Samhd1
entrez
56045
canonical
uniprot
Q60710
canonical
ensembl
ENSMUSG00000027639
resolver
ensp
ENSMUSP00000059717
resolver
ensp
ENSMUSP00000124935
resolver
genesymbol
Samhd1
resolver
genesymbol_syn
Mg21
resolver
uniprot
E9Q0K6
resolver
uniprot
F8WJE0
resolver
uniprot
Q3U5X2
resolver
uniprot
Q543A4
resolver
uniprot
Q91VK8
resolver
uniprot_entry
SAMH1_MOUSE
resolver
uniprot_sec
E9Q0K6
resolver
uniprot_sec
F8WJE0
resolver
uniprot_sec
Q3U5X2
resolver
uniprot_sec
Q543A4
resolver
uniprot_sec
Q91VK8
resolver
activity_regulation
ACTIVITY REGULATION: Allosterically activated and regulated via the combined actions of GTP and dNTPs (dATP, dGTP, dTTP and dCTP): Allosteric site 1 binds GTP, while allosteric site 2 binds dNTP. Allosteric activation promotes the formation of highly active homotetramers. Isoform 1: Phosphorylation at Thr-634 impairs homotetramerization, thereby inhibiting dNTPase activity, leading to reduced ability to restrict infection by viruses. {ECO:0000305|PubMed:29379009}.
uniprot
proteins
amino_acid_sequence
MDSLLGCGVSAAAREPVPRYLTSQPRVSEVAMQSAPLEQPAKRPRCDGSPRTPPSTPPATANLSADDDFQNTDLRTWEPEDVCSFLENRGFREKKVLDIFRDNKIAGSFLPFLDEDRLEDLGVSSLEERKKMIECIQQLSQSRIDLMKVFNDPIHGHIEFHPLLIRIIDTPQFQRLRYIKQLGGGYYVFPGASHNRFEHSLGVGYLAGCLVRALAEKQPELQISERDILCVQIAGLCHDLGHGPFSHMFDGRFIPRARPEKKWKHEQGSIEMFEHLVNSNELKLVMKNYGLVPEEDITFIKEQIMGPPITPVKDSLWPYKGRPATKSFLYEIVSNKRNGIDVDKWDYFARDCHHLGIQNNFDYKRFIKFARICEVEYKVKEDKTYIRKVKHICSREKEVGNLYDMFHTRNCLHRRAYQHKISNLIDIMITDAFLKADPYVEITGTAGKKFRISTAIDDMEAFTKLTDNIFLEVLHSTDPQLSEAQSILRNIECRNLYKYLGETQPKREKIRKEEYERLPQEVAKAKPEKAPDVELKAEDFIVDVINVDYGMEDKNPIDRVHFYCKSNSKQAVRINKEQVSQLLPEKFAEQLIRVYCKKKDGKSLDAAGKHFVQWCALRDFTKPQDGDIIAPLITPLKWNNKTSSCLQEVSKVKTCLKF
uniprot
proteins
ec_number
3.1.5.-
uniprot
proteins
function
FUNCTION: [Isoform 1]: 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 (By similarity). Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses: 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:23872947, PubMed:23972988, PubMed:26667483, PubMed:29379009, PubMed:31548683). Likewise, suppresses LINE-1 retrotransposon activity (PubMed:26667483). In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools (By similarity). Phosphorylation at Thr-634 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 (By similarity). 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 (By similarity). 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 (By similarity). Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity (By similarity). Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation (PubMed:29669924). {ECO:0000250|UniProtKB:Q9Y3Z3, ECO:0000269|PubMed:23872947, ECO:0000269|PubMed:23972988, ECO:0000269|PubMed:26667483, ECO:0000269|PubMed:29379009, ECO:0000269|PubMed:29669924, ECO:0000269|PubMed:31548683}.
uniprot
proteins
mass_dalton
75893
uniprot
proteins
mutagenesis
MUTAGEN 109; /note="F->L: In LCH mutant; abolishes formation of the tetramer and deoxynucleoside triphosphate (dNTPase) activity; when associated with C-112 and H-143."; /evidence="ECO:0000269|PubMed:29379009"; MUTAGEN 112; /note="F->C: In LCH mutant; abolishes formation of the tetramer and deoxynucleoside triphosphate (dNTPase) activity; when associated with L-109 and H-143."; /evidence="ECO:0000269|PubMed:29379009"; MUTAGEN 143; /note="R->H: In LCH mutant; abolishes formation of the tetramer and deoxynucleoside triphosphate (dNTPase) activity; when associated with L-109 and C-112."; /evidence="ECO:0000269|PubMed:29379009"; MUTAGEN 634; /note="T->A,V: Increased ability to restrict LINE-1 retrotransposon activity."; /evidence="ECO:0000269|PubMed:26667483"; MUTAGEN 634; /note="T->E: Mimicks phosphorylation state, reduced ability to restrict LINE-1 retrotransposon activity."; /evidence="ECO:0000269|PubMed:26667483
uniprot
proteins
post_translational_modification
PTM: [Isoform 1]: Phosphorylation at Thr-634 by CDK1 acts as a switch to control deoxynucleoside triphosphate (dNTPase)-dependent and -independent functions (By similarity) (PubMed:26667483). Phosphorylation at Thr-634 takes place in cycling cells: it reduces the stability of the homotetramer, impairing the dNTPase activity and subsequent ability to restrict infection by viruses (Probable). It also inhibits ability to suppress LINE-1 retrotransposon activity (PubMed:26667483). In contrast, phosphorylation at Thr-634 promotes DNA end resection at stalled replication forks in response to DNA damage (By similarity). {ECO:0000250|UniProtKB:Q9Y3Z3, ECO:0000269|PubMed:26667483, ECO:0000305|PubMed:26667483}.; PTM: [Isoform 1]: (Microbial infection) Phosphorylation at Thr-634 by mouse cytomegalovirus kinase M97 leads to a reduced level of dNTP hydrolase activity and the loss of viral restriction. {ECO:0000269|PubMed:31548683}.; PTM: [Isoform 2]: Not phosphorylated by CDK1 at the C-terminus. {ECO:0000305}.
uniprot
proteins
protein_family
SAMHD1 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
19131326
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
19525956
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23872947
uniprot
proteins
pubmed
23972988
uniprot
proteins
pubmed
26667483
uniprot
proteins
pubmed
29379009
uniprot
proteins
pubmed
29669924
uniprot
proteins
pubmed
31548683
uniprot
proteins
pubmed
7884320
uniprot
proteins
sequence_length
658
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y3Z3}. Chromosome {ECO:0000250|UniProtKB:Q9Y3Z3}. Note=Localizes to sites of DNA double-strand breaks in response to DNA damage. {ECO:0000250|UniProtKB:Q9Y3Z3}.
uniprot
proteins