SAMHD1
entrez
25939
canonical
uniprot
Q9Y3Z3
canonical
ensembl
ENSG00000101347
resolver
ensp
ENSP00000262878
resolver
ensp
ENSP00000493536
resolver
ensp
ENSP00000493928
resolver
enst
ENST00000643918
resolver
genesymbol
SAMHD1
resolver
genesymbol_syn
MOP5
resolver
hgnc
HGNC:15925
resolver
uniprot
A0A2R8YCS7
resolver
uniprot
B4E2A5
resolver
uniprot
E1P5V2
resolver
uniprot
Q59H15
resolver
uniprot
Q5JXG8
resolver
uniprot
Q8N491
resolver
uniprot
Q9H004
resolver
uniprot
Q9H005
resolver
uniprot
Q9H3U9
resolver
uniprot_entry
A0A2R8YCS7_HUMAN
resolver
uniprot_entry
Q59H15_HUMAN
resolver
uniprot_entry
SAMH1_HUMAN
resolver
uniprot_sec
B4E2A5
resolver
uniprot_sec
E1P5V2
resolver
uniprot_sec
Q5JXG8
resolver
uniprot_sec
Q8N491
resolver
uniprot_sec
Q9H004
resolver
uniprot_sec
Q9H005
resolver
uniprot_sec
Q9H3U9
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 (PubMed:22069334, PubMed:25267621, PubMed:25288794, PubMed:25760601). Allosteric activation promotes the formation of highly active homotetramers (PubMed:22056990, PubMed:24141705, PubMed:24217394, PubMed:25267621, PubMed:25288794, PubMed:25760601). Phosphorylation at Thr-592 impairs homotetramerization, thereby inhibiting dNTPase activity, leading to reduced ability to restrict infection by viruses (PubMed:23601106, PubMed:26294762, PubMed:26431200, PubMed:29610582, PubMed:29670289). {ECO:0000269|PubMed:22056990, ECO:0000269|PubMed:22069334, ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:24141705, ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25267621, ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:25760601, ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:29610582, ECO:0000269|PubMed:29670289}.
uniprot
proteins
amino_acid_sequence
MQRADSEQPSKRPRCDDSPRTPSNTPSAEADWSPGLELHPDYKTWGPEQVCSFLRRGGFEEPVLLKNIRENEITGALLPCLDESRFENLGVSSLGERKKLLSYIQRLVQIHVDTMKVINDPIHGHIELHPLLVRIIDTPQFQRLRYIKQLGGGYYVFPGASHNRFEHSLGVGYLAGCLVHALGEKQPELQISERDVLCVQIAGLCHDLGHGPFSHMFDGRFIPLARPEVKWTHEQGSVMMFEHLINSNGIKPVMEQYGLIPEEDICFIKEQIVGPLESPVEDSLWPYKGRPENKSFLYEIVSNKRNGIDVDKWDYFARDCHHLGIQNNFDYKRFIKFARVCEVDNELRICARDKEVGNLYDMFHTRNSLHRRAYQHKVGNIIDTMITDAFLKADDYIEITGAGGKKYRISTAIDDMEAYTKLTDNIFLEILYSTDPKLKDAREILKQIEYRNLFKYVGETQPTGQIKIKREDYESLPKEVASAKPKVLLDVKLKAEDFIVDVINMDYGMQEKNPIDHVSFYCKTAPNRAIRITKNQVSQLLPEKFAEQLIRVYCKKVDRKSLYAARQYFVQWCADRNFTKPQDGDVIAPLITPQKKEWNDSTSVQNPTRLREASKSRVQLFKDDPM
uniprot
proteins
disease_involvement
DISEASE: Aicardi-Goutieres syndrome 5 (AGS5) [MIM:612952]: 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. {ECO:0000269|PubMed:19525956, ECO:0000269|PubMed:20131292, ECO:0000269|PubMed:20842748, ECO:0000269|PubMed:24035396, ECO:0000269|PubMed:24183309, ECO:0000269|PubMed:28229507, ECO:0000269|PubMed:29670289}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Chilblain lupus 2 (CHBL2) [MIM:614415]: 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. {ECO:0000269|PubMed:21204240}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.5.-
uniprot
proteins
function
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 (PubMed:19525956, PubMed:21613998, PubMed:21720370, PubMed:22056990, PubMed:23601106, PubMed:23602554, 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:22056990, PubMed:23364794, PubMed:23601106, PubMed:23602554, PubMed:24336198, PubMed:25038827, PubMed:26101257, PubMed:26294762, PubMed:26431200, PubMed:28229507). Likewise, suppresses LINE-1 retrotransposon activity (PubMed:24035396, PubMed:24217394, PubMed:29610582). 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:23601106, PubMed:23602554, 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). {ECO:0000250|UniProtKB:Q60710, ECO:0000269|PubMed:19525956, ECO:0000269|PubMed:21613998, ECO:0000269|PubMed:21720370, ECO:0000269|PubMed:22056990, ECO:0000269|PubMed:23364794, ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:23858451, ECO:0000269|PubMed:24035396, ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:24336198, ECO:0000269|PubMed:25038827, ECO:0000269|PubMed:26101257, ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:27477283, ECO:0000269|PubMed:28229507, ECO:0000269|PubMed:28834754, ECO:0000269|PubMed:29610582, ECO:0000269|PubMed:29670289}.
