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Q60710 (SAMH1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Deoxynucleoside triphosphate triphosphohydrolase SAMHD1

Short name=dNTPase
EC=3.1.5.-
Alternative name(s):
Interferon-gamma-inducible protein Mg11
SAM domain and HD domain-containing protein 1
Gene names
Name:Samhd1
Synonyms:Mg11
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length627 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

dNTP + H2O = Deoxynucleoside + triphosphate.

Cofactor

Binds 1 zinc ion per subunit By similarity.

Enzyme regulation

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.

Subunit structure

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

Subcellular location

Nucleus By similarity.

Induction

By interferon alpha, beta and gamma (IFN-alpha, IFN-beta and IFN-gamma). Ref.7

Post-translational modification

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.

Sequence similarities

Belongs to the SAMHD1 family.

Contains 1 HD domain.

Contains 1 SAM (sterile alpha motif) domain.

Sequence caution

The sequence AAA66219.1 differs from that shown. Reason: Frameshift at position 576.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 627627Deoxynucleoside triphosphate triphosphohydrolase SAMHD1
PRO_0000153733

Regions

Domain46 – 11166SAM
Domain165 – 320156HD
Nucleotide binding138 – 1469dGTP By similarity
Nucleotide binding138 – 1469dGTP 1 By similarity
Nucleotide binding364 – 3663dGTP 2 By similarity
Region310 – 3167Substrate binding By similarity
Region382 – 3876Substrate binding By similarity

Sites

Active site2341 By similarity
Metal binding1681Zinc; via tele nitrogen By similarity
Metal binding2071Zinc; via tele nitrogen By similarity
Metal binding2081Zinc By similarity
Metal binding3121Zinc By similarity
Binding site1171dGTP 1 By similarity
Binding site1201dGTP 2; via amide nitrogen; shared with neighboring subunit By similarity
Binding site1501Substrate By similarity
Binding site1651Substrate By similarity
Binding site2111Substrate By similarity
Binding site3161Substrate By similarity
Binding site3201Substrate By similarity
Binding site3341dGTP 2 By similarity
Binding site3701dGTP 2 By similarity
Binding site3781Substrate By similarity
Binding site3881dGTP 2; shared with neighboring subunit By similarity
Binding site3891dGTP 2; shared with neighboring subunit By similarity
Binding site4631dGTP 1; shared with neighboring subunit By similarity
Binding site4671dGTP 1; shared with neighboring subunit By similarity
Binding site5341dGTP 2 By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue181Phosphoserine Ref.5
Modified residue211Phosphothreonine Ref.5
Modified residue6031Phosphothreonine Ref.5 Ref.6

Experimental info

Sequence conflict3401R → L in BAE31954. Ref.2
Sequence conflict3401R → L in BAE30313. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q60710 [UniParc].

Last modified August 13, 2002. Version 2.
Checksum: C68BB653C3F4B17C

FASTA62772,650
        10         20         30         40         50         60 
MQSAPLEQPA KRPRCDGSPR TPPSTPPATA NLSADDDFQN TDLRTWEPED VCSFLENRGF 

        70         80         90        100        110        120 
REKKVLDIFR DNKIAGSFLP FLDEDRLEDL GVSSLEERKK MIECIQQLSQ SRIDLMKVFN 

       130        140        150        160        170        180 
DPIHGHIEFH PLLIRIIDTP QFQRLRYIKQ LGGGYYVFPG ASHNRFEHSL GVGYLAGCLV 

       190        200        210        220        230        240 
RALAEKQPEL QISERDILCV QIAGLCHDLG HGPFSHMFDG RFIPRARPEK KWKHEQGSIE 

       250        260        270        280        290        300 
MFEHLVNSNE LKLVMKNYGL VPEEDITFIK EQIMGPPITP VKDSLWPYKG RPATKSFLYE 

       310        320        330        340        350        360 
IVSNKRNGID VDKWDYFARD CHHLGIQNNF DYKRFIKFAR ICEVEYKVKE DKTYIRKVKH 

