LOCUS       NM_006440               1941 bp    mRNA    linear   PRI 03-OCT-2024
DEFINITION  Homo sapiens thioredoxin reductase 2 (TXNRD2), transcript variant
            1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_006440
VERSION     NM_006440.5
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 1941)
  AUTHORS   Brachet,C., Laemmle,A., Cools,M., Sauter,K.S., De Baere,E.,
            Vanlander,A., Pandey,A.V., du Toit,T., Voegel,C.D., Heinrichs,C.,
            Verdin,H. and Fluck,C.E.
  TITLE     Insight into the role of TXNRD2 in steroidogenesis through a novel
            homozygous TXNRD2 splice variant
  JOURNAL   Eur J Endocrinol 191 (2), 144-155 (2024)
   PUBMED   39097530
  REMARK    GeneRIF: Insight into the role of TXNRD2 in steroidogenesis through
            a novel homozygous TXNRD2 splice variant.
REFERENCE   2  (bases 1 to 1941)
  AUTHORS   Sookaromdee,P. and Wiwanitkit,V.
  TITLE     TXNRD2 (rs35934224) CT genotype and primary open-angle glaucoma:
            correspondenceReply to 'TXNRD2 (rs35934224) CT genotype and primary
            open-angle glaucoma: correspondence'Primary open-angle
            glaucomaGenome-wide association analysis identifies TXNRD2, ATXN2
            and FOXC1 as susceptibility loci for primary open-angle
            glaucomaGenome-wide association study of primary open-angle
            glaucoma in continental and admixed African populations
  JOURNAL   Arq Bras Oftalmol 85 (2), 214-215 (2022)
   PUBMED   35416905
  REMARK    GeneRIF: TXNRD2 (rs35934224) CT genotype and primary open-angle
            glaucoma: correspondenceReply to ''TXNRD2 (rs35934224) CT genotype
            and primary open-angle glaucoma: correspondence''Primary open-angle
            glaucomaGenome-wide association analysis identifies TXNRD2, ATXN2
            and FOXC1 as susceptibility loci for primary open-angle
            glaucomaGenome-wide association study of primary open-angle
            glaucoma in continental and admixed African popula...
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 1941)
  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   4  (bases 1 to 1941)
  AUTHORS   Turanov,A.A., Su,D. and Gladyshev,V.N.
  TITLE     Characterization of alternative cytosolic forms and cellular
            targets of mouse mitochondrial thioredoxin reductase
  JOURNAL   J Biol Chem 281 (32), 22953-22963 (2006)
   PUBMED   16774913
  REMARK    GeneRIF: the function of TR3 is not limited to its role in Trx2
            reduction
REFERENCE   5  (bases 1 to 1941)
  AUTHORS   Chang,E.Y., Son,S.K., Ko,H.S., Baek,S.H., Kim,J.H. and Kim,J.R.
  TITLE     Induction of apoptosis by the overexpression of an alternative
            splicing variant of mitochondrial thioredoxin reductase
  JOURNAL   Free Radic Biol Med 39 (12), 1666-1675 (2005)
   PUBMED   16298692
REFERENCE   6  (bases 1 to 1941)
  AUTHORS   Arner,E.S. and Holmgren,A.
  TITLE     Physiological functions of thioredoxin and thioredoxin reductase
  JOURNAL   Eur J Biochem 267 (20), 6102-6109 (2000)
   PUBMED   11012661
  REMARK    Review article
REFERENCE   7  (bases 1 to 1941)
  AUTHORS   Lescure,A., Gautheret,D., Carbon,P. and Krol,A.
  TITLE     Novel selenoproteins identified in silico and in vivo by using a
            conserved RNA structural motif
  JOURNAL   J Biol Chem 274 (53), 38147-38154 (1999)
   PUBMED   10608886
REFERENCE   8  (bases 1 to 1941)
  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
REFERENCE   9  (bases 1 to 1941)
  AUTHORS   Miranda-Vizuete,A., Damdimopoulos,A.E., Pedrajas,J.R.,
            Gustafsson,J.A. and Spyrou,G.
  TITLE     Human mitochondrial thioredoxin reductase cDNA cloning, expression
            and genomic organization
  JOURNAL   Eur J Biochem 261 (2), 405-412 (1999)
   PUBMED   10215850
REFERENCE   10 (bases 1 to 1941)
  AUTHORS   Gasdaska,P.Y., Berggren,M.M., Berry,M.J. and Powis,G.
  TITLE     Cloning, sequencing and functional expression of a novel human
            thioredoxin reductase
  JOURNAL   FEBS Lett 442 (1), 105-111 (1999)
   PUBMED   9923614
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF106697.1, AF044212.1 and
            R46611.1.
            
