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Q60710

- SAMH1_MOUSE

UniProt

Q60710 - SAMH1_MOUSE

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Protein

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1

Gene

Samhd1

Organism
Mus musculus (Mouse)
Status
Reviewed - 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei117 – 1171dGTP 1By similarity
Binding sitei120 – 1201dGTP 2; via amide nitrogen; shared with neighboring subunitBy similarity
Binding sitei150 – 1501SubstrateBy similarity
Binding sitei165 – 1651SubstrateBy similarity
Metal bindingi168 – 1681Zinc; via tele nitrogenBy similarity
Metal bindingi207 – 2071Zinc; via tele nitrogenBy similarity
Metal bindingi208 – 2081ZincBy similarity
Binding sitei211 – 2111SubstrateBy similarity
Active sitei234 – 2341By similarity
Metal bindingi312 – 3121ZincBy similarity
Binding sitei316 – 3161SubstrateBy similarity
Binding sitei320 – 3201SubstrateBy similarity
Binding sitei334 – 3341dGTP 2By similarity
Binding sitei370 – 3701dGTP 2By similarity
Binding sitei378 – 3781SubstrateBy similarity
Binding sitei388 – 3881dGTP 2; shared with neighboring subunitBy similarity
Binding sitei389 – 3891dGTP 2; shared with neighboring subunitBy similarity
Binding sitei463 – 4631dGTP 1; shared with neighboring subunitBy similarity
Binding sitei467 – 4671dGTP 1; shared with neighboring subunitBy similarity
Binding sitei534 – 5341dGTP 2By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi138 – 1469dGTPBy similarity
Nucleotide bindingi138 – 1469dGTP 1By similarity
Nucleotide bindingi364 – 3663dGTP 2By similarity

GO - Molecular functioni

  1. dGTPase activity Source: UniProtKB
  2. dGTP binding Source: UniProtKB
  3. nucleic acid binding Source: UniProtKB
  4. RNA binding Source: UniProtKB
  5. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. dATP catabolic process Source: UniProtKB
  2. defense response to virus Source: UniProtKB
  3. dGTP catabolic process Source: UniProtKB
  4. innate immune response Source: UniProtKB-KW
  5. protein homotetramerization Source: Ensembl
  6. regulation of innate immune response Source: UniProtKB
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
ProteomesiUP000000589: Unplaced

Organism-specific databases

MGIiMGI:1927468. Samhd1.

Subcellular locationi

Nucleus By similarity

GO - Cellular componenti

  1. nucleus Source: UniProtKB
  2. plasma membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 627627Deoxynucleoside triphosphate triphosphohydrolase SAMHD1PRO_0000153733Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei18 – 181Phosphoserine1 Publication
Modified residuei21 – 211Phosphothreonine1 Publication
Modified residuei603 – 6031Phosphothreonine2 Publications

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

MaxQBiQ60710.
PaxDbiQ60710.
PRIDEiQ60710.

PTM databases

PhosphoSiteiQ60710.

Miscellaneous databases

PMAP-CutDBQ60710.

Expressioni

Inductioni

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

Gene expression databases

BgeeiQ60710.
CleanExiMM_SAMHD1.
ExpressionAtlasiQ60710. baseline and differential.
GenevestigatoriQ60710.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi207791. 4 interactions.
IntActiQ60710. 2 interactions.
MINTiMINT-4133768.

Structurei

3D structure databases

ProteinModelPortaliQ60710.
SMRiQ60710. Positions 24-608.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini46 – 11166SAMPROSITE-ProRule annotationAdd
BLAST
Domaini165 – 320156HDAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni310 – 3167Substrate bindingBy similarity
Regioni382 – 3876Substrate bindingBy similarity

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

eggNOGiCOG1078.
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.
IPR011510. SAM_2.
[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 AAA66219.1 differs from that shown. Reason: Frameshift at position 576. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti340 – 3401R → L in BAE31954. (PubMed:16141072)Curated
Sequence conflicti340 – 3401R → L in BAE30313. (PubMed:16141072)Curated

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 .
PIRi I49127.
RefSeqi NP_001132992.1. NM_001139520.1.
NP_061339.3. NM_018851.3.
UniGenei Mm.248478.
Mm.468781.

3D structure databases

ProteinModelPortali Q60710.
SMRi Q60710. Positions 24-608.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 207791. 4 interactions.
IntActi Q60710. 2 interactions.
MINTi MINT-4133768.

PTM databases

PhosphoSitei Q60710.

Proteomic databases

MaxQBi Q60710.
PaxDbi Q60710.
PRIDEi Q60710.

Protocols and materials databases

DNASUi 56045.
Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 56045.
KEGGi mmu:56045.

Organism-specific databases

CTDi 25939.
MGIi MGI:1927468. Samhd1.

Phylogenomic databases

eggNOGi COG1078.
HOGENOMi HOG000264286.
HOVERGENi HBG054208.
InParanoidi Q60710.
PhylomeDBi Q60710.

Miscellaneous databases

ChiTaRSi Samhd1. mouse.
NextBioi 311816.
PMAP-CutDB Q60710.
PROi Q60710.
SOURCEi Search...

Gene expression databases

Bgeei Q60710.
CleanExi MM_SAMHD1.
ExpressionAtlasi Q60710. baseline and differential.
Genevestigatori Q60710.

Family and domain databases

Gene3Di 1.10.150.50. 1 hit.
1.10.3210.10. 2 hits.
InterProi IPR003607. HD/PDEase_dom.
IPR006674. HD_domain.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011510. SAM_2.
[Graphical view ]
Pfami PF01966. HD. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view ]
SMARTi SM00471. HDc. 1 hit.
SM00454. SAM. 1 hit.
[Graphical view ]
SUPFAMi SSF47769. SSF47769. 1 hit.
PROSITEi PS50105. SAM_DOMAIN. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. 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.
    , 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.

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 26, 2014
This is version 122 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

External Data

Dasty 3