NameThioredoxin reductase 1, cytoplasmic
Synonyms
  • 1.8.1.9
  • Gene associated with retinoic and IFN-induced mortality 12 protein
  • Gene associated with retinoic and interferon-induced mortality 12 protein
  • GRIM-12
  • GRIM12
  • KDRF
  • KM-102-derived reductase-like factor
  • Thioredoxin reductase TR1
  • TR
Gene NameTXNRD1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0037154|Thioredoxin reductase 1, cytoplasmic
MGCAEGKAVAAAAPTELQTKGKNGDGRRRSAKDHHPGKTLPENPAGFTSTATADSRALLQ
AYIDGHSVVIFSRSTCTRCTEVKKLFKSLCVPYFVLELDQTEDGRALEGTLSELAAETDL
PVVFVKQRKIGGHGPTLKAYQEGRLQKLLKMNGPEDLPKSYDYDLIIIGGGSGGLAAAKE
AAQYGKKVMVLDFVTPTPLGTRWGLGGTCVNVGCIPKKLMHQAALLGQALQDSRNYGWKV
EETVKHDWDRMIEAVQNHIGSLNWGYRVALREKKVVYENAYGQFIGPHRIKATNNKGKEK
IYSAERFLIATGERPRYLGIPGDKEYCISSDDLFSLPYCPGKTLVVGASYVALECAGFLA
GIGLDVTVMVRSILLRGFDQDMANKIGEHMEEHGIKFIRQFVPIKVEQIEAGTPGRLRVV
AQSTNSEEIIEGEYNTVMLAIGRDACTRKIGLETVGVKINEKTGKIPVTDEEQTNVPYIY
AIGDILEDKVELTPVAIQAGRLLAQRLYAGSTVKCDYENVPTTVFTPLEYGACGLSEEKA
VEKFGEENIEVYHSYFWPLEWTIPSRDNNKCYAKIICNTKDNERVVGFHVLGPNAGEVTQ
GFAAALKCGLTKKQLDSTIGIHPVCAEVFTTLSVTKRSGASILQAGCUG
Number of residues649
Molecular Weight70905.58
Theoretical pI6.43
GO Classification
Functions
  • thioredoxin-disulfide reductase activity
  • protein disulfide oxidoreductase activity
  • electron carrier activity
  • flavin adenine dinucleotide binding
Processes
  • nucleobase-containing small molecule interconversion
  • signal transduction
  • response to reactive oxygen species
  • cell redox homeostasis
  • cell proliferation
  • gene expression
  • small molecule metabolic process
  • transcription initiation from RNA polymerase II promoter
  • nucleobase-containing small molecule metabolic process
  • cellular lipid metabolic process
  • mesoderm formation
Components
  • nucleus
  • cytosol
  • extracellular exosome
  • mitochondrion
General FunctionThioredoxin-disulfide reductase activity
Specific FunctionIsoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID1237038
UniProtKB IDQ16881
UniProtKB Entry NameTRXR1_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0020576|Thioredoxin reductase 1, cytoplasmic (TXNRD1)
ATGGGCTGCGCCGAGGGCAAGGCAGTGGCGGCGGCCGCCCCAACGGAGCTGCAGACGAAA
GGCAAGAACGGCGATGGCCGCCGTAGGTCAGCTAAAGATCATCACCCTGGTAAAACTTTG
CCAGAGAACCCAGCAGGATTCACCAGCACGGCCACTGCAGACTCCAGAGCCCTGCTTCAG
GCCTATATAGATGGTCACTCTGTGGTCATCTTCAGTAGGTCCACATGCACACGCTGTACT
GAGGTAAAGAAGTTATTTAAATCTCTGTGTGTTCCTTATTTTGTGCTTGAACTTGATCAA
ACAGAGGACGGTCGGGCCCTGGAAGGAACGCTCTCGGAATTGGCCGCGGAAACCGATCTG
CCCGTTGTGTTTGTGAAACAGAGAAAGATAGGCGGCCATGGTCCAACCTTGAAGGCTTAT
CAGGAGGGCAGACTTCAAAAGCTACTAAAAATGAACGGCCCTGAAGATCTTCCCAAGTCC
TATGACTATGACCTTATCATCATTGGAGGTGGCTCAGGAGGTCTGGCAGCTGCTAAGGAG
GCAGCCCAATATGGCAAGAAGGTGATGGTCCTGGACTTTGTCACTCCCACCCCTCTTGGA
ACTAGATGGGGTCTCGGAGGAACATGTGTGAATGTGGGTTGCATACCTAAAAAACTGATG
CATCAAGCAGCTTTGTTAGGACAAGCCCTGCAAGACTCTCGAAATTATGGATGGAAAGTC
GAGGAGACAGTTAAGCATGATTGGGACAGAATGATAGAAGCTGTACAGAATCACATTGGC
TCTTTGAATTGGGGCTACCGAGTAGCTCTGCGGGAGAAAAAAGTCGTCTATGAGAATGCT
TATGGGCAATTTATTGGTCCTCACAGGATTAAGGCAACAAATAATAAAGGCAAAGAAAAA
ATTTATTCAGCAGAGAGATTTCTCATTGCCACTGGTGAAAGACCACGTTACTTGGGCATC
CCTGGTGACAAAGAATACTGCATCAGCAGTGATGATCTTTTCTCCTTGCCTTACTGCCCG
