ID   SAMH1_CHICK             Reviewed;         614 AA.
AC   Q5ZJL9; F1P0T3;
DT   10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT   18-JUL-2018, sequence version 2.
DT   27-MAR-2024, entry version 98.
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};
GN   ORFNames=RCJMB04_17d8 {ECO:0000303|PubMed:15642098};
OS   Gallus gallus (Chicken).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC   Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC   Phasianinae; Gallus.
OX   NCBI_TaxID=9031;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=CB; TISSUE=Bursa of Fabricius;
RX   PubMed=15642098; DOI=10.1186/gb-2004-6-1-r6;
RA   Caldwell R.B., Kierzek A.M., Arakawa H., Bezzubov Y., Zaim J., Fiedler P.,
RA   Kutter S., Blagodatski A., Kostovska D., Koter M., Plachy J., Carninci P.,
RA   Hayashizaki Y., Buerstedde J.-M.;
RT   "Full-length cDNAs from chicken bursal lymphocytes to facilitate gene
RT   function analysis.";
RL   Genome Biol. 6:R6.1-R6.9(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Red jungle fowl;
RX   PubMed=15592404; DOI=10.1038/nature03154;
RA   Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P.,
RA   Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B.,
RA   Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C.,
RA   Fulton R.S., Graves T.A., Kremitzki C., Layman D., Magrini V.,
RA   McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O.,
RA   Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W.,
RA   Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D.,
RA   Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K.,
RA   Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L.,
RA   Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B.,
RA   Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M.,
RA   Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K.,
RA   Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E.,
RA   Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M.,
RA   Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M.,
RA   Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S.,
RA   Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M.,
RA   Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M.,
RA   Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A.,
RA   Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S.,
RA   Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J.,
RA   Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J.,
RA   Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E.,
RA   Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M.,
RA   Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A.,
RA   Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M.,
RA   Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O.,
RA   Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E.,
RA   Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S.,
RA   Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E.,
RA   Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R.,
RA   Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R.,
RA   Wilson R.K.;
RT   "Sequence and comparative analysis of the chicken genome provide unique
RT   perspectives on vertebrate evolution.";
RL   Nature 432:695-716(2004).
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}.
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DR   EMBL; AADN04000418; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AJ720415; CAG32074.1; -; mRNA.
DR   RefSeq; NP_001026016.1; NM_001030845.1.
DR   AlphaFoldDB; Q5ZJL9; -.
DR   SMR; Q5ZJL9; -.
DR   BioGRID; 680279; 1.
DR   STRING; 9031.ENSGALP00000001866; -.
DR   PaxDb; 9031-ENSGALP00000001866; -.
DR   Ensembl; ENSGALT00000001868; ENSGALP00000001866; ENSGALG00000001231.
DR   Ensembl; ENSGALT00010059587.1; ENSGALP00010036388.1; ENSGALG00010024424.1.
DR   Ensembl; ENSGALT00015045618; ENSGALP00015027040; ENSGALG00015018612.
DR   GeneID; 419125; -.
DR   KEGG; gga:419125; -.
DR   CTD; 25939; -.
DR   VEuPathDB; HostDB:geneid_419125; -.
DR   eggNOG; KOG2681; Eukaryota.
DR   GeneTree; ENSGT00390000013867; -.
DR   HOGENOM; CLU_026821_1_2_1; -.
DR   InParanoid; Q5ZJL9; -.
DR   OMA; DYIARDC; -.
DR   OrthoDB; 5474479at2759; -.
DR   PhylomeDB; Q5ZJL9; -.
DR   TreeFam; TF316113; -.
DR   Reactome; R-GGA-8956319; Nucleotide catabolism.
DR   PRO; PR:Q5ZJL9; -.
DR   Proteomes; UP000000539; Chromosome 20.
DR   Bgee; ENSGALG00000001231; Expressed in lung and 14 other cell types or tissues.
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; ISS:UniProtKB.
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   InterPro; IPR003607; HD/PDEase_dom.
DR   InterPro; IPR006674; HD_domain.
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   SMART; SM00471; HDc; 1.
DR   SUPFAM; SSF109604; HD-domain/PDEase-like; 1.
DR   SUPFAM; SSF47769; SAM/Pointed domain; 1.
DR   PROSITE; PS51831; HD; 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..614
FT                   /note="Deoxynucleoside triphosphate triphosphohydrolase
FT                   SAMHD1"
FT                   /id="PRO_0000361969"
FT   DOMAIN          37..102
FT                   /note="SAM"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT   DOMAIN          155..307
FT                   /note="HD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01175"
FT   REGION          1..33
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        224
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT   BINDING         107
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         110
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         128..136
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         140
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT   BINDING         155
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT   BINDING         158
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT   BINDING         197
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT   BINDING         198
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT   BINDING         201
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT   BINDING         300..306
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT   BINDING         302
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT   BINDING         306
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT   BINDING         310
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT   BINDING         324
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         343..345
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         349
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
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT   BINDING         361..366
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT   BINDING         367
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         368
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         442
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         446
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         515
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   CONFLICT        91
FT                   /note="K -> E (in Ref. 1; CAG32074)"
FT   CONFLICT        524
FT                   /note="I -> V (in Ref. 1; CAG32074)"
SQ   SEQUENCE   614 AA;  70233 MW;  C931D0BF5FC9C948 CRC64;
     MGSPAAGWGA APAKRARREG SAESSCGSPA DRDPRLWDTE RLCQHLSRNG VGEPGLLRRF
     RESGVTGAML LDLPACALRI THACLPDERL KVLACLNQLR QTADIMKVFN DPVHGHIEIH
     PLLVRIIDTP QFQRLRYIKQ LGGTYFVFPG ASHNRFEHSL GVGYLAGCLV RELKERQPEL
     DITQRDILCV EIAGLCHDLG HGPFSHMFDG RFIPLARQGL NWKHETASVE MFEHLITSNK
     LEEIMESYGL ILEEDIAFIK EQIGGPIDET ACEESWPYRG RPKEKSFLYE IVANKKNGID
     VDKWDYFARD CHHLGIQNNF DYRRLIKFTR VCEAGNQKHI CARDKEVGNL YDMFHTRNCL
     HRRAYQHKVG NIIEIMITEA FQKADCFFQI EGSKGKLYHI STAMEDMEAY TKLTDNIYLE
     ILHSSRPELS EAREILHKIE RRELYKFLGE TQPEKVNEIP KDEYDGLAGD IANSKPEKDP
     PDVELTAEDF IVDVVNMDYG MKDQNPIDNV LFYCKADPSK AIKISKEQVS RLLPGTFSEQ
     VIRVYCKRQD PIIVSAAKQY FVQWCIKRDF TKPQDGDVVA PHLTPLKQSW NNRSKTEYTT
     ASEPSCKQKL SFNK
//