LOCUS       NM_001161586            2293 bp    mRNA    linear   PRI 15-OCT-2024
DEFINITION  Homo sapiens malic enzyme 3 (ME3), transcript variant 3, mRNA;
            nuclear gene for mitochondrial product.
ACCESSION   NM_001161586
VERSION     NM_001161586.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2293)
  AUTHORS   Huang,Y., Yang,Y., Chen,X., Zeng,S., Chen,Y., Wang,H., Lv,X., Hu,X.
            and Teng,L.
  TITLE     Downregulation of malic enzyme 3 facilitates progression of gastric
            carcinoma via regulating intracellular oxidative stress and
            hypoxia-inducible factor-1alpha stabilization
  JOURNAL   Cell Mol Life Sci 81 (1), 375 (2024)
   PUBMED   39212717
  REMARK    GeneRIF: Downregulation of malic enzyme 3 facilitates progression
            of gastric carcinoma via regulating intracellular oxidative stress
            and hypoxia-inducible factor-1alpha stabilization.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2293)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   3  (bases 1 to 2293)
  AUTHORS   Lee,D., Zhang,M.S., Tsang,F.H., Bao,M.H., Xu,I.M., Lai,R.K.,
            Chiu,D.K., Tse,A.P., Law,C.T., Chan,C.Y., Yuen,V.W., Chui,N.N.,
            Ng,I.O., Wong,C.M. and Wong,C.C.
  TITLE     Adaptive and Constitutive Activations of Malic Enzymes Confer Liver
            Cancer Multilayered Protection Against Reactive Oxygen Species
  JOURNAL   Hepatology 74 (2), 776-796 (2021)
   PUBMED   33619771
  REMARK    GeneRIF: Adaptive and Constitutive Activations of Malic Enzymes
            Confer Liver Cancer Multilayered Protection Against Reactive Oxygen
            Species.
REFERENCE   4  (bases 1 to 2293)
  AUTHORS   Zhang,Q., Li,J., Tan,X.P. and Zhao,Q.
  TITLE     Effects of ME3 on the proliferation, invasion and metastasis of
            pancreatic cancer cells through epithelial-mesenchymal transition
  JOURNAL   Neoplasma 66 (6), 896-907 (2019)
   PUBMED   31607129
  REMARK    GeneRIF: ME3 is extensively involved in carcinogenesis of
            pancreatic cancer
REFERENCE   5  (bases 1 to 2293)
  AUTHORS   Chung,S., Low,S.K., Zembutsu,H., Takahashi,A., Kubo,M., Sasa,M. and
            Nakamura,Y.
  TITLE     A genome-wide association study of chemotherapy-induced alopecia in
            breast cancer patients
  JOURNAL   Breast Cancer Res 15 (5), R81 (2013)
   PUBMED   24025145
REFERENCE   6  (bases 1 to 2293)
  AUTHORS   Hsieh,J.Y., Chen,S.H. and Hung,H.C.
  TITLE     Functional roles of the tetramer organization of malic enzyme
  JOURNAL   J Biol Chem 284 (27), 18096-18105 (2009)
   PUBMED   19416979
  REMARK    GeneRIF: human c-NADP-ME exists mainly as a tetramer, whereas human
            m-NAD(P)-ME exists as a mixture of dimers and tetramers
REFERENCE   7  (bases 1 to 2293)
  AUTHORS   Hsieh,J.Y., Liu,J.H., Fang,Y.W. and Hung,H.C.
  TITLE     Dual roles of Lys(57) at the dimer interface of human mitochondrial
            NAD(P)+-dependent malic enzyme
  JOURNAL   Biochem J 420 (2), 201-209 (2009)
   PUBMED   19236308
  REMARK    GeneRIF: Studies demonstrate that the Lys57 residue plays dual
            functional roles in the structural integrity of the allosteric site
            and in the subunit-subunit interaction at the dimer interface of
            m-NAD(P)-ME.
            Publication Status: Online-Only
REFERENCE   8  (bases 1 to 2293)
  AUTHORS   Hsieh,J.Y., Liu,G.Y. and Hung,H.C.
  TITLE     Influential factor contributing to the isoform-specific inhibition
            by ATP of human mitochondrial NAD(P)+-dependent malic enzyme:
            functional roles of the nucleotide binding site Lys346
  JOURNAL   FEBS J 275 (21), 5383-5392 (2008)
   PUBMED   18959763
  REMARK    GeneRIF: ATP inhibition is proposed to be determined by the
            electrostatic potential involving the positive charge on the side
            chain of Lys346
REFERENCE   9  (bases 1 to 2293)
  AUTHORS   Loeber,G., Maurer-Fogy,I. and Schwendenwein,R.
  TITLE     Purification, cDNA cloning and heterologous expression of the human
            mitochondrial NADP(+)-dependent malic enzyme
  JOURNAL   Biochem J 304 (Pt 3) (Pt 3), 687-692 (1994)
   PUBMED   7818469
REFERENCE   10 (bases 1 to 2293)
  AUTHORS   Siebert,G., Ritter,H. and Kompf,J.
