LOCUS       NM_005518               2433 bp    mRNA    linear   PRI 11-SEP-2024
DEFINITION  Homo sapiens 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2),
            transcript variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_005518
VERSION     NM_005518.4
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 2433)
  AUTHORS   Zeng,X., Hu,Y., Qiao,S., Cao,X., Dai,Y., Wu,F. and Wei,Z.
  TITLE     ADORA3 activation promotes goblet cell differentiation via
            enhancing HMGCS2-mediated ketogenesis in ulcerative colitis
  JOURNAL   Int Immunopharmacol 140, 112729 (2024)
   PUBMED   39098229
  REMARK    GeneRIF: ADORA3 activation promotes goblet cell differentiation via
            enhancing HMGCS2-mediated ketogenesis in ulcerative colitis.
REFERENCE   2  (bases 1 to 2433)
  AUTHORS   Chang,L., Ding,J., Pu,J., Zhu,J., Zhou,X., Luo,Q., Li,J., Qian,M.,
            Lin,S., Li,J. and Wang,K.
  TITLE     A novel lncRNA LOC101928222 promotes colorectal cancer angiogenesis
            by stabilizing HMGCS2 mRNA and increasing cholesterol synthesis
  JOURNAL   J Exp Clin Cancer Res 43 (1), 185 (2024)
   PUBMED   38965575
  REMARK    GeneRIF: A novel lncRNA LOC101928222 promotes colorectal cancer
            angiogenesis by stabilizing HMGCS2 mRNA and increasing cholesterol
            synthesis.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 2433)
  AUTHORS   Miller,A.L., Fehling,S.C., Vance,R.B., Chen,D., Brown,E.J.,
            Hossain,M.I., Heard,E.O., Andrabi,S.A., Wang,H., Yang,E.S.,
            Buchsbaum,D.J., van Waardenburg,R.C.A.M., Bellis,S.L. and Yoon,K.J.
  TITLE     BET inhibition decreases HMGCS2 and sensitizes resistant pancreatic
            tumors to gemcitabine
  JOURNAL   Cancer Lett 592, 216919 (2024)
   PUBMED   38704133
  REMARK    GeneRIF: BET inhibition decreases HMGCS2 and sensitizes resistant
            pancreatic tumors to gemcitabine.
REFERENCE   4  (bases 1 to 2433)
  AUTHORS   Yang,J., Pan,X., Xu,M., Li,Y., Liang,C., Liu,L., Li,Z., Wang,L. and
            Yu,G.
  TITLE     Downregulation of HMGCS2 mediated AECIIs lipid metabolic alteration
            promotes pulmonary fibrosis by activating fibroblasts
  JOURNAL   Respir Res 25 (1), 176 (2024)
   PUBMED   38658970
  REMARK    GeneRIF: Downregulation of HMGCS2 mediated AECIIs lipid metabolic
            alteration promotes pulmonary fibrosis by activating fibroblasts.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2433)
  AUTHORS   Mao,H., Wang,R., Shao,F., Zhao,M., Tian,D., Xia,H. and Zhao,Y.
  TITLE     HMGCS2 serves as a potential biomarker for inhibition of renal
            clear cell carcinoma growth
  JOURNAL   Sci Rep 13 (1), 14629 (2023)
   PUBMED   37670031
  REMARK    GeneRIF: HMGCS2 serves as a potential biomarker for inhibition of
            renal clear cell carcinoma growth.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 2433)
  AUTHORS   Bouchard,L., Robert,M.F., Vinarov,D., Stanley,C.A., Thompson,G.N.,
            Morris,A., Leonard,J.V., Quant,P., Hsu,B.Y., Boneh,A.,
            Boukaftane,Y., Ashmarina,L., Wang,S., Miziorko,H. and Mitchell,G.A.
  TITLE     Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency:
            clinical course and description of causal mutations in two patients
  JOURNAL   Pediatr Res 49 (3), 326-331 (2001)
   PUBMED   11228257
REFERENCE   7  (bases 1 to 2433)
  AUTHORS   Boukaftane,Y. and Mitchell,G.A.
  TITLE     Cloning and characterization of the human mitochondrial
            3-hydroxy-3-methylglutaryl CoA synthase gene
  JOURNAL   Gene 195 (2), 121-126 (1997)
   PUBMED   9305755
REFERENCE   8  (bases 1 to 2433)
  AUTHORS   Mascaro,C., Buesa,C., Ortiz,J.A., Haro,D. and Hegardt,F.G.
  TITLE     Molecular cloning and tissue expression of human mitochondrial
            3-hydroxy-3-methylglutaryl-CoA synthase
  JOURNAL   Arch Biochem Biophys 317 (2), 385-390 (1995)
   PUBMED   7893153
REFERENCE   9  (bases 1 to 2433)
  AUTHORS   Boukaftane,Y., Duncan,A., Wang,S., Labuda,D., Robert,M.F.,
            Sarrazin,J., Schappert,K. and Mitchell,G.A.
