SAMH1_CHICK
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 03-AUG-2022, 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};
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; Q5ZJL9; -.
DR Ensembl; ENSGALT00000001868; ENSGALP00000001866; ENSGALG00000001231.
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; GPEQVCF; -.
DR OrthoDB; 835545at2759; -.
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 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: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; ISS:UniProtKB.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; ISS:UniProtKB.
DR CDD; cd00077; HDc; 1.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR006674; HD_domain.
DR InterPro; IPR013761; SAM/pointed_sf.
DR Pfam; PF01966; HD; 1.
DR SMART; SM00471; HDc; 1.
DR SUPFAM; SSF47769; SSF47769; 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
