Phospho-SAMHD1 (Thr592) Antibody - #AF3508

Protein that acts both as a host restriction factor involved in defense response to virus and as a regulator of DNA end resection at stalled replication forks. Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses, such as HIV-1: dNTPase activity reduces cellular dNTP levels to levels too low for retroviral reverse transcription to occur, blocking early-stage virus replication in dendritic and other myeloid cells. Likewise, suppresses LINE-1 retrotransposon activity. Not able to restrict infection by HIV-2 virus; because restriction activity is counteracted by HIV-2 viral protein Vpx. In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools. Phosphorylation at Thr-592 acts as a switch to control dNTPase-dependent and -independent functions: it inhibits dNTPase activity and ability to restrict infection by viruses, while it promotes DNA end resection at stalled replication forks. Functions during S phase at stalled DNA replication forks to promote the resection of gapped or reversed forks: acts by stimulating the exonuclease activity of MRE11, activating the ATR-CHK1 pathway and allowing the forks to restart replication. Its ability to promote degradation of nascent DNA at stalled replication forks is required to prevent induction of type I interferons, thereby preventing chronic inflammation. Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity. Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation (By similarity).

Phosphorylation at Thr-592 by CDK1 acts as a switch to control deoxynucleoside triphosphate (dNTPase)-dependent and -independent functions. Phosphorylation at Thr-592 takes place in cycling cells: it reduces the stability of the homotetramer, impairing the dNTPase activity and subsequent ability to restrict infection by viruses. It also inhibits ability to suppress LINE-1 retrotransposon activity. In contrast, phosphorylation at Thr-592 promotes DNA end resection at stalled replication forks in response to DNA damage.

(Microbial infection) Ubiquitinated following interaction with HIV-2 viral protein Vpx; Vpx promotes interaction and with a DCX (DDB1-CUL4-X-box) E3 ubiquitin ligase, leading to proteasomal degradation.

Nucleus. Chromosome.
Note: Localizes to sites of DNA double-strand breaks in response to DNA damage.

Expressed in heart, skeletal muscle, spleen, liver, small intestine, placenta, lung and peripheral blood leukocytes. No expression is seen in brain and thymus.

Homodimer; in absence of GTP and dNTP. Homotetramer; in GTP- and dNTP-bound form. Interacts with MRE11; leading to stimulate the exonuclease activity of MRE11. Interacts with RBBP8/CtIP. Interacts (via its C-terminus) with CD81.

(Microbial infection) Interacts with HIV-2 viral protein Vpx; promoting interaction with a E3 ubiquitin-protein ligase complex containing DCAF1, leading to subsequent ubiquitination and degradation of SAMHD1.

In human, and in contrast to mouse protein, the SAM domain is not required for deoxynucleoside triphosphate (dNTPase) activity and ability to restrict infection by viruses.

Belongs to the SAMHD1 family.