LOCUS       NM_001178058            2836 bp    mRNA    linear   ROD 05-JUN-2024
DEFINITION  Mus musculus thioredoxin reductase 3 (Txnrd3), transcript variant
            1, mRNA.
ACCESSION   NM_001178058
VERSION     NM_001178058.1
KEYWORDS    RefSeq; RefSeq Select.
SOURCE      Mus musculus (house mouse)
  ORGANISM  Mus musculus
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
            Muroidea; Muridae; Murinae; Mus; Mus.
REFERENCE   1  (bases 1 to 2836)
  AUTHORS   Liu,Y., Ma,W., Liu,Q., Liu,P., Qiao,S., Xu,L., Sun,Y., Gai,X. and
            Zhang,Z.
  TITLE     Decreased thioredoxin reductase 3 expression promotes
            nickel-induced damage to cardiac tissue via activating oxidative
            stress-induced apoptosis and inflammation
  JOURNAL   Environ Toxicol 38 (2), 436-450 (2023)
   PUBMED   36421005
  REMARK    GeneRIF: Decreased thioredoxin reductase 3 expression promotes
            nickel-induced damage to cardiac tissue via activating oxidative
            stress-induced apoptosis and inflammation.
REFERENCE   2  (bases 1 to 2836)
  AUTHORS   Dou,Q., Turanov,A.A., Mariotti,M., Hwang,J.Y., Wang,H., Lee,S.G.,
            Paulo,J.A., Yim,S.H., Gygi,S.P., Chung,J.J. and Gladyshev,V.N.
  TITLE     Selenoprotein TXNRD3 supports male fertility via the redox
            regulation of spermatogenesis
  JOURNAL   J Biol Chem 298 (8), 102183 (2022)
   PUBMED   35753352
  REMARK    GeneRIF: Selenoprotein TXNRD3 supports male fertility via the redox
            regulation of spermatogenesis.
REFERENCE   3  (bases 1 to 2836)
  AUTHORS   Liu,Q., Du,P., Zhu,Y., Zhang,X., Cai,J. and Zhang,Z.
  TITLE     Thioredoxin reductase 3 suppression promotes colitis and
            carcinogenesis via activating pyroptosis and necrosis
  JOURNAL   Cell Mol Life Sci 79 (2), 106 (2022)
   PUBMED   35094204
  REMARK    GeneRIF: Thioredoxin reductase 3 suppression promotes colitis and
            carcinogenesis via activating pyroptosis and necrosis.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 2836)
  AUTHORS   Cui,W., Dai,X., Marcho,C., Han,Z., Zhang,K., Tremblay,K.D. and
            Mager,J.
  TITLE     Towards Functional Annotation of the Preimplantation Transcriptome:
            An RNAi Screen in Mammalian Embryos
  JOURNAL   Sci Rep 6, 37396 (2016)
   PUBMED   27869233
  REMARK    Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2836)
  AUTHORS   Mariotti,M., Ridge,P.G., Zhang,Y., Lobanov,A.V., Pringle,T.H.,
            Guigo,R., Hatfield,D.L. and Gladyshev,V.N.
  TITLE     Composition and evolution of the vertebrate and mammalian
            selenoproteomes
  JOURNAL   PLoS One 7 (3), e33066 (2012)
   PUBMED   22479358
REFERENCE   6  (bases 1 to 2836)
  AUTHORS   Gerashchenko,M.V., Su,D. and Gladyshev,V.N.
  TITLE     CUG start codon generates thioredoxin/glutathione reductase
            isoforms in mouse testes
  JOURNAL   J Biol Chem 285 (7), 4595-4602 (2010)
   PUBMED   20018845
  REMARK    GeneRIF: Study shows that CUG codon is used as an inefficient start
            codon to generate protein Thioredoxin/glutathione reductase
            isoforms in mouse.
REFERENCE   7  (bases 1 to 2836)
  AUTHORS   Lothrop,A.P., Ruggles,E.L. and Hondal,R.J.
