LOCUS       NM_000581                899 bp    mRNA    linear   PRI 23-JUL-2024
DEFINITION  Homo sapiens glutathione peroxidase 1 (GPX1), transcript variant 1,
            mRNA.
ACCESSION   NM_000581
VERSION     NM_000581.4
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 899)
  AUTHORS   Panyard,D.J., Reus,L.M., Ali,M., Liu,J., Deming,Y.K., Lu,Q.,
            Kollmorgen,G., Carboni,M., Wild,N., Visser,P.J., Bertram,L.,
            Zetterberg,H., Blennow,K., Gobom,J., Western,D., Sung,Y.J.,
            Carlsson,C.M., Johnson,S.C., Asthana,S., Cruchaga,C., Tijms,B.M.,
            Engelman,C.D. and Snyder,M.P.
  TITLE     Post-GWAS multiomic functional investigation of the TNIP1 locus in
            Alzheimer's disease highlights a potential role for GPX3
  JOURNAL   Alzheimers Dement 20 (7), 5044-5053 (2024)
   PUBMED   38809917
  REMARK    GeneRIF: Post-GWAS multiomic functional investigation of the TNIP1
            locus in Alzheimer's disease highlights a potential role for GPX3.
REFERENCE   2  (bases 1 to 899)
  AUTHORS   Lei,F.J., Chiang,J.Y., Chang,H.J., Chen,D.C., Wang,H.L., Yang,H.A.,
            Wei,K.Y., Huang,Y.C., Wang,C.C., Wei,S.T. and Hsieh,C.H.
  TITLE     Cellular and exosomal GPx1 are essential for controlling hydrogen
            peroxide balance and alleviating oxidative stress in hypoxic
            glioblastoma
  JOURNAL   Redox Biol 65, 102831 (2023)
   PUBMED   37572455
  REMARK    GeneRIF: Cellular and exosomal GPx1 are essential for controlling
            hydrogen peroxide balance and alleviating oxidative stress in
            hypoxic glioblastoma.
REFERENCE   3  (bases 1 to 899)
  AUTHORS   Fallah,F., Colagar,A.H., Saleh,H.A. and Ranjbar,M.
  TITLE     Variation of the genes encoding antioxidant enzymes SOD2 (rs4880),
            GPX1 (rs1050450), and CAT (rs1001179) and susceptibility to male
            infertility: a genetic association study and in silico analysis
  JOURNAL   Environ Sci Pollut Res Int 30 (36), 86412-86424 (2023)
   PUBMED   37405601
  REMARK    GeneRIF: Variation of the genes encoding antioxidant enzymes SOD2
            (rs4880), GPX1 (rs1050450), and CAT (rs1001179) and susceptibility
            to male infertility: a genetic association study and in silico
            analysis.
REFERENCE   4  (bases 1 to 899)
  AUTHORS   Toczewska,J., Baczynska,D., Zalewska,A., Maciejczyk,M. and
            Konopka,T.
  TITLE     The mRNA expression of genes encoding selected antioxidant enzymes
            and thioredoxin, and the concentrations of their protein products
            in gingival crevicular fluid and saliva during periodontitis
  JOURNAL   Dent Med Probl 60 (2), 255-265 (2023)
   PUBMED   37390459
  REMARK    GeneRIF: The mRNA expression of genes encoding selected antioxidant
            enzymes and thioredoxin, and the concentrations of their protein
            products in gingival crevicular fluid and saliva during
            periodontitis.
REFERENCE   5  (bases 1 to 899)
  AUTHORS   Knight,J.A., Onay,U.V., Wells,S., Li,H., Shi,E.J., Andrulis,I.L.
            and Ozcelik,H.
  TITLE     Genetic variants of GPX1 and SOD2 and breast cancer risk at the
            Ontario site of the Breast Cancer Family Registry
  JOURNAL   Cancer Epidemiol Biomarkers Prev 13 (1), 146-149 (2004)
   PUBMED   14744747
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   6  (bases 1 to 899)
  AUTHORS   Moscow,J.A., Morrow,C.S., He,R., Mullenbach,G.T. and Cowan,K.H.
  TITLE     Structure and function of the 5'-flanking sequence of the human
            cytosolic selenium-dependent glutathione peroxidase gene (hgpx1)
  JOURNAL   J Biol Chem 267 (9), 5949-5958 (1992)
   PUBMED   1556108
REFERENCE   7  (bases 1 to 899)
  AUTHORS   Chada,S., Le Beau,M.M., Casey,L. and Newburger,P.E.
  TITLE     Isolation and chromosomal localization of the human glutathione
            peroxidase gene
  JOURNAL   Genomics 6 (2), 268-271 (1990)
   PUBMED   2307470
REFERENCE   8  (bases 1 to 899)
  AUTHORS   Mullenbach,G.T., Tabrizi,A., Irvine,B.D., Bell,G.I., Tainer,J.A.
            and Hallewell,R.A.
  TITLE     Selenocysteine's mechanism of incorporation and evolution revealed
            in cDNAs of three glutathione peroxidases
  JOURNAL   Protein Eng 2 (3), 239-246 (1988)
   PUBMED   2976939
REFERENCE   9  (bases 1 to 899)
  AUTHORS   Sukenaga,Y., Ishida,K., Takeda,T. and Takagi,K.
  TITLE     cDNA sequence coding for human glutathione peroxidase
  JOURNAL   Nucleic Acids Res 15 (17), 7178 (1987)
   PUBMED   3658677
REFERENCE   10 (bases 1 to 899)
  AUTHORS   Mullenbach,G.T., Tabrizi,A., Irvine,B.D., Bell,G.I. and
            Hallewell,R.A.
  TITLE     Sequence of a cDNA coding for human glutathione peroxidase confirms
            TGA encodes active site selenocysteine
  JOURNAL   Nucleic Acids Res 15 (13), 5484 (1987)
   PUBMED   2955287
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA730294.1 and BC007865.2.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_000581.3.
            
            Summary: The protein encoded by this gene belongs to the
            glutathione peroxidase family, members of which catalyze the
            reduction of organic hydroperoxides and hydrogen peroxide (H2O2) by
            glutathione, and thereby protect cells against oxidative damage.
            Other studies indicate that H2O2 is also essential for
            growth-factor mediated signal transduction, mitochondrial function,
            and maintenance of thiol redox-balance; therefore, by limiting H2O2
            accumulation, glutathione peroxidases are also involved in
            modulating these processes. Several isozymes of this gene family
            exist in vertebrates, which vary in cellular location and substrate
            specificity. This isozyme is the most abundant, is ubiquitously
            expressed and localized in the cytoplasm, and whose preferred
            substrate is hydrogen peroxide. It is also a selenoprotein,
            containing the rare amino acid selenocysteine (Sec) at its active
            site. Sec is encoded by the UGA codon, which normally signals
            translation termination. The 3' UTRs of selenoprotein mRNAs contain
            a conserved stem-loop structure, designated the Sec insertion
            sequence (SECIS) element, that is necessary for the recognition of
            UGA as a Sec codon, rather than as a stop signal. This gene
            contains an in-frame GCG trinucleotide repeat in the coding region,
            and three alleles with 4, 5 or 6 repeats have been found in the
            human population. The allele with 4 GCG repeats has been
            significantly associated with breast cancer risk in premenopausal
            women. Alternatively spliced transcript variants have been found
            for this gene. Pseudogenes of this locus have been identified on
            chromosomes X and 21. [provided by RefSeq, Aug 2017].
