LOCUS       NM_001498               3785 bp    mRNA    linear   PRI 14-OCT-2024
DEFINITION  Homo sapiens glutamate-cysteine ligase catalytic subunit (GCLC),
            transcript variant 1, mRNA.
ACCESSION   NM_001498
VERSION     NM_001498.4
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 3785)
  AUTHORS   Xu,C., Bian,Z., Wang,X., Niu,N., Liu,L., Xiao,Y., Zhu,J., Huang,N.,
            Zhang,Y., Chen,Y., Wu,Q., Sun,F., Zhu,X. and Pan,Q.
  TITLE     SNORA56-mediated pseudouridylation of 28 S rRNA inhibits
            ferroptosis and promotes colorectal cancer proliferation by
            enhancing GCLC translation
  JOURNAL   J Exp Clin Cancer Res 42 (1), 331 (2023)
   PUBMED   38049865
  REMARK    GeneRIF: SNORA56-mediated pseudouridylation of 28 S rRNA inhibits
            ferroptosis and promotes colorectal cancer proliferation by
            enhancing GCLC translation.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 3785)
  AUTHORS   Liu,C., Wu,X., Bing,X., Qi,W., Zhu,F., Guo,N., Li,C., Gao,X.,
            Cao,X., Zhao,M. and Xia,M.
  TITLE     H1N1 influenza virus infection through NRF2-KEAP1-GCLC pathway
            induces ferroptosis in nasal mucosal epithelial cells
  JOURNAL   Free Radic Biol Med 204, 226-242 (2023)
   PUBMED   37146698
  REMARK    GeneRIF: H1N1 influenza virus infection through NRF2-KEAP1-GCLC
            pathway induces ferroptosis in nasal mucosal epithelial cells.
REFERENCE   3  (bases 1 to 3785)
  AUTHORS   Da,D., Pan,Z., Zeng,L., Dang,Y., Dang,C., Huang,Y., Shi,D. and
            Li,H.
  TITLE     Glutamate-cysteine ligase catalytic and its modifier function as
            novel immunotargets in gastric adenocarcinoma
  JOURNAL   Asian J Surg 46 (1), 143-149 (2023)
   PUBMED   35241341
  REMARK    GeneRIF: Glutamate-cysteine ligase catalytic and its modifier
            function as novel immunotargets in gastric adenocarcinoma.
REFERENCE   4  (bases 1 to 3785)
  AUTHORS   Luo,L., Zhang,Z., Weng,Y. and Zeng,J.
  TITLE     Ferroptosis-Related Gene GCLC Is a Novel Prognostic Molecular and
            Correlates with Immune Infiltrates in Lung Adenocarcinoma
  JOURNAL   Cells 11 (21), 3371 (2022)
   PUBMED   36359768
  REMARK    GeneRIF: Ferroptosis-Related Gene GCLC Is a Novel Prognostic
            Molecular and Correlates with Immune Infiltrates in Lung
            Adenocarcinoma.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 3785)
  AUTHORS   Bykanova,M.A., Solodilova,M.A., Azarova,I.E., Klyosova,E.Y.,
            Bushueva,O.Y., Polonikova,A.A., Churnosov,M.I. and Polonikov,A.V.
  TITLE     Genetic variation at the catalytic subunit of glutamate cysteine
            ligase contributes to the susceptibility to sporadic colorectal
            cancer: a pilot study
  JOURNAL   Mol Biol Rep 49 (7), 6145-6154 (2022)
   PUBMED   35386070
  REMARK    GeneRIF: Genetic variation at the catalytic subunit of glutamate
            cysteine ligase contributes to the susceptibility to sporadic
            colorectal cancer: a pilot study.
REFERENCE   6  (bases 1 to 3785)
  AUTHORS   Mulcahy,R.T. and Gipp,J.J.
  TITLE     Identification of a putative antioxidant response element in the
            5'-flanking region of the human gamma-glutamylcysteine synthetase
            heavy subunit gene
  JOURNAL   Biochem Biophys Res Commun 209 (1), 227-233 (1995)
   PUBMED   7726839
REFERENCE   7  (bases 1 to 3785)
  AUTHORS   Gipp,J.J., Chang,C. and Mulcahy,R.T.