GGTAAGACCCTGGTTGTTGGAGCATCCTATGTCGCTTTGGAGTGCGCTGGATTTCTTGCT
GGTATTGGTTTAGACGTCACTGTTATGGTTAGGTCCATTCTTCTTAGAGGATTTGACCAG
GACATGGCCAACAAAATTGGTGAACACATGGAAGAACATGGCATCAAGTTTATAAGACAG
TTCGTACCAATTAAAGTTGAACAAATTGAAGCAGGGACACCAGGCCGACTCAGAGTAGTA
GCTCAGTCCACCAATAGTGAGGAAATCATTGAAGGAGAATATAATACGGTGATGCTGGCA
ATAGGAAGAGATGCTTGCACAAGAAAAATTGGCTTAGAAACCGTAGGGGTGAAGATAAAT
GAAAAGACTGGAAAAATACCTGTCACAGATGAAGAACAGACCAATGTGCCTTACATCTAT
GCCATTGGCGATATATTGGAGGATAAGGTGGAGCTCACCCCAGTTGCAATCCAGGCAGGA
AGATTGCTGGCTCAGAGGCTCTATGCAGGTTCCACTGTCAAGTGTGACTATGAAAATGTT
CCAACCACTGTATTTACTCCTTTGGAATATGGTGCTTGTGGCCTTTCTGAGGAGAAAGCT
GTGGAGAAGTTTGGGGAAGAAAATATTGAGGTTTACCATAGTTACTTTTGGCCATTGGAA
TGGACGATTCCGTCAAGAGATAACAACAAATGTTATGCAAAAATAATCTGTAATACTAAA
GACAATGAACGTGTTGTGGGCTTTCACGTACTGGGTCCAAATGCTGGAGAAGTTACACAA
GGCTTTGCAGCTGCGCTCAAATGTGGACTGACCAAAAAGCAGCTGGACAGCACAATTGGA
ATCCACCCTGTCTGTGCAGAGGTATTCACAACATTGTCTGTGACCAAGCGCTCTGGGGCA
AGCATCCTCCAGGCTGGCTGCTGAGGTTAA
GenBank Gene IDX91247
GeneCard IDNot Available
GenAtlas IDTXNRD1
HGNC IDHGNC:12437
Chromosome Location12
Locus12q23-q24.1
References
  1. Gasdaska PY, Gasdaska JR, Cochran S, Powis G: Cloning and sequencing of a human thioredoxin reductase. FEBS Lett. 1995 Oct 2;373(1):5-9. 7589432
  2. Koishi R, Kawashima I, Yoshimura C, Sugawara M, Serizawa N: Cloning and characterization of a novel oxidoreductase KDRF from a human bone marrow-derived stromal cell line KM-102. J Biol Chem. 1997 Jan 24;272(4):2570-7. 8999974
  3. Hofmann ER, Boyanapalli M, Lindner DJ, Weihua X, Hassel BA, Jagus R, Gutierrez PL, Kalvakolanu DV: Thioredoxin reductase mediates cell death effects of the combination of beta interferon and retinoic acid. Mol Cell Biol. 1998 Nov;18(11):6493-504. 9774665
  4. Rundlof AK, Janard M, Miranda-Vizuete A, Arner ES: Evidence for intriguingly complex transcription of human thioredoxin reductase 1. Free Radic Biol Med. 2004 Mar 1;36(5):641-56. 14980707
  5. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  6. Scherer SE, Muzny DM, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Montgomery KT, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Lovering RC, Wheeler DA, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clerc-Blankenburg KP, Davis C, Delgado O, Dinh HH, Draper H, Gonzalez-Garay ML, Havlak P, Jackson LR, Jacob LS, Kelly SH, Li L, Li Z, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Pasternak S, Perez LM, Plopper FJ, Santibanez J, Shen H, Tabor PE, Verduzco D, Waldron L, Wang Q, Williams GA, Zhang J, Zhou J, Allen CC, Amin AG, Anyalebechi V, Bailey M, Barbaria JA, Bimage KE, Bryant NP, Burch PE, Burkett CE, Burrell KL, Calderon E, Cardenas V, Carter K, Casias K, Cavazos I, Cavazos SR, Ceasar H, Chacko J, Chan SN, Chavez D, Christopoulos C, Chu J, Cockrell R, Cox CD, Dang M, Dathorne SR, David R, Davis CM, Davy-Carroll L, Deshazo DR, Donlin JE, D'Souza L, Eaves KA, Egan A, Emery-Cohen AJ, Escotto M, Flagg N, Forbes LD, Gabisi AM, Garza M, Hamilton C, Henderson N, Hernandez O, Hines S, Hogues ME, Huang M, Idlebird DG, Johnson R, Jolivet A, Jones S, Kagan R, King LM, Leal B, Lebow H, Lee S, LeVan JM, Lewis LC, London P, Lorensuhewa LM, Loulseged H, Lovett DA, Lucier A, Lucier RL, Ma J, Madu RC, Mapua P, Martindale