MAON_HUMAN
ID MAON_HUMAN Reviewed; 604 AA.
AC Q16798; B7Z6V0; Q8TBJ0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=NADP-dependent malic enzyme, mitochondrial {ECO:0000305};
DE Short=NADP-ME;
DE EC=1.1.1.40 {ECO:0000269|PubMed:7818469};
DE AltName: Full=Malic enzyme 3;
DE Flags: Precursor;
GN Name=ME3 {ECO:0000312|HGNC:HGNC:6985};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASN-324, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RC TISSUE=Hippocampus;
RX PubMed=7818469; DOI=10.1042/bj3040687;
RA Loeber G., Maurer-Fogy I., Schwendenwein R.;
RT "Purification, cDNA cloning and heterologous expression of the human
RT mitochondrial NADP(+)-dependent malic enzyme.";
RL Biochem. J. 304:687-692(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Small intestine;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS GLY-85 AND
RP ASN-324.
RC TISSUE=Brain;
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).
CC -!- FUNCTION: Catalyzes the oxidative decarboxylation of (S)-malate to
CC pyruvate using NADP(+) as a cofactor (PubMed:7818469). Can also reverse
CC the decarboxylation reaction, but only with significantly lower
CC efficiency (PubMed:7818469). {ECO:0000269|PubMed:7818469}.
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:7818469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18254;
CC Evidence={ECO:0000305|PubMed:7818469};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18255;
CC Evidence={ECO:0000305|PubMed:7818469};
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Divalent metal cations. Prefers magnesium or manganese.
CC {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q16798-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16798-2; Sequence=VSP_056626, VSP_056627;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in organs with a low-
CC division rate.
CC -!- SIMILARITY: Belongs to the malic enzymes family. {ECO:0000305}.
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DR EMBL; X79440; CAA55956.1; -; mRNA.
DR EMBL; AK300974; BAH13386.1; -; mRNA.
DR EMBL; AP001148; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001831; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP002492; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC022472; AAH22472.1; -; mRNA.
DR CCDS; CCDS8277.1; -. [Q16798-1]
DR PIR; S53351; S53351.
DR RefSeq; NP_001014811.1; NM_001014811.1. [Q16798-1]
DR RefSeq; NP_001155058.1; NM_001161586.1. [Q16798-1]
DR RefSeq; NP_006671.2; NM_006680.2. [Q16798-1]
DR RefSeq; XP_005273774.1; XM_005273717.1.
DR AlphaFoldDB; Q16798; -.
DR SMR; Q16798; -.
DR BioGRID; 116081; 1.
DR STRING; 9606.ENSP00000440246; -.
DR ChEMBL; CHEMBL6182; -.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB03680; Tartronate.
DR iPTMnet; Q16798; -.
DR PhosphoSitePlus; Q16798; -.
DR BioMuta; ME3; -.
DR DMDM; 215274021; -.
DR CPTAC; CPTAC-1536; -.
DR CPTAC; CPTAC-1537; -.
DR EPD; Q16798; -.
DR jPOST; Q16798; -.
DR MassIVE; Q16798; -.
DR MaxQB; Q16798; -.
DR PaxDb; Q16798; -.
DR PeptideAtlas; Q16798; -.
DR PRIDE; Q16798; -.
DR ProteomicsDB; 61073; -. [Q16798-1]
DR ProteomicsDB; 6809; -.
DR Antibodypedia; 31451; 139 antibodies from 25 providers.
DR DNASU; 10873; -.
DR Ensembl; ENST00000393324.7; ENSP00000376998.2; ENSG00000151376.18. [Q16798-1]
DR Ensembl; ENST00000524826.7; ENSP00000431182.2; ENSG00000151376.18. [Q16798-1]
DR Ensembl; ENST00000526504.5; ENSP00000433636.1; ENSG00000151376.18. [Q16798-2]
DR Ensembl; ENST00000543262.5; ENSP00000440246.1; ENSG00000151376.18. [Q16798-1]
DR GeneID; 10873; -.
DR KEGG; hsa:10873; -.
DR UCSC; uc001pbz.3; human. [Q16798-1]
DR CTD; 10873; -.
DR DisGeNET; 10873; -.
DR GeneCards; ME3; -.
DR HGNC; HGNC:6985; ME3.
DR HPA; ENSG00000151376; Low tissue specificity.
