Mouse Anti-SAMHD1 Recombinant Antibody (CBXS-4126) (CBMAB-S1380-CQ)

SAM And HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1

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.

SAM And HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1; Monocyte Protein 5; SAM Domain And HD Domain-Containing Protein 1; Dendritic Cell-Derived IFNG-Induced Protein; SAM Domain And HD Domain 1; DNTPase; MOP-5; DCIP; Deoxynucleoside Triphosphate Triphosphohydrolase SAMHD1;

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 (PubMed:19525956, PubMed:21613998, PubMed:21720370, PubMed:23602554, PubMed:23601106, PubMed:22056990, PubMed:24336198, PubMed:26294762, PubMed:26431200, PubMed:28229507, PubMed:28834754, PubMed:29670289).
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 (PubMed:19525956, PubMed:21613998, PubMed:21720370, PubMed:23602554, PubMed:23601106, PubMed:23364794, PubMed:25038827, PubMed:26101257, PubMed:22056990, PubMed:24336198, PubMed:28229507, PubMed:26294762, PubMed:26431200).
Likewise, suppresses LINE-1 retrotransposon activity (PubMed:24035396, PubMed:29610582, PubMed:24217394).
Not able to restrict infection by HIV-2 virus; because restriction activity is counteracted by HIV-2 viral protein Vpx (PubMed:21613998, PubMed:21720370).
In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools (PubMed:23858451).
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 (PubMed:23602554, PubMed:23601106, PubMed:29610582, PubMed:29670289).
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 (PubMed:29670289).
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 (PubMed:27477283, PubMed:29670289).
Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity (PubMed:29670289).
Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation (By similarity).

Cellular response to DNA damage stimulusManual Assertion Based On ExperimentIDA:UniProtKB
dATP catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Defense response to virusManual Assertion Based On ExperimentIDA:UniProtKB
Deoxyribonucleotide catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
dGTP catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
DNA strand resection involved in replication fork processingManual Assertion Based On ExperimentIDA:UniProtKB
Double-strand break repair via homologous recombinationManual Assertion Based On ExperimentIDA:UniProtKB
Immune response1 PublicationNAS:UniProtKB
Innate immune responseIEA:UniProtKB-KW
Negative regulation of type I interferon-mediated signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Protein homotetramerizationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of innate immune responseManual Assertion Based On ExperimentIDA:UniProtKB
Somatic hypermutation of immunoglobulin genesISS:UniProtKB

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

Aicardi-Goutieres syndrome 5 (AGS5):
A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.
Chilblain lupus 2 (CHBL2):
A rare cutaneous form of lupus erythematosus. Affected individuals present with painful bluish-red papular or nodular lesions of the skin in acral locations precipitated by cold and wet exposure.

Phosphorylation at Thr-592 by CDK1 acts as a switch to control deoxynucleoside triphosphate (dNTPase)-dependent and -independent functions (PubMed:29670289).
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 (PubMed:23602554, PubMed:23601106, PubMed:26294762, PubMed:26431200, PubMed:31291580).
It also inhibits ability to suppress LINE-1 retrotransposon activity (PubMed:29610582).
In contrast, phosphorylation at Thr-592 promotes DNA end resection at stalled replication forks in response to DNA damage (PubMed:29670289).
(Microbial infection) Phosphorylation at Thr-592 by Epstein-Barr virus kinase BGLF4 and human cytomegalovirus/HCMV UL97 leads to a reduced level of dCTPase and dTTPase activity and the loss of viral restriction.
(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.