  TITLE     Human mitochondrial HMG CoA synthase: liver cDNA and partial
            genomic cloning, chromosome mapping to 1p12-p13, and possible role
            in vertebrate evolution
  JOURNAL   Genomics 23 (3), 552-559 (1994)
   PUBMED   7851882
REFERENCE   10 (bases 1 to 2433)
  AUTHORS   Robinson,A.M. and Williamson,D.H.
  TITLE     Physiological roles of ketone bodies as substrates and signals in
            mammalian tissues
  JOURNAL   Physiol Rev 60 (1), 143-187 (1980)
   PUBMED   6986618
  REMARK    Review article
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BP420631.1, BC044217.1,
            BX104280.1 and AI215948.1.
            
            On Aug 31, 2019 this sequence version replaced NM_005518.3.
            
            Summary: The protein encoded by this gene belongs to the HMG-CoA
            synthase family. It is a mitochondrial enzyme that catalyzes the
            first reaction of ketogenesis, a metabolic pathway that provides
            lipid-derived energy for various organs during times of
            carbohydrate deprivation, such as fasting. Mutations in this gene
            are associated with HMG-CoA synthase deficiency. Alternatively
            spliced transcript variants encoding different isoforms have been
            found for this gene.[provided by RefSeq, Oct 2009].
            
            Transcript Variant: This variant (1) 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 :: BC044217.1, X83618.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000369406.8/
                                                  ENSP00000358414.3
            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
            1-469               BP420631.1         37-505
            470-2056            BC044217.1         450-2036
            2057-2413           BX104280.1         100-456
            2414-2433           AI215948.1         18-37               c
FEATURES             Location/Qualifiers
     source          1..2433
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p12"
     gene            1..2433
                     /gene="HMGCS2"
                     /note="3-hydroxy-3-methylglutaryl-CoA synthase 2"
                     /db_xref="GeneID:3158"
                     /db_xref="HGNC:HGNC:5008"
                     /db_xref="MIM:600234"
     exon            1..165
                     /gene="HMGCS2"
                     /inference="alignment:Splign:2.1.0"
     CDS             62..1588
                     /gene="HMGCS2"
                     /EC_number="2.3.3.10"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; 3-hydroxy-3-methylglutaryl-Coenzyme A synthase
                     2 (mitochondrial); hydroxymethylglutaryl-CoA synthase,
                     mitochondrial; testicular tissue protein Li 88; HMG-CoA
                     synthase; 3-hydroxy-3-methylglutaryl-CoA synthase 2
                     (mitochondrial)"
                     /codon_start=1
                     /product="hydroxymethylglutaryl-CoA synthase,
                     mitochondrial isoform 1 precursor"
                     /protein_id="NP_005509.1"
                     /db_xref="CCDS:CCDS905.1"
                     /db_xref="GeneID:3158"
                     /db_xref="HGNC:HGNC:5008"
                     /db_xref="MIM:600234"
                     /translation="MQRLLTPVKRILQLTRAVQETSLTPARLLPVAHQRFSTASAVPL
                     AKTDTWPKDVGILALEVYFPAQYVDQTDLEKYNNVEAGKYTVGLGQTRMGFCSVQEDI
                     NSLCLTVVQRLMERIQLPWDSVGRLEVGTETIIDKSKAVKTVLMELFQDSGNTDIEGI
                     DTTNACYGGTASLFNAANWMESSSWDGRYAMVVCGDIAVYPSGNARPTGGAGAVAMLI
                     GPKAPLALERGLRGTHMENVYDFYKPNLASEYPIVDGKLSIQCYLRALDRCYTSYRKK
                     IQNQWKQAGSDRPFTLDDLQYMIFHTPFCKMVQKSLARLMFNDFLSASSDTQTSLYKG
                     LEAFGGLKLEDTYTNKDLDKALLKASQDMFDKKTKASLYLSTHNGNMYTSSLYGCLAS
                     LLSHHSAQELAGSRIGAFSYGSGLAASFFSFRVSQDAAPGSPLDKLVSSTSDLPKRLA
                     SRKCVSPEEFTEIMNQREQFYHKVNFSPPGDTNSLFPGTWYLERVDEQHRRKYARRPV
                     "
     exon            166..620
                     /gene="HMGCS2"
                     /inference="alignment:Splign:2.1.0"
     exon            621..746
                     /gene="HMGCS2"
                     /inference="alignment:Splign:2.1.0"
     exon            747..911
