LOCUS       NM_005917               1296 bp    mRNA    linear   PRI 18-NOV-2024
DEFINITION  Homo sapiens malate dehydrogenase 1 (MDH1), transcript variant 1,
            mRNA.
ACCESSION   NM_005917
VERSION     NM_005917.4
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 1296)
  AUTHORS   Broeks,M.H., Meijer,N.W.F., Westland,D., Bosma,M., Gerrits,J.,
            German,H.M., Ciapaite,J., van Karnebeek,C.D.M., Wanders,R.J.A.,
            Zwartkruis,F.J.T., Verhoeven-Duif,N.M. and Jans,J.J.M.
  TITLE     The malate-aspartate shuttle is important for de novo serine
            biosynthesis
  JOURNAL   Cell Rep 42 (9), 113043 (2023)
   PUBMED   37647199
REFERENCE   2  (bases 1 to 1296)
  AUTHORS   Igelmann,S., Lessard,F., Uchenunu,O., Bouchard,J.,
            Fernandez-Ruiz,A., Rowell,M.C., Lopes-Paciencia,S., Papadopoli,D.,
            Fouillen,A., Ponce,K.J., Huot,G., Mignacca,L., Benfdil,M.,
            Kalegari,P., Wahba,H.M., Pencik,J., Vuong,N., Quenneville,J.,
            Guillon,J., Bourdeau,V., Hulea,L., Gagnon,E., Kenner,L.,
            Moriggl,R., Nanci,A., Pollak,M.N., Omichinski,J.G., Topisirovic,I.
            and Ferbeyre,G.
  TITLE     A hydride transfer complex reprograms NAD metabolism and bypasses
            senescence
  JOURNAL   Mol Cell 81 (18), 3848-3865 (2021)
   PUBMED   34547241
REFERENCE   3  (bases 1 to 1296)
  AUTHORS   Zerr,I., Villar-Pique,A., Schmitz,V.E., Poleggi,A., Pocchiari,M.,
            Sanchez-Valle,R., Calero,M., Calero,O., Baldeiras,I., Santana,I.,
            Kovacs,G.G., Llorens,F. and Schmitz,M.
  TITLE     Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a
            Marker in Genetic Prion Disease Patients
  JOURNAL   Biomolecules 9 (12), 800 (2019)
   PUBMED   31795176
  REMARK    GeneRIF: Evaluation of Human Cerebrospinal Fluid Malate
            Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 1296)
  AUTHORS   Stiebler,A.C., Freitag,J., Schink,K.O., Stehlik,T., Tillmann,B.A.,
            Ast,J. and Bolker,M.
  TITLE     Ribosomal readthrough at a short UGA stop codon context triggers
            dual localization of metabolic enzymes in Fungi and animals
  JOURNAL   PLoS Genet 10 (10), e1004685 (2014)
   PUBMED   25340584
  REMARK    Publication Status: Online-Only
REFERENCE   5  (bases 1 to 1296)
  AUTHORS   Lo,A.S., Liew,C.T., Ngai,S.M., Tsui,S.K., Fung,K.P., Lee,C.Y. and
            Waye,M.M.
  TITLE     Developmental regulation and cellular distribution of human
            cytosolic malate dehydrogenase (MDH1)
  JOURNAL   J Cell Biochem 94 (4), 763-773 (2005)
   PUBMED   15565635
  REMARK    GeneRIF: expression of MDH1 is maintained in the adult heart but is
            not present in levels as high as in the fetus
REFERENCE   6  (bases 1 to 1296)
  AUTHORS   Beier,H. and Grimm,M.
  TITLE     Misreading of termination codons in eukaryotes by natural nonsense
            suppressor tRNAs
  JOURNAL   Nucleic Acids Res 29 (23), 4767-4782 (2001)
   PUBMED   11726686
  REMARK    Review article
REFERENCE   7  (bases 1 to 1296)
  AUTHORS   Tanaka,T., Inazawa,J. and Nakamura,Y.
  TITLE     Molecular cloning and mapping of a human cDNA for cytosolic malate
            dehydrogenase (MDH1)
  JOURNAL   Genomics 32 (1), 128-130 (1996)
   PUBMED   8786100
REFERENCE   8  (bases 1 to 1296)
  AUTHORS   Birktoft,J.J., Rhodes,G. and Banaszak,L.J.
  TITLE     Refined crystal structure of cytoplasmic malate dehydrogenase at
            2.5-A resolution
  JOURNAL   Biochemistry 28 (14), 6065-6081 (1989)
   PUBMED   2775751
REFERENCE   9  (bases 1 to 1296)
  AUTHORS   Friedrich,C.A., Ferrell,R.E., Siciliano,M.J. and Kitto,G.B.
  TITLE     Biochemical and genetic identity of alpha-keto acid reductase and
            cytoplasmic malate dehydrogenase from human erythrocytes
  JOURNAL   Ann Hum Genet 52 (1), 25-37 (1988)
   PUBMED   3052244
REFERENCE   10 (bases 1 to 1296)
  AUTHORS   Friedrich,C.A., Morizot,D.C., Siciliano,M.J. and Ferrell,R.E.
  TITLE     The reduction of aromatic alpha-keto acids by cytoplasmic malate
            dehydrogenase and lactate dehydrogenase
  JOURNAL   Biochem Genet 25 (9-10), 657-669 (1987)
   PUBMED   2449162
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from CB266998.1 and BC001484.2.
            
            On Nov 22, 2018 this sequence version replaced NM_005917.3.
            
            Summary: This gene encodes an enzyme that catalyzes the
            NAD/NADH-dependent, reversible oxidation of malate to oxaloacetate
            in many metabolic pathways, including the citric acid cycle. Two
            main isozymes are known to exist in eukaryotic cells: one is found
            in the mitochondrial matrix and the other in the cytoplasm. This
            gene encodes the cytosolic isozyme, which plays a key role in the
            malate-aspartate shuttle that allows malate to pass through the
            mitochondrial membrane to be transformed into oxaloacetate for
            further cellular processes. Alternatively spliced transcript
            variants have been found for this gene. A recent study showed that
            a C-terminally extended isoform is produced by use of an
            alternative in-frame translation termination codon via a stop codon
            readthrough mechanism, and that this isoform is localized in the
            peroxisomes. Pseudogenes have been identified on chromosomes X and
            6. [provided by RefSeq, Feb 2016].
            
            Transcript Variant: This variant (1) represents the predominant
            transcript and encodes two isoforms, which result from the use of
            alternative in-frame translation termination codons. The shorter
            isoform (MDH1) results from translation termination at the upstream
            UGA stop codon, while the longer isoform (MDH1x) results from UGA
            stop codon readthrough to the downstream UGA termination codon.
            This RefSeq represents the shorter isoform (MDH1), which is
            localized in the cytosol.
            
            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 :: SRR3476690.1025765.1,
                                           SRR3476690.1059713.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000233114.13/ ENSP00000233114.8
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-25                CB266998.1         355-379
            26-1296             BC001484.2         1-1271
FEATURES             Location/Qualifiers
     source          1..1296
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p15"
     gene            1..1296
                     /gene="MDH1"
                     /gene_synonym="DEE88; EIEE88; HEL-S-32; KAR; MDH-s; MDHA;
                     MGC:1375; MOR2"
                     /note="malate dehydrogenase 1"
                     /db_xref="GeneID:4190"
                     /db_xref="HGNC:HGNC:6970"
                     /db_xref="MIM:154200"
     exon            1..84
                     /gene="MDH1"
                     /gene_synonym="DEE88; EIEE88; HEL-S-32; KAR; MDH-s; MDHA;
                     MGC:1375; MOR2"
                     /inference="alignment:Splign:2.1.0"
     CDS             82..1086
                     /gene="MDH1"
                     /gene_synonym="DEE88; EIEE88; HEL-S-32; KAR; MDH-s; MDHA;
                     MGC:1375; MOR2"
                     /EC_number="1.1.1.37"
                     /EC_number="1.1.1.96"
                     /note="isoform MDH1 is encoded by transcript variant 1;
                     soluble malate dehydrogenase; malate dehydrogenase,
                     cytoplasmic; cytosolic malate dehydrogenase;
                     diiodophenylpyruvate reductase; epididymis secretory
                     protein Li 32; malate dehydrogenase 1, NAD (soluble);
                     malate dehydrogenase, peroxisomal; aromatic alpha-keto
                     acid reductase"
                     /codon_start=1
                     /product="malate dehydrogenase, cytoplasmic isoform MDH1"
                     /protein_id="NP_005908.1"
                     /db_xref="CCDS:CCDS1874.1"
                     /db_xref="GeneID:4190"
                     /db_xref="HGNC:HGNC:6970"