            
            Transcript Variant: This variant (1) encodes the longest 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 :: HM005391.1, SRR1163655.478345.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match              :: ENST00000419783.3/
                                               ENSP00000407375.1
            protein contains selenocysteine :: PMID: 2955287
            RefSeq Select criteria          :: based on conservation,
                                               expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-65                DA730294.1         379-443
            66-899              BC007865.2         1-834
FEATURES             Location/Qualifiers
     source          1..899
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3p21.31"
     gene            1..899
                     /gene="GPX1"
                     /gene_synonym="GPXD; GSHPX1"
                     /note="glutathione peroxidase 1"
                     /db_xref="GeneID:2876"
                     /db_xref="HGNC:HGNC:4553"
                     /db_xref="MIM:138320"
     exon            1..327
                     /gene="GPX1"
                     /gene_synonym="GPXD; GSHPX1"
                     /inference="alignment:Splign:2.1.0"
     CDS             76..687
                     /gene="GPX1"
                     /gene_synonym="GPXD; GSHPX1"
                     /EC_number="1.11.1.9"
                     /EC_number="1.11.1.12"
                     /note="UGA stop codon recoded as selenocysteine; isoform 1
                     is encoded by transcript variant 1; cellular glutathione
                     peroxidase; GSHPx-1; selenoprotein GPX1;
                     phospholipid-hydroperoxide glutathione peroxidase GPX1"
                     /codon_start=1
                     /transl_except=(pos:220..222,aa:Sec)
                     /product="glutathione peroxidase 1 isoform 1"
                     /protein_id="NP_000572.2"
                     /db_xref="CCDS:CCDS43091.1"
                     /db_xref="GeneID:2876"
                     /db_xref="HGNC:HGNC:4553"
                     /db_xref="MIM:138320"
                     /translation="MCAARLAAAAAAAQSVYAFSARPLAGGEPVSLGSLRGKVLLIEN
                     VASLUGTTVRDYTQMNELQRRLGPRGLVVLGFPCNQFGHQENAKNEEILNSLKYVRPG
                     GGFEPNFMLFEKCEVNGAGAHPLFAFLREALPAPSDDATALMTDPKLITWSPVCRNDV
                     AWNFEKFLVGPDGVPLRRYSRRFQTIDIEPDIEALLSQGPSCA"
     exon            328..899
                     /gene="GPX1"
                     /gene_synonym="GPXD; GSHPX1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      740..808
                     /regulatory_class="recoding_stimulatory_region"
                     /gene="GPX1"
                     /gene_synonym="GPXD; GSHPX1"
                     /note="SECIS_element"
                     /function="essential for recoding UGA to specify
                     selenocysteine"
     regulatory      875..880
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GPX1"
                     /gene_synonym="GPXD; GSHPX1"
                     /note="hexamer: AATAAA"
     polyA_site      899
                     /gene="GPX1"
                     /gene_synonym="GPXD; GSHPX1"
                     /note="major polyA site"
ORIGIN      
        1 aaaaggaggc gcctgctggc ctccccttac agtgcttgtt cggggcgctc cgctggcttc
       61 ttggacaatt gcgccatgtg tgctgctcgg ctagcggcgg cggcggcggc ggcccagtcg
      121 gtgtatgcct tctcggcgcg cccgctggcc ggcggggagc ctgtgagcct gggctccctg
      181 cggggcaagg tactacttat cgagaatgtg gcgtccctct gaggcaccac ggtccgggac
      241 tacacccaga tgaacgagct gcagcggcgc ctcggacccc ggggcctggt ggtgctcggc
      301 ttcccgtgca accagtttgg gcatcaggag aacgccaaga acgaagagat tctgaattcc
      361 ctcaagtacg tccggcctgg tggtgggttc gagcccaact tcatgctctt cgagaagtgc
      421 gaggtgaacg gtgcgggggc gcaccctctc ttcgccttcc tgcgggaggc cctgccagct
      481 cccagcgacg acgccaccgc gcttatgacc gaccccaagc tcatcacctg gtctccggtg
      541 tgtcgcaacg atgttgcctg gaactttgag aagttcctgg tgggccctga cggtgtgccc
      601 ctacgcaggt acagccgccg cttccagacc attgacatcg agcctgacat cgaagccctg
      661 ctgtctcaag ggcccagctg tgcctagggc gcccctccta ccccggctgc ttggcagttg
      721 cagtgctgct gtctcggggg ggttttcatc tatgagggtg tttcctctaa acctacgagg
      781 gaggaacacc tgatcttaca gaaaatacca cctcgagatg ggtgctggtc ctgttgatcc
      841 cagtctctgc cagaccaagg cgagtttccc cactaataaa gtgccgggtg tcagcagaa
//