            On Nov 22, 2018 this sequence version replaced NM_006440.4.
            
            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 a mitochondrial form important for scavenging reactive
            oxygen species in mitochondria. 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, including a few localized in the cytosol and
            some lacking the C-terminal Sec residue, have been found for this
            gene. [provided by RefSeq, Jun 2017].
            
            Transcript Variant: This variant (1) represents the predominant
            transcript and encodes the longest isoform (1, also known as
            hTR3a). This isoform is localized to the mitochondria
            (PMID:16774913).
            
            CCDS Note: This CCDS ID represents the protein described in PMIDs:
            9923614 and 10215850. This transcript is supported by AF106697.1.
            It should be noted this transcript is predicted to undergo
            nonsense-mediated mRNA decay (NMD). However, the protein is
            represented because it was detected endogenously in PMID: 9923614.
            It is likely that the majority of transcripts representing this
            variant will undergo NMD, while some low level of NMD escape may
            allow for the expression of this protein.
            
            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 :: AF171054.1, AF106697.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: PMID: 10215850; reported by
                                                  MitoCarta
            MANE Ensembl match                 :: ENST00000400521.7/
                                                  ENSP00000383365.1
            NMD candidate                      :: PMID: 9923614
            protein contains selenocysteine    :: PMID: 9923614
            RefSeq Select criteria             :: based on conservation,
                                                  longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-191               AF106697.1         175-365
            192-1938            AF044212.1         187-1933
            1939-1941           R46611.1           13-15               c
FEATURES             Location/Qualifiers
     source          1..1941
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="22"
                     /map="22q11.21"
     gene            1..1941
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /note="thioredoxin reductase 2"
                     /db_xref="GeneID:10587"
                     /db_xref="HGNC:HGNC:18155"
                     /db_xref="MIM:606448"
     exon            1..118
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     CDS             16..1590
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /EC_number="1.8.1.9"
                     /note="UGA stop codon recoded as selenocysteine; isoform 1
                     precursor is encoded by transcript variant 1;
                     selenoprotein Z; thioredoxin reductase 3; thioredoxin
                     reductase 2, mitochondrial; thioredoxin reductase beta;
                     thioredoxin reductase TR3"
                     /codon_start=1
                     /transl_except=(pos:1582..1584,aa:Sec)
                     /product="thioredoxin reductase 2, mitochondrial isoform 1
                     precursor"
                     /protein_id="NP_006431.2"
                     /db_xref="CCDS:CCDS42981.1"
                     /db_xref="GeneID:10587"
                     /db_xref="HGNC:HGNC:18155"
                     /db_xref="MIM:606448"
                     /translation="MAAMAVALRGLGGRFRWRTQAVAGGVRGAARGAAAGQRDYDLLV
                     VGGGSGGLACAKEAAQLGRKVAVVDYVEPSPQGTRWGLGGTCVNVGCIPKKLMHQAAL
                     LGGLIQDAPNYGWEVAQPVPHDWRKMAEAVQNHVKSLNWGHRVQLQDRKVKYFNIKAS
                     FVDEHTVCGVAKGGKEILLSADHIIIATGGRPRYPTHIEGALEYGITSDDIFWLKESP
                     GKTLVVGASYVALECAGFLTGIGLDTTIMMRSIPLRGFDQQMSSMVIEHMASHGTRFL
                     RGCAPSRVRRLPDGQLQVTWEDSTTGKEDTGTFDTVLWAIGRVPDTRSLNLEKAGVDT
                     SPDTQKILVDSREATSVPHIYAIGDVVEGRPELTPIAIMAGRLLVQRLFGGSSDLMDY
                     DNVPTTVFTPLEYGCVGLSEEEAVARHGQEHVEVYHAHYKPLEFTVAGRDASQCYVKM
                     VCLREPPQLVLGLHFLGPNAGEVTQGFALGIKCGASYAQVMRTVGIHPTCSEEVVKLR
                     ISKRSGLDPTVTGCUG"
