ID SAMH1_DANRE Reviewed; 622 AA. AC Q502K2; DT 10-FEB-2009, integrated into UniProtKB/Swiss-Prot. DT 10-FEB-2009, sequence version 2. DT 27-MAR-2024, entry version 92. DE RecName: Full=Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 {ECO:0000305}; DE Short=dNTPase {ECO:0000305}; DE EC=3.1.5.- {ECO:0000250|UniProtKB:Q9Y3Z3}; GN Name=samhd1 {ECO:0000250|UniProtKB:Q9Y3Z3}; OS Danio rerio (Zebrafish) (Brachydanio rerio). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes; OC Danionidae; Danioninae; Danio. OX NCBI_TaxID=7955; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary; RG NIH - Zebrafish Gene Collection (ZGC) project; RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Protein that acts both as a host restriction factor involved CC in defense response to virus and as a regulator of DNA end resection at CC stalled replication forks. Has deoxynucleoside triphosphate (dNTPase) CC activity, which is required to restrict infection by viruses: dNTPase CC activity reduces cellular dNTP levels to levels too low for retroviral CC reverse transcription to occur, blocking early-stage virus replication CC in dendritic and other myeloid cells. Functions during S phase at CC stalled DNA replication forks to promote the resection of gapped or CC reversed forks: acts by stimulating the exonuclease activity of MRE11, CC activating the ATR-CHK1 pathway and allowing the forks to restart CC replication. Its ability to promote degradation of nascent DNA at CC stalled replication forks is required to prevent induction of type I CC interferons, thereby preventing chronic inflammation. Ability to CC promote DNA end resection at stalled replication forks is independent CC of dNTPase activity. {ECO:0000250|UniProtKB:Q9Y3Z3}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + H2O = a 2'- CC deoxyribonucleoside + H(+) + triphosphate; Xref=Rhea:RHEA:46148, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:18036, CC ChEBI:CHEBI:18274, ChEBI:CHEBI:61560; CC Evidence={ECO:0000250|UniProtKB:Q9Y3Z3}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:Q9Y3Z3}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9Y3Z3}; CC -!- ACTIVITY REGULATION: Allosterically activated and regulated via the CC combined actions of GTP and dNTPs (dATP, dGTP, dTTP and dCTP): CC Allosteric site 1 binds GTP, while allosteric site 2 binds dNTP. CC Allosteric activation promotes the formation of highly active CC homotetramers. {ECO:0000250|UniProtKB:Q9Y3Z3}. CC -!- SUBUNIT: Homodimer; in absence of GTP and dNTP. Homotetramer; in CC GTP- and dNTP-bound form (By similarity). Interacts with rbbp8/CtIP (By CC similarity). {ECO:0000250|UniProtKB:Q6INN8, CC ECO:0000250|UniProtKB:Q9Y3Z3}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y3Z3}. CC Chromosome {ECO:0000250|UniProtKB:Q9Y3Z3}. Note=Localizes to sites of CC DNA double-strand breaks in response to DNA damage. CC {ECO:0000250|UniProtKB:Q9Y3Z3}. CC -!- SIMILARITY: Belongs to the SAMHD1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH95665.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BC095665; AAH95665.1; ALT_INIT; mRNA. DR AlphaFoldDB; Q502K2; -. DR SMR; Q502K2; -. DR STRING; 7955.ENSDARP00000096087; -. DR PaxDb; 7955-ENSDARP00000096087; -. DR AGR; ZFIN:ZDB-GENE-090313-386; -. DR ZFIN; ZDB-GENE-090313-386; samhd1. DR eggNOG; KOG2681; Eukaryota. DR InParanoid; Q502K2; -. DR PhylomeDB; Q502K2; -. DR Reactome; R-DRE-8956319; Nucleotide catabolism. DR PRO; PR:Q502K2; -. DR Proteomes; UP000000437; Genome assembly. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB. DR GO; GO:0106375; F:deoxynucleoside triphosphate hydrolase activity; IEA:RHEA. DR GO; GO:0032567; F:dGTP binding; ISS:UniProtKB. DR GO; GO:0008832; F:dGTPase activity; ISS:UniProtKB. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW. DR GO; GO:0003676; F:nucleic acid binding; ISS:UniProtKB. DR GO; GO:0003723; F:RNA binding; ISS:UniProtKB. DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB. DR GO; GO:0016793; F:triphosphoric monoester hydrolase activity; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB. DR GO; GO:0046061; P:dATP catabolic process; ISS:UniProtKB. DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB. DR GO; GO:0009264; P:deoxyribonucleotide catabolic process; ISS:UniProtKB. DR GO; GO:0006203; P:dGTP catabolic process; ISS:UniProtKB. DR GO; GO:0006974; P:DNA damage response; ISS:UniProtKB. DR GO; GO:0110025; P:DNA strand resection involved in replication fork processing; ISS:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISS:UniProtKB. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; ISS:UniProtKB. DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB. DR GO; GO:0045088; P:regulation of innate immune response; IMP:ZFIN. DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; ISS:UniProtKB. DR CDD; cd00077; HDc; 1. DR CDD; cd09508; SAM_HD; 1. DR Gene3D; 3.30.70.2760; -; 1. DR Gene3D; 1.10.3210.10; Hypothetical protein af1432; 1. DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1. DR InterPro; IPR003607; HD/PDEase_dom. DR InterPro; IPR006674; HD_domain. DR InterPro; IPR001660; SAM. DR InterPro; IPR013761; SAM/pointed_sf. DR PANTHER; PTHR11373; DEOXYNUCLEOSIDE TRIPHOSPHATE TRIPHOSPHOHYDROLASE; 1. DR PANTHER; PTHR11373:SF4; DEOXYNUCLEOSIDE TRIPHOSPHATE TRIPHOSPHOHYDROLASE SAMHD1; 1. DR Pfam; PF01966; HD; 1. DR Pfam; PF07647; SAM_2; 1. DR SMART; SM00471; HDc; 1. DR SMART; SM00454; SAM; 1. DR SUPFAM; SSF109604; HD-domain/PDEase-like; 1. DR SUPFAM; SSF47769; SAM/Pointed domain; 1. DR PROSITE; PS51831; HD; 1. DR PROSITE; PS50105; SAM_DOMAIN; 1. PE 2: Evidence at transcript level; KW Allosteric enzyme; Antiviral defense; Chromosome; DNA damage; DNA repair; KW DNA replication; GTP-binding; Hydrolase; Immunity; Innate immunity; KW Metal-binding; Nucleotide-binding; Nucleus; Reference proteome; Zinc. FT CHAIN 1..622 FT /note="Deoxynucleoside triphosphate triphosphohydrolase FT SAMHD1" FT /id="PRO_0000361970" FT DOMAIN 26..89 FT /note="SAM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184" FT DOMAIN 143..296 FT /note="HD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01175" FT REGION 571..622 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 574..596 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 212 FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 95 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 98 FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate" FT /ligand_id="ChEBI:CHEBI:61560" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 116..124 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 128 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 143 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 146 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 185 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 186 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 189 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 289..295 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 291 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 295 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 299 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 313 FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate" FT /ligand_id="ChEBI:CHEBI:61560" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 332..334 FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate" FT /ligand_id="ChEBI:CHEBI:61560" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 338 FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate" FT /ligand_id="ChEBI:CHEBI:61560" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 346 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 350..355 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 356 FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate" FT /ligand_id="ChEBI:CHEBI:61560" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 357 FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate" FT /ligand_id="ChEBI:CHEBI:61560" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 431 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 435 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" FT BINDING 502 FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate" FT /ligand_id="ChEBI:CHEBI:61560" FT /ligand_note="ligand shared between two neighboring FT subunits" FT /note="in other chain" FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3" SQ SEQUENCE 622 AA; 71668 MW; C4DA54301CD2C77D CRC64; MENRIKRPRV DGECVKSINN GEFDRWDVED TVAYLRGEGL QEWAQIFKDN GITGAGLLCL TEAHLEKMGV SPLGARLHIL HCLQKLSQIS TEPMKVFNDP IHGHIELHPL LLHFIDTPQF QRLRHIKQLG GTYLVFPGAS HNRFEHSIGV GYLAGCLVKA LNERQPELFI TKQDILCVQI AGLCHDLGHG PFSHMFDGMF IPKARPADKW KHEIASVQMF DHLVEVNGLE AVMLHHGMRL PEDLIFIKEQ IAGPLESAVL DQSQWPYKGR PVEKSFLYEV VANKRNGIDV DKWDYFARDC YHLGIQNNFD YQRFLRFARV CEVKGRKHIC TRDKEVGNLY DMFHTRNCLH RRAYQHKVGN IIETMITEAF LKADPHIQIQ GSSGRIFTIS SAIEDMEAYS KLTDHIFEQI LYSSGPELSE ARAILQNIIC RRLYKCVGQT TSETNVDVSQ EKLLDWAKEL ARSKPTGTEG NLIAEDFVVS VIHMDYGMKE KNPINNVHFY CKNDPTKAIK IHKKQVSKLL PERFAEQLIR VYCKKTDDKS LEAAKKYFVQ WCMDRNFTKP QDGDIIAPEL TPLKQDWHAR EDEDEEEEEK HRQNQTLPHH TPQRTGRNVK VDLFQARGET KL //