SAMH1_BOVIN
ID SAMH1_BOVIN Reviewed; 589 AA.
AC Q0VCA5;
DT 10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 100.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal medulla;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) 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 (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.
CC Likewise, suppresses LINE-1 retrotransposon activity (By similarity).
CC In addition to virus restriction, dNTPase activity acts as a regulator
CC of DNA precursor pools by regulating dNTP pools. Functions during S
CC phase at stalled DNA replication forks to promote the resection of
CC gapped or reversed forks: acts by stimulating the exonuclease activity
CC of MRE11, activating the ATR-CHK1 pathway and allowing the forks to
CC restart replication. Its ability to promote degradation of nascent DNA
CC at 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 (By similarity). Enhances immunoglobulin
CC hypermutation in B-lymphocytes by promoting transversion mutation (By
CC similarity). {ECO:0000250|UniProtKB:Q60710,
CC 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. Interacts with MRE11; leading to stimulate
CC the exonuclease activity of MRE11. Interacts with RBBP8/CtIP. Interacts
CC (via its C-terminus) with CD81. {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; BC120271; AAI20272.1; -; mRNA.
DR RefSeq; NP_001069329.1; NM_001075861.1.
DR AlphaFoldDB; Q0VCA5; -.
DR SMR; Q0VCA5; -.
DR STRING; 9913.ENSBTAP00000041236; -.
DR PaxDb; Q0VCA5; -.
DR PeptideAtlas; Q0VCA5; -.
DR PRIDE; Q0VCA5; -.
DR Ensembl; ENSBTAT00000043682; ENSBTAP00000041236; ENSBTAG00000022007.
DR GeneID; 524683; -.
DR KEGG; bta:524683; -.
DR CTD; 25939; -.
DR VEuPathDB; HostDB:ENSBTAG00000022007; -.
DR VGNC; VGNC:34277; SAMHD1.
DR eggNOG; KOG2681; Eukaryota.
DR GeneTree; ENSGT00390000013867; -.
DR HOGENOM; CLU_026821_1_2_1; -.
DR InParanoid; Q0VCA5; -.
DR OMA; GPEQVCF; -.
DR OrthoDB; 835545at2759; -.
DR Proteomes; UP000009136; Chromosome 13.
DR Bgee; ENSBTAG00000022007; Expressed in blood and 111 other tissues.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0097197; C:tetraspanin-enriched microdomain; IEA:Ensembl.
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:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0003676; F:nucleic acid binding; ISS:UniProtKB.
DR GO; GO:0004540; F:ribonuclease activity; 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 Gene3D; 1.10.150.50; -; 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 Acetylation; Allosteric enzyme; Antiviral defense; Chromosome; DNA damage;
KW DNA repair; DNA replication; GTP-binding; Hydrolase; Immunity;
KW Innate immunity; Isopeptide bond; Metal-binding; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation; Zinc.
FT CHAIN 1..589
FT /note="Deoxynucleoside triphosphate triphosphohydrolase
FT SAMHD1"
FT /id="PRO_0000361968"
FT DOMAIN 45..100
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT DOMAIN 152..277
FT /note="HD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01175"
FT REGION 1..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 221
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 104
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 107
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 125..133
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 137
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 152
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 155
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 194
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 195
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 198
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 298..304
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 300
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 304
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 308
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 322
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 341..343
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 347
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 355
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 359..364
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT BINDING 365
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 366
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 440
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 444
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 512
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 MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60710"
FT MOD_RES 21
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q60710"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
FT CROSSLNK 457
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Z3"
SQ SEQUENCE 589 AA; 68239 MW; 260B7E035B2A6F85 CRC64;
MQSADSQNTP KRPRRDGSPR TPPDSPLADA ETSPSHDLDP DYRTWGPEQV WSFLRRCGFS
DSELLKRCRE KRMSGSLLPF PEDLGISSHG KKMKLLNCIQ DTMKVINDPI HGHIEFHPLL
MRIIDTPQFQ RLRYIKQLGG GYYVFPGASH NRFEHSLGVG YLAGRLVREL SEKQPELQIS
ERDILCVQIA GLCHDLGHGP FSHMFDGRFI PLARPEIKWT HEQGSVMMFE HLINSNGLQD
VMKYYGLIPE EDILFIKEQI TGPPESPIKD ASKWLYKGRP KEKSFLYEIV ANKRNGIDVD
KWDYFARDCH HLGIQNSFDY KRFLKFARVC EVDNMKHICT REKEVGNLYD MFHTRNCLHR
RAYQHKVGNI IDTMITDAFL KADDHIEITG SAGRKYHIST AIDDMEAFTK LTDNIFLEIL
YSTDPNLNDA RMILKKIESR NLYKFVGETQ PMIQRIKKEN YEHLPNEVAS AKPSDVELEA
ELKAEDLIVD VINMDYGMED KNPIDHVRFY CKSDLSKAVM ITRNQVSQFL PETFAEQLIR
VYCKKTDEKT LFAARQHFVH WCLINDFTKP QIKKLPLRKL KKELTTATG
