LOCUS       NM_000191               1570 bp    mRNA    linear   PRI 11-FEB-2025
DEFINITION  Homo sapiens 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL),
            transcript variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_000191
VERSION     NM_000191.3
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 1570)
  AUTHORS   Wang,Z., Yin,X., Yang,P., Gong,B. and Liu,H.
  TITLE     miR-1202 regulates BPH-1 cell proliferation, apoptosis, and
            epithelial-to-mesenchymal transition through targeting HMGCL
  JOURNAL   Acta Biochim Biophys Sin (Shanghai) 56 (5), 675-687 (2024)
   PUBMED   38551020
  REMARK    GeneRIF: miR-1202 regulates BPH-1 cell proliferation, apoptosis,
            and epithelial-to-mesenchymal transition through targeting HMGCL.
REFERENCE   2  (bases 1 to 1570)
  AUTHORS   Sun,Y., Mu,G., Zhang,X., Wu,Y., Wang,S., Wang,X., Xue,Z., Wang,C.,
            Liu,J., Li,W., Zhang,L., Guo,Y., Zhao,F., Liu,X., Xue,Z., Zhang,Y.,
            Ni,S., Wang,J., Li,X., Han,M. and Huang,B.
  TITLE     Metabolic modulation of histone acetylation mediated by HMGCL
            activates the FOXM1/beta-catenin pathway in glioblastoma
  JOURNAL   Neuro Oncol 26 (4), 653-669 (2024)
   PUBMED   38069906
  REMARK    GeneRIF: Metabolic modulation of histone acetylation mediated by
            HMGCL activates the FOXM1/beta-catenin pathway in glioblastoma.
REFERENCE   3  (bases 1 to 1570)
  AUTHORS   Cui,X., Yun,X., Sun,M., Li,R., Lyu,X., Lao,Y., Qin,X. and Yu,W.
  TITLE     HMGCL-induced beta-hydroxybutyrate production attenuates
            hepatocellular carcinoma via DPP4-mediated ferroptosis
            susceptibility
  JOURNAL   Hepatol Int 17 (2), 377-392 (2023)
   PUBMED   36508088
  REMARK    GeneRIF: HMGCL-induced beta-hydroxybutyrate production attenuates
            hepatocellular carcinoma via DPP4-mediated ferroptosis
            susceptibility.
            Erratum:[Hepatol Int. 2023 Apr;17(2):516. doi:
            10.1007/s12072-022-10476-8.. PMID: 36635611]
REFERENCE   4  (bases 1 to 1570)
  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   5  (bases 1 to 1570)
  AUTHORS   Luo,W., Qin,L., Li,B., Liao,Z., Liang,J., Xiao,X., Xiao,X., Mo,Y.,
            Huang,G., Zhang,Z., Zhou,X. and Li,P.
  TITLE     Inactivation of HMGCL promotes proliferation and metastasis of
            nasopharyngeal carcinoma by suppressing oxidative stress
  JOURNAL   Sci Rep 7 (1), 11954 (2017)
   PUBMED   28931870
  REMARK    GeneRIF: The expression of HMGCL was silenced in nasopharyngeal
            carcinoma tissue. Downregulation of HMGCL in nasopharyngeal
            carcinoma was associated with low intracellular
            beta-hydroxybutyrate (beta-HB) production, thereby reducing
            reactive oxygen species (ROS) generation.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 1570)
  AUTHORS   Ashmarina,L.I., Rusnak,N., Miziorko,H.M. and Mitchell,G.A.
  TITLE     3-Hydroxy-3-methylglutaryl-CoA lyase is present in mouse and human
            liver peroxisomes
  JOURNAL   J Biol Chem 269 (50), 31929-31932 (1994)
   PUBMED   7527399
REFERENCE   7  (bases 1 to 1570)
  AUTHORS   Roberts,J.R., Narasimhan,C., Hruz,P.W., Mitchell,G.A. and
            Miziorko,H.M.
  TITLE     3-Hydroxy-3-methylglutaryl-CoA lyase: expression and isolation of
            the recombinant human enzyme and investigation of a mechanism for
            regulation of enzyme activity
  JOURNAL   J Biol Chem 269 (27), 17841-17846 (1994)
   PUBMED   8027038
REFERENCE   8  (bases 1 to 1570)
  AUTHORS   Mitchell,G.A., Robert,M.F., Hruz,P.W., Wang,S., Fontaine,G.,
            Behnke,C.E., Mende-Mueller,L.M., Schappert,K., Lee,C., Gibson,K.M.,
            Miziorko,H.M. et al.
