MAOX_RAT
ID MAOX_RAT Reviewed; 572 AA.
AC P13697;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=NADP-dependent malic enzyme;
DE Short=NADP-ME;
DE EC=1.1.1.40 {ECO:0000269|PubMed:2416344};
DE AltName: Full=Malic enzyme 1;
GN Name=Me1; Synonyms=Mod-1, Mod1;
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], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2699453; DOI=10.3109/07435808909036351;
RA Nikodem V.M., Magnuson M.A., Dozin B., Morioka H.;
RT "Coding nucleotide sequence of rat malic enzyme mRNA and tissue specific
RT regulation by thyroid hormone.";
RL Endocr. Res. 15:547-564(1989).
RN [2]
RP PRELIMINARY NUCLEOTIDE SEQUENCE.
RC STRAIN=Sprague-Dawley;
RX PubMed=3753699; DOI=10.1016/s0021-9258(17)36073-8;
RA Magnuson M.A., Morioka H., Tecce M.F., Nikodem V.M.;
RT "Coding nucleotide sequence of rat liver malic enzyme mRNA.";
RL J. Biol. Chem. 261:1183-1186(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35.
RX PubMed=3211151; DOI=10.1128/mcb.8.8.3542-3545.1988;
RA Morioka H., Tennyson G.E., Nikodem V.M.;
RT "Structural and functional analysis of the rat malic enzyme gene
RT promoter.";
RL Mol. Cell. Biol. 8:3542-3545(1988).
RN [4]
RP PROTEIN SEQUENCE OF 15-20; 27-35; 65-81; 147-155; 263-286; 428-445 AND
RP 499-507, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=2740332; DOI=10.1073/pnas.86.13.4912;
RA Morioka H., Magnuson M.A., Mitsuhashi T., Song M.-K.H., Rall J.E.,
RA Nikodem V.M.;
RT "Structural characterization of the rat malic enzyme gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:4912-4916(1989).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=2416344; DOI=10.1021/bi00341a044;
RA Dozin B., Magnuson M.A., Nikodem V.M.;
RT "Tissue-specific regulation of two functional malic enzyme mRNAs by
RT triiodothyronine.";
RL Biochemistry 24:5581-5586(1985).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-336, 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).
CC -!- FUNCTION: Catalyzes the oxidative decarboxylation of (S)-malate in the
CC presence of NADP(+) and divalent metal ions, and decarboxylation of
CC oxaloacetate. {ECO:0000269|PubMed:2416344}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-malate + NADP(+) = CO2 + NADPH + pyruvate;
CC Xref=Rhea:RHEA:18253, ChEBI:CHEBI:15361, ChEBI:CHEBI:15589,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.40;
CC Evidence={ECO:0000269|PubMed:2416344};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18254;
CC Evidence={ECO:0000305|PubMed:2416344};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18255;
CC Evidence={ECO:0000250|UniProtKB:P48163};
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=1.1.1.40;
CC Evidence={ECO:0000250|UniProtKB:P48163};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15642;
CC Evidence={ECO:0000250|UniProtKB:P48163};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P48163};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P48163};
CC Note=Divalent metal cations. Prefers magnesium or manganese.
CC {ECO:0000250|UniProtKB:P48163};
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P48163}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:2416344}.
CC -!- TISSUE SPECIFICITY: Ubiquitous (PubMed:2416344). Up-regulated by
CC 3,5,3'-triiodo-L-thyronine in the liver, kidney and heart
CC (PubMed:2416344). {ECO:0000269|PubMed:2416344}.
CC -!- SIMILARITY: Belongs to the malic enzymes family. {ECO:0000305}.
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DR EMBL; M26594; AAA41563.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M26581; AAA41563.1; JOINED; Genomic_DNA.
DR EMBL; M26582; AAA41563.1; JOINED; Genomic_DNA.
DR EMBL; M26583; AAA41563.1; JOINED; Genomic_DNA.
DR EMBL; M26584; AAA41563.1; JOINED; Genomic_DNA.
DR EMBL; M26585; AAA41563.1; JOINED; Genomic_DNA.
DR EMBL; M26586; AAA41563.1; JOINED; Genomic_DNA.
