MAOM_MOUSE
ID MAOM_MOUSE Reviewed; 589 AA.
AC Q99KE1; Q3TBM8;
DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=NAD-dependent malic enzyme, mitochondrial;
DE Short=NAD-ME;
DE EC=1.1.1.38 {ECO:0000250|UniProtKB:P23368};
DE AltName: Full=Malic enzyme 2;
DE Flags: Precursor;
GN Name=Me2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Spleen, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Lung, Pancreas, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: NAD-dependent mitochondrial malic enzyme that catalyzes the
CC oxidative decarboxylation of malate to pyruvate.
CC {ECO:0000250|UniProtKB:P23368}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-malate + NAD(+) = CO2 + NADH + pyruvate;
CC Xref=Rhea:RHEA:12653, ChEBI:CHEBI:15361, ChEBI:CHEBI:15589,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.38;
CC Evidence={ECO:0000250|UniProtKB:P23368};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + oxaloacetate = CO2 + pyruvate; Xref=Rhea:RHEA:15641,
CC ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16452,
CC ChEBI:CHEBI:16526; EC=1.1.1.38;
CC Evidence={ECO:0000250|UniProtKB:P23368};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P23368};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P23368};
CC Note=Divalent metal cations. Prefers magnesium or manganese.
CC {ECO:0000250|UniProtKB:P23368};
CC -!- ACTIVITY REGULATION: Subject to allosteric activation by fumarate.
CC {ECO:0000250|UniProtKB:P23368}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P23368}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P23368}.
CC -!- MISCELLANEOUS: This isoenzyme can also use NADP(+) but is more
CC effective with NAD(+). {ECO:0000250|UniProtKB:P23368}.
CC -!- SIMILARITY: Belongs to the malic enzymes family. {ECO:0000305}.
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DR EMBL; AK042289; BAC31216.1; -; mRNA.
DR EMBL; AK050933; BAC34467.1; -; mRNA.
DR EMBL; AK050980; BAC34483.1; -; mRNA.
DR EMBL; AK156403; BAE33701.1; -; mRNA.
DR EMBL; AK171157; BAE42281.1; -; mRNA.
DR EMBL; BC004709; AAH04709.1; -; mRNA.
DR CCDS; CCDS29339.1; -.
DR RefSeq; NP_663469.1; NM_145494.2.
DR AlphaFoldDB; Q99KE1; -.
DR SMR; Q99KE1; -.
DR BioGRID; 223188; 3.
DR STRING; 10090.ENSMUSP00000025439; -.
DR PhosphoSitePlus; Q99KE1; -.
DR SwissPalm; Q99KE1; -.
DR REPRODUCTION-2DPAGE; Q99KE1; -.
DR EPD; Q99KE1; -.
DR jPOST; Q99KE1; -.
DR MaxQB; Q99KE1; -.
DR PaxDb; Q99KE1; -.
DR PeptideAtlas; Q99KE1; -.
DR PRIDE; Q99KE1; -.
DR ProteomicsDB; 295813; -.
DR Antibodypedia; 1636; 221 antibodies from 33 providers.
DR DNASU; 107029; -.
DR Ensembl; ENSMUST00000025439; ENSMUSP00000025439; ENSMUSG00000024556.
DR GeneID; 107029; -.
DR KEGG; mmu:107029; -.
DR UCSC; uc008fox.1; mouse.
DR CTD; 4200; -.
DR MGI; MGI:2147351; Me2.
DR VEuPathDB; HostDB:ENSMUSG00000024556; -.
DR eggNOG; KOG1257; Eukaryota.
DR GeneTree; ENSGT00950000183134; -.
DR HOGENOM; CLU_011405_5_0_1; -.
DR InParanoid; Q99KE1; -.
DR OMA; QMWDPVY; -.
DR OrthoDB; 435571at2759; -.
DR PhylomeDB; Q99KE1; -.
DR TreeFam; TF300537; -.
DR BRENDA; 1.1.1.38; 3474.
DR Reactome; R-MMU-71403; Citric acid cycle (TCA cycle).
DR BioGRID-ORCS; 107029; 7 hits in 73 CRISPR screens.
