LOCUS       NM_006859               3572 bp    mRNA    linear   PRI 21-SEP-2024
DEFINITION  Homo sapiens lipoic acid synthetase (LIAS), transcript variant 1,
            mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_006859
VERSION     NM_006859.4
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 3572)
  AUTHORS   Dreishpoon,M.B., Bick,N.R., Petrova,B., Warui,D.M., Cameron,A.,
            Booker,S.J., Kanarek,N., Golub,T.R. and Tsvetkov,P.
  TITLE     FDX1 regulates cellular protein lipoylation through direct binding
            to LIAS
  JOURNAL   J Biol Chem 299 (9), 105046 (2023)
   PUBMED   37453661
  REMARK    GeneRIF: FDX1 regulates cellular protein lipoylation through direct
            binding to LIAS.
REFERENCE   2  (bases 1 to 3572)
  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 3572)
  AUTHORS   Hendricks,A.L., Wachnowsky,C., Fries,B., Fidai,I. and Cowan,J.A.
  TITLE     Characterization and Reconstitution of Human Lipoyl Synthase (LIAS)
            Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered
            Mechanism of Cluster Assembly
  JOURNAL   Int J Mol Sci 22 (4), 1598 (2021)
   PUBMED   33562493
  REMARK    GeneRIF: Characterization and Reconstitution of Human Lipoyl
            Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors
            and an Ordered Mechanism of Cluster Assembly.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 3572)
  AUTHORS   Krishnamoorthy,E., Hassan,S., Hanna,L.E., Padmalayam,I., Rajaram,R.
            and Viswanathan,V.
  TITLE     Homology modeling of Homo sapiens lipoic acid synthase: Substrate
            docking and insights on its binding mode
  JOURNAL   J Theor Biol 420, 259-266 (2017)
   PUBMED   27717843
  REMARK    GeneRIF: this study used a bioinformatics approach to predict its
            structure. . A homology model for LIAS protein was generated using
            X-ray crystallographic structure of Thermosynechococcus elogatsu.
            The active site of LIAS protein was mapped and docked with
            S-Adenosyl Methionine
REFERENCE   5  (bases 1 to 3572)
  AUTHORS   Burr,S.P., Costa,A.S., Grice,G.L., Timms,R.T., Lobb,I.T.,
            Freisinger,P., Dodd,R.B., Dougan,G., Lehner,P.J., Frezza,C. and
            Nathan,J.A.
  TITLE     Mitochondrial Protein Lipoylation and the 2-Oxoglutarate
            Dehydrogenase Complex Controls HIF1alpha Stability in Aerobic
            Conditions
  JOURNAL   Cell Metab 24 (5), 740-752 (2016)
   PUBMED   27923773
  REMARK    GeneRIF: oxoglutarate dehydrogenase (OGDH) and lipoic acid synthase
            (LIAS), which when mutated stabilize HIF1alpha in a
            non-hydroxylated form.
REFERENCE   6  (bases 1 to 3572)
  AUTHORS   Mayr,J.A., Zimmermann,F.A., Fauth,C., Bergheim,C., Meierhofer,D.,
            Radmayr,D., Zschocke,J., Koch,J. and Sperl,W.
  TITLE     Lipoic acid synthetase deficiency causes neonatal-onset epilepsy,
            defective mitochondrial energy metabolism, and glycine elevation
  JOURNAL   Am J Hum Genet 89 (6), 792-797 (2011)
   PUBMED   22152680
  REMARK    GeneRIF: We identified the homozygous mutation c.746G>A
            (p.Arg249His) in LIAS in an individual with neonatal-onset
            epilepsy, muscular hypotonia, lactic acidosis, and elevated glycine
            concentration in plasma and urine
REFERENCE   7  (bases 1 to 3572)
  AUTHORS   Hendrickson,S.L., Lautenberger,J.A., Chinn,L.W., Malasky,M.,
            Sezgin,E., Kingsley,L.A., Goedert,J.J., Kirk,G.D., Gomperts,E.D.,
            Buchbinder,S.P., Troyer,J.L. and O'Brien,S.J.
