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Protein

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1

Gene

SAMHD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Protein that acts both as a host restriction factor involved in defense response to virus and as a regulator of DNA end resection at stalled replication forks (PubMed:19525956, PubMed:21613998, PubMed:21720370, PubMed:23602554, PubMed:23601106, PubMed:22056990, PubMed:24336198, PubMed:26294762, PubMed:26431200, PubMed:28229507, PubMed:28834754, PubMed:29670289). Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses, such as HIV-1: dNTPase activity reduces cellular dNTP levels to levels too low for retroviral reverse transcription to occur, blocking early-stage virus replication in dendritic and other myeloid cells (PubMed:19525956, PubMed:21613998, PubMed:21720370, PubMed:23602554, PubMed:23601106, PubMed:23364794, PubMed:25038827, PubMed:26101257, PubMed:22056990, PubMed:24336198, PubMed:28229507, PubMed:26294762, PubMed:26431200). Likewise, suppresses LINE-1 retrotransposon activity (PubMed:24035396, PubMed:29610582, PubMed:24217394). Not able to restrict infection by HIV-2 virus; because restriction activity is counteracted by HIV-2 viral protein Vpx (PubMed:21613998, PubMed:21720370). In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools (PubMed:23858451). Phosphorylation at Thr-592 acts as a switch to control dNTPase-dependent and -independent functions: it inhibits dNTPase activity and ability to restrict infection by viruses, while it promotes DNA end resection at stalled replication forks (PubMed:23602554, PubMed:23601106, PubMed:29610582, PubMed:29670289). Functions during S phase at stalled DNA replication forks to promote the resection of gapped or reversed forks: acts by stimulating the exonuclease activity of MRE11, activating the ATR-CHK1 pathway and allowing the forks to restart replication (PubMed:29670289). Its ability to promote degradation of nascent DNA at stalled replication forks is required to prevent induction of type I interferons, thereby preventing chronic inflammation (PubMed:27477283, PubMed:29670289). Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity (PubMed:29670289). Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation (By similarity).By similarity20 Publications

Caution

Was intially thought to be allosterically stimulated by dGTP (PubMed:22056990, PubMed:24141705, PubMed:24217394). However, it was later shown that it is allosterically activated and regulated via the combined actions of GTP and dNTPs (dATP, dGTP, dTTP and dCTP), which bind two separate binding sites (PubMed:25288794, PubMed:25267621, PubMed:25760601).6 Publications
Phosphorylation at Thr-592 was initially thought to impair ability to restrict infection by viruses without affecting the deoxynucleoside triphosphate (dNTPase) activity (PubMed:23601106). However, it was later shown that phosphorylation reduces the stability of the homotetramer, leading to impair the dNTPase activity (PubMed:26294762, PubMed:26431200).3 Publications
Was initially thought to have 3'-5' exonuclease activity, acting on single-stranded RNA (PubMed:23364794, PubMed:25038827). A publication also reported some DNA 3'-5' exonuclease activity (PubMed:23364794). However, it was later shown that SAMHD1 does not possess DNA and/or RNA exonuclease activities and that these activities are due to contamination during the purification process that can be removed after chromatography steps (PubMed:26101257). The exonuclease activity observed was maybe due to the presence of MRE11 during the purification steps (PubMed:29670289).4 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Zn2+5 PublicationsNote: Binds 1 zinc ion per subunit.5 Publications

