LOCUS       NM_001093771            3860 bp    mRNA    linear   PRI 08-JUN-2024
DEFINITION  Homo sapiens thioredoxin reductase 1 (TXNRD1), transcript variant
            7, mRNA.
ACCESSION   NM_001093771
VERSION     NM_001093771.3
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 3860)
  AUTHORS   Hsieh,M.S., Ling,H.H., Setiawan,S.A., Hardianti,M.S., Fong,I.H.,
            Yeh,C.T. and Chen,J.H.
  TITLE     Therapeutic targeting of thioredoxin reductase 1 causes ferroptosis
            while potentiating anti-PD-1 efficacy in head and neck cancer
  JOURNAL   Chem Biol Interact 395, 111004 (2024)
   PUBMED   38636790
  REMARK    GeneRIF: Therapeutic targeting of thioredoxin reductase 1 causes
            ferroptosis while potentiating anti-PD-1 efficacy in head and neck
            cancer.
REFERENCE   2  (bases 1 to 3860)
  AUTHORS   Shen,X., Xia,Y., Lu,H., Zheng,P., Wang,J., Chen,Y., Xu,C., Qiu,C.,
            Zhang,Y., Xiao,Z., Zou,P., Cui,R. and Ni,D.
  TITLE     Synergistic targeting of TrxR1 and ATM/AKT pathway in human colon
            cancer cells
  JOURNAL   Biomed Pharmacother 174, 116507 (2024)
   PUBMED   38565059
  REMARK    GeneRIF: Synergistic targeting of TrxR1 and ATM/AKT pathway in
            human colon cancer cells.
REFERENCE   3  (bases 1 to 3860)
  AUTHORS   Shi,W., Sun,S., Liu,H., Meng,Y., Ren,K., Wang,G., Liu,M., Wu,J.,
            Zhang,Y., Huang,H., Shi,M., Xu,W., Ma,Q., Sun,B. and Xu,J.
  TITLE     Guiding bar motif of thioredoxin reductase 1 modulates enzymatic
            activity and inhibitor binding by communicating with the co-factor
            FAD and regulating the flexible C-terminal redox motif
  JOURNAL   Redox Biol 70, 103050 (2024)
   PUBMED   38277963
  REMARK    GeneRIF: Guiding bar motif of thioredoxin reductase 1 modulates
            enzymatic activity and inhibitor binding by communicating with the
            co-factor FAD and regulating the flexible C-terminal redox motif.
REFERENCE   4  (bases 1 to 3860)
  AUTHORS   Nalvarte,I., Damdimopoulos,A.E., Ruegg,J. and Spyrou,G.
  TITLE     The expression and activity of thioredoxin reductase 1 splice
            variants v1 and v2 regulate the expression of genes associated with
            differentiation and adhesion
  JOURNAL   Biosci Rep 35 (6), e00269 (2015)
   PUBMED   26464515
  REMARK    GeneRIF: TXNRD1_v1 and TXNRD1_v2 have distinct roles in
            differentiation, possibly by altering the expression of the genes
            associated with differentiation, and further emphasize the
            importance in distinguishing each unique action of different TrxR1
            splice forms
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 3860)
  AUTHORS   Dammeyer,P., Damdimopoulos,A.E., Nordman,T., Jimenez,A.,
            Miranda-Vizuete,A. and Arner,E.S.
  TITLE     Induction of cell membrane protrusions by the N-terminal
            glutaredoxin domain of a rare splice variant of human thioredoxin
            reductase 1
  JOURNAL   J Biol Chem 283 (5), 2814-2821 (2008)
   PUBMED   18042542
  REMARK    GeneRIF: the Grx domain of TXNRD1_v3 localizes first in the
            emerging cell membrane protrusion and is then followed into the
            protrusions by actin and subsequently by tubulin
REFERENCE   6  (bases 1 to 3860)
  AUTHORS   Gladyshev,V.N., Jeang,K.T. and Stadtman,T.C.
  TITLE     Selenocysteine, identified as the penultimate C-terminal residue in
            human T-cell thioredoxin reductase, corresponds to TGA in the human
            placental gene
  JOURNAL   Proc Natl Acad Sci U S A 93 (12), 6146-6151 (1996)
   PUBMED   8650234
REFERENCE   7  (bases 1 to 3860)
  AUTHORS   Tamura,T. and Stadtman,T.C.
  TITLE     A new selenoprotein from human lung adenocarcinoma cells:
            purification, properties, and thioredoxin reductase activity
  JOURNAL   Proc Natl Acad Sci U S A 93 (3), 1006-1011 (1996)
   PUBMED   8577704
REFERENCE   8  (bases 1 to 3860)
  AUTHORS   Cha,M.K. and Kim,I.H.