AD, Martinez E, Massey E, Mawhiney S, Meador MG, Mendez S, Mercado C, Mercado IC, Merritt CE, Miner ZL, Minja E, Mitchell T, Mohabbat F, Mohabbat K, Montgomery B, Moore N, Morris S, Munidasa M, Ngo RN, Nguyen NB, Nickerson E, Nwaokelemeh OO, Nwokenkwo S, Obregon M, Oguh M, Oragunye N, Oviedo RJ, Parish BJ, Parker DN, Parrish J, Parks KL, Paul HA, Payton BA, Perez A, Perrin W, Pickens A, Primus EL, Pu LL, Puazo M, Quiles MM, Quiroz JB, Rabata D, Reeves K, Ruiz SJ, Shao H, Sisson I, Sonaike T, Sorelle RP, Sutton AE, Svatek AF, Svetz LA, Tamerisa KS, Taylor TR, Teague B, Thomas N, Thorn RD, Trejos ZY, Trevino BK, Ukegbu ON, Urban JB, Vasquez LI, Vera VA, Villasana DM, Wang L, Ward-Moore S, Warren JT, Wei X, White F, Williamson AL, Wleczyk R, Wooden HS, Wooden SH, Yen J, Yoon L, Yoon V, Zorrilla SE, Nelson D, Kucherlapati R, Weinstock G, Gibbs RA: The finished DNA sequence of human chromosome 12. Nature. 2006 Mar 16;440(7082):346-51. 16541075
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  8. Gladyshev VN, Jeang KT, Stadtman TC: Selenocysteine, identified as the penultimate C-terminal residue in human T-cell thioredoxin reductase, corresponds to TGA in the human placental gene. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6146-51. 8650234
  9. Tamura T, Stadtman TC: A new selenoprotein from human lung adenocarcinoma cells: purification, properties, and thioredoxin reductase activity. Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1006-11. 8577704
  10. Su D, Gladyshev VN: Alternative splicing involving the thioredoxin reductase module in mammals: a glutaredoxin-containing thioredoxin reductase 1. Biochemistry. 2004 Sep 28;43(38):12177-88. 15379556
  11. Damdimopoulos AE, Miranda-Vizuete A, Treuter E, Gustafsson JA, Spyrou G: An alternative splicing variant of the selenoprotein thioredoxin reductase is a modulator of estrogen signaling. J Biol Chem. 2004 Sep 10;279(37):38721-9. Epub 2004 Jun 14. 15199063
  12. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. 15592455
  13. Wong JJ, Pung YF, Sze NS, Chin KC: HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates type I IFN-induced ISGylation of protein targets. Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10735-40. Epub 2006 Jun 30. 16815975
  14. Dammeyer P, Damdimopoulos AE, Nordman T, Jimenez A, Miranda-Vizuete A, Arner ES: Induction of cell membrane protrusions by the N-terminal glutaredoxin domain of a rare splice variant of human thioredoxin reductase 1. J Biol Chem. 2008 Feb 1;283(5):2814-21. Epub 2007 Nov 27. 18042542
  15. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. 19413330
  16. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  17. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  18. Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C: Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-alpha-acetylation features. Mol Cell Proteomics. 2012 Jun;11(6):M111.015131. doi: 10.1074/mcp.M111.015131. Epub 2012 Jan 5. 22223895
  19. Fritz-Wolf K, Urig S, Becker K: The structure of human thioredoxin reductase 1 provides insights into C-terminal rearrangements during catalysis. J Mol Biol. 2007 Jun 29;370(1):116-27. Epub 2007 Apr 24. 17512005