     exon            119..187
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            188..244
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            245..389
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            390..464
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            465..543
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            544..606
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            607..677
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            678..697
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            698..789
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            790..964
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            965..1101
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            1102..1197
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            1198..1290
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            1291..1362
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            1363..1460
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            1461..1655
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     exon            1656..1941
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1837..1907
                     /regulatory_class="recoding_stimulatory_region"
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /note="SECIS_element"
                     /function="essential for recoding UGA to specify
                     selenocysteine"
     regulatory      1918..1923
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /note="hexamer: AATAAA"
     polyA_site      1941
                     /gene="TXNRD2"
                     /gene_synonym="GCCD5; SELZ; TR; TR-BETA; TR3; TRXR2;
                     TXNR2"
                     /note="major polyA site"
ORIGIN      
        1 agaagcccca cgacgatggc ggcaatggcg gtggcgctgc ggggattagg agggcgcttc
       61 cggtggcgga cgcaggccgt ggcgggcggg gtgcggggcg cggcgcgggg cgcagcagca
      121 ggtcagcggg actatgatct cctggtggtc ggcgggggat ctggtggcct ggcttgtgcc
      181 aaggaggccg cccagctggg aaggaaggtg gccgtggtgg actacgtgga accttctccc
      241 caaggcaccc ggtggggcct cggcggcacc tgcgtcaacg tgggctgcat ccccaagaag
      301 ctgatgcacc aggcggcact gctgggaggc ctgatccaag atgcccccaa ctatggctgg
      361 gaggtggccc agcccgtgcc gcatgactgg aggaagatgg cagaagctgt tcaaaatcac
      421 gtgaaatcct tgaactgggg ccaccgtgtc cagcttcagg acagaaaagt caagtacttt
      481 aacatcaaag ccagctttgt tgacgagcac acggtttgcg gcgttgccaa aggtgggaaa
      541 gagattctgc tgtcagccga tcacatcatc attgctactg gagggcggcc gagatacccc
      601 acgcacatcg aaggtgcctt ggaatatgga atcacaagtg atgacatctt ctggctgaag
      661 gaatcccctg gaaaaacgtt ggtggtcggg gccagctatg tggccctgga gtgtgctggc
      721 ttcctcaccg ggattgggct ggacaccacc atcatgatgc gcagcatccc cctccgcggc
      781 ttcgaccagc aaatgtcctc catggtcata gagcacatgg catctcatgg cacccggttc
      841 ctgaggggct gtgccccctc gcgggtcagg aggctccctg atggccagct gcaggtcacc
      901 tgggaggaca gcaccaccgg caaggaggac acgggcacct ttgacaccgt cctgtgggcc
      961 ataggtcgag tcccagacac cagaagtctg aatttggaga aggctggggt agatactagc
     1021 cccgacactc agaagatcct ggtggactcc cgggaagcca cctctgtgcc ccacatctac
     1081 gccattggtg acgtggtgga ggggcggcct gagctgacac ccatagcgat catggccggg
     1141 aggctcctgg tgcagcggct cttcggcggg tcctcagatc tgatggacta cgacaatgtt
     1201 cccacgaccg tcttcacccc gctggagtat ggctgtgtgg ggctgtccga ggaggaggca
     1261 gtggctcgcc acgggcagga gcatgttgag gtctatcacg cccattataa accactggag
     1321 ttcacggtgg ctggacgaga tgcatcccag tgttatgtaa agatggtgtg cctgagggag
     1381 cccccacagc tggtgctggg cctgcatttc cttggcccca acgcaggcga agttactcaa
     1441 ggatttgctc tggggatcaa gtgtggggct tcctatgcgc aggtgatgcg gaccgtgggt
     1501 atccatccca catgctctga ggaggtagtc aagctgcgca tctccaagcg ctcaggcctg
     1561 gaccccacgg tgacaggctg ctgagggtaa gcgccatccc tgcaggccag ggcacacggt
     1621 gcgcccgccg ccagctcctc ggaggccaga cccaggatgg ctgcaggcca ggtttggggg
     1681 gcctcaaccc tctcctggag cgcctgtgag atggtcagcg tggagcgcaa gtgctggaca
     1741 ggtggcccgt gtgccccaca gggatggctc aggggactgt ccacctcacc cctgcacctc
     1801 tcagcctctg ccgccgggca ccccccccca ggctcctggt gccagatgat gacgacctgg
     1861 gtggaaacct accctgtggg cacccatgtc cgagccccct ggcatttctg caatgcaaat
     1921 aaagagggta ctttttctga a
//
