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Protein

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1

Gene

Samhd1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Host restriction nuclease that blocks early-stage virus replication in dendritic and other myeloid cells. Likewise, suppresses LINE-1 retrotransposon activity. May function by reducing the cellular dNTP levels to levels too low for retroviral reverse transcription to occur. May play a role in mediating proinflammatory responses to TNF-alpha signaling (By similarity).By similarity

Catalytic activityi

dNTP + H2O = Deoxynucleoside + triphosphate.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

Allosterically stimulated by dGTP which binds in a cleft at the interface of the homodimer and promotes the formation of highly active homotetramers. Each allosteric site binds two molecules of dGTP (dGTP1 and dGTP 2) between adjoining subunits. Not activated by dATP, dCTP and dTTP (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei117dGTP 1By similarity1
Binding sitei120dGTP 2; via amide nitrogen; shared with neighboring subunitBy similarity1
Binding sitei150SubstrateBy similarity1
Binding sitei165SubstrateBy similarity1
Metal bindingi168Zinc; via tele nitrogenBy similarity1
Metal bindingi207Zinc; via tele nitrogenBy similarity1
Metal bindingi208ZincBy similarity1
Binding sitei211SubstrateBy similarity1
Active sitei234By similarity1
Metal bindingi312ZincBy similarity1
Binding sitei316SubstrateBy similarity1
Binding sitei320SubstrateBy similarity1
Binding sitei334dGTP 2By similarity1
Binding sitei370dGTP 2By similarity1
Binding sitei378SubstrateBy similarity1
Binding sitei388dGTP 2; shared with neighboring subunitBy similarity1
Binding sitei389dGTP 2; shared with neighboring subunitBy similarity1
Binding sitei463dGTP 1; shared with neighboring subunitBy similarity1
Binding sitei467dGTP 1; shared with neighboring subunitBy similarity1
Binding sitei534dGTP 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi138 – 146dGTPBy similarity9
Nucleotide bindingi138 – 146dGTP 1By similarity9
Nucleotide bindingi364 – 366dGTP 2By similarity3

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Antiviral defense, Immunity, Innate immunity

Keywords - Ligandi

Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (EC:3.1.5.-)
Short name:
dNTPase
Alternative name(s):
Interferon-gamma-inducible protein Mg11
SAM domain and HD domain-containing protein 1
Gene namesi
Name:Samhd1
Synonyms:Mg11
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1927468. Samhd1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001537331 – 627Deoxynucleoside triphosphate triphosphohydrolase SAMHD1Add BLAST627

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei18PhosphoserineCombined sources1
Modified residuei21PhosphothreonineCombined sources1
Modified residuei24PhosphoserineCombined sources1
Modified residuei25PhosphothreonineCombined sources1
Modified residuei33PhosphoserineBy similarity1
Modified residuei94PhosphoserineBy similarity1
Modified residuei603PhosphothreonineCombined sources1

Post-translational modificationi

Ubiquitinated and targeted for proteasomal degradation by a DCX (DDB1-CUL4-X-box) E3 ubiquitin ligase with the help of the viral accessory protein Vpx.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ60710.
MaxQBiQ60710.
PaxDbiQ60710.
PeptideAtlasiQ60710.
PRIDEiQ60710.

PTM databases

iPTMnetiQ60710.
PhosphoSitePlusiQ60710.
SwissPalmiQ60710.

Miscellaneous databases

PMAP-CutDBQ60710.

Expressioni

Inductioni

By interferon alpha, beta and gamma (IFN-alpha, IFN-beta and IFN-gamma).1 Publication

Gene expression databases

BgeeiENSMUSG00000027639.
CleanExiMM_SAMHD1.

Interactioni

Subunit structurei

Homodimer. Homotetramer; in dGTP-bound form (By similarity).By similarity

Protein-protein interaction databases

BioGridi207791. 11 interactors.
IntActiQ60710. 2 interactors.
MINTiMINT-4133768.
STRINGi10090.ENSMUSP00000059717.

Structurei

3D structure databases

ProteinModelPortaliQ60710.
SMRiQ60710.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini46 – 111SAMPROSITE-ProRule annotationAdd BLAST66
Domaini165 – 320HDAdd BLAST156

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni310 – 316Substrate bindingBy similarity7
Regioni382 – 387Substrate bindingBy similarity6

