LOCUS       NM_001278590            3443 bp    mRNA    linear   PRI 20-SEP-2024
DEFINITION  Homo sapiens lipoic acid synthetase (LIAS), transcript variant 3,
            mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_001278590
VERSION     NM_001278590.2
KEYWORDS    RefSeq.
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 3443)
  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 3443)
  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 3443)
  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 3443)
  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 3443)
  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 3443)
  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 3443)
  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 3443)
  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 3443)
  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 3443)
  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, AL528262.3,
            BC023635.2, AK026289.1 and AC021148.8.
            
            On May 31, 2019 this sequence version replaced NM_001278590.1.
            
            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 (3) lacks an in-frame coding exon,
            compared to variant 1. The resulting isoform (3) lacks an internal
            segment, compared to 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,
                              SAMEA1968189 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-595               AK292238.1         33-627
            596-949             AL528262.3         578-931
            950-1148            BC023635.2         1056-1254
            1149-1590           AK026289.1         1278-1719
            1591-3443           AC021148.8         43471-45323
FEATURES             Location/Qualifiers
     source          1..3443
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4p14"
     gene            1..3443
                     /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..1052
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /EC_number="2.8.1.8"
                     /note="isoform 3 precursor is encoded by transcript
                     variant 3; lipoate synthase; lipoyl synthase,
                     mitochondrial; lip-syn"
                     /codon_start=1
                     /product="lipoyl synthase, mitochondrial isoform 3
                     precursor"
                     /protein_id="NP_001265519.1"
                     /db_xref="CCDS:CCDS63950.1"
                     /db_xref="GeneID:11019"
                     /db_xref="HGNC:HGNC:16429"
                     /db_xref="MIM:607031"
                     /translation="MSLRCGDAARTLGPRVFGRYFCSPVRPLSSLPDKKKELLQNGPD
                     LQDFVSGDLADRSTWDEYKGNLKRQKGERLRLPPWLKTEIPMGKNYNKLKNTLRNLNL
                     HTVCEEARCPNIGECWGGGEYATATATIMLMGDTCTRGCRFCSVKTARNPPPLDASEP
                     YNTAKAIAEWGLDYVVLTSVDRDDMPDGGAEHIAKTVSYLKESKVRDPRANFDQSLRV
                     LKHAKKVQPDVISKTSIMLGLGENDEQVYATMKALREADVDCLTLGQYMQPTRRHLKV
                     EEYITPEKFKYWEKVGNELGFHYTASGPLVRSSYKAGEFFLKNLVAKRKTKDL"
     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..816
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     exon            817..887
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     exon            888..999
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     exon            1000..3443
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1493..1498
                     /regulatory_class="polyA_signal_sequence"
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /note="hexamer: AATAAA"
     polyA_site      1521
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
     regulatory      1556..1561
                     /regulatory_class="polyA_signal_sequence"
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /note="hexamer: ATTAAA"
     polyA_site      1590
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /note="major polyA site"
     regulatory      1632..1637