  TITLE     Cloning and nucleotide sequence of a full-length cDNA for human
            liver gamma-glutamylcysteine synthetase
  JOURNAL   Biochem Biophys Res Commun 185 (1), 29-35 (1992)
   PUBMED   1350904
REFERENCE   8  (bases 1 to 3785)
  AUTHORS   Beutler,E., Moroose,R., Kramer,L., Gelbart,T. and Forman,L.
  TITLE     Gamma-glutamylcysteine synthetase deficiency and hemolytic anemia
  JOURNAL   Blood 75 (1), 271-273 (1990)
   PUBMED   2294991
REFERENCE   9  (bases 1 to 3785)
  AUTHORS   Lebo,R.V. and Kredich,N.M.
  TITLE     Inactivation of human gamma-glutamylcysteine synthetase by
            cystamine. Demonstration and quantification of enzyme-ligand
            complexes
  JOURNAL   J Biol Chem 253 (8), 2615-2623 (1978)
   PUBMED   24639
REFERENCE   10 (bases 1 to 3785)
  AUTHORS   Konrad,P.N., Richards,F. 2nd, Valentine,W.N. and Paglia,D.E.
  TITLE     -Glutamyl-cysteine synthetase deficiency. A cause of hereditary
            hemolytic anemia
  JOURNAL   N Engl J Med 286 (11), 557-561 (1972)
   PUBMED   5058793
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BI550814.1, AL531593.3,
            AK313480.1, AB262176.1 and BC039894.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 8, 2018 this sequence version replaced NM_001498.3.
            
            Summary: Glutamate-cysteine ligase, also known as
            gamma-glutamylcysteine synthetase is the first rate-limiting enzyme
            of glutathione synthesis. The enzyme consists of two subunits, a
            heavy catalytic subunit and a light regulatory subunit. This locus
            encodes the catalytic subunit, while the regulatory subunit is
            derived from a different gene located on chromosome 1p22-p21.
            Mutations at this locus have been associated with hemolytic anemia
            due to deficiency of gamma-glutamylcysteine synthetase and
            susceptibility to myocardial infarction.[provided by RefSeq, Oct
            2010].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (a).
            
            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 :: SRR1803614.95345.1, AB262176.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000650454.1/ ENSP00000497574.1
            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
            1-56                BI550814.1         34-89
            57-62               AL531593.3         91-96
            63-2370             AK313480.1         1-2308
            2371-3784           AB262176.1         2302-3715
            3785-3785           BC039894.1         3410-3410
FEATURES             Location/Qualifiers
     source          1..3785
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6p12.1"
     gene            1..3785
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /note="glutamate-cysteine ligase catalytic subunit"
                     /db_xref="GeneID:2729"
                     /db_xref="HGNC:HGNC:4311"
                     /db_xref="MIM:606857"
     exon            1..606
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     CDS             457..2370
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /EC_number="6.3.2.2"
                     /note="isoform a is encoded by transcript variant 1;
                     gamma-glutamylcysteine synthetase; gamma-ECS; GCS heavy
                     chain"
                     /codon_start=1
                     /product="glutamate--cysteine ligase catalytic subunit
                     isoform a"
                     /protein_id="NP_001489.1"
                     /db_xref="CCDS:CCDS4952.1"
                     /db_xref="GeneID:2729"
                     /db_xref="HGNC:HGNC:4311"
                     /db_xref="MIM:606857"