DR ChiTaRS; Me2; mouse.
DR PRO; PR:Q99KE1; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q99KE1; protein.
DR Bgee; ENSMUSG00000024556; Expressed in small intestine Peyer's patch and 258 other tissues.
DR Genevisible; Q99KE1; MM.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0004471; F:malate dehydrogenase (decarboxylating) (NAD+) activity; IEA:UniProtKB-EC.
DR GO; GO:0004473; F:malate dehydrogenase (decarboxylating) (NADP+) activity; IBA:GO_Central.
DR GO; GO:0004470; F:malic enzyme activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0008948; F:oxaloacetate decarboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0006108; P:malate metabolic process; IBA:GO_Central.
DR GO; GO:0006090; P:pyruvate metabolic process; IBA:GO_Central.
DR GO; GO:1902031; P:regulation of NADP metabolic process; ISO:MGI.
DR Gene3D; 3.40.50.10380; -; 1.
DR InterPro; IPR046346; Aminiacid_DH-like_N_sf.
DR InterPro; IPR015884; Malic_enzyme_CS.
DR InterPro; IPR012301; Malic_N_dom.
DR InterPro; IPR037062; Malic_N_dom_sf.
DR InterPro; IPR012302; Malic_NAD-bd.
DR InterPro; IPR001891; Malic_OxRdtase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF00390; malic; 1.
DR Pfam; PF03949; Malic_M; 1.
DR PIRSF; PIRSF000106; ME; 1.
DR PRINTS; PR00072; MALOXRDTASE.
DR SMART; SM01274; malic; 1.
DR SMART; SM00919; Malic_M; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53223; SSF53223; 1.
DR PROSITE; PS00331; MALIC_ENZYMES; 1.
PE 1: Evidence at protein level;
KW Acetylation; Allosteric enzyme; Metal-binding; Mitochondrion; NAD;
KW Oxidoreductase; Reference proteome; Transit peptide.
FT TRANSIT 1..18
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT CHAIN 19..589
FT /note="NAD-dependent malic enzyme, mitochondrial"
FT /id="PRO_0000018538"
FT ACT_SITE 112
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT ACT_SITE 183
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 67
FT /ligand="fumarate"
FT /ligand_id="ChEBI:CHEBI:29806"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 91
FT /ligand="fumarate"
FT /ligand_id="ChEBI:CHEBI:29806"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 165..173
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 165
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 255
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 256
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 259
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 279
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 311..328
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 421
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 466
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT MOD_RES 156
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT MOD_RES 224
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT MOD_RES 240
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT MOD_RES 272
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT MOD_RES 346
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P23368"
SQ SEQUENCE 589 AA; 65799 MW; CD77AD5744B08CAB CRC64;
MFSRLRAVTT PCTLTCRRVH LKEKGKPLML NPRTNKGMAF TLQERQMLGL QGLLPPKIET
QDIQALRFHR NLKKMTSPLE KYIYIMGIQE RNEKLFYRIL QDDIESLMPI VYTPTVGLAC
CQYGHIFRRP KGLFISISDR GHVRSIVDNW PENHVKAVVV TDGERILGLG DLGVYGMGIP
VGKLCLYTAC AGIQPEKCLP VCIDVGTDNM ALLKDPFYMG LYQKRDRSQL YDDLMDEFMK
AITDRYGRNT LIQFEDFGNH NAFRFLRKYQ QKYCTFNDDI QGTAAVALSG LLAAQRVINK
PVSEHKILFL GAGEAALGIA NLIVLSMVES GLSEEEAQRK IWMFDKSGLL VKGRTASIDS
NQEPYAHAAP ESIPATFEDA VNKLKPSVII GVAGAGPLFT HGVIKAMASI NERPIIFALS
NPTAQAECTA EDAYTLTEGR CLFASGSPFE PVKLQDGRVF TPGQGNNAYI FPGVALAVIL
CEARHISDTV FLEAAKALTT QLTDAELAQG RLYPSLANIQ EVSANIAIKL AEYLYANKMA
FRYPEPEDKA RYVRERIWRS NYVSLLPDVY DWPESSLTPP QITEEKLPH