       370        380        390        400        410        420 
ICSREKEVGN LYDMFHTRNC LHRRAYQHKI SNLIDIMITD AFLKADPYVE ITGTAGKKFR 

       430        440        450        460        470        480 
ISTAIDDMEA FTKLTDNIFL EVLHSTDPQL SEAQSILRNI ECRNLYKYLG ETQPKREKIR 

       490        500        510        520        530        540 
KEEYERLPQE VAKAKPEKAP DVELKAEDFI VDVINVDYGM EDKNPIDRVH FYCKSNSKQA 

       550        560        570        580        590        600 
VRINKEQVSQ LLPEKFAEQL IRVYCKKKDG KSLDAAGKHF VQWCALRDFT KPQDGDIIAP 

       610        620 
LITPLKWNNK TSSCLQEVSK VKTCLKF 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of a novel cDNA that is IFN-gamma-induced in mouse peritoneal macrophages and encodes a putative GTP-binding protein."
Lafuse W.P., Brown D., Castle L., Zwilling B.S.
J. Leukoc. Biol. 57:477-483(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Macrophage.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Bone marrow and Ovary.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain and Mammary gland.
[5]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18; THR-21 AND THR-603, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[6]"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry."
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.
Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-603, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[7]"Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response."
Rice G.I., Bond J., Asipu A., Brunette R.L., Manfield I.W., Carr I.M., Fuller J.C., Jackson R.M., Lamb T., Briggs T.A., Ali M., Gornall H., Couthard L.R., Aeby A., Attard-Montalto S.P., Bertini E., Bodemer C., Brockmann K. expand/collapse author list , Brueton L.A., Corry P.C., Desguerre I., Fazzi E., Cazorla A.G., Gener B., Hamel B.C.J., Heiberg A., Hunter M., van der Knaap M.S., Kumar R., Lagae L., Landrieu P.G., Lourenco C.M., Marom D., McDermott M.F., van der Merwe W., Orcesi S., Prendiville J.S., Rasmussen M., Shalev S.A., Soler D.M., Shinawi M., Spiegel R., Tan T.Y., Vanderver A., Wakeling E.L., Wassmer E., Whittaker E., Lebon P., Stetson D.B., Bonthron D.T., Crow Y.J.
Nat. Genet. 41:829-832(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRI49127.
RefSeqNP_001132992.1. NM_001139520.1.
NP_061339.3. NM_018851.3.
UniGeneMm.248478.
Mm.468781.

3D structure databases

ProteinModelPortalQ60710.
SMRQ60710. Positions 24-608.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ60710. 2 interactions.
MINTMINT-4133768.

PTM databases

PhosphoSiteQ60710.

Proteomic databases

PaxDbQ60710.
PRIDEQ60710.

Protocols and materials databases

DNASU56045.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID56045.
KEGGmmu:56045.

Organism-specific databases

CTD25939.
MGIMGI:1927468. Samhd1.

Phylogenomic databases

eggNOGCOG1078.
HOGENOMHOG000264286.
HOVERGENHBG054208.
InParanoidQ543A4.
PhylomeDBQ60710.

Gene expression databases

ArrayExpressQ60710.
BgeeQ60710.
CleanExMM_SAMHD1.
GenevestigatorQ60710.

Family and domain databases

Gene3D1.10.150.50. 1 hit.
1.10.3210.10. 2 hits.
InterProIPR003607. HD/PDEase_dom.
IPR006674. HD_domain.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011510. SAM_2.
[Graphical view]
PfamPF01966. HD. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view]
SMARTSM00471. HDc. 1 hit.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMSSF47769. SSF47769. 1 hit.
PROSITEPS50105. SAM_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSAMHD1. mouse.
NextBio311816.
PMAP-CutDBQ60710.
PROQ60710.
SOURCESearch...

Entry information

Entry nameSAMH1_MOUSE
AccessionPrimary (citable) accession number: Q60710
Secondary accession number(s): Q3U5X2, Q543A4, Q91VK8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: August 13, 2002
Last modified: April 16, 2014
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot