LOCUS       NM_000108               3537 bp    mRNA    linear   PRI 08-DEC-2024
DEFINITION  Homo sapiens dihydrolipoamide dehydrogenase (DLD), transcript
            variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_000108
VERSION     NM_000108.5
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 3537)
  AUTHORS   Lin,J., Wang,G., Cheng,S., Hu,Y., Li,H., Feng,W., Liu,X. and Xu,C.
  TITLE     Pan-Cancer Analysis of the Cuproptosis-Related Gene DLD
  JOURNAL   Mediators Inflamm 2023, 5533444 (2023)
   PUBMED   38077227
  REMARK    GeneRIF: Pan-Cancer Analysis of the Cuproptosis-Related Gene DLD.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 3537)
  AUTHORS   Wongkittichote,P., Cuddapah,S.R., Master,S.R., Grange,D.K.,
            Dietzen,D., Roper,S.M. and Ganetzky,R.D.
  TITLE     Biochemical characterization of patients with dihydrolipoamide
            dehydrogenase deficiency
  JOURNAL   JIMD Rep 64 (5), 367-374 (2023)
   PUBMED   37701333
  REMARK    Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3537)
  AUTHORS   Szabo,E. and Ambrus,A.
  TITLE     Lipoamide dehydrogenase (LADH) deficiency: medical perspectives of
            the structural and functional characterization of LADH and its
            pathogenic variants
  JOURNAL   Biol Futur 74 (1-2), 109-118 (2023)
   PUBMED   36842090
  REMARK    GeneRIF: Lipoamide dehydrogenase (LADH) deficiency: medical
            perspectives of the structural and functional characterization of
            LADH and its pathogenic variants.
            Review article
REFERENCE   4  (bases 1 to 3537)
  AUTHORS   Babady,N.E., Pang,Y.P., Elpeleg,O. and Isaya,G.
  TITLE     Cryptic proteolytic activity of dihydrolipoamide dehydrogenase
  JOURNAL   Proc Natl Acad Sci U S A 104 (15), 6158-6163 (2007)
   PUBMED   17404228
  REMARK    GeneRIF: Certain DLD mutations can simultaneously induce the loss
            of a primary metabolic activity and the gain of a moonlighting
            proteolytic activity thus contributing to the metabolic derangement
            associated with DLD deficiency.
            GeneRIF: Human, mouse, and pig Dld has moonlighting function as a
            protease in addition to its canonical function as a a
            dehydrogenase.
REFERENCE   5  (bases 1 to 3537)
  AUTHORS   Ganetzky,R., McCormick,E.M. and Falk,M.J.
  TITLE     Primary Pyruvate Dehydrogenase Complex Deficiency Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   34138529
REFERENCE   6  (bases 1 to 3537)
  AUTHORS   Rahman,S. and Thorburn,D.
  TITLE     Nuclear Gene-Encoded Leigh Syndrome Spectrum Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   26425749
REFERENCE   7  (bases 1 to 3537)
  AUTHORS   Quinonez,S.C. and Thoene,J.G.
  TITLE     Dihydrolipoamide Dehydrogenase Deficiency
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   25032271
REFERENCE   8  (bases 1 to 3537)
  AUTHORS   Johanning,G.L., Morris,J.I., Madhusudhan,K.T., Samols,D. and
            Patel,M.S.
  TITLE     Characterization of the transcriptional regulatory region of the
            human dihydrolipoamide dehydrogenase gene
  JOURNAL   Proc Natl Acad Sci U S A 89 (22), 10964-10968 (1992)
   PUBMED   1332063
REFERENCE   9  (bases 1 to 3537)
  AUTHORS   Kume,A., Koyata,H., Sakakibara,T., Ishiguro,Y., Kure,S. and
            Hiraga,K.
  TITLE     The glycine cleavage system. Molecular cloning of the chicken and
            human glycine decarboxylase cDNAs and some characteristics involved
            in the deduced protein structures
  JOURNAL   J Biol Chem 266 (5), 3323-3329 (1991)
   PUBMED   1993704
REFERENCE   10 (bases 1 to 3537)
  AUTHORS   Scherer,S.W., Otulakowski,G., Robinson,B.H. and Tsui,L.C.
  TITLE     Localization of the human dihydrolipoamide dehydrogenase gene (DLD)
            to 7q31----q32
  JOURNAL   Cytogenet Cell Genet 56 (3-4), 176-177 (1991)
   PUBMED   2055113
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK312346.1, BC018648.2 and
            AC005046.3.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_000108.4.
            
            Summary: This gene encodes a member of the class-I pyridine
            nucleotide-disulfide oxidoreductase family. The encoded protein has
            been identified as a moonlighting protein based on its ability to
            perform mechanistically distinct functions. In homodimeric form,
            the encoded protein functions as a dehydrogenase and is found in
            several multi-enzyme complexes that regulate energy metabolism.
            However, as a monomer, this protein can function as a protease.
            Mutations in this gene have been identified in patients with
            E3-deficient maple syrup urine disease and lipoamide dehydrogenase
            deficiency. Alternative splicing results in multiple transcript
            variants. [provided by RefSeq, Jan 2014].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: SRR1163655.72997.1,
                                           SRR1660805.174470.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000205402.10/
                                                  ENSP00000205402.3
            multifunctional gene product(s)    :: PMID: 17404228
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1598              AK312346.1         24-1621
            1599-2084           BC018648.2         1584-2069
            2085-3537           AC005046.3         137556-139008
FEATURES             Location/Qualifiers
     source          1..3537
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q31.1"
     gene            1..3537
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /note="dihydrolipoamide dehydrogenase"
                     /db_xref="GeneID:1738"
                     /db_xref="HGNC:HGNC:2898"
                     /db_xref="MIM:238331"
     exon            1..107
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /inference="alignment:Splign:2.1.0"
     CDS             69..1598
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /EC_number="1.8.1.4"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; E3 component of pyruvate dehydrogenase complex,
                     2-oxo-glutarate complex, branched chain keto acid
                     dehydrogenase complex; dihydrolipoyl dehydrogenase,
                     mitochondrial; glycine cleavage system protein L;
                     lipoamide reductase; lipoamide dehydrogenase; lipoyl
                     dehydrogenase; diaphorase; glycine cleavage system L
                     protein; epididymis secretory sperm binding protein;
                     pyruvate dehydrogenase complex subunit E3, 2-oxo-glutarate
                     complex, branched chain keto acid dehydrogenase complex,
                     glycine cleavage system protein L"
                     /codon_start=1
                     /product="dihydrolipoyl dehydrogenase, mitochondrial
                     isoform 1 precursor"
                     /protein_id="NP_000099.2"
                     /db_xref="CCDS:CCDS5749.1"
                     /db_xref="GeneID:1738"
                     /db_xref="HGNC:HGNC:2898"
                     /db_xref="MIM:238331"
                     /translation="MQSWSRVYCSLAKRGHFNRISHGLQGLSAVPLRTYADQPIDADV
                     TVIGSGPGGYVAAIKAAQLGFKTVCIEKNETLGGTCLNVGCIPSKALLNNSHYYHMAH
                     GKDFASRGIEMSEVRLNLDKMMEQKSTAVKALTGGIAHLFKQNKVVHVNGYGKITGKN