  TITLE     Genetic variants in nuclear-encoded mitochondrial genes influence
            AIDS progression
  JOURNAL   PLoS One 5 (9), e12862 (2010)
   PUBMED   20877624
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
            Publication Status: Online-Only
REFERENCE   8  (bases 1 to 3572)
  AUTHORS   Padmalayam,I., Hasham,S., Saxena,U. and Pillarisetti,S.
  TITLE     Lipoic acid synthase (LASY): a novel role in inflammation,
            mitochondrial function, and insulin resistance
  JOURNAL   Diabetes 58 (3), 600-608 (2009)
   PUBMED   19074983
  REMARK    GeneRIF: Lipoic acid synthetase deficiency results in an overall
            disturbance in the antioxidant defense network, leading to
            increased inflammation, insulin resistance, and mitochondrial
            dysfunction.
REFERENCE   9  (bases 1 to 3572)
  AUTHORS   Morikawa,T., Yasuno,R. and Wada,H.
  TITLE     Do mammalian cells synthesize lipoic acid? Identification of a
            mouse cDNA encoding a lipoic acid synthase located in mitochondria
  JOURNAL   FEBS Lett 498 (1), 16-21 (2001)
   PUBMED   11389890
REFERENCE   10 (bases 1 to 3572)
  AUTHORS   Stanchi,F., Bertocco,E., Toppo,S., Dioguardi,R., Simionati,B.,
            Cannata,N., Zimbello,R., Lanfranchi,G. and Valle,G.
  TITLE     Characterization of 16 novel human genes showing high similarity to
            yeast sequences
  JOURNAL   Yeast 18 (1), 69-80 (2001)
   PUBMED   11124703
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK292238.1, BC023635.2,
            AK026289.1 and AC021148.8.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_006859.3.
            
            Summary: The protein encoded by this gene belongs to the biotin and
            lipoic acid synthetases family. Localized in the mitochondrion,
            this iron-sulfur enzyme catalyzes the final step in the de novo
            pathway for the biosynthesis of lipoic acid, a potent antioxidant.
            The deficient expression of this enzyme has been linked to
            conditions such as diabetes, atherosclerosis and neonatal-onset
            epilepsy. Alternative splicing occurs at this locus, and several
            transcript variants encoding distinct isoforms have been
            identified. [provided by RefSeq, Aug 2020].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest 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##
            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                 :: ENST00000640888.2/
                                                  ENSP00000492260.1
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-595               AK292238.1         33-627
            596-819             BC023635.2         573-796
            820-1355            AK292238.1         852-1387
            1356-1719           AK026289.1         1356-1719
            1720-3572           AC021148.8         43471-45323
FEATURES             Location/Qualifiers
     source          1..3572
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4p14"
     gene            1..3572
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /note="lipoic acid synthetase"
                     /db_xref="GeneID:11019"
                     /db_xref="HGNC:HGNC:16429"
                     /db_xref="MIM:607031"
     exon            1..107
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     CDS             63..1181
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /EC_number="2.8.1.8"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; lipoate synthase; lipoyl synthase,
                     mitochondrial; lip-syn"
                     /codon_start=1
