LOCUS       NM_001195103            2875 bp    mRNA    linear   PRI 14-OCT-2024
DEFINITION  Homo sapiens glutathione-disulfide reductase (GSR), transcript
            variant 3, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_001195103
VERSION     NM_001195103.3
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 2875)
  AUTHORS   Vyas,B., Bhowmik,R., Akhter,M. and Ahmad,F.J.
  TITLE     Identification, analysis of deleterious SNPs of the human GSR gene
            and their effects on the structure and functions of associated
            proteins and other diseases
  JOURNAL   Sci Rep 12 (1), 5474 (2022)
   PUBMED   35361806
  REMARK    GeneRIF: Identification, analysis of deleterious SNPs of the human
            GSR gene and their effects on the structure and functions of
            associated proteins and other diseases.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2875)
  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 2875)
  AUTHORS   Zhang,C. and Zhao,D.
  TITLE     MicroRNA-362-5p promotes the proliferation and inhibits apoptosis
            of trophoblast cells via targeting glutathione-disulfide reductase
  JOURNAL   Bioengineered 12 (1), 2410-2419 (2021)
   PUBMED   34107852
  REMARK    GeneRIF: MicroRNA-362-5p promotes the proliferation and inhibits
            apoptosis of trophoblast cells via targeting glutathione-disulfide
            reductase.
REFERENCE   4  (bases 1 to 2875)
  AUTHORS   Lorestani,S., Bahari,A., Asadi,M. and Zahedi Avval,F.
  TITLE     Evaluation of glutathione reductase activity in colon tissue of
            patients with irritable bowel syndrome
  JOURNAL   Horm Mol Biol Clin Investig 42 (2), 195-198 (2021)
   PUBMED   34090318
  REMARK    GeneRIF: Evaluation of glutathione reductase activity in colon
            tissue of patients with irritable bowel syndrome.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2875)
  AUTHORS   Wang,Y.N., Lu,Y.X., Liu,J., Jin,Y., Bi,H.C., Zhao,Q., Liu,Z.X.,
            Li,Y.Q., Hu,J.J., Sheng,H., Jiang,Y.M., Zhang,C., Tian,F., Chen,Y.,
            Pan,Z.Z., Chen,G., Zeng,Z.L., Liu,K.Y., Ogasawara,M., Yun,J.P.,
            Ju,H.Q., Feng,J.X., Xie,D., Gao,S., Jia,W.H., Kopetz,S., Xu,R.H.
            and Wang,F.
  TITLE     AMPKalpha1 confers survival advantage of colorectal cancer cells
            under metabolic stress by promoting redox balance through the
            regulation of glutathione reductase phosphorylation
  JOURNAL   Oncogene 39 (3), 637-650 (2020)
   PUBMED   31530934
  REMARK    GeneRIF: AMPKalpha1 is overexpressed in colorectal cancer (CRC)
            patient specimens and the high expression is correlated with poor
            survival. AMPKalpha1 maintains high level of reduced glutathione to
            keep redox homeostasis under stress conditions, thus promoting CRC
            cell survival. Mechanistically, AMPKalpha1 regulate the glutathione
            reductase (GSR) phosphorylation possibly through residue Thr507
            which enhances its activity.
REFERENCE   6  (bases 1 to 2875)
  AUTHORS   Kelner,M.J. and Montoya,M.A.
  TITLE     Structural organization of the human glutathione reductase gene:
            determination of correct cDNA sequence and identification of a
            mitochondrial leader sequence
  JOURNAL   Biochem Biophys Res Commun 269 (2), 366-368 (2000)
   PUBMED   10708558
REFERENCE   7  (bases 1 to 2875)
  AUTHORS   Tutic,M., Lu,X.A., Schirmer,R.H. and Werner,D.
  TITLE     Cloning and sequencing of mammalian glutathione reductase cDNA
  JOURNAL   Eur J Biochem 188 (3), 523-528 (1990)
   PUBMED   2185014
REFERENCE   8  (bases 1 to 2875)
  AUTHORS   Krohne-Ehrich,G., Schirmer,R.H. and Untucht-Grau,R.
  TITLE     Glutathione reductase from human erythrocytes. Isolation of the
            enzyme and sequence analysis of the redox-active peptide
  JOURNAL   Eur J Biochem 80 (1), 65-71 (1977)
   PUBMED   923580
REFERENCE   9  (bases 1 to 2875)
  AUTHORS   Sinet,P.M., Bresson,J.L., Couturier,J., Laurent,C., Prieur,M.,
            Rethore,M.O., Taillemite,J.L., Toudic,D., Jerome,H. and Lejeune,J.
  TITLE     [Possible localization of the glutathione reductase (EC 1.6.4.2) on
            the 8p21 band]
  JOURNAL   Ann Genet 20 (1), 13-17 (1977)
   PUBMED   302667
REFERENCE   10 (bases 1 to 2875)
  AUTHORS   Loos,H., Roos,D., Weening,R. and Houwerzijl,J.