uniprot
proteins
mass_dalton
72201
uniprot
proteins
mutagenesis
MUTAGEN 77; /note="L->F: Increased stability of the tetramer and increased deoxynucleoside triphosphate (dNTPase) activity; when associated with F-77 and F-80 and R-111."; /evidence="ECO:0000269|PubMed:29379009"; MUTAGEN 80; /note="C->F: Increased stability of the tetramer and increased deoxynucleoside triphosphate (dNTPase) activity; when associated with F-77 and R-111."; /evidence="ECO:0000269|PubMed:29379009"; MUTAGEN 111; /note="H->R: Increased stability of the tetramer and increased deoxynucleoside triphosphate (dNTPase) activity; when associated with F-77 and F-80."; /evidence="ECO:0000269|PubMed:29379009"; MUTAGEN 137; /note="D->A: Impairs homotetramerization and nearly abolishes dNTPase activity."; /evidence="ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25038827, ECO:0000269|PubMed:25288794"; MUTAGEN 142; /note="Q->E,A: Impairs homotetramerization and nearly abolishes dNTPase activity; when associated with K-145."; /evidence="ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:25288794"; MUTAGEN 143; /note="R->A: Abolished ability to restrict infection by viruses."; /evidence="ECO:0000269|PubMed:26431200"; MUTAGEN 145; /note="R->A: Impairs homotetramerization and nearly abolishes dNTPase activity. Abolished ability to restrict infection by viruses."; /evidence="ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:26431200"; MUTAGEN 145; /note="R->K: Impairs homotetramerization and nearly abolishes dNTPase activity; when associated with E-145."; /evidence="ECO:0000269|PubMed:24217394"; MUTAGEN 149; /note="Q->A: Abolished dNTPase activity without affecting homotetramerization. Abolished dNTPase activity; when associated with A-319."; /evidence="ECO:0000269|PubMed:24141705, ECO:0000269|PubMed:25288794"; MUTAGEN 164; /note="R->A: Abolished ability to restrict infection by viruses."; /evidence="ECO:0000269|PubMed:26431200"; MUTAGEN 167; /note="H->A: Abolished ability to restrict infection by viruses."; /evidence="ECO:0000269|PubMed:26431200"; MUTAGEN 206..207; /note="HD->RN: Abolishes zinc binding and dNTPase activity. Does not affect ability to promote DNA end resection at stalled replication forks."; /evidence="ECO:0000269|PubMed:21613998, ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:24141705, ECO:0000269|PubMed:26101257, ECO:0000269|PubMed:28834754"; MUTAGEN 206; /note="H->A: Abolished ability to restrict infection by viruses."; /evidence="ECO:0000269|PubMed:26431200"; MUTAGEN 207; /note="D->A: Abolished ability to restrict infection by viruses."; /evidence="ECO:0000269|PubMed:26431200"; MUTAGEN 207; /note="D->N,A: Loss of dNTPase activity."; /evidence="ECO:0000269|PubMed:25038827, ECO:0000269|PubMed:26101257"; MUTAGEN 210; /note="H->A: Abolished dNTPase activity without affecting homotetramerization."; /evidence="ECO:0000269|PubMed:25288794"; MUTAGEN 215; /note="H->A: Abolished dNTPase activity without affecting homotetramerization."; /evidence="ECO:0000269|PubMed:25288794"; MUTAGEN 226; /note="R->G: Loss of function in defense response to virus."; /evidence="ECO:0000269|PubMed:28229507"; MUTAGEN 233; /note="H->A: Abolished dNTPase activity without affecting homotetramerization. Abolished ability to restrict infection by viruses."; /evidence="ECO:0000269|PubMed:25288794, ECO:0000269|PubMed:26431200"; MUTAGEN 311; /note="D->A: Loss of function in defense response to virus. Loss of dNTPase activity. Does not affect oligomerization."; /evidence="ECO:0000269|PubMed:25038827, ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:28229507"; MUTAGEN 312; /note="K->A: Abolishes dNTPase activity; when associated with A-315 and A-366. Does not affect ability to promote DNA end resection at stalled replication forks; when associated with