  TITLE     Thioredoxin-linked peroxidase from human red blood cell: evidence
            for the existence of thioredoxin and thioredoxin reductase in human
            red blood cell
  JOURNAL   Biochem Biophys Res Commun 217 (3), 900-907 (1995)
   PUBMED   8554614
REFERENCE   9  (bases 1 to 3860)
  AUTHORS   Gasdaska,P.Y., Gasdaska,J.R., Cochran,S. and Powis,G.
  TITLE     Cloning and sequencing of a human thioredoxin reductase
  JOURNAL   FEBS Lett 373 (1), 5-9 (1995)
   PUBMED   7589432
REFERENCE   10 (bases 1 to 3860)
  AUTHORS   Schallreuter,K.U., Grebe,T., Pittelkow,M.R. and Wood,J.M.
  TITLE     [3H]-13-cis-retinoic acid covalently binds to thioredoxin reductase
            in human keratinocytes
  JOURNAL   Skin Pharmacol 4 (1), 14-20 (1991)
   PUBMED   2064786
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DC418649.1, AY057105.1,
            AK226071.1, BC018122.1 and AI097548.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_001093771.2.
            
            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 an ubiquitously expressed, cytosolic form of TrxR, which
            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. Alternative splicing,
            primarily at the 5' end, results in transcript variants encoding
            same or different isoforms, including a glutaredoxin-containing
            isoform that is predominantly expressed in testis. [provided by
            RefSeq, May 2017].
            
            Transcript Variant: This variant (7, also known as beta 1)
            represents use of an alternate upstream promoter, and contains
            additional exons at the 5' end compared to variant 1. The encoded
            isoform (5, also known as TXNRD1_v3 or v3) has a longer and
            distinct N-terminus, resulting from translation initiation at an
            in-frame upstream start codon, compared to isoform 1. It is
            predominantly expressed in Leydig cells of testis, and contains an
            atypical N-terminal glutaredoxin domain, which induces actin and
            tubulin polymerization, leading to formation of cell membrane
            protrusions (PMID:18042542).
            
            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 :: HM005669.1, SRR1803611.267438.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968968, SAMEA2145240
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match              :: ENST00000525566.6/
                                               ENSP00000434516.1
            protein contains selenocysteine :: PMID: 7589432, 8650234
            RefSeq Select criteria          :: based on conservation, longest
                                               protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-24                DC418649.1         1-24
            25-638              AY057105.1         1-614
            639-2293            AK226071.1         447-2101
            2294-3808           BC018122.1         2007-3521
            3809-3860           AI097548.1         10-61               c
FEATURES             Location/Qualifiers
     source          1..3860
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q23.3"
     gene            1..3860
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /note="thioredoxin reductase 1"
                     /db_xref="GeneID:7296"
                     /db_xref="HGNC:HGNC:12437"
                     /db_xref="MIM:601112"
     exon            1..115
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     CDS             25..1974
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /EC_number="1.8.1.9"
                     /EC_number="1.11.1.2"
                     /note="UGA stop codon recoded as selenocysteine; isoform 5
                     is encoded by transcript variant 7; KM-102-derived
                     reductase-like factor; thioredoxin reductase GRIM-12;
                     thioredoxin reductase 1, cytoplasmic; oxidoreductase;
                     thioredoxin reductase TR1; gene associated with retinoic
                     and IFN-induced mortality 12 protein; selenoprotein
                     TXNRD1; gene associated with retinoic and