  TITLE     Mitochondrial malic enzyme (E.C.1.1.1.40) in human leukocytes:
            formal genetics and population genetics
  JOURNAL   Hum Genet 51 (3), 319-322 (1979)
   PUBMED   511162
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AP001831.5, AP002492.3 and
            AP001148.4.
            
            On Aug 19, 2021 this sequence version replaced NM_001161586.2.
            
            Summary: Malic enzyme catalyzes the oxidative decarboxylation of
            malate to pyruvate using either NAD+ or NADP+ as a cofactor.
            Mammalian tissues contain 3 distinct isoforms of malic enzyme: a
            cytosolic NADP(+)-dependent isoform, a mitochondrial
            NADP(+)-dependent isoform, and a mitochondrial NAD(+)-dependent
            isoform. This gene encodes a mitochondrial NADP(+)-dependent
            isoform. Multiple alternatively spliced transcript variants have
            been found for this gene, but the biological validity of some
            variants has not been determined. [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (3) has an alternate 5' UTR and
            encodes the same protein, as compared to variant 1. Variants 1-4
            all encode the same protein.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK313695.1, SRR18074967.1998142.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000543262.6/
                                                  ENSP00000440246.1
            RefSeq Select criteria             :: based on manual assertion,
                                                  conservation, expression,
                                                  longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-293               AP001831.5         163161-163453       c
            294-490             AP001831.5         162599-162795       c
            491-624             AP001831.5         50527-50660         c
            625-774             AP001831.5         47390-47539         c
            775-850             AP002492.3         50456-50531         c
            851-1012            AP002492.3         39627-39788         c
            1013-1116           AP002492.3         29001-29104         c
            1117-1226           AP002492.3         6755-6864           c
            1227-1324           AP001148.4         159155-159252       c
            1325-1438           AP001148.4         158743-158856       c
            1439-1544           AP001148.4         157004-157109       c
            1545-1687           AP001148.4         155919-156061       c
            1688-1861           AP001148.4         155168-155341       c
            1862-1960           AP001148.4         151675-151773       c
            1961-2293           AP001148.4         149962-150294       c
FEATURES             Location/Qualifiers
     source          1..2293
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11q14.2"
     gene            1..2293
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /note="malic enzyme 3"
                     /db_xref="GeneID:10873"
                     /db_xref="HGNC:HGNC:6985"
                     /db_xref="MIM:604626"
     exon            1..293
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     exon            294..490
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     CDS             308..2122
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /EC_number="1.1.1.40"
                     /note="isoform 1 is encoded by transcript variant 3; malic
                     enzyme, NADP+-dependent, mitochondrial; pyruvic-malic
                     carboxylase; NADP-dependent malic enzyme, mitochondrial;
                     mitochondrial NADP(+)-dependent malic enzyme 3; malic
                     enzyme 3, NADP(+)-dependent, mitochondrial; malate
                     dehydrogenase (oxaloacetate-decarboxylating) (NADP(+))"
                     /codon_start=1
                     /product="NADP-dependent malic enzyme, mitochondrial
                     isoform 1"
                     /protein_id="NP_001155058.1"
                     /db_xref="CCDS:CCDS8277.1"
                     /db_xref="GeneID:10873"
                     /db_xref="HGNC:HGNC:6985"
                     /db_xref="MIM:604626"
                     /translation="MGAALGTGTRLAPWPGRACGALPRWTPTAPAQGCHSKPGPARPV
                     PLKKRGYDVTRNPHLNKGMAFTLEERLQLGIHGLIPPCFLSQDVQLLRIMRYYERQQS
                     DLDKYIILMTLQDRNEKLFYRVLTSDVEKFMPIVYTPTVGLACQHYGLTFRRPRGLFI
                     TIHDKGHLATMLNSWPEDNIKAVVVTDGERILGLGDLGCYGMGIPVGKLALYTACGGV
                     NPQQCLPVLLDVGTNNEELLRDPLYIGLKHQRVHGKAYDDLLDEFMQAVTDKFGINCL
                     IQFEDFANANAFRLLNKYRNKYCMFNDDIQGTASVAVAGILAALRITKNKLSNHVFVF
                     QGAGEAAMGIAHLLVMALEKEGVPKAEATRKIWMVDSKGLIVKGRSHLNHEKEMFAQD