DR EMBL; M26587; AAA41563.1; JOINED; Genomic_DNA.
DR EMBL; M26588; AAA41563.1; JOINED; Genomic_DNA.
DR EMBL; M26589; AAA41563.1; JOINED; Genomic_DNA.
DR EMBL; M26590; AAA41563.1; JOINED; Genomic_DNA.
DR EMBL; M26591; AAA41563.1; JOINED; Genomic_DNA.
DR EMBL; M26592; AAA41563.1; JOINED; Genomic_DNA.
DR EMBL; M26593; AAA41563.1; JOINED; Genomic_DNA.
DR PIR; A37228; DERTMX.
DR AlphaFoldDB; P13697; -.
DR SMR; P13697; -.
DR STRING; 10116.ENSRNOP00000013244; -.
DR ChEMBL; CHEMBL2293; -.
DR iPTMnet; P13697; -.
DR PhosphoSitePlus; P13697; -.
DR World-2DPAGE; 0004:P13697; -.
DR jPOST; P13697; -.
DR PaxDb; P13697; -.
DR PRIDE; P13697; -.
DR UCSC; RGD:3074; rat.
DR RGD; 3074; Me1.
DR eggNOG; KOG1257; Eukaryota.
DR InParanoid; P13697; -.
DR PhylomeDB; P13697; -.
DR Reactome; R-RNO-70268; Pyruvate metabolism.
DR SABIO-RK; P13697; -.
DR PRO; PR:P13697; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:CACAO.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0004471; F:malate dehydrogenase (decarboxylating) (NAD+) activity; IEA:InterPro.
DR GO; GO:0004473; F:malate dehydrogenase (decarboxylating) (NADP+) activity; IDA:UniProtKB.
DR GO; GO:0004470; F:malic enzyme activity; IDA:RGD.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0050661; F:NADP binding; IDA:RGD.
DR GO; GO:0008948; F:oxaloacetate decarboxylase activity; ISS:UniProtKB.
DR GO; GO:0006108; P:malate metabolic process; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0006090; P:pyruvate metabolic process; IBA:GO_Central.
DR GO; GO:1902031; P:regulation of NADP metabolic process; ISO:RGD.
DR GO; GO:0009725; P:response to hormone; IDA:UniProtKB.
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; Cytoplasm; Direct protein sequencing; Metal-binding; NADP;
KW Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..572
FT /note="NADP-dependent malic enzyme"
FT /id="PRO_0000160195"
FT ACT_SITE 102
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT ACT_SITE 173
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 155
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 245
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 246
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 269
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:P23368"
FT BINDING 269
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 301..318
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 408
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT SITE 269
FT /note="Important for activity"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P48163"
FT MOD_RES 336
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 572 AA; 64003 MW; 7D6EB48F3BA7D95B CRC64;
MDPRAPRRRH THQRGYLLTR DPHLNKDLAF TLEERQQLKI HGLLPPCIVN QEIQVLRVIK
NFERLNSDFD RYLLLMDLQD RNEKLFYSVL MSNVEKFMPI VYTPTVGLAC QQYSLAFRKP
RGLFISIHDK GHIASVLNAW PEDVVKAIVV TDGERILGLG DLGCNGMGIP VGKLALYTAC
GGVNPQQCLP ITLDVGTENE ELLKDPLYIG LRHRRVRGPE YDAFLDEFME AASSKYGMNC
LIQFEDFANL NAFRLLNKYR NKYCTFNDDI QGTASVAVAG LLAALRITKN KLSDQTVLFQ
GAGEAALGIA HLIVMAMEKE GLSKEKARQK IWLVDSKGLI VKGRASLTEE KEVFAHEHEE
MKNLEAIVQK IKPTALIGVA AIGGAFTEQI LKDMAAFNER PIIFALSNPT SKAECSAEEC
YKVTKGRAIF ASGSPFDPVT LPDGRTLFPG QGNNSYVFPG VALGVVACGL RHINDSVFLT
TAEVISQQVS DKHLEEGRLY PPLNTIRDVS LKIAVKIVQD AYKEKMATVY PEPQNKEEFV
SSQMYSTNYD QILPDCYSWP EEVQKIQTKV NQ