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Allosterically activated and regulated via the combined actions of GTP and dNTPs (dATP, dGTP, dTTP and dCTP): Allosteric site 1 binds GTP, while allosteric site 2 binds dNTP (PubMed:25288794, PubMed:25267621, PubMed:25760601). Allosteric activation promotes the formation of highly active homotetramers (PubMed:22056990, PubMed:24141705, PubMed:24217394, PubMed:25288794, PubMed:25267621, PubMed:25760601). Phosphorylation at Thr-592 impairs homotetramerization, thereby inhibiting dNTPase activity, leading to reduced ability to restrict infection by viruses (PubMed:23602554, PubMed:23601106, PubMed:26294762, PubMed:26431200, PubMed:29610582, PubMed:29670289).12 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei116GTP7 Publications1
Binding sitei119dNTP; via amide nitrogen; shared with neighboring subunit7 Publications1
Binding sitei149Substrate1 Publication1
Binding sitei164Substrate1 Publication1
<p>This subsection of the ‘Function’ section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi167Zinc; via tele nitrogen5 Publications1
Metal bindingi206Zinc; via tele nitrogen5 Publications1
Metal bindingi207Zinc5 Publications1
Binding sitei210Substrate1 Publication1
<p>This subsection of the ‘Function’ section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei2331 Publication1
Metal bindingi311Zinc5 Publications1
Binding sitei315Substrate1 Publication1
Binding sitei319Substrate1 Publication1
Binding sitei333dNTP7 Publications1
Binding sitei358dNTP7 Publications1
Binding sitei366Substrate1 Publication1
Binding sitei376dNTP; shared with neighboring subunit7 Publications1
Binding sitei377dNTP; shared with neighboring subunit7 Publications1
Binding sitei451GTP; shared with neighboring subunit7 Publications1
Binding sitei455GTP; shared with neighboring subunit7 Publications1
Binding sitei523dNTP7 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi137 – 145GTP7 Publications9
Nucleotide bindingi352 – 354dNTP7 Publications3

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionAllosteric enzyme, Hydrolase
Biological processAntiviral defense, DNA damage, DNA repair, DNA replication, Immunity, Innate immunity
LigandGTP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-8956319 Nucleobase catabolism
R-HSA-909733 Interferon alpha/beta signaling

SIGNOR Signaling Network Open Resource

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SIGNORi
Q9Y3Z3

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Deoxynucleoside triphosphate triphosphohydrolase SAMHD1Curated (EC:3.1.5.-6 Publications)
Short name:
dNTPaseCurated
Alternative name(s):
Dendritic cell-derived IFNG-induced protein1 Publication
Short name:
DCIP1 Publication
Monocyte protein 51 Publication
Short name:
MOP-51 Publication
SAM domain and HD domain-containing protein 1Curated
Short name:
hSAMHD11 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:SAMHD1Imported
Synonyms:MOP51 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 20

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000101347.8

Human Gene Nomenclature Database

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HGNCi
HGNC:15925 SAMHD1

Online Mendelian Inheritance in Man (OMIM)

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MIMi
606754 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_Q9Y3Z3

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Aicardi-Goutieres syndrome 5 (AGS5)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.
See also OMIM:612952
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_078239120 – 123Missing in AGS5. 1 Publication4
Natural variantiVAR_058481123H → P in AGS5; loss of oligomerization; decreased ability to restrict LINE-1 retrotransposon activity. 4 PublicationsCorresponds to variant dbSNP:rs121434520EnsemblClinVar.1
Natural variantiVAR_058482143R → C in AGS5; loss of oligomerization. 2 PublicationsCorresponds to variant dbSNP:rs387906948EnsemblClinVar.1
Natural variantiVAR_058483143R → H in AGS5; loss of oligomerization; decreased ability to restrict LINE-1 retrotransposon activity. 4 PublicationsCorresponds to variant dbSNP:rs369035155EnsemblClinVar.1
Natural variantiVAR_058484145R → Q in AGS5; loss of oligomerization; decreased ability to restrict LINE-1 retrotransposon activity. 3 PublicationsCorresponds to variant dbSNP:rs515726145EnsemblClinVar.1
Natural variantiVAR_070633167H → Y in AGS5; loss of function in defense response to virus; loss of oligomerization; decreased ability to restrict LINE-1 retrotransposon activity. 3 Publications1
Natural variantiVAR_058486209G → S in AGS5; does not affect oligomerization; decreased ability to restrict LINE-1 retrotransposon activity; does not affect localization to nucleus. 3 PublicationsCorresponds to variant dbSNP:rs121434516EnsemblClinVar.1
Natural variantiVAR_058487254M → V in AGS5; loss of function in defense response to virus; does not affect oligomerization; decreased ability to restrict LINE-1 retrotransposon activity. 4 PublicationsCorresponds to variant dbSNP:rs121434521EnsemblClinVar.1
Natural variantiVAR_070634290R → H in AGS5; loss of oligomerization; decreased ability to restrict LINE-1 retrotransposon activity. 3 PublicationsCorresponds to variant dbSNP:rs559553527Ensembl.1
Natural variantiVAR_058488369L → S in AGS5; loss of function in defense response to virus; decreased oligomerization. 2 PublicationsCorresponds to variant dbSNP:rs515726139EnsemblClinVar.1
Natural variantiVAR_058489385M → V in AGS5; loss of function in defense response to virus; loss of oligomerization. 3 PublicationsCorresponds to variant dbSNP:rs515726140EnsemblClinVar.1
Natural variantiVAR_078240448I → T in AGS5; loss of function in defense response to virus; decreased oligomerization; does not affect localization to nucleus; novel localization to the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs774964432EnsemblClinVar.1
Natural variantiVAR_080530548 – 626Missing in AGS5; Does not affect dNTP regulation, while affecting ability to promote DNA end resection at stalled replication forks. 1 PublicationAdd BLAST79
Chilblain lupus 2 (CHBL2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare cutaneous form of lupus erythematosus. Affected individuals present with painful bluish-red papular or nodular lesions of the skin in acral locations precipitated by cold and wet exposure at temperatures less than 10 degrees centigrade.
See also OMIM:614415

