LOCUS       NM_001933               2813 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens dihydrolipoamide S-succinyltransferase (DLST),
            transcript variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_001933
VERSION     NM_001933.5
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 2813)
  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   2  (bases 1 to 2813)
  AUTHORS   Anderson,N.M., Qin,X., Finan,J.M., Lam,A., Athoe,J., Missiaen,R.,
            Skuli,N., Kennedy,A., Saini,A.S., Tao,T., Zhu,S., Nissim,I.,
            Look,A.T., Qing,G., Simon,M.C. and Feng,H.
  TITLE     Metabolic Enzyme DLST Promotes Tumor Aggression and Reveals a
            Vulnerability to OXPHOS Inhibition in High-Risk Neuroblastoma
  JOURNAL   Cancer Res 81 (17), 4417-4430 (2021)
   PUBMED   34233924
  REMARK    GeneRIF: Metabolic Enzyme DLST Promotes Tumor Aggression and
            Reveals a Vulnerability to OXPHOS Inhibition in High-Risk
            Neuroblastoma.
REFERENCE   3  (bases 1 to 2813)
  AUTHORS   Buffet,A., Zhang,J., Rebel,H., Corssmit,E.P.M., Jansen,J.C.,
            Hensen,E.F., Bovee,J.V.M.G., Morini,A., Gimenez-Roqueplo,A.P.,
            Hes,F.J., Devilee,P., Favier,J. and Bayley,J.P.
  TITLE     Germline DLST Variants Promote Epigenetic Modifications in
            Pheochromocytoma-Paraganglioma
  JOURNAL   J Clin Endocrinol Metab 106 (2), 459-471 (2021)
   PUBMED   33180916
  REMARK    GeneRIF: Germline DLST Variants Promote Epigenetic Modifications in
            Pheochromocytoma-Paraganglioma.
REFERENCE   4  (bases 1 to 2813)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   5  (bases 1 to 2813)
  AUTHORS   Remacha,L., Pirman,D., Mahoney,C.E., Coloma,J., Calsina,B.,
            Curras-Freixes,M., Leton,R., Torres-Perez,R., Richter,S., Pita,G.,
            Herraez,B., Cianchetta,G., Honrado,E., Maestre,L., Urioste,M.,
            Aller,J., Garcia-Uriarte,O., Galvez,M.A., Luque,R.M., Lahera,M.,
            Moreno-Rengel,C., Eisenhofer,G., Montero-Conde,C.,
            Rodriguez-Antona,C., Llorca,O., Smolen,G.A., Robledo,M. and
            Cascon,A.
  TITLE     Recurrent Germline DLST Mutations in Individuals with Multiple
            Pheochromocytomas and Paragangliomas
  JOURNAL   Am J Hum Genet 104 (4), 651-664 (2019)
   PUBMED   30929736
  REMARK    GeneRIF: five germline variants affecting DLST in eight unrelated
            individuals were identified; all except one were diagnosed with
            multiple pheochromocytomas and paragangliomas
            Erratum:[Am J Hum Genet. 2019 May 2;104(5):1008-1010. doi:
            10.1016/j.ajhg.2019.04.010.. PMID: 31051110]
REFERENCE   6  (bases 1 to 2813)
  AUTHORS   Chuang,D.T., Fisher,C.W., Lau,K.S., Griffin,T.A., Wynn,R.M. and
            Cox,R.P.
  TITLE     Maple syrup urine disease: domain structure, mutations and exon
            skipping in the dihydrolipoyl transacylase (E2) component of the
            branched-chain alpha-keto acid dehydrogenase complex
  JOURNAL   Mol Biol Med 8 (1), 49-63 (1991)
   PUBMED   1943690
REFERENCE   7  (bases 1 to 2813)
  AUTHORS   Reed,L.J. and Hackert,M.L.
  TITLE     Structure-function relationships in dihydrolipoamide
            acyltransferases
  JOURNAL   J Biol Chem 265 (16), 8971-8974 (1990)
   PUBMED   2188967
  REMARK    Review article
REFERENCE   8  (bases 1 to 2813)
  AUTHORS   Fregeau,D.R., Prindiville,T., Coppel,R.L., Kaplan,M., Dickson,E.R.
            and Gershwin,M.E.
  TITLE     Inhibition of alpha-ketoglutarate dehydrogenase activity by a
            distinct population of autoantibodies recognizing dihydrolipoamide
            succinyltransferase in primary biliary cirrhosis
  JOURNAL   Hepatology 11 (6), 975-981 (1990)
   PUBMED   2365294
REFERENCE   9  (bases 1 to 2813)
  AUTHORS   Ono,K., Hakozaki,M., Kimura,A. and Kochi,H.
  TITLE     Purification, resolution, and reconstitution of rat liver
            branched-chain alpha-keto acid dehydrogenase complex
  JOURNAL   J Biochem 101 (1), 19-27 (1987)
   PUBMED   3571202
REFERENCE   10 (bases 1 to 2813)
  AUTHORS   Kochi,H., Seino,H. and Ono,K.