                     interferon-induced mortality 12 protein; testis tissue
                     sperm-binding protein Li 46a; peroxidase TXNRD1"
                     /codon_start=1
                     /transl_except=(pos:1966..1968,aa:Sec)
                     /product="thioredoxin reductase 1, cytoplasmic isoform 5"
                     /protein_id="NP_001087240.1"
                     /db_xref="CCDS:CCDS53820.1"
                     /db_xref="GeneID:7296"
                     /db_xref="HGNC:HGNC:12437"
                     /db_xref="MIM:601112"
                     /translation="MGCAEGKAVAAAAPTELQTKGKNGDGRRRSAKDHHPGKTLPENP
                     AGFTSTATADSRALLQAYIDGHSVVIFSRSTCTRCTEVKKLFKSLCVPYFVLELDQTE
                     DGRALEGTLSELAAETDLPVVFVKQRKIGGHGPTLKAYQEGRLQKLLKMNGPEDLPKS
                     YDYDLIIIGGGSGGLAAAKEAAQYGKKVMVLDFVTPTPLGTRWGLGGTCVNVGCIPKK
                     LMHQAALLGQALQDSRNYGWKVEETVKHDWDRMIEAVQNHIGSLNWGYRVALREKKVV
                     YENAYGQFIGPHRIKATNNKGKEKIYSAERFLIATGERPRYLGIPGDKEYCISSDDLF
                     SLPYCPGKTLVVGASYVALECAGFLAGIGLDVTVMVRSILLRGFDQDMANKIGEHMEE
                     HGIKFIRQFVPIKVEQIEAGTPGRLRVVAQSTNSEEIIEGEYNTVMLAIGRDACTRKI
                     GLETVGVKINEKTGKIPVTDEEQTNVPYIYAIGDILEDKVELTPVAIQAGRLLAQRLY
                     AGSTVKCDYENVPTTVFTPLEYGACGLSEEKAVEKFGEENIEVYHSYFWPLEWTIPSR
                     DNNKCYAKIICNTKDNERVVGFHVLGPNAGEVTQGFAAALKCGLTKKQLDSTIGIHPV
                     CAEVFTTLSVTKRSGASILQAGCUG"
     exon            116..267
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            268..328
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            329..438
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            439..561
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            562..634
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            635..754
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            755..897
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            898..1013
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            1014..1239
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            1240..1332
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            1333..1409
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            1410..1566
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            1567..1674
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            1675..1770
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            1771..1905
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     exon            1906..3860
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2189..2275
                     /regulatory_class="recoding_stimulatory_region"
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /note="SECIS_element"
                     /function="essential for recoding UGA to specify
                     selenocysteine"
     regulatory      3818..3823
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /note="hexamer: ATTAAA"
     regulatory      3831..3836
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /note="hexamer: AATAAT"
     polyA_site      3837
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
                     /note="major polyA site"
     polyA_site      3860
                     /gene="TXNRD1"
                     /gene_synonym="GRIM-12; TR; TR1; TRXR1; TXNR; TXNR1"
ORIGIN      
        1 agttcccaca gggccttgtg cgacatgggc tgcgccgagg gcaaggcagt ggcggcggcc
       61 gccccaacgg agctgcagac gaaaggcaag aacggcgatg gccgccgtag gtcagctaaa
      121 gatcatcacc ctggtaaaac tttgccagag aacccagcag gattcaccag cacggccact
      181 gcagactcca gagccctgct tcaggcctat atagatggtc actctgtggt catcttcagt
      241 aggtccacat gcacacgctg tactgaggta aagaagttat ttaaatctct gtgtgttcct
      301 tattttgtgc ttgaacttga tcaaacagag gacggtcggg ccctggaagg aacgctctcg
      361 gaattggccg cggaaaccga tctgcccgtt gtgtttgtga aacagagaaa gataggcggc
      421 catggtccaa ccttgaaggc ttatcaggag ggcagacttc aaaagctact aaaaatgaac
      481 ggccctgaag atcttcccaa gtcctatgac tatgacctta tcatcattgg aggtggctca