A-315."; /evidence="ECO:0000269|PubMed:24141705, ECO:0000269|PubMed:29670289"; MUTAGEN 315; /note="Y->A: Abolished ability to restrict infection by viruses. Abolishes dNTPase activity; when associated with A-312 and A-366. Does not affect ability to promote DNA end resection at stalled replication forks; when associated with A-312."; /evidence="ECO:0000269|PubMed:24141705, ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:29670289"; MUTAGEN 319; /note="D->A: Abolishes dNTPase activity; when associated with A-149."; /evidence="ECO:0000269|PubMed:24141705"; MUTAGEN 321; /note="H->A: Abolished ability to restrict infection by viruses."; /evidence="ECO:0000269|PubMed:26431200"; MUTAGEN 330; /note="D->A: Impaired homotetramerization and slightly reduced dNTPase activity. Impaired homotetramerization and reduced dNTPase activity; when associated with A-358."; /evidence="ECO:0000269|PubMed:24141705, ECO:0000269|PubMed:25288794"; MUTAGEN 333; /note="R->E: Decreases dNTPase activity. Impairs homotetramerization and nearly abolishes dNTPase activity; when associated with E-451."; /evidence="ECO:0000269|PubMed:24141705, ECO:0000269|PubMed:24217394"; MUTAGEN 352; /note="R->A: Impairs homotetramerization and abolishes dNTPase activity; when associated with A-376 and A-377."; /evidence="ECO:0000269|PubMed:24141705"; MUTAGEN 358; /note="N->A: Impaired homotetramerization and slightly reduced dNTPase activity. Impaired homotetramerization and reduced dNTPase activity A-330."; /evidence="ECO:0000269|PubMed:24141705, ECO:0000269|PubMed:25288794"; MUTAGEN 361; /note="D->R: Impairs homotetramerization and nearly abolishes dNTPase activity; when associated with K-364."; /evidence="ECO:0000269|PubMed:24141705"; MUTAGEN 364; /note="H->K: Impairs homotetramerization and nearly abolishes dNTPase activity; when associated with R-361."; /evidence="ECO:0000269|PubMed:24141705"; MUTAGEN 366; /note="R->A: Abolishes dNTPase activity; when associated with A-312 and A-315."; /evidence="ECO:0000269|PubMed:24141705"; MUTAGEN 370; /note="H->A: Abolishes dNTPase activity; when associated with G-374."; /evidence="ECO:0000269|PubMed:24141705"; MUTAGEN 372; /note="R->D: Abolished homotetramerization and dNTPase activity."; /evidence="ECO:0000269|PubMed:26431200"; MUTAGEN 374; /note="Y->G: Abolishes dNTPase activity; when associated with A-370."; /evidence="ECO:0000269|PubMed:24141705"; MUTAGEN 375; /note="Q->A: Abolished dNTPase activity without affecting homotetramerization."; /evidence="ECO:0000269|PubMed:25288794"; MUTAGEN 376; /note="H->A: Impairs homotetramerization and abolishes dNTPase activity; when associated with A-352 and A-377."; /evidence="ECO:0000269|PubMed:24141705"; MUTAGEN 377; /note="K->A: Impairs homotetramerization and abolishes dNTPase activity; when associated with A-352 and A-376."; /evidence="ECO:0000269|PubMed:24141705"; MUTAGEN 451; /note="R->E: Impairs homotetramerization and abolishes dNTPase activity."; /evidence="ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:26101257"; MUTAGEN 534; /note="K->A: Impairs homotetramerization and abolishes dNTPase activity; when associated with A-537 and D-540."; /evidence="ECO:0000269|PubMed:24141705"; MUTAGEN 537; /note="V->A: Impairs homotetramerization and abolishes dNTPase activity; when associated with A-534 and D-540."; /evidence="ECO:0000269|PubMed:24141705"; MUTAGEN 540; /note="L->D: Impairs homotetramerization and abolishes dNTPase activity; when associated with A-537 and A-534."; /evidence="ECO:0000269|PubMed:24141705"; MUTAGEN 548; /note="Q->A: Loss of function in defense response to virus. Does not affect oligomerization. Retains dNTPase activity."; /evidence="ECO:0000269|PubMed:26101257, ECO:0000269|PubMed:28229507"; MUTAGEN 592; /note="T->A,V: Impaired ability to promote DNA end resection at stalled replication forks. Promotes dNTPase activity and