  TITLE     Inhibition of glycine oxidation by pyruvate, alpha-ketoglutarate,
            and branched-chain alpha-keto acids in rat liver mitochondria:
            presence of interaction between the glycine cleavage system and
            alpha-keto acid dehydrogenase complexes
  JOURNAL   Arch Biochem Biophys 249 (2), 263-272 (1986)
   PUBMED   3753002
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK289414.1, CX163292.1,
            CN422511.1, BM929953.1 and AI087261.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_001933.4.
            
            Summary: This gene encodes a mitochondrial protein that belongs to
            the 2-oxoacid dehydrogenase family. This protein is one of the
            three components (the E2 component) of the 2-oxoglutarate
            dehydrogenase complex that catalyzes the overall conversion of
            2-oxoglutarate to succinyl-CoA and CO(2). Alternatively spliced
            transcript variants have been found for this gene. [provided by
            RefSeq, Oct 2011].
            
            Transcript Variant: This variant (1) represents the predominant
            transcript, and encodes the longer isoform (1).
            
            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 :: BC000302.2, SRR3476690.920610.1
                                           [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                 :: ENST00000334220.9/
                                                  ENSP00000335304.4
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1681              AK289414.1         24-1704
            1682-2051           CX163292.1         125-494
            2052-2375           CN422511.1         100-423
            2376-2682           BM929953.1         59-365
            2683-2813           AI087261.1         3-133               c
FEATURES             Location/Qualifiers
     source          1..2813
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="14"
                     /map="14q24.3"
     gene            1..2813
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /note="dihydrolipoamide S-succinyltransferase"
                     /db_xref="GeneID:1743"
                     /db_xref="HGNC:HGNC:2911"
                     /db_xref="MIM:126063"
     exon            1..101
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     CDS             39..1400
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /EC_number="2.3.1.61"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; dihydrolipoyllysine-residue succinyltransferase
                     component of 2-oxoglutarate dehydrogenase complex,
                     mitochondrial; E2K; OGDC-E2; dihydrolipoamide
                     S-succinyltransferase (E2 component of 2-oxo-glutarate
                     complex)"
                     /codon_start=1
                     /product="dihydrolipoyllysine-residue succinyltransferase
                     component of 2-oxoglutarate dehydrogenase complex,
                     mitochondrial isoform 1 precursor"
                     /protein_id="NP_001924.2"
                     /db_xref="CCDS:CCDS9833.1"
                     /db_xref="GeneID:1743"
                     /db_xref="HGNC:HGNC:2911"
                     /db_xref="MIM:126063"
                     /translation="MLSRSRCVSRAFSRSLSAFQKGNCPLGRRSLPGVSLCQGPGYPN
                     SRKVVINNSVFSVRFFRTTAVCKDDLVTVKTPAFAESVTEGDVRWEKAVGDTVAEDEV
                     VCEIETDKTSVQVPSPANGVIEALLVPDGGKVEGGTPLFTLRKTGAAPAKAKPAEAPA
                     AAAPKAEPTAAAVPPPAAPIPTQMPPVPSPSQPPSGKPVSAVKPTVAPPLAEPGAGKG
                     LRSEHREKMNRMRQRIAQRLKEAQNTCAMLTTFNEIDMSNIQEMRARHKEAFLKKHNL
                     KLGFMSAFVKASAFALQEQPVVNAVIDDTTKEVVYRDYIDISVAVATPRGLVVPVIRN
                     VEAMNFADIERTITELGEKARKNELAIEDMDGGTFTISNGGVFGSLFGTPIINPPQSA
                     ILGMHGIFDRPVAIGGKVEVRPMMYVALTYDHRLIDGREAVTFLRKIKAAVEDPRVLL
                     LDL"
     exon            102..135
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     exon            136..184
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     exon            185..237
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     exon            238..312
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     exon            313..368
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     exon            369..480
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     exon            481..633
