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Identification
HMDB Protein ID HMDBP00134
Secondary Accession Numbers
  • 5366
  • HMDBP03429
Name Thioredoxin reductase 1, cytoplasmic
Synonyms
  1. GRIM-12
  2. Gene associated with retinoic and IFN-induced mortality 12 protein
  3. Gene associated with retinoic and interferon-induced mortality 12 protein
  4. KM-102-derived reductase-like factor
  5. TR
  6. Thioredoxin reductase TR1
Gene Name TXNRD1
Protein Type Unknown
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function Isoform 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.
Pathways
  • Pyrimidine metabolism
  • Selenocompound metabolism
Reactions
Thioredoxin + NADP → thioredoxin disulfide + NADPH details
Thioredoxin + NADP → Thioredoxin disulfide + NADPH + Hydrogen Ion details
Hydrogen selenide + NADP + Water → Selenite + NADPH + Hydrogen Ion details
NADPH + Hydrogen Ion + Methylselenic acid → NADP + Water + Methaneselenol details
GO Classification
Biological Process
cell redox homeostasis
signal transduction
nucleobase-containing small molecule interconversion
cell proliferation
electron transport chain
mesoderm formation
cellular lipid metabolic process
hydrogen peroxide catabolic process
Cellular Component
cytosol
mitochondrion
nucleolus
Component
cell part
intracellular part
cytoplasm
Function
binding
nucleotide binding
catalytic activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
electron carrier activity
nadp or nadph binding
antioxidant activity
thioredoxin-disulfide reductase activity
oxidoreductase activity, acting on a sulfur group of donors
disulfide oxidoreductase activity
protein disulfide oxidoreductase activity
oxidoreductase activity
oxidoreductase activity, acting on nadh or nadph
oxidoreductase activity, acting on a sulfur group of donors, nad or nadp as acceptor
fad or fadh2 binding
Molecular Function
electron carrier activity
thioredoxin-disulfide reductase activity
protein disulfide oxidoreductase activity
NADP binding
flavin adenine dinucleotide binding
Process
metabolic process
cellular process
oxidation reduction
cellular homeostasis
cell redox homeostasis
Cellular Location
  1. Isoform 5:Cytoplasm
Gene Properties
Chromosome Location 12
Locus 12q23-q24.1
SNPs TXNRD1
Gene Sequence
>1950 bp
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
Protein Properties
Number of Residues 649
Molecular Weight 70905.58
Theoretical pI 7.385
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Thioredoxin reductase 1, cytoplasmic
MGCAEGKAVAAAAPTELQTKGKNGDGRRRSAKDHHPGKTLPENPAGFTSTATADSRALLQ
AYIDGHSVVIFSRSTCTRCTEVKKLFKSLCVPYFVLELDQTEDGRALEGTLSELAAETDL
PVVFVKQRKIGGHGPTLKAYQEGRLQKLLKMNGPEDLPKSYDYDLIIIGGGSGGLAAAKE
AAQYGKKVMVLDFVTPTPLGTRWGLGGTCVNVGCIPKKLMHQAALLGQALQDSRNYGWKV
EETVKHDWDRMIEAVQNHIGSLNWGYRVALREKKVVYENAYGQFIGPHRIKATNNKGKEK
IYSAERFLIATGERPRYLGIPGDKEYCISSDDLFSLPYCPGKTLVVGASYVALECAGFLA
GIGLDVTVMVRSILLRGFDQDMANKIGEHMEEHGIKFIRQFVPIKVEQIEAGTPGRLRVV
AQSTNSEEIIEGEYNTVMLAIGRDACTRKIGLETVGVKINEKTGKIPVTDEEQTNVPYIY
AIGDILEDKVELTPVAIQAGRLLAQRLYAGSTVKCDYENVPTTVFTPLEYGACGLSEEKA
VEKFGEENIEVYHSYFWPLEWTIPSRDNNKCYAKIICNTKDNERVVGFHVLGPNAGEVTQ
GFAAALKCGLTKKQLDSTIGIHPVCAEVFTTLSVTKRSGASILQAGCUG
GenBank ID Protein 148277071
UniProtKB/Swiss-Prot ID Q16881
UniProtKB/Swiss-Prot Entry Name TRXR1_HUMAN
PDB IDs
GenBank Gene ID NM_001093771.1
GeneCard ID TXNRD1
GenAtlas ID TXNRD1
HGNC ID HGNC:12437
References
General References
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  2. 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. [PubMed:15592455 ]
  3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  4. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ: Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203. [PubMed:18083107 ]
  5. 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. [PubMed:7589432 ]
  6. 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. [PubMed:8999974 ]
  7. 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. [PubMed:9774665 ]
  8. 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. [PubMed:14980707 ]
  9. 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. [PubMed:8650234 ]
  10. 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. [PubMed:8577704 ]
  11. 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. [PubMed:15379556 ]
  12. 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. [PubMed:15199063 ]
  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. [PubMed: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. [PubMed:18042542 ]
  15. 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. [PubMed:17512005 ]