                     HPEVNSLEEVVRLVKPTAIIGVAAIAGAFTEQILRDMASFHERPIIFALSNPTSKAEC
                     TAEKCYRVTEGRGIFASGSPFKSVTLEDGKTFIPGQGNNAYVFPGVALGVIAGGIRHI
                     PDEIFLLTAEQIAQEVSEQHLSQGRLYPPLSTIRDVSLRIAIKVLDYAYKHNLASYYP
                     EPKDKEAFVRSLVYTPDYDSFTLDSYTWPKEAMNVQTV"
     exon            491..624
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     exon            625..774
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     exon            775..850
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     exon            851..1012
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     exon            1013..1116
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     exon            1117..1226
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     exon            1227..1324
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     exon            1325..1438
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     exon            1439..1544
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     exon            1545..1687
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     exon            1688..1861
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     exon            1862..1960
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     exon            1961..2293
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2177..2182
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /note="hexamer: TATAAA"
     polyA_site      2207
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /note="major polyA site"
     regulatory      2273..2278
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
                     /note="hexamer: AATAAA"
     polyA_site      2293
                     /gene="ME3"
                     /gene_synonym="NADP-ME"
ORIGIN      
        1 gcatttagtc ttgccaagat ggagagtctc aggcgggcat tctgagctgc ttcttgtcac
       61 tggggaaaac cacgtgcacg cagtgctgag gcgccccacg cgcgtcctca ggggaagcca
      121 ggcactgaga acaaaggttg tgggaccgct ctttgaggaa ctcaccagct ccgcgagctc
      181 gcggccgcca gcgcggtcca cccattggcg ggagaggact cacagaccgc agctcctcac
      241 cccgcctgct ccgcagcggg accgcgtaga cctcagctcc ccgagcagcg caggtctgcc
      301 aaggaccatg ggtgccgcgc tggggacagg cacgcggctg gctccctggc cgggccgggc
      361 ctgcggcgcc ctcccgcgct ggacacccac cgcgcccgcc caaggctgcc actccaagcc
      421 tggcccggcg cgccctgtgc ccctgaagaa gcgcggatac gatgtcacca ggaaccctca
      481 tctcaacaag gggatggcct ttacccttga agaaaggctg cagcttggaa tccacggcct
      541 aatcccgccc tgctttctga gccaggacgt ccagctcctc cgaatcatga gatattacga
      601 gcggcagcag agtgacctgg acaagtacat cattctcatg acactccaag accggaacga
      661 gaagctcttc taccgagtgc tgacttcgga cgtggagaag ttcatgccaa tcgtgtacac
      721 gcctaccgtg gggctggcct gtcagcacta tggcctgact ttccgcaggc cccgtggact
      781 gttcatcacc attcatgaca aaggtcatct tgcaacaatg ctgaattctt ggccagaaga
      841 caatattaag gccgtggtgg tgactgatgg ggagcgcatc ctgggcctgg gagacctggg
      901 ctgctacggc atgggcatcc ctgtgggcaa gctggccctg tacacggcat gcggaggggt
      961 gaacccgcag cagtgcctcc ctgtgctgct ggacgtcggc accaacaatg aggagctgct
     1021 cagagaccct ctgtacatcg gcctgaaaca ccagcgcgtg cacgggaagg catacgatga
     1081 cttgctggat gagttcatgc aggctgtgac agacaagttt ggaataaatt gcctcatcca
     1141 atttgaagac ttcgccaatg ccaatgcctt ccgcctgctc aacaaatacc gtaacaagta
     1201 ctgcatgttc aatgatgaca tccaaggcac agcctccgtt gctgtggcag ggatcttggc
     1261 tgctctgcga atcaccaaga acaagctttc caatcacgtg tttgttttcc aaggtgcagg
     1321 cgaggcagct atgggcattg cccacctcct tgtcatggcc ctagagaaag aaggtgtacc
     1381 gaaggcagag gccacaagaa agatctggat ggtggactct aaagggctca ttgtcaaggg
     1441 gaggagccac ctgaaccatg aaaaggagat gtttgcccaa gaccatcctg aagtcaactc
     1501 cctggaggag gtggtgaggc tggtgaagcc cacagccatc ataggtgttg ctgccatcgc
     1561 aggagccttc acggagcaga ttctgaggga catggcctcc ttccacgagc gccctatcat
     1621 ctttgccctg agcaacccca ccagcaaggc cgagtgcacg gctgagaagt gctaccgggt
     1681 caccgagggc cgagggattt ttgccagtgg aagtcctttt aagagtgtga ctctggaaga
     1741 tggcaagacc ttcattcctg ggcagggaaa caatgcttac gtgttccccg gggtggcact
     1801 gggagtcatc gccggcggga tccggcacat cccagatgag atcttcctcc tgacagcaga
     1861 gcaaattgcc caggaagtct ctgagcagca tctgtcccag gggagactct acccaccact
     1921 cagcaccatc cgagacgtgt ctttgagaat tgccatcaaa gttctcgact acgcgtacaa
     1981 acacaacctg gcttcctact acccagagcc taaggacaag gaggcttttg taagatccct
     2041 ggtctacact ccagactatg actcctttac actggacagc tacacttggc ccaaggaagc
     2101 catgaatgtt cagacggtct gaggcagtct cagaggctag tatggggcta gatgaagccc
     2161 agagtaacac ccacaatata aatgggttcc aaaatggccc aagtgaatcc ttgtcgctgt
     2221 gttttttctt ttaaactttc tggtgtgaga ggagatgcca aggcatacag tgaataaaag
     2281 ccttgtctct gaa
//
