Samhd1

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1

658 amino acids

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:23972988, PubMed:23872947, PubMed:26667483, PubMed:29379009). 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).

Belongs to the SAMHD1 family.

75.893 kDa

MDSLLGCGVSAAAREPVPRYLTSQPRVSEVAMQSAPLEQPAKRPRCDGSPRTPPSTPPATANLSADDDFQNTDLRTWEPEDVCSFLENRGFREKKVLDIFRDNKIAGSFLPFLDEDRLEDLGVSSLEERKKMIECIQQLSQSRIDLMKVFNDPIHGHIEFHPLLIRIIDTPQFQRLRYIKQLGGGYYVFPGASHNRFEHSLGVGYLAGCLVRALAEKQPELQISERDILCVQIAGLCHDLGHGPFSHMFDGRFIPRARPEKKWKHEQGSIEMFEHLVNSNELKLVMKNYGLVPEEDITFIKEQIMGPPITPVKDSLWPYKGRPATKSFLYEIVSNKRNGIDVDKWDYFARDCHHLGIQNNFDYKRFIKFARICEVEYKVKEDKTYIRKVKHICSREKEVGNLYDMFHTRNCLHRRAYQHKISNLIDIMITDAFLKADPYVEITGTAGKKFRISTAIDDMEAFTKLTDNIFLEVLHSTDPQLSEAQSILRNIECRNLYKYLGETQPKREKIRKEEYERLPQEVAKAKPEKAPDVELKAEDFIVDVINVDYGMEDKNPIDRVHFYCKSNSKQAVRINKEQVSQLLPEKFAEQLIRVYCKKKDGKSLDAAGKHFVQWCALRDFTKPQDGDIIAPLITPLKWNNKTSSCLQEVSKVKTCLKF

samhd1

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1

632 amino acids

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 (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 (PubMed:29670289). Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity (PubMed:29670289).

Belongs to the SAMHD1 family.

72.749 kDa

MKGINGAKRVRHDASPSAQDGYVTPEKRVKRWSGGQTAANYREWDVEEVCLFLASHGLGELEVIFRENKIKGRILEYLTDSHLKDLQISSVALRLDLLSCLRMLCQNSPSIMKVFNDPIHGHIELHPLLVRIIDTPEFQRLRYIKQLGGSYYVFPGASHNRFEHSIGVGYLAGCLVQALHERQPDLQIDMRDMLCVQIAGLCHDLGHGPFSHMFDGRFMPLACPQKKFKHESASVAMFDHLIQSNGLEEAMKENGLCLPDDLTFIKEQIAGPLSSEAEQQFNSSPNSSSWPYRGRTEEKSFLYEIVANKRNGIDVDKWDYFARDCHHLGIQNNFDYKRFLKFARVCEVGSKKHICTRDKEVGNLYDMFHTRNCLHRRAYQHKVGNIIETMITDAFVKADPHIKIEGANGKYYSISGSVDDMVAYTKLTDNIYHQILYSNDPNLKEAREILQKVERRHLYKYIGQTHPHSNSRIEPDKYDKLPADLASSVPQTSAKDVELHAEDFIVDVIHMDYGMKEQNPINNVRFYCKADPRKAIKIRRDQVSQLLPEKFAEQIIRVYCKKTDEKSLETAKRYFIQWCMNKDFSKPQDGDVVAPDMTPLKASWVDDDDDEDNEGKQQTELLHKSRVKLFTN

SAMHD1

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1

626 amino acids

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).

Belongs to the SAMHD1 family.

72.201 kDa

MQRADSEQPSKRPRCDDSPRTPSNTPSAEADWSPGLELHPDYKTWGPEQVCSFLRRGGFEEPVLLKNIRENEITGALLPCLDESRFENLGVSSLGERKKLLSYIQRLVQIHVDTMKVINDPIHGHIELHPLLVRIIDTPQFQRLRYIKQLGGGYYVFPGASHNRFEHSLGVGYLAGCLVHALGEKQPELQISERDVLCVQIAGLCHDLGHGPFSHMFDGRFIPLARPEVKWTHEQGSVMMFEHLINSNGIKPVMEQYGLIPEEDICFIKEQIVGPLESPVEDSLWPYKGRPENKSFLYEIVSNKRNGIDVDKWDYFARDCHHLGIQNNFDYKRFIKFARVCEVDNELRICARDKEVGNLYDMFHTRNSLHRRAYQHKVGNIIDTMITDAFLKADDYIEITGAGGKKYRISTAIDDMEAYTKLTDNIFLEILYSTDPKLKDAREILKQIEYRNLFKYVGETQPTGQIKIKREDYESLPKEVASAKPKVLLDVKLKAEDFIVDVINMDYGMQEKNPIDHVSFYCKTAPNRAIRITKNQVSQLLPEKFAEQLIRVYCKKVDRKSLYAARQYFVQWCADRNFTKPQDGDVIAPLITPQKKEWNDSTSVQNPTRLREASKSRVQLFKDDPM

samhd1

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1

622 amino acids

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: 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. 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.