  TITLE     Familial deficiency of glutathione reductase in human blood cells
  JOURNAL   Blood 48 (1), 53-62 (1976)
   PUBMED   947404
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BM148117.1, AB519180.1,
            AC103959.18 and CA944703.1.
            
            On Aug 13, 2020 this sequence version replaced NM_001195103.2.
            
            Summary: This gene encodes a member of the class-I pyridine
            nucleotide-disulfide oxidoreductase family. This enzyme is a
            homodimeric flavoprotein. It is a central enzyme of cellular
            antioxidant defense, and reduces oxidized glutathione disulfide
            (GSSG) to the sulfhydryl form GSH, which is an important cellular
            antioxidant. Rare mutations in this gene result in hereditary
            glutathione reductase deficiency. Multiple alternatively spliced
            transcript variants encoding different isoforms have been found.
            [provided by RefSeq, Aug 2010].
            
            Transcript Variant: This variant (3, also known as delta9) lacks an
            in-frame coding exon, as compared to variant 1. The resulting
            isoform (3) lacks an internal segment, as compared to isoform 1.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: AB519180.1, SRR14038194.2470707.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: PMID: 10708558; reported by
                                                  MitoCarta
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-11                BM148117.1         125-135
            12-1421             AB519180.1         1-1410
            1422-2798           AC103959.18        94712-96088         c
            2799-2875           CA944703.1         18-94               c
FEATURES             Location/Qualifiers
     source          1..2875
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="8"
                     /map="8p12"
     gene            1..2875
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /note="glutathione-disulfide reductase"
                     /db_xref="GeneID:2936"
                     /db_xref="HGNC:HGNC:4623"
                     /db_xref="MIM:138300"
     exon            1..317
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /inference="alignment:Splign:2.1.0"
     CDS             12..1421
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /EC_number="1.8.1.7"
                     /note="isoform 3 is encoded by transcript variant 3;
                     glutathione reductase, mitochondrial; glutathione
                     S-reductase; epididymis luminal protein 75; GRase;
                     epididymis secretory sperm binding protein Li 122m"
                     /codon_start=1
                     /product="glutathione reductase, mitochondrial isoform 3"
                     /protein_id="NP_001182032.1"
                     /db_xref="CCDS:CCDS56532.1"
                     /db_xref="GeneID:2936"
                     /db_xref="HGNC:HGNC:4623"
                     /db_xref="MIM:138300"
                     /translation="MALLPRALSAGAGPSWRRAARAFRGFLLLLPEPAALTRALSRAM
                     ACRQEPQPQGPPPAAGAVASYDYLVIGGGSGGLASARRAAELGARAAVVESHKLGGTC
                     VNVGCVPKKVMWNTAVHSEFMHDHADYGFPSCEGKFNWRVIKEKRDAYVSRLNAIYQN
                     NLTKSHIEIIRGHAAFTSDPKPTIEVSGKKYTAPHILIATGGMPSTPHESQIPGASLG
                     ITSDGFFQLEELPGRSVIVGAGYIAVEMAGILSALGSKTSLMIRHDKVLRSFDSMIST
                     NCTEELENAGVEVLKFSQGIQTDDKGHIIVDEFQNTNVKGIYAVGDVCGKALLTPVAI
                     AAGRKLAHRLFEYKEDSKLDYNNIPTVVFSHPPIGTVGLTEDEAIHKYGIENVKTYST
                     SFTPMYHAVTKRKTKCVMKMVCANKEEKVVGIHMQGLGCDEMLQGFAVAVKMGATKAD
                     FDNTVAIHPTSSEELVTLR"
     exon            318..344
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /inference="alignment:Splign:2.1.0"
     exon            345..433
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /inference="alignment:Splign:2.1.0"
     exon            434..503
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /inference="alignment:Splign:2.1.0"
     exon            504..651
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /inference="alignment:Splign:2.1.0"
     exon            652..706
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /inference="alignment:Splign:2.1.0"
     exon            707..806
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /inference="alignment:Splign:2.1.0"
     exon            807..893