ability to restrict infection by viruses."; /evidence="ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:29610582, ECO:0000269|PubMed:29670289"; MUTAGEN 592; /note="T->A: Loss of phosphorylation by human cytomegalovirus/HCMV kinase UL97."; /evidence="ECO:0000269|PubMed:31548682"; MUTAGEN 592; /note="T->E: Mimicks phosphorylation state, retains ability to promote DNA end resection at stalled replication forks. Induces large conformational changes that impair homotetramerization, leading to reduced dNTPase activity and decreased ability to restrict infection by viruses."; /evidence="ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:26101257, ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:29610582, ECO:0000269|PubMed:29670289"; MUTAGEN 593; /note="P->A: Promotes ability to restrict infection by viruses."; /evidence="ECO:0000269|PubMed:23601106"; MUTAGEN 609; /note="R->A,E: Abolishes proteasomal degradation triggered by the viral accessory protein vpx."; /evidence="ECO:0000269|PubMed:24336198"; MUTAGEN 617; /note="R->A,E: Abolishes proteasomal degradation triggered by the viral accessory protein vpx."; /evidence="ECO:0000269|PubMed:24336198"; MUTAGEN 622; /note="K->A,E: Abolishes proteasomal degradation triggered by the viral accessory protein vpx."; /evidence="ECO:0000269|PubMed:24336198
uniprot
proteins
post_translational_modification
PTM: 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:23601106, PubMed:23602554, 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). {ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:29610582, ECO:0000269|PubMed:29670289}.; PTM: (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. {ECO:0000269|PubMed:31291580, ECO:0000269|PubMed:31548682}.; PTM: (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. {ECO:0000269|PubMed:21613998, ECO:0000269|PubMed:21720370, ECO:0000269|PubMed:22056990, ECO:0000269|PubMed:24336198}.
uniprot
proteins
protein_family
SAMHD1 family
uniprot
proteins
pubmed
11064105
uniprot
proteins
pubmed
11230166
uniprot
proteins
pubmed
11780052
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18546154
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19525956
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20131292
uniprot
proteins
pubmed
20842748
uniprot
proteins
pubmed
21204240
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21613998
uniprot
proteins
pubmed
21720370
uniprot
proteins
pubmed
22056990
uniprot
proteins
pubmed
22069334
uniprot
proteins
pubmed
23092512
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23364794
uniprot
proteins
pubmed
23601106
uniprot
proteins
pubmed
23602554
uniprot
proteins
pubmed
23858451
uniprot
proteins
pubmed
24035396
uniprot
proteins
pubmed
24141705
uniprot
proteins
pubmed
24183309
uniprot
proteins
pubmed
24217394
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24336198
uniprot
proteins
pubmed
25038827
uniprot
proteins
pubmed
25267621
uniprot
proteins
pubmed
25288794
uniprot
proteins
pubmed
25760601
uniprot
proteins
pubmed
26101257
uniprot
proteins
pubmed
26294762
uniprot
proteins
pubmed
26431200
uniprot
proteins
pubmed
27477283
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28229507
uniprot
proteins
pubmed
28834754
uniprot
proteins
pubmed
28871089
uniprot
proteins
pubmed
29379009
uniprot
proteins
pubmed
29610582
uniprot
proteins
pubmed
29670289
uniprot
proteins
pubmed
31291580
uniprot
proteins
pubmed
31548682
uniprot
proteins
sequence_length
626
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19525956, ECO:0000269|PubMed:23092512, ECO:0000269|PubMed:23858451, ECO:0000269|PubMed:24035396, ECO:0000269|PubMed:28229507, ECO:0000269|PubMed:28871089}. Chromosome {ECO:0000269|PubMed:28834754}. Note=Localizes to sites of DNA double-strand breaks in response to DNA damage. {ECO:0000269|PubMed:28834754}.
uniprot
proteins