DR MIM; 604626; gene.
DR neXtProt; NX_Q16798; -.
DR OpenTargets; ENSG00000151376; -.
DR PharmGKB; PA30725; -.
DR VEuPathDB; HostDB:ENSG00000151376; -.
DR eggNOG; KOG1257; Eukaryota.
DR GeneTree; ENSGT00950000183134; -.
DR HOGENOM; CLU_011405_5_2_1; -.
DR InParanoid; Q16798; -.
DR OMA; DDLYVGW; -.
DR OrthoDB; 435571at2759; -.
DR PhylomeDB; Q16798; -.
DR TreeFam; TF300537; -.
DR PathwayCommons; Q16798; -.
DR Reactome; R-HSA-71403; Citric acid cycle (TCA cycle).
DR SABIO-RK; Q16798; -.
DR SignaLink; Q16798; -.
DR BioGRID-ORCS; 10873; 13 hits in 1072 CRISPR screens.
DR ChiTaRS; ME3; human.
DR GenomeRNAi; 10873; -.
DR Pharos; Q16798; Tbio.
DR PRO; PR:Q16798; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q16798; protein.
DR Bgee; ENSG00000151376; Expressed in apex of heart and 183 other tissues.
DR ExpressionAtlas; Q16798; baseline and differential.
DR Genevisible; Q16798; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
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:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0070401; F:NADP+ binding; IDA:UniProtKB.
DR GO; GO:0008948; F:oxaloacetate decarboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0009060; P:aerobic respiration; TAS:UniProtKB.
DR GO; GO:0006108; P:malate metabolic process; IDA:UniProtKB.
DR GO; GO:0072592; P:oxygen metabolic process; TAS:UniProtKB.
DR GO; GO:0006090; P:pyruvate metabolic process; 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 Alternative splicing; Metal-binding; Mitochondrion; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..604
FT /note="NADP-dependent malic enzyme, mitochondrial"
FT /id="PRO_0000018539"
FT REGION 29..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 137
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT ACT_SITE 208
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 190
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 280
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 281
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 304
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 304
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 443
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT SITE 304
FT /note="Important for activity"
FT /evidence="ECO:0000250"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06801"
FT VAR_SEQ 309..342
FT /note="ASVAVAGILAALRITKNKLSNHVFVFQGAGEAAM -> TCHTFSCPWHLWAQ
FT VMFQHIPGPMGFSEWLPRNS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056626"
FT VAR_SEQ 343..604
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056627"
FT VARIANT 85
FT /note="S -> G (in dbSNP:rs17856661)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_047369"
FT VARIANT 324
FT /note="K -> N (in dbSNP:rs1042780)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7818469"
FT /id="VAR_047370"
FT CONFLICT 95
FT /note="R -> G (in Ref. 4; AAH22472)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 604 AA; 67068 MW; E0E79A75F3CAC524 CRC64;
MGAALGTGTR LAPWPGRACG ALPRWTPTAP AQGCHSKPGP ARPVPLKKRG YDVTRNPHLN
KGMAFTLEER LQLGIHGLIP PCFLSQDVQL LRIMRYYERQ QSDLDKYIIL MTLQDRNEKL
FYRVLTSDVE KFMPIVYTPT VGLACQHYGL TFRRPRGLFI TIHDKGHLAT MLNSWPEDNI
KAVVVTDGER ILGLGDLGCY GMGIPVGKLA LYTACGGVNP QQCLPVLLDV GTNNEELLRD
PLYIGLKHQR VHGKAYDDLL DEFMQAVTDK FGINCLIQFE DFANANAFRL LNKYRNKYCM
FNDDIQGTAS VAVAGILAAL RITKNKLSNH VFVFQGAGEA AMGIAHLLVM ALEKEGVPKA
EATRKIWMVD SKGLIVKGRS HLNHEKEMFA QDHPEVNSLE EVVRLVKPTA IIGVAAIAGA
FTEQILRDMA SFHERPIIFA LSNPTSKAEC TAEKCYRVTE GRGIFASGSP FKSVTLEDGK
TFIPGQGNNA YVFPGVALGV IAGGIRHIPD EIFLLTAEQI AQEVSEQHLS QGRLYPPLST
IRDVSLRIAI KVLDYAYKHN LASYYPEPKD KEAFVRSLVY TPDYDSFTLD SYTWPKEAMN
VQTV