  TITLE     No selenium required: reactions catalyzed by mammalian thioredoxin
            reductase that are independent of a selenocysteine residue
  JOURNAL   Biochemistry 48 (26), 6213-6223 (2009)
   PUBMED   19366212
REFERENCE   8  (bases 1 to 2836)
  AUTHORS   Su,D., Novoselov,S.V., Sun,Q.A., Moustafa,M.E., Zhou,Y., Oko,R.,
            Hatfield,D.L. and Gladyshev,V.N.
  TITLE     Mammalian selenoprotein thioredoxin-glutathione reductase. Roles in
            disulfide bond formation and sperm maturation
  JOURNAL   J Biol Chem 280 (28), 26491-26498 (2005)
   PUBMED   15901730
REFERENCE   9  (bases 1 to 2836)
  AUTHORS   Sun,Q.A., Kirnarsky,L., Sherman,S. and Gladyshev,V.N.
  TITLE     Selenoprotein oxidoreductase with specificity for thioredoxin and
            glutathione systems
  JOURNAL   Proc Natl Acad Sci U S A 98 (7), 3673-3678 (2001)
   PUBMED   11259642
REFERENCE   10 (bases 1 to 2836)
  AUTHORS   Sun,Q.A., Wu,Y., Zappacosta,F., Jeang,K.T., Lee,B.J., Hatfield,D.L.
            and Gladyshev,V.N.
  TITLE     Redox regulation of cell signaling by selenocysteine in mammalian
            thioredoxin reductases
  JOURNAL   J Biol Chem 274 (35), 24522-24530 (1999)
   PUBMED   10455115
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK041046.1 and BC076605.1.
            
            [WARNING] On Jan 27, 2025 this sequence was replaced by
            NM_001178058.2.
            
            Summary: The protein encoded by this gene belongs to the pyridine
            nucleotide-disulfide oxidoreductase family, and is a member of the
            thioredoxin (Trx) system. Three thioredoxin reductase (TrxR)
            isozymes are found in mammals. TrxRs are selenocysteine-containing
            flavoenzymes, which reduce thioredoxins, as well as other
            substrates, and play a key role in redox homoeostasis. This gene
            encodes the third TrxR, which unlike the other two isozymes,
            contains an additional N-terminal glutaredoxin (Grx) domain, and
            shows highest expression in testis. The Grx domain allows this
            isozyme to participate in both Trx and glutathione systems. It
            functions as a homodimer containing FAD, and selenocysteine (Sec)
            at the active site. Sec is encoded by UGA codon that normally
            signals translation termination. The 3' UTRs of selenoprotein mRNAs
            contain a conserved stem-loop structure, the Sec insertion sequence
            (SECIS) element, which is necessary for the recognition of UGA as a
            Sec codon rather than as a stop signal. Alternatively spliced
            transcript variants encoding different isoforms have been found for
            this gene. There is evidence for additional isoforms resulting from
            the use of a non-AUG (CUG), and an in-frame downstream AUG as
            translation initiation codons (PMID:20018845). [provided by RefSeq,
            Aug 2017].
            
            Transcript Variant: This variant (1) represents the predominant and
            longer transcript. It contains two in-frame translation initiation
            codons: an upstream non-AUG (CUG) and a downstream AUG codon. The
            isoform (1, also known as TGR-L) represented in this RefSeq results
            from the use of the CUG start codon; it is the longest isoform.