                     /db_xref="MIM:154200"
                     /translation="MSEPIRVLVTGAAGQIAYSLLYSIGNGSVFGKDQPIILVLLDIT
                     PMMGVLDGVLMELQDCALPLLKDVIATDKEDVAFKDLDVAILVGSMPRREGMERKDLL
                     KANVKIFKSQGAALDKYAKKSVKVIVVGNPANTNCLTASKSAPSIPKENFSCLTRLDH
                     NRAKAQIALKLGVTANDVKNVIIWGNHSSTQYPDVNHAKVKLQGKEVGVYEALKDDSW
                     LKGEFVTTVQQRGAAVIKARKLSSAMSAAKAICDHVRDIWFGTPEGEFVSMGVISDGN
                     SYGVPDDLLYSFPVVIKNKTWKFVEGLPINDFSREKMDLTAKELTEEKESAFEFLSSA
                     "
     exon            85..183
                     /gene="MDH1"
                     /gene_synonym="DEE88; EIEE88; HEL-S-32; KAR; MDH-s; MDHA;
                     MGC:1375; MOR2"
                     /inference="alignment:Splign:2.1.0"
     exon            184..280
                     /gene="MDH1"
                     /gene_synonym="DEE88; EIEE88; HEL-S-32; KAR; MDH-s; MDHA;
                     MGC:1375; MOR2"
                     /inference="alignment:Splign:2.1.0"
     exon            281..456
                     /gene="MDH1"
                     /gene_synonym="DEE88; EIEE88; HEL-S-32; KAR; MDH-s; MDHA;
                     MGC:1375; MOR2"
                     /inference="alignment:Splign:2.1.0"
     exon            457..579
                     /gene="MDH1"
                     /gene_synonym="DEE88; EIEE88; HEL-S-32; KAR; MDH-s; MDHA;
                     MGC:1375; MOR2"
                     /inference="alignment:Splign:2.1.0"
     exon            580..756
                     /gene="MDH1"
                     /gene_synonym="DEE88; EIEE88; HEL-S-32; KAR; MDH-s; MDHA;
                     MGC:1375; MOR2"
                     /inference="alignment:Splign:2.1.0"
     exon            757..870
                     /gene="MDH1"
                     /gene_synonym="DEE88; EIEE88; HEL-S-32; KAR; MDH-s; MDHA;
                     MGC:1375; MOR2"
                     /inference="alignment:Splign:2.1.0"
     exon            871..960
                     /gene="MDH1"
                     /gene_synonym="DEE88; EIEE88; HEL-S-32; KAR; MDH-s; MDHA;
                     MGC:1375; MOR2"
                     /inference="alignment:Splign:2.1.0"
     exon            961..1296
                     /gene="MDH1"
                     /gene_synonym="DEE88; EIEE88; HEL-S-32; KAR; MDH-s; MDHA;
                     MGC:1375; MOR2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1278..1283
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MDH1"
                     /gene_synonym="DEE88; EIEE88; HEL-S-32; KAR; MDH-s; MDHA;
                     MGC:1375; MOR2"
                     /note="hexamer: AATATA"
     polyA_site      1296
                     /gene="MDH1"
                     /gene_synonym="DEE88; EIEE88; HEL-S-32; KAR; MDH-s; MDHA;
                     MGC:1375; MOR2"
                     /note="major polyA site"
ORIGIN      
        1 gagtcagttc cgcggtagag gtgacctgac tctctgaggc tcattttgca gttgttgaaa
       61 ttgtccccgc agttttcaat catgtctgaa ccaatcagag tccttgtgac tggagcagct
      121 ggtcaaattg catattcact gctgtacagt attggaaatg gatctgtctt tggtaaagat
      181 cagcctataa ttcttgtgct gttggatatc acccccatga tgggtgtcct ggacggtgtc
      241 ctaatggaac tgcaagactg tgcccttccc ctcctgaaag atgtcatcgc aacagataaa
      301 gaagacgttg ccttcaaaga cctggatgtg gccattcttg tgggctccat gccaagaagg
      361 gaaggcatgg agagaaaaga tttactgaaa gcaaatgtga aaatcttcaa atcccagggt
      421 gcagccttag ataaatacgc caagaagtca gttaaggtta ttgttgtggg taatccagcc
      481 aataccaact gcctgactgc ttccaagtca gctccatcca tccccaagga gaacttcagt
      541 tgcttgactc gtttggatca caaccgagct aaagctcaaa ttgctcttaa acttggtgtg
      601 actgctaatg atgtaaagaa tgtcattatc tggggaaacc attcctcgac tcagtatcca
      661 gatgtcaacc atgccaaggt gaaattgcaa ggaaaggaag ttggtgttta tgaagctctg
      721 aaagatgaca gctggctcaa gggagaattt gtcacgactg tgcagcagcg tggcgctgct
      781 gtcatcaagg ctcgaaaact atccagtgcc atgtctgctg caaaagccat ctgtgaccac
      841 gtcagggaca tctggtttgg aaccccagag ggagagtttg tgtccatggg tgttatctct
      901 gatggcaact cctatggtgt tcctgatgat ctgctctact cattccctgt tgtaatcaag
      961 aataagacct ggaagtttgt tgaaggtctc cctattaatg atttctcacg tgagaagatg
     1021 gatcttactg caaaggaact gacagaagaa aaagaaagtg cttttgaatt tctttcctct
     1081 gcctgactag acaatgatgt tactaaatgc ttcaaagctg aagaatctaa atgtcgtctt
     1141 tgactcaagt accaaataat aataatgcta tacttaaatt acttgtgaaa aacaacacat
     1201 tttaaagatt acgtgcttct tggtacaggt ttgtgaatga cagtttatcg tcatgctgtt
     1261 agtgtgcatt ctaaataaat atatattcaa atgaaa
//