Belongs to the SAMHD1 family.

71.668 kDa

MENRIKRPRVDGECVKSINNGEFDRWDVEDTVAYLRGEGLQEWAQIFKDNGITGAGLLCLTEAHLEKMGVSPLGARLHILHCLQKLSQISTEPMKVFNDPIHGHIELHPLLLHFIDTPQFQRLRHIKQLGGTYLVFPGASHNRFEHSIGVGYLAGCLVKALNERQPELFITKQDILCVQIAGLCHDLGHGPFSHMFDGMFIPKARPADKWKHEIASVQMFDHLVEVNGLEAVMLHHGMRLPEDLIFIKEQIAGPLESAVLDQSQWPYKGRPVEKSFLYEVVANKRNGIDVDKWDYFARDCYHLGIQNNFDYQRFLRFARVCEVKGRKHICTRDKEVGNLYDMFHTRNCLHRRAYQHKVGNIIETMITEAFLKADPHIQIQGSSGRIFTISSAIEDMEAYSKLTDHIFEQILYSSGPELSEARAILQNIICRRLYKCVGQTTSETNVDVSQEKLLDWAKELARSKPTGTEGNLIAEDFVVSVIHMDYGMKEKNPINNVHFYCKNDPTKAIKIHKKQVSKLLPERFAEQLIRVYCKKTDDKSLEAAKKYFVQWCMDRNFTKPQDGDIIAPELTPLKQDWHAREDEDEEEEEKHRQNQTLPHHTPQRTGRNVKVDLFQARGETKL

SAMHD1

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1

614 amino acids

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: 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. 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.

Belongs to the SAMHD1 family.

70.233 kDa

MGSPAAGWGAAPAKRARREGSAESSCGSPADRDPRLWDTERLCQHLSRNGVGEPGLLRRFRESGVTGAMLLDLPACALRITHACLPDERLKVLACLNQLRQTADIMKVFNDPVHGHIEIHPLLVRIIDTPQFQRLRYIKQLGGTYFVFPGASHNRFEHSLGVGYLAGCLVRELKERQPELDITQRDILCVEIAGLCHDLGHGPFSHMFDGRFIPLARQGLNWKHETASVEMFEHLITSNKLEEIMESYGLILEEDIAFIKEQIGGPIDETACEESWPYRGRPKEKSFLYEIVANKKNGIDVDKWDYFARDCHHLGIQNNFDYRRLIKFTRVCEAGNQKHICARDKEVGNLYDMFHTRNCLHRRAYQHKVGNIIEIMITEAFQKADCFFQIEGSKGKLYHISTAMEDMEAYTKLTDNIYLEILHSSRPELSEAREILHKIERRELYKFLGETQPEKVNEIPKDEYDGLAGDIANSKPEKDPPDVELTAEDFIVDVVNMDYGMKDQNPIDNVLFYCKADPSKAIKISKEQVSRLLPGTFSEQVIRVYCKRQDPIIVSAAKQYFVQWCIKRDFTKPQDGDVVAPHLTPLKQSWNNRSKTEYTTASEPSCKQKLSFNK

SAMHD1

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1

589 amino acids

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. Likewise, suppresses LINE-1 retrotransposon activity (By similarity). In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools. 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 (By similarity). Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation (By similarity).

Belongs to the SAMHD1 family.

68.239 kDa

MQSADSQNTPKRPRRDGSPRTPPDSPLADAETSPSHDLDPDYRTWGPEQVWSFLRRCGFSDSELLKRCREKRMSGSLLPFPEDLGISSHGKKMKLLNCIQDTMKVINDPIHGHIEFHPLLMRIIDTPQFQRLRYIKQLGGGYYVFPGASHNRFEHSLGVGYLAGRLVRELSEKQPELQISERDILCVQIAGLCHDLGHGPFSHMFDGRFIPLARPEIKWTHEQGSVMMFEHLINSNGLQDVMKYYGLIPEEDILFIKEQITGPPESPIKDASKWLYKGRPKEKSFLYEIVANKRNGIDVDKWDYFARDCHHLGIQNSFDYKRFLKFARVCEVDNMKHICTREKEVGNLYDMFHTRNCLHRRAYQHKVGNIIDTMITDAFLKADDHIEITGSAGRKYHISTAIDDMEAFTKLTDNIFLEILYSTDPNLNDARMILKKIESRNLYKFVGETQPMIQRIKKENYEHLPNEVASAKPSDVELEAELKAEDLIVDVINMDYGMEDKNPIDHVRFYCKSDLSKAVMITRNQVSQFLPETFAEQLIRVYCKKTDEKTLFAARQHFVHWCLINDFTKPQIKKLPLRKLKKELTTATG