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi77L → F: Increased stability of the tetramer and increased deoxynucleoside triphosphate (dNTPase) activity; when associated with F-77 and F-80 and R-111. 1 Publication1
Mutagenesisi80C → F: Increased stability of the tetramer and increased deoxynucleoside triphosphate (dNTPase) activity; when associated with F-77 and R-111. 1 Publication1
Mutagenesisi111H → R: Increased stability of the tetramer and increased deoxynucleoside triphosphate (dNTPase) activity; when associated with F-77 and F-80. 1 Publication1
Mutagenesisi137D → A: Impairs homotetramerization and nearly abolishes dNTPase activity. 3 Publications1
Mutagenesisi142Q → E or A: Impairs homotetramerization and nearly abolishes dNTPase activity; when associated with K-145. 2 Publications1
Mutagenesisi143R → A: Abolished ability to restrict infection by viruses. 1 Publication1
Mutagenesisi145R → A: Impairs homotetramerization and nearly abolishes dNTPase activity. Abolished ability to restrict infection by viruses. 2 Publications1
Mutagenesisi145R → K: Impairs homotetramerization and nearly abolishes dNTPase activity; when associated with E-145. 1 Publication1
Mutagenesisi149Q → A: Abolished dNTPase activity without affecting homotetramerization. Abolished dNTPase activity; when associated with A-319. 2 Publications1
Mutagenesisi164R → A: Abolished ability to restrict infection by viruses. 1 Publication1
Mutagenesisi167H → A: Abolished ability to restrict infection by viruses. 1 Publication1
Mutagenesisi206 – 207HD → RN: Abolishes zinc binding and dNTPase activity. Does not affect ability to promote DNA end resection at stalled replication forks. 5 Publications2
Mutagenesisi206H → A: Abolished ability to restrict infection by viruses. 1 Publication1
Mutagenesisi207D → A: Abolished ability to restrict infection by viruses. 1 Publication1
Mutagenesisi207D → N or A: Loss of dNTPase activity. 2 Publications1
Mutagenesisi210H → A: Abolished dNTPase activity without affecting homotetramerization. 1 Publication1
Mutagenesisi215H → A: Abolished dNTPase activity without affecting homotetramerization. 1 Publication1
Mutagenesisi226R → G: Loss of function in defense response to virus. 1 Publication1
Mutagenesisi233H → A: Abolished dNTPase activity without affecting homotetramerization. Abolished ability to restrict infection by viruses. 2 Publications1
Mutagenesisi311D → A: Loss of function in defense response to virus. Loss of dNTPase activity. Does not affect oligomerization. 3 Publications1
Mutagenesisi312K → A: Abolishes dNTPase activity; when associated with A-315 and A-366. Does not affect ability to promote DNA end resection at stalled replication forks; when associated with A-315. 2 Publications1
Mutagenesisi315Y → A: Abolished ability to restrict infection by viruses. Abolishes dNTPase activity; when associated with A-312 and A-366. Does not affect ability to promote DNA end resection at stalled replication forks; when associated with A-312. 3 Publications1
Mutagenesisi319D → A: Abolishes dNTPase activity; when associated with A-149. 1 Publication1
Mutagenesisi321H → A: Abolished ability to restrict infection by viruses. 1 Publication1
Mutagenesisi330D → A: Impaired homotetramerization and slightly reduced dNTPase activity. Impaired homotetramerization and reduced dNTPase activity; when associated with A-358. 2 Publications1
Mutagenesisi333R → E: Decreases dNTPase activity. Impairs homotetramerization and nearly abolishes dNTPase activity; when associated with E-451. 2 Publications1
Mutagenesisi352R → A: Impairs homotetramerization and abolishes dNTPase activity; when associated with A-376 and A-377. 1 Publication1
Mutagenesisi358N → A: Impaired homotetramerization and slightly reduced dNTPase activity. Impaired homotetramerization and reduced dNTPase activity A-330. 2 Publications1
Mutagenesisi361D → R: Impairs homotetramerization and nearly abolishes dNTPase activity; when associated with K-364. 1 Publication1
Mutagenesisi364H → K: Impairs homotetramerization and nearly abolishes dNTPase activity; when associated with R-361. 1 Publication1
Mutagenesisi366R → A: Abolishes dNTPase activity; when associated with A-312 and A-315. 1 Publication1
Mutagenesisi370H → A: Abolishes dNTPase activity; when associated with G-374. 1 Publication1
Mutagenesisi372R → D: Abolished homotetramerization and dNTPase activity. 1 Publication1
Mutagenesisi374Y → G: Abolishes dNTPase activity; when associated with A-370. 1 Publication1
Mutagenesisi375Q → A: Abolished dNTPase activity without affecting homotetramerization. 1 Publication1
Mutagenesisi376H → A: Impairs homotetramerization and abolishes dNTPase activity; when associated with A-352 and A-377. 1
Mutagenesisi377K → A: Impairs homotetramerization and abolishes dNTPase activity; when associated with A-352 and A-376. 1
Mutagenesisi451R → E: Impairs homotetramerization and abolishes dNTPase activity. 2 Publications1
Mutagenesisi534K → A: Impairs homotetramerization and abolishes dNTPase activity; when associated with A-537 and D-540. 1 Publication1
Mutagenesisi537V → A: Impairs homotetramerization and abolishes dNTPase activity; when associated with A-534 and D-540. 1 Publication1
Mutagenesisi540L → D: Impairs homotetramerization and abolishes dNTPase activity; when associated with A-537 and A-534. 1 Publication1
Mutagenesisi548Q → A: Loss of function in defense response to virus. Does not affect oligomerization. Retains dNTPase activity. 2 Publications1
Mutagenesisi592T → A or V: Impaired ability to promote DNA end resection at stalled replication forks. Promotes dNTPase activity and ability to restrict infection by viruses. 6 Publications1
Mutagenesisi592T → E: Mimicks phosphorylation state, retains ability to promote DNA end resection at stalled replication forks. Induces large conformational changes that impair homotetramerization, leading to reduced dNTPase activity and decreased ability to restrict infection by viruses. 7 Publications1
Mutagenesisi593P → A: Promotes ability to restrict infection by viruses. 1 Publication1
Mutagenesisi609R → A or E: Abolishes proteasomal degradation triggered by the viral accessory protein vpx. 1 Publication1
Mutagenesisi617R → A or E: Abolishes proteasomal degradation triggered by the viral accessory protein vpx. 1 Publication1
Mutagenesisi622K → A or E: Abolishes proteasomal degradation triggered by the viral accessory protein vpx. 1 Publication1

