SAMHD1 Protein, Human (sf9, His, Strep)

SAMHD1 is a multifunctional protein that serves as both a host restriction factor in antiviral defense and a regulator of DNA end resection at stalled replication forks. Its deoxynucleoside triphosphate (dNTPase) activity restricts viral infections like HIV-1 by depleting cellular dNTP pools below the threshold required for retroviral reverse transcription, thereby blocking early-stage replication in dendritic and myeloid cells, while also suppressing LINE-1 retrotransposon activity. This restriction is counteracted by HIV-2's Vpx protein. The dNTPase activity additionally maintains DNA precursor homeostasis by regulating dNTP pools. Phosphorylation at Thr-592 acts as a molecular switch, inhibiting dNTPase-dependent antiviral functions while promoting DNA end resection at stalled forks. During S phase, SAMHD1 stimulates MRE11 exonuclease activity to process gapped or reversed replication forks, facilitating replication restart and preventing chronic inflammation by averting type I interferon induction (a function independent of dNTPase activity). By similarity, it enhances immunoglobulin hypermutation in B-lymphocytes via transversion mutations.