SAMHD1

SAMHD1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSAMHD1, CHBL2, DCIP, HDDC1, MOP-5, SBBI88, SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1, hSAMHD1
External IDsOMIM: 606754; MGI: 1927468; HomoloGene: 9160; GeneCards: SAMHD1; OMA:SAMHD1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

25939

56045

Ensembl

ENSG00000101347

ENSMUSG00000027639

UniProt

Q9Y3Z3

Q60710

RefSeq (mRNA)

NM_015474
NM_001363729
NM_001363733

NM_001139520
NM_018851
NM_001370610

RefSeq (protein)

NP_056289
NP_001350658
NP_001350662

NP_001132992
NP_061339
NP_001357539

Location (UCSC)Chr 20: 36.89 – 36.95 MbChr 2: 156.94 – 156.98 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

SAM domain and HD domain-containing protein 1 is a protein that in humans is encoded by the SAMHD1 gene. SAMHD1 is a cellular enzyme, responsible for blocking replication of HIV in dendritic cells,[5] macrophages,[6] monocytes[7] and resting CD4+ T lymphocytes.[8] It is an enzyme that exhibits phosphohydrolase activity,[9][10] converting deoxynucleoside triphosphates (dNTPs) to inorganic phosphate (iPPP) and a 2'-deoxynucleoside (i.e. deoxynucleosides without a phosphate group). In doing so, SAMHD1 depletes the pool of dNTPs available to a reverse transcriptase for viral cDNA synthesis and thus prevents viral replication.[11] SAMHD1 has also shown nuclease activity.[12] Although a ribonuclease activity was described to be required for HIV-1 restriction,[13] recent data confirmed that SAMHD1-mediated HIV-1 restriction in cells does not involve ribonuclease activity.[14]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000101347 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027639 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Ségéral E, Yatim A, Emiliani S, Schwartz O, Benkirane M (May 2011). "SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx". Nature. 474 (7353): 654–7. doi:10.1038/nature10117. PMC 3595993. PMID 21613998.
  6. ^ Hrecka K, Hao C, Gierszewska M, Swanson SK, Kesik-Brodacka M, Srivastava S, Florens L, Washburn MP, Skowronski J (June 2011). "Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein". Nature. 474 (7353): 658–61. doi:10.1038/nature10195. PMC 3179858. PMID 21720370.
  7. ^ Berger A, Sommer AF, Zwarg J, Hamdorf M, Welzel K, Esly N, Panitz S, Reuter A, Ramos I, Jatiani A, Mulder LC, Fernandez-Sesma A, Rutsch F, Simon V, König R, Flory E (December 2011). "SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection". PLOS Pathogens. 7 (12): e1002425. doi:10.1371/journal.ppat.1002425. PMC 3234228. PMID 22174685.
  8. ^ Pan X, Baldauf HM, Keppler OT, Fackler OT (June 2013). "Restrictions to HIV-1 replication in resting CD4+ T lymphocytes". Cell Research. 23 (7): 876–885. doi:10.1038/cr.2013.74. PMC 3698640. PMID 23732522.
  9. ^ Powell RD, Holland PJ, Hollis T, Perrino FW (December 2011). "Aicardi-Goutieres syndrome gene and HIV-1 restriction factor SAMHD1 is a dGTP-regulated deoxynucleotide triphosphohydrolase". The Journal of Biological Chemistry. 286 (51): 43596–600. doi:10.1074/jbc.C111.317628. PMC 3243528. PMID 22069334.
  10. ^ Goldstone DC, Ennis-Adeniran V, Hedden JJ, Groom HC, Rice GI, Christodoulou E, Walker PA, Kelly G, Haire LF, Yap MW, de Carvalho LP, Stoye JP, Crow YJ, Taylor IA, Webb M (November 2011). "HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase". Nature. 480 (7377): 379–82. Bibcode:2011Natur.480..379G. doi:10.1038/nature10623. PMID 22056990. S2CID 205226940.
  11. ^ Lahouassa H, Daddacha W, Hofmann H, Ayinde D, Logue EC, Dragin L, Bloch N, Maudet C, Bertrand M, Gramberg T, Pancino G, Priet S, Canard B, Laguette N, Benkirane M, Transy C, Landau NR, Kim B, Margottin-Goguet F (February 2012). "SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates". Nature Immunology. 13 (3): 223–8. doi:10.1038/ni.2236. PMC 3771401. PMID 22327569.
  12. ^ Beloglazova N, Flick R, Tchigvintsev A, Brown G, Popovic A, Nocek B, Yakunin AF. “Nuclease activity of the human SAMHD1 protein implicated in the Aicardi-Goutieres syndrome and HIV-1 restriction”. Beloglazova N, Flick R, Tchigvintsev A, Brown G, Popovic A, Nocek B, Yakunin AF (March 2013). "Nuclease activity of the human SAMHD1 protein implicated in the Aicardi-Goutieres syndrome and HIV-1 restriction". The Journal of Biological Chemistry. 288 (12): 8101–10. doi:10.1074/jbc.M112.431148. PMC 3605629. PMID 23364794.
  13. ^ Ryoo J, Choi J, Oh C, Kim S, Seo M, Kim SY, Seo D, Kim J, White TE, Brandariz-Nuñez A, Diaz-Griffero F, Yun CH, Hollenbaugh JA, Kim B, Baek D, Ahn K (August 2014). "The ribonuclease activity of SAMHD1 is required for HIV-1 restriction". Nature Medicine. 20 (8): 936–41. doi:10.1038/nm.3626. PMC 4318684. PMID 25038827.
  14. ^ Antonucci JM, St Gelais C, de Silva S, Yount JS, Tang C, Ji X, Shepard C, Xiong Y, Kim B, Wu L (October 2016). "SAMHD1-mediated HIV-1 restriction in cells does not involve ribonuclease activity". Nature Medicine. 22 (10): 1072–1074. doi:10.1038/nm.4163. PMC 5069697. PMID 27711056.