                     QVTATKADGGTQVIDTKNILIATGSEVTPFPGITIDEDTIVSSTGALSLKKVPEKMVV
                     IGAGVIGVELGSVWQRLGADVTAVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNT
                     KVTGATKKSDGKIDVSIEAASGGKAEVITCDVLLVCIGRRPFTKNLGLEELGIELDPR
                     GRIPVNTRFQTKIPNIYAIGDVVAGPMLAHKAEDEGIICVEGMAGGAVHIDYNCVPSV
                     IYTHPEVAWVGKSEEQLKEEGIEYKVGKFPFAANSRAKTNADTDGMVKILGQKSTDRV
                     LGAHILGPGAGEMVNEAALALEYGASCEDIARVCHAHPTLSEAFREANLAASFGKSIN
                     F"
     exon            108..186
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /inference="alignment:Splign:2.1.0"
     exon            187..266
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /inference="alignment:Splign:2.1.0"
     exon            267..335
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /inference="alignment:Splign:2.1.0"
     exon            336..405
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /inference="alignment:Splign:2.1.0"
     exon            406..506
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /inference="alignment:Splign:2.1.0"
     exon            507..650
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /inference="alignment:Splign:2.1.0"
     exon            651..752
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /inference="alignment:Splign:2.1.0"
     exon            753..943
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /inference="alignment:Splign:2.1.0"
     exon            944..1114
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /inference="alignment:Splign:2.1.0"
     exon            1115..1304
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /inference="alignment:Splign:2.1.0"
     exon            1305..1442
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /inference="alignment:Splign:2.1.0"
     exon            1443..1532
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /inference="alignment:Splign:2.1.0"
     exon            1533..3537
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2060..2065
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /note="hexamer: TATAAA"
     polyA_site      2084
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /note="major polyA site"
     regulatory      2284..2289
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /note="hexamer: AATAAA"
     polyA_site      2304
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /note="major polyA site"
     regulatory      3500..3505
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /note="hexamer: AATAAA"
     regulatory      3514..3519
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
                     /note="hexamer: AATAAA"
     polyA_site      3523
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
     polyA_site      3537
                     /gene="DLD"
                     /gene_synonym="DLDD; DLDH; E3; GCSL; LAD; OGDC-E3; PHE3"
ORIGIN      
        1 cttggcggag cggcggaggc gcccagcgga ggtgaaagta ttggcggaaa ggaaaataca
       61 gcggaaaaat gcagagctgg agtcgtgtgt actgctcctt ggccaagaga ggccatttca
      121 atcgaatatc tcatggccta cagggacttt ctgcagtgcc tctgagaact tacgcagatc
      181 agccgattga tgctgatgta acagttatag gttctggtcc tggaggatat gttgctgcta
      241 ttaaagctgc ccagttaggc ttcaagacag tctgcattga gaaaaatgaa acacttggtg
      301 gaacatgctt gaatgttggt tgtattcctt ctaaggcttt attgaacaac tctcattatt
      361 accatatggc ccatggaaaa gattttgcat ctagaggaat tgaaatgtcc gaagttcgct
      421 tgaatttaga caagatgatg gagcagaaga gtactgcagt aaaagcttta acaggtggaa
      481 ttgcccactt attcaaacag aataaggttg ttcatgtcaa tggatatgga aagataactg
      541 gcaaaaatca agtcactgct acgaaagctg atggcggcac tcaggttatt gatacaaaga
