SAMHD1

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SAMHD1
SAMHD1
according to PDB  3u1n
other names
  • CHBL2
  • DCIP
  • HDDC1
  • MOP-5
  • SBBI88
Mass / length primary structure 626 amino acids , 72.2 kDa
Identifier
External IDs
Orthologue
human House mouse
Entrez 25939 56045
Ensemble ENSG00000101347 ENSMUSG00000027639
UniProt Q9Y3Z3 Q60710
Refseq (mRNA) NM_015474 NM_001139520
Refseq (protein) NP_056289 NP_001132992
Gene locus Chr 20: 36.89 - 36.95 Mb Chr 2: 157.1 - 157.14 Mb
PubMed search 25939 56045

SAMHD1 ( English SAM domain and HD domain-containing protein 1 ) is a phosphohydrolase and a resistance factor against lentiviruses .

properties

SAMHD1 inhibits the replication of HIV in dendritic cells , macrophages and monocytes of primates . The inhibition takes place through the hydrolysis of dNTPs to nucleosides and triphosphate , which are then no longer available for the reverse transcriptase during replication. SAMHD1 also has a 3 '→ 5' exonuclease activity, which is involved in HIV resistance, and an RNase activity. HIV possesses the protein Vpx for immune evasion by inhibiting SAMHD1.

In dividing cells , SAMHD1 is inactivated by phosphorylation at T 592, while it is active in resting cells .

SAMHD1 is involved in the development of Aicardi-Goutières syndrome .

literature

  • A. Sze, D. Olagnier, R. Lin, J. van Grevenynghe, J. Hiscott: SAMHD1 host restriction factor: a link with innate immune sensing of retrovirus infection. In: Journal of molecular biology. Volume 425, number 24, December 2013, ISSN  1089-8638 , pp. 4981-4994, doi : 10.1016 / j.jmb.2013.10.022 , PMID 24161438 .

Individual evidence

  1. ↑ N. Laguette, B. Sobhian, N. Casartelli, M. Ringeard, C. Chable-Bessia, E. Ségéral, A. Yatim, S. Emiliani, O. Schwartz, M. Benkirane: SAMHD1 is the dendritic and myeloid -cell-specific HIV-1 restriction factor counteracted by Vpx. In: Nature. Volume 474, number 7353, June 2011, ISSN  1476-4687 , pp. 654-657, doi : 10.1038 / nature10117 , PMID 21613998 , PMC 3595993 (free full text).
  2. ↑ K. Hrecka, C. Hao, M. Gierszewska, SK Swanson, M. Kesik-Brodacka, S. Srivastava, L. Florens, MP Washburn, J. Skowronski: Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. In: Nature. Volume 474, number 7353, June 2011, ISSN  1476-4687 , pp. 658-661, doi : 10.1038 / nature10195 , PMID 21720370 , PMC 3179858 (free full text).
  3. ↑ A. Berger, AF Sommer, J. Zwarg, M. Hamdorf, K. Welzel, N. Esly, S. Panitz, A. Reuter, I. Ramos, A. Jatiani, LC Mulder, A. Fernandez-Sesma, F. Rutsch, V. Simon, R. König, E. Flory: SAMHD1-deficient CD14 + cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection. In: PLoS pathogens. Volume 7, number 12, December 2011, ISSN  1553-7374 , p. E1002425, doi : 10.1371 / journal.ppat.1002425 , PMID 22174685 , PMC 3234228 (free full text).
  4. ↑ H. Lahouassa, W. Daddacha, H. Hofmann, D. Ayinde, EC Logue, L. Dragin, N. Bloch, C. Maudet, M. Bertrand, T. Gramberg, G. Pancino, S. Priet, B. Canard, N. Laguette, M. Benkirane, C. Transy, NR Landau, B. Kim, F. Margottin-Goguet: SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates. In: Nature Immunology . Volume 13, number 3, March 2012, ISSN  1529-2916 , pp. 223-28, doi : 10.1038 / ni.2236 , PMID 22327569 , PMC 3771401 (free full text).
  5. ↑ N. Beloglazova, R. Flick, A. Tchigvintsev, G. Brown, A. Popovic, B. Nocek, AF Yakunin: Nuclease activity of the human SAMHD1 protein implicated in the Aicardi-Goutieres syndrome and HIV-1 restriction. In: The Journal of biological chemistry. Volume 288, Number 12, March 2013, ISSN  1083-351X , pp. 8101-8110, doi : 10.1074 / jbc.M112.431148 , PMID 23364794 , PMC 3605629 (free full text).
  6. ↑ J. Ryoo, J. Choi, C. Oh, S. Kim, M. Seo, SY Kim, D. Seo, J. Kim, TE White, A. Brandariz-Nuñez, F. Diaz-Griffero, CH Yun, JA Hollenbaugh, B. Kim, D. Baek, K. Ahn: The ribonuclease activity of SAMHD1 is required for HIV-1 restriction. In: Nature medicine. Volume 20, number 8, August 2014, ISSN  1546-170X , pp. 936-941, doi : 10.1038 / nm.3626 , PMID 25038827 , PMC 4318684 (free full text).
  7. ↑ T. Schaller, H. Bauby, S. Hué, MH Malim, C. Goujon: New insights into an X-traordinary viral protein. In: Frontiers in microbiology. Volume 5, 2014, ISSN  1664-302X , p. 126, doi : 10.3389 / fmicb.2014.00126 , PMID 24782834 , PMC 3986551 (free full text).
  8. ↑ TE White, A. Brandariz-Nuñez, JC Valle-Casuso, S. Amie, LA Nguyen, B. Kim, M. Tuzova, F. Diaz-Griffero: The retroviral restriction ability of SAMHD1, but not its deoxynucleotide triphosphohydrolase activity, is regulated by phosphorylation. In: Cell host & microbe. Volume 13, number 4, April 2013, ISSN  1934-6069 , pp. 441-451, doi : 10.1016 / j.chom.2013.03.005 , PMID 23601106 , PMC 3864637 (free full text).
  9. ↑ Z. Chen, L. Zhang, S. Ying: SAMHD1: a novel antiviral factor in intrinsic immunity. In: Future microbiology. Volume 7, number 9, September 2012, ISSN  1746-0921 , pp. 1117-1126, doi : 10.2217 / fmb.12.81 , PMID 22953710 .