  TITLE     3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL). Cloning of human
            and chicken liver HL cDNAs and characterization of a mutation
            causing human HL deficiency
  JOURNAL   J Biol Chem 268 (6), 4376-4381 (1993)
   PUBMED   8440722
REFERENCE   9  (bases 1 to 1570)
  AUTHORS   Wang,S., Nadeau,J.H., Duncan,A., Robert,M.F., Fontaine,G.,
            Schappert,K., Johnson,K.R., Zietkiewicz,E., Hruz,P., Miziorko,H. et
            al.
  TITLE     3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL): cloning and
            characterization of a mouse liver HL cDNA and subchromosomal
            mapping of the human and mouse HL genes
  JOURNAL   Mamm Genome 4 (7), 382-387 (1993)
   PUBMED   8102917
REFERENCE   10 (bases 1 to 1570)
  AUTHORS   Barash,V., Mandel,H., Sella,S. and Geiger,R.
  TITLE     3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: biochemical
            studies and family investigation of four generations
  JOURNAL   J Inherit Metab Dis 13 (2), 156-164 (1990)
   PUBMED   2116546
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL590728.26, AL031295.1 and
            AI202943.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_000191.2.
            
            Summary: The protein encoded by this gene belongs to the HMG-CoA
            lyase family. It is a mitochondrial enzyme that catalyzes the final
            step of leucine degradation and plays a key role in ketone body
            formation. Mutations in this gene are associated with HMG-CoA lyase
            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 :: SRR3476690.750542.1,
                                           SRR5189652.81976.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000374490.8/
                                                  ENSP00000363614.3
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-74                AL590728.26        2493-2566           c
            75-158              AL031295.1         119648-119731       c
            159-266             AL031295.1         116614-116721       c
            267-362             AL031295.1         115813-115908       c
            363-511             AL031295.1         113328-113476       c
            512-575             AL031295.1         109874-109937       c
            576-764             AL031295.1         107273-107461       c
            765-890             AL031295.1         103538-103663       c
            891-1562            AL031295.1         101031-101702       c
            1563-1570           AI202943.1         18-25               c
FEATURES             Location/Qualifiers
     source          1..1570
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p36.11"
     gene            1..1570
                     /gene="HMGCL"
                     /gene_synonym="HL; HMGCL1"
                     /note="3-hydroxy-3-methylglutaryl-CoA lyase"
                     /db_xref="GeneID:3155"
                     /db_xref="HGNC:HGNC:5005"
                     /db_xref="MIM:613898"
     exon            1..74
                     /gene="HMGCL"
                     /gene_synonym="HL; HMGCL1"
                     /inference="alignment:Splign:2.1.0"
     CDS             15..992
                     /gene="HMGCL"
                     /gene_synonym="HL; HMGCL1"
                     /EC_number="4.1.3.4"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; hydroxymethylglutaricaciduria;
                     hydroxymethylglutaryl-CoA lyase, mitochondrial; HMG-CoA
                     lyase; 3-hydroxy-3-methylglutarate-CoA lyase;
                     mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase;
                     3-hydroxymethyl-3-methylglutaryl-CoA lyase;
                     3-hydroxymethyl-3-methylglutaryl-Coenzyme A lyase"
                     /codon_start=1
                     /product="hydroxymethylglutaryl-CoA lyase, mitochondrial
                     isoform 1 precursor"
                     /protein_id="NP_000182.2"
                     /db_xref="CCDS:CCDS243.1"
                     /db_xref="GeneID:3155"
                     /db_xref="HGNC:HGNC:5005"
                     /db_xref="MIM:613898"