                     /regulatory_class="polyA_signal_sequence"
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /note="hexamer: ATTAAA"
     polyA_site      1656
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
     regulatory      1988..1993
                     /regulatory_class="polyA_signal_sequence"
                     /gene="LIAS"
                     /gene_synonym="HGCLAS; HUSSY-01; LAS; LIP1; LS; PDHLD"
                     /note="hexamer: AATAAA"
     polyA_site      2015
                     /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 taaggttcgt gatcctcggg ccaattttga tcagtcccta cgtgtactga
      721 aacatgccaa gaaggttcag cctgatgtta tttctaaaac atctataatg ttgggtttag
      781 gcgagaatga tgagcaagta tatgcaacaa tgaaagcact tcgtgaggca gatgtagact
      841 gcttgacttt aggacaatat atgcagccaa caaggcgtca ccttaaggtt gaagaatata
      901 ttactcctga aaaattcaaa tactgggaaa aagtaggaaa tgaacttgga tttcattata
      961 ctgcaagtgg ccctttggtg cgttcttcat ataaagcagg tgaatttttc ctgaaaaatc
     1021 tagtggctaa aagaaaaaca aaagacctct aaaacttcaa caagaccttc aagatcacag
     1081 aaatttttaa aatttgattc cagttaataa cagaggtggt gccagaatgc ctggactgca
     1141 gtggatgtgc cccacctctt tgcttaaaaa aaaaaatgtc aatagccagg catagtggct
     1201 cacgcctgta atcccagcac tttaggaggc caaggcgggt ggatcacctg aggtcaggag
     1261 ttcgagacca gcctggccaa catggtgaaa tcctgtctcc actaaaaaca caaaaattag
     1321 tcaggcgtgg tagtgggtgc ctgtaatccc agctactcgg gaggctaagg caggagaatc
     1381 acttgaacct gggaggggga ggttgcagtg agccaagatc gctccattgc cctccagcct
     1441 gggtgacaag agcaaaactc catctcaaat aaataaaaag gaaaaaaaag tcaataaact
     1501 gtacaaattt aattacagta attcatttgg cttttagtgt atcttctttg tcccaattaa
     1561 acagttgctt gctgtgatgt aatcttaaaa tatctttgta agaattttct tttaacataa
     1621 ttttaaaatg cattaaaaac atggcatggt ggctcacacc tataatccca acattttggg
     1681 aggccagggc gggtggatca cttgaaccca ggagttcgag accagcctgg gcaacatgat
     1741 gagaccttat ctctacaaaa aattagccag acgtggtggc acgcacccgt agtcccagct
     1801 actcaggctg aggtgagagg atcacttgaa cctggaaagc agaggttgca atgagctgag
     1861 gtggtgccac tgctctccag cctgggcgct acaactgctc tccagactct gtcttgaaaa
     1921 aaaaacccaa aaacttccag aagattttcc aatccactgt taacatcatt acatttcatt
     1981 tatgaaaaat aaaaacttca tttatgttac tgtgatgaaa cagtcaacat agattgaaac
     2041 tcatcagttt agcatttcat tcaactttag cattcattca acgtagattg aaactcatca
     2101 gattagcatt tgtccttgta atattggaat aatttagaaa ggcttaagag tgaatgttgg
     2161 ccagatgtgg tggctcatgc ctgtaattcc agcactctga gaggccgagg tgggcagatc
     2221 acctgaggtc gggagtttga gaacagcctg gccaacctgg tgaaactcca ttgctactaa
     2281 aaataaaaaa attagctagg tgtgttggca ggtgcctgta atcccagcta cttgggaggc
     2341 tgaggcacga gaattacttg agcctgtgaa gcagagattg cagtgaggcg atatcgtgcc
     2401 actgcactcc agcccgggca acagagtgag actgtctcaa aaaaaaagta aatgttgatt
     2461 ttttacattg gtgtgactac ttcagaacct gcaaaatagt tttatgctga ttacatttag
     2521 tccctctgaa aacaccaagg ccataatgct gcctaagaca tggaaataga acctagaaat
     2581 attaaccctt atttgtatag tagcttgcta aatccacatg ccctattcct ttcatttctc
     2641 acattggttg tattatatga tggtaaaggc ctgagaaagg aatttccttc caaaatacta
     2701 ataactcaga ttcatctttt gactgaatcc tgcctttcta ctttttctgc atatctaaaa
     2761 ggacactttt aggtggccat gttgtaaaat atgtaaagtg gatagccaat tctgttttga
     2821 attcttataa cgagccagta ttataaaagt aatgcacatc cttgccaggt gtggtggctc
     2881 acgcctgtaa tcccaccacc ttgggaggct gaggcgggtg aatcagttga gctcaggagt
     2941 ttgagactag cctgggcaac acagtcagac ccccatctct accaaaaata caaaaaatta
     3001 gctgggtgtg gtggcacatg cttgtaatct cagctatttg ggaggctgag gcaggagaat
     3061 cacttgaacc tgacaggcag aggttgcagt gagctgagat cacatcactg tactccagcc
     3121 tgggtgacag agaccgtgtc tcaaaaaaaa tttttttaag taatgcatgg gccgggcatg
     3181 gtggcttaat gcctgtaatt ccaacgtttt gggaggccga ggcaggtgga tcacctgagg
     3241 tcaggagttt gagaccagcc tgaacaacat ggtgaaacac tgtctctact aaaaattaaa
     3301 aaattagcca agtgtggtgg cgcatgtctg taatcccagc tactcaggag gctgagacag
     3361 gagaatcctt gaacctggga ggcagaggtt gcagtgagct gagatcacac cattgcactc
     3421 cagcctggac aacgagtgaa act
//