                     /product="lipoyl synthase, mitochondrial isoform 1
                     precursor"
                     /protein_id="NP_006850.2"
                     /db_xref="CCDS:CCDS3453.1"
                     /db_xref="GeneID:11019"
                     /db_xref="HGNC:HGNC:16429"
                     /db_xref="MIM:607031"
                     /translation="MSLRCGDAARTLGPRVFGRYFCSPVRPLSSLPDKKKELLQNGPD
                     LQDFVSGDLADRSTWDEYKGNLKRQKGERLRLPPWLKTEIPMGKNYNKLKNTLRNLNL
                     HTVCEEARCPNIGECWGGGEYATATATIMLMGDTCTRGCRFCSVKTARNPPPLDASEP
                     YNTAKAIAEWGLDYVVLTSVDRDDMPDGGAEHIAKTVSYLKERNPKILVECLTPDFRG
                     DLKAIEKVALSGLDVYAHNVETVPELQSKVRDPRANFDQSLRVLKHAKKVQPDVISKT
                     SIMLGLGENDEQVYATMKALREADVDCLTLGQYMQPTRRHLKVEEYITPEKFKYWEKV
                     GNELGFHYTASGPLVRSSYKAGEFFLKNLVAKRKTKDL"
     exon            108..280
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     exon            281..374
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     exon            375..455
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     exon            456..612
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     exon            613..670
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     exon            671..799
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     exon            800..945
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     exon            946..1016
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     exon            1017..1128
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     exon            1129..3572
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1622..1627
                     /regulatory_class="polyA_signal_sequence"
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /note="hexamer: AATAAA"
     polyA_site      1650
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
     regulatory      1685..1690
                     /regulatory_class="polyA_signal_sequence"
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /note="hexamer: ATTAAA"
     polyA_site      1719
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /note="major polyA site"
     regulatory      1761..1766
                     /regulatory_class="polyA_signal_sequence"
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /note="hexamer: ATTAAA"
     polyA_site      1785
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
     regulatory      2117..2122
                     /regulatory_class="polyA_signal_sequence"
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /note="hexamer: AATAAA"
     polyA_site      2144
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
ORIGIN      
        1 ctgtcctttc ccgggagtta gcgatccctc aacccctgca ctgcgctagt cctaaagagg
       61 aaatgtctct acgctgcggg gatgcagccc gcaccctggg gccccgggta tttgggagat
      121 atttttgcag cccagtcaga ccgttaagct ccttgccaga taaaaaaaag gaactcctac
      181 agaatggacc agaccttcaa gattttgtat ctggtgatct tgcagacagg agcacctggg
      241 atgaatataa aggaaaccta aaacgccaga aaggagaaag gttaagacta cctccatggc
      301 taaagacaga gattcccatg gggaaaaatt acaataaact gaaaaatact ttgcggaatt
      361 taaatctcca tacagtatgt gaggaagctc gatgtcccaa tattggagag tgttggggag
      421 gtggagaata tgccaccgcc acagccacga tcatgttgat gggtgacaca tgtacaagag
      481 gttgcagatt ttgttctgtt aagactgcaa gaaatcctcc tccactggat gccagtgagc
      541 cctacaatac tgcaaaggca attgcagaat ggggtctgga ttatgttgtc ctgacatctg
      601 tggatcgaga tgatatgcct gatgggggag ctgaacacat tgcaaagacc gtatcatatt
      661 taaaggaaag gaatccaaaa atccttgtgg agtgtcttac tcctgatttt cgaggtgatc