Sequence similaritiesi

Belongs to the SAMHD1 family.Curated
Contains 1 HD domain.Curated
Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2681. Eukaryota.
COG1078. LUCA.
HOGENOMiHOG000264286.
HOVERGENiHBG054208.
InParanoidiQ60710.
PhylomeDBiQ60710.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
1.10.3210.10. 2 hits.
InterProiIPR003607. HD/PDEase_dom.
IPR006674. HD_domain.
IPR001660. SAM.
IPR013761. SAM/pointed.
[Graphical view]
PfamiPF01966. HD. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view]
SMARTiSM00471. HDc. 1 hit.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
PROSITEiPS50105. SAM_DOMAIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q60710-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQSAPLEQPA KRPRCDGSPR TPPSTPPATA NLSADDDFQN TDLRTWEPED
60 70 80 90 100
VCSFLENRGF REKKVLDIFR DNKIAGSFLP FLDEDRLEDL GVSSLEERKK
110 120 130 140 150
MIECIQQLSQ SRIDLMKVFN DPIHGHIEFH PLLIRIIDTP QFQRLRYIKQ
160 170 180 190 200
LGGGYYVFPG ASHNRFEHSL GVGYLAGCLV RALAEKQPEL QISERDILCV
210 220 230 240 250
QIAGLCHDLG HGPFSHMFDG RFIPRARPEK KWKHEQGSIE MFEHLVNSNE
260 270 280 290 300
LKLVMKNYGL VPEEDITFIK EQIMGPPITP VKDSLWPYKG RPATKSFLYE
310 320 330 340 350
IVSNKRNGID VDKWDYFARD CHHLGIQNNF DYKRFIKFAR ICEVEYKVKE
360 370 380 390 400
DKTYIRKVKH ICSREKEVGN LYDMFHTRNC LHRRAYQHKI SNLIDIMITD
410 420 430 440 450
AFLKADPYVE ITGTAGKKFR ISTAIDDMEA FTKLTDNIFL EVLHSTDPQL
460 470 480 490 500
SEAQSILRNI ECRNLYKYLG ETQPKREKIR KEEYERLPQE VAKAKPEKAP
510 520 530 540 550
DVELKAEDFI VDVINVDYGM EDKNPIDRVH FYCKSNSKQA VRINKEQVSQ
560 570 580 590 600
LLPEKFAEQL IRVYCKKKDG KSLDAAGKHF VQWCALRDFT KPQDGDIIAP
610 620
LITPLKWNNK TSSCLQEVSK VKTCLKF
Length:627
Mass (Da):72,650
Last modified:August 13, 2002 - v2
Checksum:iC68BB653C3F4B17C
GO

Sequence cautioni

The sequence AAA66219 differs from that shown. Reason: Frameshift at position 576.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti340R → L in BAE31954 (PubMed:16141072).Curated1
Sequence conflicti340R → L in BAE30313 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U15635 mRNA. Translation: AAA66219.1. Frameshift.
AK054490 mRNA. Translation: BAC35801.1.
AK151335 mRNA. Translation: BAE30313.1.
AK153390 mRNA. Translation: BAE31954.1.
AL669828 Genomic DNA. Translation: CAM15970.1.
BC012721 mRNA. Translation: AAH12721.1.
BC067198 mRNA. Translation: AAH67198.1.
PIRiI49127.
RefSeqiNP_001132992.1. NM_001139520.1.
NP_061339.3. NM_018851.3.
UniGeneiMm.248478.
Mm.468781.

Genome annotation databases

GeneIDi56045.
KEGGimmu:56045.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U15635 mRNA. Translation: AAA66219.1. Frameshift.
AK054490 mRNA. Translation: BAC35801.1.
AK151335 mRNA. Translation: BAE30313.1.
AK153390 mRNA. Translation: BAE31954.1.
AL669828 Genomic DNA. Translation: CAM15970.1.
BC012721 mRNA. Translation: AAH12721.1.
BC067198 mRNA. Translation: AAH67198.1.
PIRiI49127.
RefSeqiNP_001132992.1. NM_001139520.1.
NP_061339.3. NM_018851.3.
UniGeneiMm.248478.
Mm.468781.

3D structure databases

ProteinModelPortaliQ60710.
SMRiQ60710.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi207791. 11 interactors.
IntActiQ60710. 2 interactors.
MINTiMINT-4133768.
STRINGi10090.ENSMUSP00000059717.

PTM databases

iPTMnetiQ60710.
PhosphoSitePlusiQ60710.
SwissPalmiQ60710.

Proteomic databases

EPDiQ60710.
MaxQBiQ60710.
PaxDbiQ60710.
PeptideAtlasiQ60710.
PRIDEiQ60710.

Protocols and materials databases

DNASUi56045.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi56045.
KEGGimmu:56045.

Organism-specific databases

CTDi25939.
MGIiMGI:1927468. Samhd1.

Phylogenomic databases

eggNOGiKOG2681. Eukaryota.
COG1078. LUCA.
HOGENOMiHOG000264286.
HOVERGENiHBG054208.
InParanoidiQ60710.
PhylomeDBiQ60710.

Miscellaneous databases

ChiTaRSiSamhd1. mouse.
PMAP-CutDBQ60710.
PROiQ60710.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000027639.
CleanExiMM_SAMHD1.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
1.10.3210.10. 2 hits.
InterProiIPR003607. HD/PDEase_dom.
IPR006674. HD_domain.
IPR001660. SAM.
IPR013761. SAM/pointed.
[Graphical view]
PfamiPF01966. HD. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view]
SMARTiSM00471. HDc. 1 hit.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
PROSITEiPS50105. SAM_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSAMH1_MOUSE
AccessioniPrimary (citable) accession number: Q60710
Secondary accession number(s): Q3U5X2, Q543A4, Q91VK8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: August 13, 2002
Last modified: November 2, 2016
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.