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     exon            634..710
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     exon            711..808
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     exon            809..939
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     exon            940..1013
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     exon            1014..1097
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     exon            1098..1265
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     exon            1266..2813
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2791..2796
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /note="hexamer: ATTAAA"
     polyA_site      2813
                     /gene="DLST"
                     /gene_synonym="DLTS; KGD2; PGL7; PPGL7"
                     /note="major polyA site"
ORIGIN      
        1 atatccggtg tccgcccgcc ctcggctcct ccgccgtgat gctgtcccga tcccgctgtg
       61 tgtctcgggc gttcagccgc tcgctctccg ccttccagaa ggggaactgc cctctaggga
      121 gacgttccct gcctggggtc tccttatgcc agggaccagg ttaccctaac agcaggaagg
      181 ttgtcattaa caacagtgtc ttcagtgttc gctttttcag aactacagct gtatgcaagg
      241 atgacttggt tacagtcaaa accccagcgt ttgcagaatc tgtcacagag ggagatgtca
      301 ggtgggagaa agctgttgga gacacagttg cagaagatga agtggtttgt gagattgaaa
      361 ctgacaagac atctgtgcag gttccatcac cagcaaatgg cgtgattgaa gctcttttgg
      421 tacctgatgg gggaaaagtc gaaggaggca ctccactttt cacactcagg aaaactggtg
      481 ctgctcctgc taaggccaag ccggctgaag ctcctgctgc tgcagcccca aaagcagaac
      541 ctacagcagc ggcagttcct ccccctgcag cacccatacc cactcagatg ccaccggtgc
      601 cctcgccctc acagcctcct tctggcaaac ctgtgtctgc agtaaaaccc actgttgccc
      661 caccactagc tgagccagga gctggcaaag gtctgcgttc agaacatcgg gagaaaatga
      721 acaggatgcg gcagcgcatt gctcagcgtc tgaaggaggc ccagaataca tgtgcaatgc
      781 tgacaacttt taatgagatt gacatgagta acatccagga gatgagggct cggcacaaag
      841 aggctttttt gaagaaacat aacctcaaac taggcttcat gtcggcattt gtgaaggcct
      901 cagcctttgc cttgcaggaa cagcctgttg taaatgcagt gattgacgac acaaccaaag
      961 aggtggtgta tagggattat attgacatca gtgttgcagt ggccacccca cggggtctgg
     1021 tggttccagt catcaggaat gtggaagcta tgaattttgc agatattgaa cggaccatca
     1081 ctgaactggg agagaaggcc cgaaagaatg aacttgccat tgaagatatg gatggcggta
     1141 ccttcaccat tagcaatgga ggcgtttttg gctcgctctt tggaacaccc attatcaacc
     1201 cccctcagtc tgccatcctg gggatgcatg gcatctttga caggccagtg gctataggag
     1261 gcaaggtaga ggtgcggccc atgatgtacg tggcactgac ctatgatcac cggctgattg
     1321 atggcagaga ggctgtgact ttcctccgca aaatcaaggc agcggtagag gatcccagag
     1381 tcctcctcct ggatctttag gaggaaccca cacaccctac aagttgatca tgcaggaact
     1441 gaaaaccagt cttctccctg tcccctcatg ggtcccgggt tagcctggtg acaggcagac
     1501 acatgctgtt ggcctcaagc aaggaagcag agcactgtgt aaccagcagt cacaggtctt
     1561 ttcttggcgt tcctgccagg ctctccctct ctgcacctgt ctcatagcct cgaatatctt
     1621 aattccttag gcttaagaga gagagcctta atggatgctc attcatattc ctgcctttct
     1681 tccatcagct ctctgcaaag atgattttgc ttttccctag tgctggtata ctatagagaa
     1741 acccctgggg accatgtgat taagttccta tcttttgaaa gtttgttctg cagagacttc
     1801 taggaggatg ctgtgcctcc caagctcaga gcagcctctg tcctggctgt gcacattctc
     1861 ccttgattcc acttgtgtgg agggattgaa cacaggcaaa gaggtgctgc tttgcttctt
     1921 caatggcacc ttcattctcc gttgtcattg acttcaagat gcctcttcta cctcttccag
     1981 gaagcacagg ccaggggatc tgggtgtgtg agtgggagga gagggcagag gtcccctgag
     2041 gtcatgcatt gtaatcatca tagaaggaga gcccaggcct gccctcacgc tctccatcat
     2101 aggctgacac caagaagact cgtcttggca caatctcaca cagctggggc tgtagcaacc
     2161 ctttccaacc cctttgctgg ttgctgggcc tcattctagc accttgttct tagagcagat
     2221 tctagcacat catggcagtg ggaccaagcg tggtcccgag gaagggccag agcctggtag
     2281 agactaggga agggaggtct cctctagact gactcacatt gccttgagct tttcagttaa
     2341 gttgctgtaa gcacctgggc tgaggaggca gtttttgttc cttcctgcgt tatagcgggg
     2401 ccttgtctct tcctctgcag gacacagatc tggaggacgt ggactggggt aggaaaccac
     2461 cctgagggtg ttagtaccta gtggtgaaac ggatgaggtc atttctaagg tgtgttgccc
     2521 gtggatctgg gcacaatcat tggaattcct tggagccact gggattcatg gctttgtatc
     2581 caactgcatc caggcctgag gctgctgacg tttgacacca gggccagtag agagtgccct
     2641 tttgtatctt aagccaagaa gtgaggcctg ggggtggggg aggggggaag gggtgggagc
     2701 caatactgag tgcctgcagc atctactact ctgtcttcac tattcagaac ttgtaactaa
     2761 agtatttaaa gaaactgatt ttaaatgcaa attaaagggc agatattctc aaa
//