      721 tcaaagcaat agaaaaagtt gctctgtcag gattagatgt gtatgcacat aatgtagaaa
      781 cagtcccgga attacagagt aaggttcgtg atcctcgggc caattttgat cagtccctac
      841 gtgtactgaa acatgccaag aaggttcagc ctgatgttat ttctaaaaca tctataatgt
      901 tgggtttagg cgagaatgat gagcaagtat atgcaacaat gaaagcactt cgtgaggcag
      961 atgtagactg cttgacttta ggacaatata tgcagccaac aaggcgtcac cttaaggttg
     1021 aagaatatat tactcctgaa aaattcaaat actgggaaaa agtaggaaat gaacttggat
     1081 ttcattatac tgcaagtggc cctttggtgc gttcttcata taaagcaggt gaatttttcc
     1141 tgaaaaatct agtggctaaa agaaaaacaa aagacctcta aaacttcaac aagaccttca
     1201 agatcacaga aatttttaaa atttgattcc agttaataac agaggtggtg ccagaatgcc
     1261 tggactgcag tggatgtgcc ccacctcttt gcttaaaaaa aaaaatgtca atagccaggc
     1321 atagtggctc acgcctgtaa tcccagcact ttaggaggcc aaggcgggtg gatcacctga
     1381 ggtcaggagt tcgagaccag cctggccaac atggtgaaat cctgtctcca ctaaaaacac
     1441 aaaaattagt caggcgtggt agtgggtgcc tgtaatccca gctactcggg aggctaaggc
     1501 aggagaatca cttgaacctg ggagggggag gttgcagtga gccaagatcg ctccattgcc
     1561 ctccagcctg ggtgacaaga gcaaaactcc atctcaaata aataaaaagg aaaaaaaagt
     1621 caataaactg tacaaattta attacagtaa ttcatttggc ttttagtgta tcttctttgt
     1681 cccaattaaa cagttgcttg ctgtgatgta atcttaaaat atctttgtaa gaattttctt
     1741 ttaacataat tttaaaatgc attaaaaaca tggcatggtg gctcacacct ataatcccaa
     1801 cattttggga ggccagggcg ggtggatcac ttgaacccag gagttcgaga ccagcctggg
     1861 caacatgatg agaccttatc tctacaaaaa attagccaga cgtggtggca cgcacccgta
     1921 gtcccagcta ctcaggctga ggtgagagga tcacttgaac ctggaaagca gaggttgcaa
     1981 tgagctgagg tggtgccact gctctccagc ctgggcgcta caactgctct ccagactctg
     2041 tcttgaaaaa aaaacccaaa aacttccaga agattttcca atccactgtt aacatcatta
     2101 catttcattt atgaaaaata aaaacttcat ttatgttact gtgatgaaac agtcaacata
     2161 gattgaaact catcagttta gcatttcatt caactttagc attcattcaa cgtagattga
     2221 aactcatcag attagcattt gtccttgtaa tattggaata atttagaaag gcttaagagt
     2281 gaatgttggc cagatgtggt ggctcatgcc tgtaattcca gcactctgag aggccgaggt
     2341 gggcagatca cctgaggtcg ggagtttgag aacagcctgg ccaacctggt gaaactccat
     2401 tgctactaaa aataaaaaaa ttagctaggt gtgttggcag gtgcctgtaa tcccagctac
     2461 ttgggaggct gaggcacgag aattacttga gcctgtgaag cagagattgc agtgaggcga
     2521 tatcgtgcca ctgcactcca gcccgggcaa cagagtgaga ctgtctcaaa aaaaaagtaa
     2581 atgttgattt tttacattgg tgtgactact tcagaacctg caaaatagtt ttatgctgat
     2641 tacatttagt ccctctgaaa acaccaaggc cataatgctg cctaagacat ggaaatagaa
     2701 cctagaaata ttaaccctta tttgtatagt agcttgctaa atccacatgc cctattcctt
     2761 tcatttctca cattggttgt attatatgat ggtaaaggcc tgagaaagga atttccttcc
     2821 aaaatactaa taactcagat tcatcttttg actgaatcct gcctttctac tttttctgca
     2881 tatctaaaag gacactttta ggtggccatg ttgtaaaata tgtaaagtgg atagccaatt
     2941 ctgttttgaa ttcttataac gagccagtat tataaaagta atgcacatcc ttgccaggtg
     3001 tggtggctca cgcctgtaat cccaccacct tgggaggctg aggcgggtga atcagttgag
     3061 ctcaggagtt tgagactagc ctgggcaaca cagtcagacc cccatctcta ccaaaaatac
     3121 aaaaaattag ctgggtgtgg tggcacatgc ttgtaatctc agctatttgg gaggctgagg
     3181 caggagaatc acttgaacct gacaggcaga ggttgcagtg agctgagatc acatcactgt
     3241 actccagcct gggtgacaga gaccgtgtct caaaaaaaat ttttttaagt aatgcatggg
     3301 ccgggcatgg tggcttaatg cctgtaattc caacgttttg ggaggccgag gcaggtggat
     3361 cacctgaggt caggagtttg agaccagcct gaacaacatg gtgaaacact gtctctacta
     3421 aaaattaaaa aattagccaa gtgtggtggc gcatgtctgt aatcccagct actcaggagg
     3481 ctgagacagg agaatccttg aacctgggag gcagaggttg cagtgagctg agatcacacc
     3541 attgcactcc agcctggaca acgagtgaaa ct
//