                     /translation="MGLLSQGSPLSWEETKRHADHVRRHGILQFLHIYHAVKDRHKDV
                     LKWGDEVEYMLVSFDHENKKVRLVLSGEKVLETLQEKGERTNPNHPTLWRPEYGSYMI
                     EGTPGQPYGGTMSEFNTVEANMRKRRKEATSILEENQALCTITSFPRLGCPGFTLPEV
                     KPNPVEGGASKSLFFPDEAINKHPRFSTLTRNIRHRRGEKVVINVPIFKDKNTPSPFI
                     ETFTEDDEASRASKPDHIYMDAMGFGMGNCCLQVTFQACSISEARYLYDQLATICPIV
                     MALSAASPFYRGYVSDIDCRWGVISASVDDRTREERGLEPLKNNNYRISKSRYDSIDS
                     YLSKCGEKYNDIDLTIDKEIYEQLLQEGIDHLLAQHVAHLFIRDPLTLFEEKIHLDDA
                     NESDHFENIQSTNWQTMRFKPPPPNSDIGWRVEFRPMEVQLTDFENSAYVVFVVLLTR
                     VILSYKLDFLIPLSKVDENMKVAQKRDAVLQGMFYFRKDICKGGNAVVDGCGKAQNST
                     ELAAEEYTLMSIDTIINGKEGVFPGLIPILNSYLENMEVDVDTRCSILNYLKLIKKRA
                     SGELMTVARWMREFIANHPDYKQDSVITDEMNYSLILKCNQIANELCECPELLGSAFR
                     KVKYSGSKTDSSN"
     exon            607..719
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     exon            720..902
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     exon            903..1016
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     exon            1017..1075
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     exon            1076..1209
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     exon            1210..1284
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     exon            1285..1401
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     exon            1402..1540
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     exon            1541..1653
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     exon            1654..1746
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     exon            1747..1851
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     exon            1852..1933
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     exon            1934..2037
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     exon            2038..2158
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     exon            2159..3785
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2962..2967
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /note="hexamer: AATAAA"
     polyA_site      2984
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
     regulatory      3753..3758
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /note="hexamer: AATAAA"
     polyA_site      3785
                     /gene="GCLC"
                     /gene_synonym="CNSHA7; GCL; GCS; GLCL; GLCLC"
                     /note="major polyA site"
ORIGIN      
        1 aggagcggcg agctagcgga cgcaaagact gggcatgctc cgcggcggcg caggttttgg
       61 tcacaagtag gaagaagcca gtgcaccaga ccggcaaaga gaagcgggag ccgccgcggc
      121 agcgcggccg tggggtccgc cgccgccgca tcggagcggg aggaggagca gcggggaggg
      181 cgaggccgcc gggccgagag ccgtcccgcc tgctctcggt cttctgcctt cgcctccgcg
      241 cggtgcgtcg gacccagggt ctgtcacctg ggcgccaggg gccgccgccg gggagccgga
      301 gcgggcagga ccctccctcc gccgactgcg gcccgagagc gcccccgcgg ggtggagcgg
      361 cagccgcctt ctgcgggcgg ctgagtgtcc gtctcgcgcc cggagcgggc gaccgccgtc
      421 agcccggagg aggaggagga ggaggagggg gcggccatgg ggctgctgtc ccagggctcg
      481 ccgctgagct gggaggaaac caagcgccat gccgaccacg tgcggcggca cgggatcctc
      541 cagttcctgc acatctacca cgccgtcaag gaccggcaca aggacgttct caagtggggc
      601 gatgaggtgg aatacatgtt ggtatctttt gatcatgaaa ataaaaaagt ccggttggtc
      661 ctgtctgggg agaaagttct tgaaactctg caagagaagg gggaaaggac aaacccaaac
      721 catcctaccc tttggagacc agagtatggg agttacatga ttgaagggac accaggacag
      781 ccctacggag gaacaatgtc cgagttcaat acagttgagg ccaacatgcg aaaacgccgg
