.
4. Habets, G. G. M.; van der Kammen, R. A.; Willemsen, V.; Balemans,
M.; Wiegant, J.; Collard, J. G.: Sublocalization of an invasion-inducing
locus and other genes on human chromosome 7. Cytogenet. Cell Genet. 60:
200-205, 1992.
5. Shimizu, N.; Shimizu, Y.; Ruddle, F. H.: Assignment of the human
mitochondrial NAD-linked malate dehydrogenase gene to the p22-qter
region of chromosome 7. Cytogenet. Cell Genet. 22: 441-445, 1978.
6. 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.
7. Van Heyningen, V.; Bobrow, M.; Bodmer, W. F.; Gardiner, S. E.;
Povey, S.; Hopkinson, D. A.: Chromosome assignment of some human
enzyme loci: mitochondrial malate dehydrogenase to 7, mannosephosphate
isomerase and pyruvate kinase to 15 and probably, esterase D to 13. Ann.
Hum. Genet. 38: 295-303, 1975.
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
carol: 12/13/2001
carol: 6/8/1999
carol: 1/9/1995
terry: 5/16/1994
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988