SAMH1_DANRE
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 03-AUG-2022, entry version 87.
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};
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DR EMBL; BC095665; AAH95665.1; ALT_INIT; mRNA.
DR AlphaFoldDB; Q502K2; -.
DR SMR; Q502K2; -.
DR STRING; 7955.ENSDARP00000096087; -.
DR PaxDb; Q502K2; -.
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 Proteomes; UP000814640; Unplaced.
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:0006974; P:cellular response to DNA damage stimulus; 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: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 Gene3D; 1.10.150.50; -; 1.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR006674; HD_domain.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR Pfam; PF01966; HD; 1.
DR Pfam; PF07647; SAM_2; 1.
DR SMART; SM00471; HDc; 1.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 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
