MDHM_RAT
ID MDHM_RAT Reviewed; 338 AA.
AC P04636; Q6GSM4;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Malate dehydrogenase, mitochondrial;
DE EC=1.1.1.37;
DE Flags: Precursor;
GN Name=Mdh2; Synonyms=Mor1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3755817; DOI=10.1093/nar/14.15.6053;
RA Grant P.M., Tellam J., May V.L., Strauss A.W.;
RT "Isolation and nucleotide sequence of a cDNA clone encoding rat
RT mitochondrial malate dehydrogenase.";
RL Nucleic Acids Res. 14:6053-6066(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary anterior lobe;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 25-338.
RX PubMed=3828294; DOI=10.1021/bi00375a019;
RA Grant P.M., Roderick S.L., Grant G.A., Banaszak L.J., Strauss A.W.;
RT "Comparison of the precursor and mature forms of rat heart mitochondrial
RT malate dehydrogenase.";
RL Biochemistry 26:128-134(1987).
RN [4]
RP PROTEIN SEQUENCE OF 27-52; 53-74; 166-185; 192-203; 216-239; 242-296 AND
RP 308-324, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, Hippocampus, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE SPECIFICITY.
RX PubMed=19423663; DOI=10.1530/rep-09-0052;
RA Khan S.A., Suryawanshi A.R., Ranpura S.A., Jadhav S.V., Khole V.V.;
RT "Identification of novel immunodominant epididymal sperm proteins using
RT combinatorial approach.";
RL Reproduction 138:81-93(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [7]
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION AT SER-33.
RX PubMed=24098488; DOI=10.1371/journal.pone.0076399;
RA Cao W., Cao J., Huang J., Yao J., Yan G., Xu H., Yang P.;
RT "Discovery and confirmation of O-GlcNAcylated proteins in rat liver
RT mitochondria by combination of mass spectrometry and immunological
RT methods.";
RL PLoS ONE 8:E76399-E76399(2013).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-malate + NAD(+) = H(+) + NADH + oxaloacetate;
CC Xref=Rhea:RHEA:21432, ChEBI:CHEBI:15378, ChEBI:CHEBI:15589,
CC ChEBI:CHEBI:16452, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.37;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10004};
CC -!- ACTIVITY REGULATION: Enzyme activity is enhanced by acetylation.
CC {ECO:0000250|UniProtKB:P40926}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P00346}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:24098488}.
CC -!- TISSUE SPECIFICITY: Expressed in flagella of epididymal sperm.
CC {ECO:0000269|PubMed:19423663}.
CC -!- PTM: Acetylation is enhanced after treatment either with trichostin A
CC (TCA) or with nicotinamide (NAM) with the appearance of tri- and
CC tetraacetylations. Glucose also increases acetylation.
CC {ECO:0000250|UniProtKB:P40926}.
CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 1 family.
CC {ECO:0000305}.
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DR EMBL; X04240; CAA27812.1; -; mRNA.
DR EMBL; BC063165; AAH63165.1; -; mRNA.
DR PIR; A25509; DERTMM.
DR RefSeq; NP_112413.2; NM_031151.2.
DR AlphaFoldDB; P04636; -.
DR SMR; P04636; -.
DR BioGRID; 249687; 3.
DR IntAct; P04636; 3.
DR MINT; P04636; -.
DR STRING; 10116.ENSRNOP00000001958; -.
DR ChEMBL; CHEMBL2176835; -.
DR CarbonylDB; P04636; -.
DR GlyGen; P04636; 1 site.
DR iPTMnet; P04636; -.
DR PhosphoSitePlus; P04636; -.
DR SwissPalm; P04636; -.
DR World-2DPAGE; 0004:P04636; -.
DR jPOST; P04636; -.
DR PaxDb; P04636; -.
DR PRIDE; P04636; -.
DR Ensembl; ENSRNOT00000001958; ENSRNOP00000001958; ENSRNOG00000001440.
DR GeneID; 81829; -.
DR KEGG; rno:81829; -.
DR UCSC; RGD:619719; rat.
DR CTD; 4191; -.
DR RGD; 619719; Mdh2.
DR eggNOG; KOG1494; Eukaryota.
DR GeneTree; ENSGT00390000016686; -.
DR HOGENOM; CLU_047181_0_1_1; -.