                     /translation="MAAMRKALPRRLVGLASLRAVSTSSMGTLPKRVKIVEVGPRDGL
                     QNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGIN
                     YPVLTPNLKGFEAAVAAGAKEVVIFGAASELFTKKNINCSIEESFQRFDAILKAAQSA
                     NISVRGYVSCALGCPYEGKISPAKVAEVTKKFYSMGCYEISLGDTIGVGTPGIMKDML
                     SAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPYAQGASGNL
                     ATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQALNRKTSSKVAQATCKL"
     exon            75..158
                     /gene="HMGCL"
                     /gene_synonym="HL; HMGCL1"
                     /inference="alignment:Splign:2.1.0"
     exon            159..266
                     /gene="HMGCL"
                     /gene_synonym="HL; HMGCL1"
                     /inference="alignment:Splign:2.1.0"
     exon            267..362
                     /gene="HMGCL"
                     /gene_synonym="HL; HMGCL1"
                     /inference="alignment:Splign:2.1.0"
     exon            363..511
                     /gene="HMGCL"
                     /gene_synonym="HL; HMGCL1"
                     /inference="alignment:Splign:2.1.0"
     exon            512..575
                     /gene="HMGCL"
                     /gene_synonym="HL; HMGCL1"
                     /inference="alignment:Splign:2.1.0"
     exon            576..764
                     /gene="HMGCL"
                     /gene_synonym="HL; HMGCL1"
                     /inference="alignment:Splign:2.1.0"
     exon            765..890
                     /gene="HMGCL"
                     /gene_synonym="HL; HMGCL1"
                     /inference="alignment:Splign:2.1.0"
     exon            891..1570
                     /gene="HMGCL"
                     /gene_synonym="HL; HMGCL1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1545..1550
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HMGCL"
                     /gene_synonym="HL; HMGCL1"
                     /note="hexamer: ATTAAA"
     polyA_site      1570
                     /gene="HMGCL"
                     /gene_synonym="HL; HMGCL1"
                     /note="major polyA site"
ORIGIN      
        1 gattctgggc caagatggca gcaatgagga aggcgcttcc gcggcgactg gtgggcttgg
       61 cgtccctccg ggctgtcagc acctcatcta tgggcacttt accaaagcgg gtgaaaattg
      121 tggaagttgg tccccgagat ggactacaaa atgaaaagaa tatcgtatct actccagtga
      181 aaatcaagct gatagacatg ctttctgaag caggactctc tgttatagaa accaccagct
      241 ttgtgtctcc taagtgggtt ccccagatgg gtgaccacac tgaagtcttg aagggcattc
      301 agaagtttcc tggcatcaac tacccagtcc tgaccccaaa tttgaaaggc ttcgaggcag
      361 cggttgctgc tggagccaag gaagtagtca tctttggagc tgcctcagag ctcttcacca
      421 agaagaacat caattgttcc atagaggaga gttttcagag gtttgacgca atcctgaagg
      481 cagcgcagtc agccaatatt tctgtgcggg ggtacgtctc ctgtgctctt ggctgccctt
      541 atgaagggaa gatctcccca gctaaagtag ctgaggtcac caagaagttc tactcaatgg
      601 gctgctacga gatctccctg ggggacacca ttggtgtggg caccccaggg atcatgaaag
      661 acatgctatc tgctgtcatg caggaagtgc ctctggctgc cctggctgtc cactgccatg
      721 acacctatgg tcaagccctg gccaacacct tgatggccct gcagatggga gtgagtgtcg
      781 tggactcttc tgtggcagga cttggaggct gtccctacgc acagggggca tcaggaaact
      841 tggccacaga agacctggtc tacatgctag agggcttggg cattcacacg ggtgtgaatc
      901 tccagaagct tctggaagct ggaaacttta tctgtcaagc cctgaacaga aaaactagct
      961 ccaaagtggc tcaggctacc tgtaaactct gagccccttg cccacctgaa gccctgggga
     1021 tgatgtggaa ataggggcac acacagatga ttcatggatg gggacatgga aatgagaata
     1081 ggttaaatgg tgcaggtacc tcatagccag ctctacacag aggtctctcc tggcagaaag
     1141 caggcgaagg gcaggaggag ctgcttggca gaaggacctc ctgcccagac ctgaggagtg
     1201 agaggctttg agggctgaag tctccctttg ttacggaccc tggcccagga gttgaatgcc
     1261 tgaggacgtg tgggaacccc gttccctact tagcatgatc cttgagtctc ctctctggat
     1321 ggaatccgcg agctggccac ctggccaccc tctacacggc tccaccctgc catggccgtg
     1381 gggcccttgc tctctgactt ctcaggacac aggtcatgga ggttcttccc aagctggcag
     1441 aggccatttg tggaaagtgg agagctacgt ggtggccgtc tgccaactcc agcatctctg
     1501 gaaaatctcc acgctgaatg tgatttttga aaacagctta tgtaattaaa ggttgaatgg
     1561 cacatcataa
//