                     /gene="HMGCS2"
                     /inference="alignment:Splign:2.1.0"
     exon            912..1077
                     /gene="HMGCS2"
                     /inference="alignment:Splign:2.1.0"
     exon            1078..1248
                     /gene="HMGCS2"
                     /inference="alignment:Splign:2.1.0"
     exon            1249..1355
                     /gene="HMGCS2"
                     /inference="alignment:Splign:2.1.0"
     exon            1356..1481
                     /gene="HMGCS2"
                     /inference="alignment:Splign:2.1.0"
     exon            1482..1593
                     /gene="HMGCS2"
                     /inference="alignment:Splign:2.1.0"
     exon            1594..2433
                     /gene="HMGCS2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2034..2039
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HMGCS2"
                     /note="hexamer: ATTAAA"
     polyA_site      2056
                     /gene="HMGCS2"
                     /note="major polyA site"
     regulatory      2416..2421
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HMGCS2"
                     /note="hexamer: AATAAA"
     polyA_site      2433
                     /gene="HMGCS2"
ORIGIN      
        1 atctctttca aggtttctgc tgggtttctg aactgctggg tttctgcttg ctcctctgga
       61 gatgcagcgt ctgttgactc cagtgaagcg cattctgcaa ctgacaagag cggtgcagga
      121 aacctccctc acacctgctc gcctgctccc agtagcccac caaaggtttt ctacagcctc
      181 tgctgtcccc ctggccaaaa cagatacttg gccaaaggac gtgggcatcc tggccctgga
      241 ggtctacttc ccagcccaat atgtggacca aactgacctg gagaagtata acaatgtgga
      301 agcaggaaag tatacagtgg gcttgggcca gacccgtatg ggcttctgct cagtccaaga
      361 ggacatcaac tccctgtgcc tgacggtggt gcaacggctg atggagcgca tacagctccc
      421 atgggactct gtgggcaggc tggaagtagg cactgagacc atcattgaca agtccaaagc
      481 tgtcaaaaca gtgctcatgg aactcttcca ggattcaggc aatactgata ttgagggcat
      541 agataccacc aatgcctgct acggtggtac tgcctccctc ttcaatgctg ccaactggat
      601 ggagtccagt tcctgggatg gtcgttatgc catggtggtc tgtggagaca ttgccgtcta
      661 tcccagtggt aatgctcgtc ccacaggtgg ggccggagct gtggctatgc tgattgggcc
      721 caaggcccct ctggccctgg agcgagggct gaggggaacc catatggaga atgtgtatga
      781 cttctacaaa ccaaatttgg cctcggagta cccaatagtg gatgggaagc tttccatcca
      841 gtgctacttg cgggccttgg atcgatgtta cacatcatac cgtaaaaaaa tccagaatca
      901 gtggaagcaa gctggcagcg atcgaccctt cacccttgac gatttacagt acatgatctt
      961 tcatacaccc ttttgcaaga tggtccagaa gtctctggct cgcctgatgt tcaatgactt
     1021 cctgtcagcc agcagtgaca cacaaaccag cttatataag gggctggagg ctttcggggg
     1081 gctaaagctg gaagacacct acaccaacaa ggacctggat aaagcacttc taaaggcctc
     1141 tcaggacatg ttcgacaaga aaaccaaggc ttccctttac ctctccactc acaatgggaa
     1201 catgtacacc tcatccctgt acgggtgcct ggcctcgctt ctgtcccacc actctgccca
     1261 agaactggct ggctccagga ttggtgcctt ctcttatggc tctggtttag cagcaagttt
     1321 cttttcattt cgagtatccc aggatgctgc tccaggctct cccctggaca agttggtgtc
     1381 cagcacatca gacctgccaa aacgcctagc ctcccgaaag tgtgtgtctc ctgaggagtt
     1441 cacagaaata atgaaccaaa gagagcaatt ctaccataag gtgaatttct ccccacctgg
     1501 tgacacaaac agccttttcc caggtacttg gtacctggag cgagtggacg agcagcatcg
     1561 ccgaaagtat gcccggcgtc ccgtctaaag gtgttctgca gatccatgga aagcttcctg
     1621 ggaaacgtat gctagcagag cttctccccg tgaatcatat ttttaagatc ccactcttag
     1681 ctggtaaatg aatttgaatc gacatagtag ccccataagc atcagccctg tagagtgagg
     1741 agccatctct agcgggccct tcattcctct ccatgctgca atcactgtcc tgggcttatg
     1801 gtgctatgga ctaggggtcc tttgtgaaag agcaagatgg agcaatggag agaagacctc
     1861 ttcctgaatc actggactcc agaaatgtgc atgcagatca gctgttgcct tcaagatcca
     1921 gataaacttt cctgtcatgt gttagaactt tattattatt aatattgtta aacttctgtg
     1981 ctgttcctgt gaatctccaa attttgtacc ttgttctaag ctaatatata gcaattaaaa
     2041 agagagaaag aggaaatgat tcctgcgttt cttggaaccc agaatacaaa cccagcctaa
     2101 catgcagcaa gcctgctaga ccttgtgggt cagagggctg ggtccttgcc tcacaggctg
     2161 cctctgtccc cttgcaattc cattctattt ctgccacatg ccaagtgcta tgacaggtac
     2221 aaggcaaata agaacggtag aacacagctt cccccagccc acttccctgt tctaaagaca
     2281 ccacatagac agagagcagc agacaggggc cagcaggagc tgtagttcag atcttcttgg
     2341 tcattccttg ccgctgttat ttgaacaaat aaacacagcg caaaggttaa caagtttttg
     2401 ccttctatag ccaaaaataa aaaaataaat aaa
//