      601 acattcttat agccacgggt tcagaagtta ctccttttcc tggaatcacg atagatgaag
      661 atacaatagt gtcatctaca ggtgctttat ctttaaaaaa agttccagaa aagatggttg
      721 ttattggtgc aggagtaata ggtgtagaat tgggttcagt ttggcaaaga cttggtgcag
      781 atgtgacagc agttgaattt ttaggtcatg taggtggagt tggaattgat atggagatat
      841 ctaaaaactt tcaacgcatc cttcaaaaac aggggtttaa atttaaattg aatacaaagg
      901 ttactggtgc taccaagaag tcagatggaa aaattgatgt ttctattgaa gctgcttctg
      961 gtggtaaagc tgaagttatc acttgtgatg tactcttggt ttgcattggc cgacgaccct
     1021 ttactaagaa tttgggacta gaagagctgg gaattgaact agatcccaga ggtagaattc
     1081 cagtcaatac cagatttcaa actaaaattc caaatatcta tgccattggt gatgtagttg
     1141 ctggtccaat gctggctcac aaagcagagg atgaaggcat tatctgtgtt gaaggaatgg
     1201 ctggtggtgc tgtgcacatt gactacaatt gtgtgccatc agtgatttac acacaccctg
     1261 aagttgcttg ggttggcaaa tcagaagagc agttgaaaga agagggtatt gagtacaaag
     1321 ttgggaaatt cccatttgct gctaacagca gagctaagac aaatgctgac acagatggca
     1381 tggtgaagat ccttgggcag aaatcgacag acagagtact gggagcacat attcttggac
     1441 caggtgctgg agaaatggta aatgaagctg ctcttgcttt ggaatatgga gcatcctgtg
     1501 aagatatagc tagagtctgt catgcacatc cgaccttatc agaagctttt agagaagcaa
     1561 atcttgctgc gtcatttggc aaatcaatca acttttgaat tagaagatta tatatatttt
     1621 tttctgaaat ttcctgggag cttttgtaga agtcacattc ctgaacagga tattctcaca
     1681 gctccaagaa tttctaggac tgaattatga aacttttgga aggtatttaa taggtttgga
     1741 caaaatggaa tactcttata tctatatttt acataaattt agtattttgt ttcagtgcac
     1801 taatgtgtaa gacaaaaagc tacttattgt agcatcctgg aatatctccg tcaactcata
     1861 ttttcatgct gttcatgaaa gattcaatgc ccctgaattt aaatagcttt tttctctgat
     1921 acagaaaagt tgaattttac atggctggag ctagaatttg atatgtgaac agttgtgttt
     1981 gaagcacagt gatcaagtta tttttaattt ggttttcaca ttggaaacaa gtcagtcatt
     2041 cagatatgat tcaaatgtct ataaaccgaa ctgatgtaag taaacggtct ctcacttgtt
     2101 ttatttaacc tctaaattct ttcattttag gggtagcatt tgtgttgaag aggttttaaa
     2161 gcttccattg ttgtctgcaa ctctgaaggg taattatata gttacccaaa ttaagagagt
     2221 ctatttacgg aactcaaata cgtgggcatt caaatgtatt acagtgggga atgaagatac
     2281 tgaaataaac gtcttaaata ttcatttact ggttatcatg agtacgtgtt gagatggtca
     2341 tagttttttt tatgactact tctagtgtat attctaattt cttttctagg cctgaatgta
     2401 tctttatttt catgttatag gacaatatta aggcatttta aaggtcatca tcctttcatc
     2461 tattttagat acacctacta aatgtttaat atatactttt ggagaagtac aacataaggg
     2521 agtctttaat ctgtgttttc cttggctggg ttaatgactg tttatttaaa gagtgttgta
     2581 aaattggatg tgtggtgttt aaaatggcca tgtcctgagg aaacttaagt aacaaagtac
     2641 taaatgctaa gtaggctttt gcatattgta actaaattta agaataattc agattaagta
     2701 gttctgaaat ttggtataga tagcatagat tgtctcatgc tcatgagtga cataatgacc
     2761 ctggattctg ttacatactt ctaaagaaaa ttgattgttg tcttaggagg cagttaactt
     2821 ggctgaacac caactccaca ctctgtcttg tttgtaggtg gcagcagctg aaatctcttc
     2881 tcagttgttt tagctttagc tatgctgctg gaagtctttc ccatgcaagt gtgtagttca
     2941 ggggtcaacc agagtttggg cagaaggaag tctgcccctt ctgtgcctcc tgttttttgg
     3001 gggtttcccc tttatgttcc agctgttgtg gttgccccat attctgcctt ctgatcctta
     3061 accaataaaa cttggctttt gtttccccct caagtgagaa cccgttaaaa atgagacatt
     3121 gagccagtgc tgttcacttt ttaagtgcca acttccctct actttccact tgtttatagt
     3181 tgtttccagt gcctttagtt ttttctaaaa tatatttgtt cagagtttgc agttgctatc
     3241 agcaggaggg ttggtctgat atctgtgtgc tactttgcca ttattggaag tgaactctgc
     3301 atctttttaa aaatttgaaa tcccggtatc atgtgaagtg ctgtttatgt aaatctcaac
     3361 atatccctta ctcagggaaa aaaaagtttt tagttaggga atagtgaaat ataatttaat
     3421 atggaattct agctgtagag ttaaatccat ctttaagtgt ttacattcag tatgagaatg
     3481 caaatttatc tgtatgggga ataaagtcct aggaataaaa caagttttaa gtgttca
//