      841 aaggaggcta cttctatatt agaagaaaat caggctcttt gcacaataac ttcatttccc
      901 agattaggct gtcctgggtt cacactgccc gaggtcaaac ccaacccagt ggaaggagga
      961 gcttccaagt ccctcttctt tccagatgaa gcaataaaca agcaccctcg cttcagtacc
     1021 ttaacaagaa atatccgaca taggagagga gaaaaggttg tcatcaatgt accaatattt
     1081 aaggacaaga atacaccatc tccatttata gaaacattta ctgaggatga tgaagcttca
     1141 agggcttcta agccggatca tatttacatg gatgccatgg gatttggaat gggcaattgc
     1201 tgtctccagg tgacattcca agcctgcagt atatctgagg ccagatacct ttatgatcag
     1261 ttggctacta tctgtccaat tgttatggct ttgagtgctg catctccctt ttaccgaggc
     1321 tatgtgtcag acattgattg tcgctgggga gtgatttctg catctgtaga tgatagaact
     1381 cgggaggagc gaggactgga gccattgaag aacaataact ataggatcag taaatcccga
     1441 tatgactcaa tagacagcta tttatctaag tgtggtgaga aatataatga catcgacttg
     1501 acgatagata aagagatcta cgaacagctg ttgcaggaag gcattgatca tctcctggcc
     1561 cagcatgttg ctcatctctt tattagagac ccactgacac tgtttgaaga gaaaatacac
     1621 ctggatgatg ctaatgagtc tgaccatttt gagaatattc agtccacaaa ttggcagaca
     1681 atgagattta agccccctcc tccaaactca gacattggat ggagagtaga atttcgaccc
     1741 atggaggtgc aattaacaga ctttgagaac tctgcctatg tggtgtttgt ggtactgctc
     1801 accagagtga tcctttccta caaattggat tttctcattc cactgtcaaa ggttgatgag
     1861 aacatgaagg tagcacagaa aagagatgct gtcttgcagg gaatgtttta tttcaggaaa
     1921 gatatttgca aaggtggcaa tgcagtggtg gatggttgtg gcaaggccca gaacagcacg
     1981 gagctcgctg cagaggagta caccctcatg agcatagaca ccatcatcaa tgggaaggaa
     2041 ggtgtgtttc ctggactgat cccaattctg aactcttacc ttgaaaacat ggaagtggat
     2101 gtggacacca gatgtagtat tctgaactac ctaaagctaa ttaagaagag agcatctgga
     2161 gaactaatga cagttgccag atggatgagg gagtttatcg caaaccatcc tgactacaag
     2221 caagacagtg tcataactga tgaaatgaat tatagcctta ttttgaagtg taaccaaatt
     2281 gcaaatgaat tatgtgaatg cccagagtta cttggatcag catttaggaa agtaaaatat
     2341 agtggaagta aaactgactc atccaactag acattctaca gaaagaaaaa tgcattattg
     2401 acgaactggc tacagtacca tgcctctcag ccagcccgtg tgtataatat gaagaccaaa
     2461 tgatagaact gtactgtttt ctgggccagt gagccagaaa ttgattaagg ctttctttgg
     2521 taggtaaatc tagagtttat acagtgtaca tgtacatagt aaagtatttt tgattaacaa
     2581 tgtattttaa taacatatct aaagtcatca tgaactggct tgtacatttt taaattctta
     2641 ctctggagca acctactgtc taagcagttt tgtaaatgta ctggtaattg tacaatactt
     2701 gcattccaga gttaaaatgt ttactgtaaa tttttgttct tttaaagact acctgggacc
     2761 tgatttattg aaatttttct ctttaaaaac attttctctc gttaattttc ctttgtcatt
     2821 tcctttgttg tctacattaa atcacttgaa tccattgaaa gtgcttcaag ggtaatcttg
     2881 ggtttctagc accttatcta tgatgtttct tttgcaattg gaataatcac ttggtcacct
     2941 tgccccaagc tttcccctct gaataaatac ccattgaact ctgatggctg ttatcaaagg
     3001 aacttttctt tgtttaaatt tgctgatgca ggaattaagt ttaaacacaa ctctatagaa
     3061 agaaaggaga ttattaccca gaattcacat gtagtgatta ttaaggacaa tttttttttt
     3121 taactaaaaa agttggcggc aggggtgggg ggtggcaatc atttttcttc ctatacatac
     3181 aaaggatatt gtcaaaaatg gcgttcttct cttgtggcct gttattctga ttgctgctgt
     3241 atacagtttt gtcactcttt agtttttagt taagcatact gatagacttt cctctaaaag
     3301 ccattcactc cagattttac ctggggaata ttctacatac tgcttacttt ctctataaaa
     3361 ctcatcaata aatcatgaaa ggcactgagt tttgtaaatc aggaccctaa atgtttaatt
     3421 gtaaataagt ttcagataat tattatagct ttgcgttgaa gtttgttgtt ttttttctca
     3481 actagttaag tcaactgctt ctgaaataac tctgtattgt agattatgca gatctttaca
     3541 ggcataaata tttaaactgt aatatgctaa cttgaagaga ttgcaataaa gctgcttcag
     3601 ctaaccctgt ttatgtttaa atactagggt ttgttctata ttttatacat gcattttgga
     3661 tgattaaaga atgcctggtt ttcgtttgca atttgcttgt gtaaatcagg ttgtaaaaag
     3721 gcagataaat tgaaatgttt gtggtatgag gaaataaaag aatggaatta gctttcattc
     3781 agaaa
//
