Recombinant Human SAM domain and HD domain-containing protein 1 (SAMHD1)

Uniprot Id

Q9Y3Z3

Target Species

Human

Target Name

SAMHD1

Target Full Name

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1

Target Function

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.

Target Involvement

Aicardi-Goutieres syndrome 5 (AGS5); Chilblain lupus 2 (CHBL2)

Target Subcellular Location

Nucleus. Chromosome.

Target Protein Families

SAMHD1 family

Target Tissue Specificity

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

Target Synonyms

CHBL2; DCIP; Dendritic cell derived IFNG induced protein; Dendritic cell-derived IFNG-induced protein; Deoxynucleoside triphosphate triphosphohydrolase SAMHD1; dNTPase; HD domain containing 1; HDDC1 ; Mg11 ; Monocyte protein 5; MOP 5 ; MOP-5; MOP5 ; OTTHUMP00000030889; SAM domain and HD domain 1; SAM domain and HD domain containing protein 1; SAM domain and HD domain-containing protein 1; SAMH1_HUMAN; Samhd1; SBBI88

Target Background

This gene may play a role in regulation of the innate immune response. The encoded protein is upregulated in response to viral infection and may be involved in mediation of tumor necrosis factor-alpha proinflammatory responses. Mutations in this gene have been associated with Aicardi-Goutieres syndrome.