DR InParanoid; P04636; -.
DR OMA; MGWTSQA; -.
DR OrthoDB; 976445at2759; -.
DR PhylomeDB; P04636; -.
DR TreeFam; TF300834; -.
DR Reactome; R-RNO-70263; Gluconeogenesis.
DR Reactome; R-RNO-71403; Citric acid cycle (TCA cycle).
DR PRO; PR:P04636; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Bgee; ENSRNOG00000001440; Expressed in duodenum and 20 other tissues.
DR Genevisible; P04636; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0030060; F:L-malate dehydrogenase activity; IDA:RGD.
DR GO; GO:0046554; F:malate dehydrogenase (NADP+) activity; IDA:RGD.
DR GO; GO:0016615; F:malate dehydrogenase activity; IDA:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0043621; F:protein self-association; IDA:RGD.
DR GO; GO:0009060; P:aerobic respiration; ISO:RGD.
DR GO; GO:0006094; P:gluconeogenesis; ISO:RGD.
DR GO; GO:0006108; P:malate metabolic process; IDA:RGD.
DR GO; GO:0006734; P:NADH metabolic process; IDA:RGD.
DR GO; GO:0006107; P:oxaloacetate metabolic process; IDA:RGD.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IDA:RGD.
DR CDD; cd01337; MDH_glyoxysomal_mitochondrial; 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; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF02866; Ldh_1_C; 1.
DR Pfam; PF00056; Ldh_1_N; 1.
DR PIRSF; PIRSF000102; Lac_mal_DH; 1.
DR SUPFAM; SSF51735; SSF51735; 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 Acetylation; Direct protein sequencing; Glycoprotein; Mitochondrion; NAD;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Transit peptide;
KW Tricarboxylic acid cycle.
FT TRANSIT 1..24
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:3828294"
FT CHAIN 25..338
FT /note="Malate dehydrogenase, mitochondrial"
FT /id="PRO_0000018631"
FT ACT_SITE 200
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00346"
FT BINDING 31..37
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40926"
FT BINDING 57
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40926"
FT BINDING 104
FT /ligand="substrate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10004"
FT BINDING 110
FT /ligand="substrate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10004"
FT BINDING 117
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40926"
FT BINDING 140..142
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40926"
FT BINDING 142
FT /ligand="substrate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10004"
FT BINDING 176
FT /ligand="substrate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10004"
FT BINDING 251
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40926"
FT MOD_RES 78
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 78
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 91
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 91
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 165
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P40926"
FT MOD_RES 185
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q32LG3"
FT MOD_RES 185
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 203
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 215
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 215
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 239
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 239
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q32LG3"
FT MOD_RES 239
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q32LG3"
FT MOD_RES 246
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 269
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 296
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 296
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 301
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P40926"
FT MOD_RES 301
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q32LG3"
FT MOD_RES 307
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q32LG3"
FT MOD_RES 307
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P40926"
FT MOD_RES 307
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 314
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q32LG3"
FT MOD_RES 314
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 324
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 324
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P40926"
FT MOD_RES 328
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q32LG3"
FT MOD_RES 328
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q32LG3"
FT MOD_RES 329
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P40926"
FT MOD_RES 329
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q32LG3"
FT MOD_RES 335
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P40926"
FT MOD_RES 335
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08249"
FT CARBOHYD 33
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000269|PubMed:24098488"
FT CONFLICT 229
FT /note="R -> K (in Ref. 1; CAA27812)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 338 AA; 35684 MW; 13849CCFB78C87E7 CRC64;
MLSALARPVG AALRRSFSTS AQNNAKVAVL GASGGIGQPL SLLLKNSPLV SRLTLYDIAH
TPGVAADLSH IETRANVKGY LGPEQLPDCL KGCDVVVIPA GVPRKPGMTR DDLFNTNATI
VATLTAACAQ HCPEAMICII SNPVNSTIPI TAEVFKKHGV YNPNKIFGVT TLDIVRANTF
VAELKGLDPA RVNVPVIGGH AGKTIIPLIS QCTPKVDFPQ DQLATLTGRI QEAGTEVVKA
KAGAGSATLS MAYAGARFVF SLVDAMNGKE GVIECSFVQS KETECTYFST PLLLGKKGLE
KNLGIGKITP FEEKMIAEAI PELKASIKKG EDFVKNMK