      541 ggaggtctgg cagctgctaa ggaggcagcc caatatggca agaaggtgat ggtcctggac
      601 tttgtcactc ccacccctct tggaactaga tggggtctcg gaggaacatg tgtgaatgtg
      661 ggttgcatac ctaaaaaact gatgcatcaa gcagctttgt taggacaagc cctgcaagac
      721 tctcgaaatt atggatggaa agtcgaggag acagttaagc atgattggga cagaatgata
      781 gaagctgtac agaatcacat tggctctttg aattggggct accgagtagc tctgcgggag
      841 aaaaaagtcg tctatgagaa tgcttatggg caatttattg gtcctcacag gattaaggca
      901 acaaataata aaggcaaaga aaaaatttat tcagcagaga gatttctcat tgccactggt
      961 gaaagaccac gttacttggg catccctggt gacaaagaat actgcatcag cagtgatgat
     1021 cttttctcct tgccttactg cccgggtaag accctggttg ttggagcatc ctatgtcgct
     1081 ttggagtgcg ctggatttct tgctggtatt ggtttagacg tcactgttat ggttaggtcc
     1141 attcttctta gaggatttga ccaggacatg gccaacaaaa ttggtgaaca catggaagaa
     1201 catggcatca agtttataag acagttcgta ccaattaaag ttgaacaaat tgaagcaggg
     1261 acaccaggcc gactcagagt agtagctcag tccaccaata gtgaggaaat cattgaagga
     1321 gaatataata cggtgatgct ggcaatagga agagatgctt gcacaagaaa aattggctta
     1381 gaaaccgtag gggtgaagat aaatgaaaag actggaaaaa tacctgtcac agatgaagaa
     1441 cagaccaatg tgccttacat ctatgccatt ggcgatatat tggaggataa ggtggagctc
     1501 accccagttg caatccaggc aggaagattg ctggctcaga ggctctatgc aggttccact
     1561 gtcaagtgtg actatgaaaa tgttccaacc actgtattta ctcctttgga atatggtgct
     1621 tgtggccttt ctgaggagaa agctgtggag aagtttgggg aagaaaatat tgaggtttac
     1681 catagttact tttggccatt ggaatggacg attccgtcaa gagataacaa caaatgttat
     1741 gcaaaaataa tctgtaatac taaagacaat gaacgtgttg tgggctttca cgtactgggt
     1801 ccaaatgctg gagaagttac acaaggcttt gcagctgcgc tcaaatgtgg actgaccaaa
     1861 aagcagctgg acagcacaat tggaatccac cctgtctgtg cagaggtatt cacaacattg
     1921 tctgtgacca agcgctctgg ggcaagcatc ctccaggctg gctgctgagg ttaagcccca
     1981 gtgtggatgc tgttgccaag actgcaaacc actggctcgt ttccgtgccc aaatccaagg
     2041 cgaagttttc tagagggttc ttgggctctt ggcacctgcg tgtcctgtgc ttaccaccgc
     2101 ccaaggcccc cttggatctc ttggatagga gttggtgaat agaaggcagg cagcatcaca
     2161 ctggggtcac tgacagactt gaagctgaca tttggcaggg catcgaaggg atgcatccat
     2221 gaagtcacca gtctcaagcc catgtggtag gcggtgatgg aacaactgtc aaatcagttt
     2281 tagcatgacc tttccttgtg gattttctta ttctcgttgt caagttttct agggttgaat
     2341 ttttttcttt tttctccatg gtgttaatga tattagagat gaaaaacgtt agcagttgat
     2401 ttttgtccaa aagcaagtca tggctagagt atccatgcaa ggtgtcttgt tgcatggaag
     2461 ggatagtttg gctcccttgg aggctatgta ggcttgtccc gggaaagaga actgtcctgc
     2521 agctgaaatg gactgttctt tactgacctg ctcagcagtt tcttctctca tatattccca
     2581 aaacaagtac atctgcgatc aactctagcc aaatttgccc ctgtgtgcta catgatggat
     2641 gattattatt ttaaggtctg tttaggaagg gaaatggcta cttggccagc cattgcctgg
     2701 catttggtag tatagtatga ttctcaccat tatttgtcat ggaggcagac atacaccaga
     2761 aatgggggag aaacagtaca tatctttctg tctttagttt attgtgtgct ggtctaagca
     2821 agctgagatc atttgcaatg gaaaacacgt aacttgttta aaagtttttc tggtagcttt
     2881 agctttatgc taaaaaaaat aatgacattg ggtatctatt tctttctaag actacattag
     2941 taggaaaata agtcttttca tgcttatgat ttagctgttt tgtggtaatt gctttttaaa
     3001 ggaagttatt aatatcataa gttattatta atattttgaa cacaggtgga tgtgaaggat
     3061 tttcatttaa aaaccaagtg gttttgactt tttctgttga atgaacaact gtgccttgtg
     3121 gaatttttgc agaagtgttt atgctttgtt agcatttcaa cttgcattat tataaagagg
     3181 tattaatgcc tcagttatgt gtttgtcaat gtactggctg aggattctat ctcagctgtc
     3241 ttttctaact gtgtaggttg agttttgaac acgtgcttgt ggacatcagg cctcctgcca
     3301 gcagttcttg aagcttcttt ttcattcctg ctactctacc tgtatttctc agttgcagca
     3361 ctgagtggtc aaaatacatt tctgggccac ctcagggaac ccatgcatct gcctggcatt
     3421 taggcagcag agcccctgac cgtcccccac agggctctgc ctcacgtcct catctcattt
     3481 ggctgtgtaa agaaatggga aaagggaaaa ggagagagca attgaggcag ttgaccatat
     3541 tcagttttat ttatttattt ttaatttgtt tttttctcca agtccaccag tctctgaaat
     3601 tagaacagta ggcggtatga gataatcagg cctaatcatg ttgtgattct cttttcttag
     3661 tggagtggaa tgttctatcc ccacaagaag gattatatct tatagacttg tcttgttcag
     3721 attctgtatt tacccatttt attgaaacat atactaagtt ccatgtattt ttgttacaaa
     3781 tcttctgaaa aaaaacaaaa caatgtgaaa cattaaaatt aaaaggcatt aataatatcc
     3841 acgtgtgcct tcttactgaa
//
