SAMH1_XENLA
ID SAMH1_XENLA Reviewed; 632 AA.
AC Q6INN8;
DT 10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 2.
DT 03-AUG-2022, entry version 80.
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 Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RBBP8.
RX PubMed=29670289; DOI=10.1038/s41586-018-0050-1;
RA Coquel F., Silva M.J., Techer H., Zadorozhny K., Sharma S.,
RA Nieminuszczy J., Mettling C., Dardillac E., Barthe A., Schmitz A.L.,
RA Promonet A., Cribier A., Sarrazin A., Niedzwiedz W., Lopez B., Costanzo V.,
RA Krejci L., Chabes A., Benkirane M., Lin Y.L., Pasero P.;
RT "SAMHD1 acts at stalled replication forks to prevent interferon
RT induction.";
RL Nature 557:57-61(2018).
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 (By similarity). Has deoxynucleoside
CC triphosphate (dNTPase) activity, which is required to restrict
CC infection by viruses: dNTPase activity reduces cellular dNTP levels to
CC levels too low for retroviral reverse transcription to occur, blocking
CC early-stage virus replication in dendritic and other myeloid cells (By
CC similarity). Functions during S phase at stalled DNA replication forks
CC to promote the resection of gapped or reversed forks: acts by
CC stimulating the exonuclease activity of mre11, activating the ATR-CHK1
CC pathway and allowing the forks to restart replication
CC (PubMed:29670289). Ability to promote DNA end resection at stalled
CC replication forks is independent of dNTPase activity (PubMed:29670289).
CC {ECO:0000250|UniProtKB:Q9Y3Z3, ECO:0000269|PubMed:29670289}.
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 (By similarity).
CC Homotetramer; in GTP- and dNTP-bound form (By similarity). Interacts
CC with rbbp8/CtIP (PubMed:29670289). {ECO:0000250|UniProtKB:Q9Y3Z3,
CC ECO:0000269|PubMed:29670289}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y3Z3}.
CC Chromosome {ECO:0000269|PubMed:29670289}. Note=Localizes to sites of
CC DNA double-strand breaks in response to DNA damage.
CC {ECO:0000269|PubMed:29670289}.
CC -!- SIMILARITY: Belongs to the SAMHD1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH72238.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; BC072238; AAH72238.1; ALT_INIT; mRNA.
DR AlphaFoldDB; Q6INN8; -.
DR SMR; Q6INN8; -.
DR Proteomes; UP000186698; Genome assembly.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA: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; IMP: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; ISS:UniProtKB.
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 1: Evidence at protein 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..632
FT /note="Deoxynucleoside triphosphate triphosphohydrolase
FT SAMHD1"
FT /id="PRO_0000361971"
FT DOMAIN 44..107
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT DOMAIN 161..321
FT /note="HD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01175"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 230
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 113
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 116
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 134..142
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 146
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 161
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 164
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 203
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 204
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 207
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 314..320
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 316
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 320
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 324
FT /ligand="substrate"
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 357..359
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 363
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 371
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 375..380
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 381
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 382
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 456
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 460
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 529
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 632 AA; 72749 MW; 7ABC13B7AD363DD1 CRC64;
MKGINGAKRV RHDASPSAQD GYVTPEKRVK RWSGGQTAAN YREWDVEEVC LFLASHGLGE
LEVIFRENKI KGRILEYLTD SHLKDLQISS VALRLDLLSC LRMLCQNSPS IMKVFNDPIH
GHIELHPLLV RIIDTPEFQR LRYIKQLGGS YYVFPGASHN RFEHSIGVGY LAGCLVQALH
ERQPDLQIDM RDMLCVQIAG LCHDLGHGPF SHMFDGRFMP LACPQKKFKH ESASVAMFDH
LIQSNGLEEA MKENGLCLPD DLTFIKEQIA GPLSSEAEQQ FNSSPNSSSW PYRGRTEEKS
FLYEIVANKR NGIDVDKWDY FARDCHHLGI QNNFDYKRFL KFARVCEVGS KKHICTRDKE
VGNLYDMFHT RNCLHRRAYQ HKVGNIIETM ITDAFVKADP HIKIEGANGK YYSISGSVDD
MVAYTKLTDN IYHQILYSND PNLKEAREIL QKVERRHLYK YIGQTHPHSN SRIEPDKYDK
LPADLASSVP QTSAKDVELH AEDFIVDVIH MDYGMKEQNP INNVRFYCKA DPRKAIKIRR
DQVSQLLPEK FAEQIIRVYC KKTDEKSLET AKRYFIQWCM NKDFSKPQDG DVVAPDMTPL
KASWVDDDDD EDNEGKQQTE LLHKSRVKLF TN
