TXNIP

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Thioredoxin interacting protein
other names

Thioredoxin-binding protein 2, vitamin D3 up-regulated protein 1

Properties of human protein
Mass / length primary structure 391 amino acids , 43,661 Da
Identifier
External IDs
Orthologue (human)
Entrez 10628
Ensemble ENSG00000265972
UniProt Q9H3M7
Refseq (mRNA) NM_001313972.1
Refseq (protein) NP_001300901.1
PubMed search 10628

TXNIP (thioredoxin Interacting Protein, synonym EST01027, HHCPA78, THIF, VDUP1, ARRDC6) is a protein from the redox - metabolism .

genetics

In humans, the TXNIP gene is located on chromosome 1, position 1q21.1, start 145,992,435 bp, end 145,996,600 bp. TXNIP was also detected in mice.

function

TXNIP binds to thioredoxin and ZBTB32.

TAR syndrome

TXNIP has been linked to TAR syndrome . TAR stands for Thrombocytopenia with Absent Radius. It is a rare genetic disease with low blood platelet counts ( thrombocytopenia ) and a lack of the forearm bone radius . A genetic analysis of 30 patients with TAR syndrome found a heterozygous deletion in chromosome segment 1q21.1 in all cases, i.e. parts of the region in which TXNIP is located were missing on one of the 2 chromomes no. 1. However, it is problematic that other genes are also found in this region and that the same mutation was also found in 32% of healthy family members.

Key molecule of aging

In 2018, the DKFZ scientists in the working group led by Peter Krammer and Karsten Gülow published the results of experiments which discovered that TXNIP is a key molecule in aging. TXNIP indirectly inhibits the breakdown of reactive oxygen species. With age, TXNIP increases and prevents the breakdown of oxidative stress . Experiments on genetically modified flies showed that high TXNIP concentrations shortened their lifespan.

Thioredoxin

TXNIP is a negative regulator of thioredoxin. Thioredoxin is a protein that acts as an antioxidant. It mediates the reduction (antioxidation) of other proteins via the cysteine-thiol-disulfide exchange.

Inflammasome

TXNIP inhibits activation of the NLRP3 - inflammasome and thus the secretion of IL-1β ( interleukin-1β ).

Individual evidence

  1. ↑ http://may2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000265972;r=1:145992435-145996600
  2. ↑ Nishiyama A, Matsui M, Iwata S, Hirota K, Masutani H, Nakamura H, Takagi Y, Sono H, Gon Y, Yodoi J: "Identification of thioredoxin-binding protein-2 / vitamin D (3) up-regulated protein 1 as a negative regulator of thioredoxin function and expression ". In: The Journal of Biological Chemistry 1999; Volume 274 Issue 31: Pages 21645-50. doi: 10.1074 / jbc.274.31.21645
  3. ↑ Han SH, Jeon JH, Ju HR, Jung U, Kim KY, Yoo HS, Lee YH, Song KS, Hwang HM, Na YS, Yang Y, Lee KN, Choi I ​​(Jun 2003). "VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression". Oncogene 2003; Volume 22 Issue 26: Pages 4035-46. doi: 10.1038 / sj.onc.1206610
  4. ↑ Klopocki E, Schulze H, Strauss G, and others. Complex Inheritance Pattern Resembling Autosomal Recessive Inheritance Involving a Microdeletion in Thrombocytopenia – Absent Radius Syndrome. American Journal of Human Genetics 2007; Volume 80 Issue 2: Pages 232-240. doi: 10.1086 / 510919
  5. ↑ Insight (publication by the German Cancer Research Center) 2018; Issue 3: Page 5. https://www.dkfz.de/de/presse/veroeffnahmungen/einblick/einblick.html
  6. ↑ Tina Oberacker, Jörg Bajorat, Sabine Ziola, Anne Schroeder, Daniel Röth, Lena Kastl, Bruce A. Edgar, Wolfgang Wagner, Karsten Gülow, Peter H. Krammer: Enhanced expression of thioredoxin-interacting-protein regulates oxidative DNA damage and aging . In: FEBS Letters . 592, No. 13, 2018, ISSN  0014-5793 , pp. 2297-2307. doi : 10.1002 / 1873-3468.13156 .
  7. ↑ Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J: thioredoxin-interacting protein links oxidative stress to inflammasomes activation. In: National Immunology 2010; Volume 11: Pages 136-140
  8. ↑ Cao Z, Fang Y, Lu Y, Tan D, Du C, Li Y: Melatonin alleviates cadmium-induced liver injury by inhibiting the TXNIP-NLRP3 inflammasome. J Pineal Research 2017; Volume 62 Issue 3. PMID 28099758 . doi: 10.1111 / jpi.12389