            
            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 :: AK041046.1, AK080362.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMN00849375, SAMN00849380
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            non-AUG initiation codon        :: PMID: 20018845
            protein contains selenocysteine :: PMID: 11259642, 20018845
            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
            1-42                AK041046.1         2-43
            43-2250             BC076605.1         1-2208
            2251-2836           AK041046.1         2254-2839
FEATURES             Location/Qualifiers
     source          1..2836
                     /organism="Mus musculus"
                     /mol_type="mRNA"
                     /strain="C57BL/6"
                     /db_xref="taxon:10090"
                     /chromosome="6"
                     /map="6 40.01 cM"
     gene            1..2836
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /note="thioredoxin reductase 3"
                     /db_xref="GeneID:232223"
                     /db_xref="MGI:MGI:2386711"
     exon            1..415
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     CDS             146..2104
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /EC_number="1.8.1.9"
                     /note="UGA stop codon recoded as selenocysteine; isoform 1
                     is encoded by transcript variant 1; non-AUG (CUG)
                     translation initiation codon; thioredoxin reductase TR2;
                     thioredoxin and glutathione reductase"
                     /codon_start=1
                     /transl_except=(pos:2096..2098,aa:Sec)
                     /product="thioredoxin reductase 3 isoform 1"
                     /protein_id="NP_001171529.1"
                     /db_xref="GeneID:232223"
                     /db_xref="MGI:MGI:2386711"
                     /translation="MEKPPSPPPPPRAQTSPGLGKVGVLPNRRLGAVRGGLMSSPPGR
                     RARLASPGTSRPSSEAREELRRRLRDLIEGNRVMIFSKSYCPHSTRVKELFSSLGVVY
                     NILELDQVDDGASVQEVLTEISNQKTVPNIFVNKVHVGGCDRTFQAHQNGLLQKLLQD
                     DSAHDYDLIIIGGGSGGLSCAKEAANLGKKVMVLDFVVPSPQGTTWGLGGTCVNVGCI
                     PKKLMHQAALLGHALQDAKKYGWEYNQQVKHNWEAMTEAIQSHIGSLNWGYRVTLREK
                     GVTYVNSFGEFVDLHKIKATNKKGQETFYTASKFVIATGERPRYLGIQGDKEYCITSD
                     DLFSLPYCPGCTLVVGASYVGLECAGFLAGLGLDVTVMVRSVLLRGFDQEMAEKVGSY
                     LEQQGVKFQRKFTPILVQQLEKGLPGKLKVVAKSTEGPETVEGIYNTVLLAIGRDSCT
                     RKIGLEKIGVKINEKNGKIPVNDVEQTNVPHVYAIGDILDGKPELTPVAIQAGKLLAR
                     RLFGVSLEKCDYINIPTTVFTPLEYGCCGLSEEKAIEMYKKENLEVYHTLFWPLEWTV
                     AGRDNNTCYAKIICNKFDNERVVGFHLLGPNAGEITQGFAAAMKCGLTKQLLDDTIGI
                     HPTCGEVFTTLEITKSSGLDITQKGCUG"
     exon            416..476
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     exon            477..586
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     exon            587..691
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     exon            692..764
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     exon            765..884
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     exon            885..1027
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     exon            1028..1143
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     exon            1144..1369
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     exon            1370..1462
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     exon            1463..1539
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     exon            1540..1696
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     exon            1697..1804
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     exon            1805..1900
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     exon            1901..2035
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     exon            2036..2836
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2272..2344
                     /regulatory_class="recoding_stimulatory_region"