Keywords - Diseasei

Aicardi-Goutieres syndrome, Disease mutation

Organism-specific databases

DisGeNET

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DisGeNETi
25939

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
SAMHD1

MalaCards human disease database

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MalaCardsi
SAMHD1
MIMi612952 phenotype
614415 phenotype

Open Targets

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OpenTargetsi
ENSG00000101347

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
51 Aicardi-Goutieres syndrome
481662 Familial Chilblain lupus

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA34938

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
SAMHD1

Domain mapping of disease mutations (DMDM)

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DMDMi
22257047

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001537321 – 626Deoxynucleoside triphosphate triphosphohydrolase SAMHD1Add BLAST626

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei1N-acetylmethionineCombined sources1 Publication1
Modified residuei18PhosphoserineBy similarity1
Modified residuei21PhosphothreonineBy similarity1
Modified residuei25PhosphothreonineBy similarity1
Modified residuei33PhosphoserineCombined sources1
Modified residuei93PhosphoserineCombined sources1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki467Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki469Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki492Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei592Phosphothreonine; by CDK1Combined sources6 Publications1
Cross-linki622Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylation at Thr-592 by CDK1 acts as a switch to control deoxynucleoside triphosphate (dNTPase)-dependent and -independent functions (PubMed:29670289). Phosphorylation at Thr-592 takes place in cycling cells: it reduces the stability of the homotetramer, impairing the dNTPase activity and subsequent ability to restrict infection by viruses (PubMed:23602554, PubMed:23601106, PubMed:26294762, PubMed:26431200). It also inhibits ability to suppress LINE-1 retrotransposon activity (PubMed:29610582). In contrast, phosphorylation at Thr-592 promotes DNA end resection at stalled replication forks in response to DNA damage (PubMed:29670289).6 Publications
(Microbial infection) Ubiquitinated following interaction with HIV-2 viral protein Vpx; Vpx promotes interaction and with a DCX (DDB1-CUL4-X-box) E3 ubiquitin ligase, leading to proteasomal degradation.4 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q9Y3Z3

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q9Y3Z3

PeptideAtlas

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PeptideAtlasi
Q9Y3Z3

PRoteomics IDEntifications database

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PRIDEi
Q9Y3Z3

ProteomicsDB human proteome resource

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ProteomicsDBi
86088

PTM databases

CarbonylDB database of protein carbonylation sites

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CarbonylDBi
Q9Y3Z3

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q9Y3Z3

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
Q9Y3Z3

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in heart, skeletal muscle, spleen, liver, small intestine, placenta, lung and peripheral blood leukocytes (PubMed:11064105). No expression is seen in brain and thymus (PubMed:11064105).1 Publication

<p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

By IFNG/IFN-gamma. Up-regulated in TNF treated lung fibroblasts.2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000101347 Expressed in 234 organ(s), highest expression level in bronchial epithelial cell

CleanEx database of gene expression profiles

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CleanExi
HS_SAMHD1

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q9Y3Z3 HS

Organism-specific databases

Human Protein Atlas

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HPAi
HPA047072

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer; in absence of GTP and dNTP (PubMed:24141705, PubMed:24217394, PubMed:28229507, PubMed:25760601). Homotetramer; in GTP- and dNTP-bound form (PubMed:23601106, PubMed:26101257, PubMed:24141705, PubMed:24217394, PubMed:28229507, PubMed:26294762, PubMed:26431200, PubMed:25288794, PubMed:25267621, PubMed:25760601). Interacts with MRE11; leading to stimulate the exonuclease activity of MRE11 (PubMed:28834754, PubMed:29670289). Interacts with RBBP8/CtIP (PubMed:28834754).12 Publications
(Microbial infection) Interacts with HIV-2 viral protein Vpx; promoting interaction with a E3 ubiquitin-protein ligase complex containing DCAF1, leading to subsequent ubiquitination and degradation of SAMHD1.3 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
117436, 79 interactors

Database of interacting proteins

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DIPi
DIP-50704N

Protein interaction database and analysis system

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IntActi
Q9Y3Z3, 30 interactors

STRING: functional protein association networks

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STRINGi
9606.ENSP00000262878

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1626
Legend: HelixTurnBeta strandPDB Structure known for this area
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