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /inference="alignment:Splign:2.1.0"
     exon            894..1005
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /inference="alignment:Splign:2.1.0"
     exon            1006..1137
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /inference="alignment:Splign:2.1.0"
     exon            1138..1271
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /inference="alignment:Splign:2.1.0"
     exon            1272..2875
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2850..2855
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /note="hexamer: AATAAA"
     polyA_site      2875
                     /gene="GSR"
                     /gene_synonym="CNSHA10; GR; GSRD; HEL-75; HEL-S-122m"
                     /note="major polyA site"
ORIGIN      
        1 cttccgcgtg catggccctg ctgccccgag ccctgagcgc cggcgcggga ccgagctggc
       61 ggcgggcggc gcgcgccttc cgaggcttcc tgctgcttct gcccgagccc gcggccctca
      121 cgcgcgccct ctcccgtgcc atggcctgca ggcaggagcc gcagccgcag ggcccgccgc
      181 ccgctgctgg cgccgtggcc tcctatgact acctggtgat cgggggcggc tcgggcgggc
      241 tggccagcgc gcgcagggcg gccgagctgg gtgccagggc cgccgtggtg gagagccaca
      301 agctgggtgg cacttgcgtg aatgttggat gtgtacccaa aaaggtaatg tggaacacag
      361 ctgtccactc tgaattcatg catgatcatg ctgattatgg ctttccaagt tgtgagggta
      421 aattcaattg gcgtgttatt aaggaaaagc gggatgccta tgtgagccgc ctgaatgcca
      481 tctatcaaaa caatctcacc aagtcccata tagaaatcat ccgtggccat gcagccttca
      541 cgagtgatcc caagcccaca atagaggtca gtgggaaaaa gtacaccgcc ccacacatcc
      601 tgatcgccac aggtggtatg ccctccaccc ctcatgagag ccagatcccc ggtgccagct
      661 taggaataac cagcgatgga ttttttcagc tggaagaatt gcccggccgc agcgtcattg
      721 ttggtgcagg ttacattgct gtggagatgg cagggatcct gtcagccctg ggttctaaga
      781 catcactgat gatacggcat gataaggtac ttagaagttt tgattcaatg atcagcacca
      841 actgcacgga ggagctggag aacgctggcg tggaggtgct gaagttctcc caggggattc
      901 aaaccgatga caagggtcat atcatcgtag acgaattcca gaataccaac gtcaaaggca
      961 tctatgcagt tggggatgta tgtggaaaag ctcttcttac tccagttgca atagctgctg
     1021 gccgaaaact tgcccatcga ctttttgaat ataaggaaga ttccaaatta gattataaca
     1081 acatcccaac tgtggtcttc agccaccccc ctattgggac agtgggactc acggaagatg
     1141 aagccattca taaatatgga atagaaaatg tgaagaccta ttcaacgagc tttaccccga
     1201 tgtatcacgc agttaccaaa aggaaaacaa aatgtgtgat gaaaatggtc tgtgctaaca
     1261 aggaagaaaa ggtggttggg atccatatgc agggacttgg gtgtgatgaa atgctgcagg
     1321 gttttgctgt tgcagtgaag atgggagcaa cgaaggcaga ctttgacaac acagtcgcca
     1381 ttcaccctac ctcttcagaa gagctggtca cacttcgttg agaaccagga gacacgtgtg
     1441 gcgggcagtg ggacccatag atcttctgaa atgaaacaaa taatcacatt gacttactgt
     1501 ttgagtttta tgtatttctt tattttaatc aggatcttct gatagtggaa atttttagta
     1561 cataatagaa cttatttatg gagttagaaa tttgtagtgt tatccaggat tgattttcat
     1621 ttgatcacat ctcacagtaa ttaatatttt caagtttttt ttttattaac agctctgtgc
     1681 tagttttttt tttctgtttt agcctcatcc caaatataaa gctttgtgaa gtacaattaa
     1741 cttaatgtac ttgaatgaat agaacttgct actttttttt tttttttttt tgagacagag
     1801 ttttgctctc attgcccagg ctggagtgcg gtggtgctat ttcagctcac cacaacctct
     1861 gcctcctggg ttcaagtgat tctcctgcct tagcctcccg aatagctgga attacaggca
     1921 cgcaccacca tgcctgacta attttgtatt tttagtagac atggggtttc tccatgttgg
     1981 tcaggctggt ctcaaactcc caccttcagg tgatccgccc acctcggcct cctgaggtgc
     2041 tgagattaca ggcgtgagcc actgtgccag cttgctaatt ttcacagaag ttgatggcaa
     2101 ttcttcacat gtaaacagtg ccagtgcaca gaacctttat atattttttg aagccagtac
     2161 tgtgctctgc atataacaaa gctgcttcaa ggatgagacc tttttctaaa agcatgtaat
     2221 gtgagaagcc ggcctgcctt attttctttt ttctttttta atgattaaaa atagtttgtg
     2281 gcaaggcacg gtggctcagg cctgtaattc tagcactttg ggaggccgag gcaggaggat
     2341 tacttgagcc tacaagtttg aggccagcat gcacagcata gcaagactgc atctctacag
     2401 agagtaaaaa aaattacccg agtgtggtga tgtgcatctg taatctcagc tacttgggag
     2461 gctgaggtga gaggatcact tgagcttggg tgaggtgagg ctgcagtgag tcctgatcat
     2521 gctgctgcac tcaatcttgg acaacagagc aagaccctgt ctcaaaaaaa aaaaaaaaaa
     2581 atatatatat atatatatat tatttttatg aggtgaagtg catcaaactt gggaaagatt
     2641 tgaggaggct gggaacctcc tggaaaacca ctccttgaag aaagatatga gagacattta
     2701 gaagtgattc ctgctttcag aaggaggtgg attcaaatac atcaaaagtc ccttcctctg
     2761 ctaagtgttt atagttcaat gaataatttc aatatttgta tgtgttcttg tcattttatt
     2821 tttttctgaa aaacttccaa aaatttgaaa ataaaattac agccttttct tctta
//