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /note="SECIS_element"
                     /function="essential for recoding UGA to specify
                     selenocysteine"
     regulatory      2730..2735
                     /regulatory_class="polyA_signal_sequence"
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /note="hexamer: ATTAAA"
     polyA_site      2751
                     /gene="Txnrd3"
                     /gene_synonym="TGR; TR2"
                     /note="major polyA site"
ORIGIN      
        1 gtggccccgt agctgtccgg tgcgcccgcg gccagtgcgt agcgttctca agttctcagc
       61 ggctttgccg gcgtcgtccc ctaggcggcc gcccgcgtcc cggttcctca gcaggcccgg
      121 ctcggcccgg agcgacaaca aagccctgga gaagccaccg tccccgccgc cgcctcctcg
      181 ggcgcagacc tcgcccgggc tggggaaggt tggagtcctc cccaaccgcc gcctgggtgc
      241 tgtccgtggc ggcctcatgt cgtcgccacc cggccgccgc gcccgcctgg cctcccctgg
      301 gaccagccgc ccgtcttctg aggcccgcga ggagctgcgg cgccgcctgc gggacctcat
      361 cgagggcaac agggtgatga tcttcagcaa gagttactgt ccacacagca cgcgggttaa
      421 ggaactcttt tcgtccttgg gagtggtcta taacatcctg gaacttgatc aagttgatga
      481 cggggccagt gttcaggaag tgctgacaga aatcagtaac cagaaaacgg tgcccaatat
      541 ttttgtgaat aaagtgcacg tgggtggatg tgaccgaact ttccaggcac atcagaatgg
      601 tttactgcag aagctcctcc aagatgactc ggctcatgat tacgacctca tcatcatcgg
      661 cgggggttct ggcggcctct cttgtgccaa ggaagctgcc aacttgggaa agaaggtcat
      721 ggtgctagac tttgtggtcc catcgcctca gggcacgacc tggggccttg gcggcacctg
      781 tgtgaacgta ggctgtattc caaagaagct gatgcatcag gcagccctcc tggggcatgc
      841 tttgcaagat gccaagaaat atggctggga gtataaccag caggtgaagc acaactggga
      901 ggccatgaca gaagctatcc agagccacat tggctccttg aactggggct acagggtaac
      961 ccttcgggag aaaggcgtga cctatgtcaa ctccttcggg gagtttgtgg acctgcataa
     1021 aataaaggca accaataaga aagggcagga aacgttttac acggcttcga agtttgtcat
     1081 agcaacaggt gaaaggcctc ggtacttggg aatccaggga gataaagagt actgtattac
     1141 gagtgacgac ctgttctctc tgccatactg cccgggatgt acattagtcg taggcgcttc
     1201 ttatgttggt ctggagtgtg cgggcttttt ggctggtttg gggttagatg tgacagtcat
     1261 ggtacgctcc gtccttcttc gtggctttga tcaagaaatg gcagagaaag tgggatccta
     1321 cctggaacaa caaggtgtca agttccaaag gaaattcacc cccattttgg ttcaacagtt
     1381 ggagaaaggt ttaccaggaa aattgaaagt cgtggctaag tccaccgaag gaccggaaac
     1441 agtagaaggg atatacaaca cggttttgtt agcaattggt cgtgactcct gtacaaggaa
     1501 aatagggctg gagaagatcg gggtcaaaat caatgagaag aatggcaaaa taccagtaaa
     1561 cgatgtggag cagaccaacg tgcctcatgt ttatgctatt ggggacatac tggacggcaa
     1621 accagagctc acccccgttg ccatacaggc aggcaagctg ctagctcgaa gactctttgg
     1681 ggtctcttta gaaaagtgtg attatattaa catcccaaca acggtgttca cacctctgga
     1741 atatggctgt tgtggactgt cggaagagaa agccatcgaa atgtataaaa aagagaatct
     1801 ggaagtgtat cacaccttgt tttggcctct cgagtggaca gttgctggca gagacaacaa
     1861 cacctgttat gcaaagataa tctgcaacaa attcgacaac gaacgtgtgg tgggatttca
     1921 ccttctgggg ccaaatgctg gtgaaatcac gcagggattt gcagctgcaa tgaaatgtgg
     1981 gctcacgaag cagctactgg atgataccat tggaatccac cccacctgtg gtgaggtatt
     2041 cacaacattg gaaatcacaa agtcctcagg gctggacatt actcagaaag gctgctgagg
     2101 ctagccctgc tgctgttggg tttccctgtc acactctcac tctgtgccca tgacatctgc
     2161 ttgggcactg gggaccagtg ccggactttc tcctggcata gagacgagaa ggcggcagag
     2221 gaccagcagc agcagcagca tctggagtct cagctgacgg catgcagcag ccaggctgct
     2281 tccttgacac cttggctcgg aacctgcaga ggtgagccaa ggccgacttc tgcacgtcag
     2341 cctcgacttc accccacgag gccttagatg gcacagtgag cccacctccc tttcccagtt
     2401 gctagtgctt tgacccctca ctttgtttcc atgaagagat tatctttcag ttgtggactt
     2461 gactgtaaag aggcttgttg cccagagtgt agcacttatg gatctgtggt gtttggggag
     2521 ccaggttaga gcaattggct gcactggcct cccactaata taacctgctg tcagaagcct
     2581 gactcaagcc tcactccttg catagctcct gaggggagaa ccgtggagcc attctcctcc
     2641 cagcctctag tctaacggag catcacaaag aagagaaaaa aaatgtcctt gtattgctat
     2701 tggttttcca tgtttatctt aagggtacta ttaaaaaaga ttttactaca atttgtgtga
     2761 tctaattcgt taaacatgat ttgttaagtc atgatccatt gaaaactatt acactaaaat
     2821 taaaaaaaaa tgcctg
//
