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Q8C6L5 (CGAS_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 74. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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:
Cyclic GMP-AMP synthase

Short name=cGAMP synthase
Short name=cGAS
Short name=m-cGAS
EC=2.7.7.86
Alternative name(s):
Mab-21 domain-containing protein 1
Gene names
Name:Mb21d1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length507 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP. Catalysis involves both the formation of a 2',5' phosphodiester linkage at the GpA step and the formation of a 3',5' phosphodiester linkage at the ApG step, producing c[G(2',5')pA(3',5')p]. Has antiviral activity by acting as a key cytosolic DNA sensor, the presence of double-stranded DNA (dsDNA) in the cytoplasm being a danger signal that triggers the immune responses. Binds cytosolic DNA directly, leading to activation and synthesis of cGAMP, a second messenger that binds to and activates TMEM173/STING, thereby triggering type-I interferon production. Ref.1 Ref.6 Ref.7

Catalytic activity

ATP + GTP = 2 diphosphate + cyclic 3',5'-AMP-GMP. Ref.7

Cofactor

Binds 1 Mg2+ per subunit. Is also active with Mn2+. Ref.7

Enzyme regulation

Nucleotidyltransferase activity is stimulated by double-stranded DNA but not RNA By similarity.

Subcellular location

Cytoplasmcytosol Ref.1.

Sequence similarities

Belongs to the mab-21 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 507507Cyclic GMP-AMP synthase
PRO_0000421764

Regions

Nucleotide binding364 – 3718GTP
Nucleotide binding420 – 4245ATP
Region158 – 20144DNA-binding
Region372 – 39524DNA-binding

Sites

Metal binding2111Magnesium; catalytic
Metal binding2131Magnesium; catalytic
Metal binding3071Magnesium; catalytic
Metal binding3781Zinc
Metal binding3841Zinc
Metal binding3851Zinc
Metal binding3921Zinc
Binding site1971GTP
Binding site1991ATP
Binding site3071GTP
Binding site3711ATP
Binding site4021ATP

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue4021N6-acetyllysine By similarity

Experimental info

Mutagenesis2111E → A: Abolishes ability to promote type-I interferon production. Ref.1
Mutagenesis2131D → A: Abolishes ability to promote type-I interferon production. Ref.1
Sequence conflict61R → I in BAE26335. Ref.2
Sequence conflict4711P → R in BAE26335. Ref.2

Secondary structure

.................................................................. 507
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8C6L5 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: 9FDA84DF5E4859CA

FASTA50758,194
        10         20         30         40         50         60 
MEDPRRRTTA PRAKKPSAKR APTQPSRTRA HAESCGPQRG ARSRRAERDG DTTEKPRAPG 

        70         80         90        100        110        120 
PRVHPARATE LTKDAQPSAM DAAGATARPA VRVPQQQAIL DPELPAVREP QPPADPEARK 

       130        140        150        160        170        180 
VVRGPSHRRG ARSTGQPRAP RGSRKEPDKL KKVLDKLRLK RKDISEAAET VNKVVERLLR 

       190        200        210        220        230        240 
RMQKRESEFK GVEQLNTGSY YEHVKISAPN EFDVMFKLEV PRIELQEYYE TGAFYLVKFK 

       250        260        270        280        290        300 
RIPRGNPLSH FLEGEVLSAT KMLSKFRKII KEEVKEIKDI DVSVEKEKPG SPAVTLLIRN 

       310        320        330        340        350        360 
PEEISVDIIL ALESKGSWPI STKEGLPIQG WLGTKVRTNL RREPFYLVPK NAKDGNSFQG 

       370        380        390        400        410        420 
ETWRLSFSHT EKYILNNHGI EKTCCESSGA KCCRKECLKL MKYLLEQLKK EFQELDAFCS 

       430        440        450        460        470        480 
YHVKTAIFHM WTQDPQDSQW DPRNLSSCFD KLLAFFLECL RTEKLDHYFI PKFNLFSQEL 

       490        500 
IDRKSKEFLS KKIEYERNNG FPIFDKL 

« Hide

References

« Hide 'large scale' references
[1]"Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway."
Sun L., Wu J., Du F., Chen X., Chen Z.J.
Science 339:786-791(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DNA-BINDING, SUBCELLULAR LOCATION, MUTAGENESIS OF GLU-211 AND ASP-213.
[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: Mammary gland 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]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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].
Tissue: Brain and Limb.
[6]"cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that activates STING."
Ablasser A., Goldeck M., Cavlar T., Deimling T., Witte G., Rohl I., Hopfner K.P., Ludwig J., Hornung V.
Nature 498:380-384(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Cyclic [G(2',5')pA(3',5')p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase."
Gao P., Ascano M., Wu Y., Barchet W., Gaffney B.L., Zillinger T., Serganov A.A., Liu Y., Jones R.A., Hartmann G., Tuschl T., Patel D.J.
Cell 153:1094-1107(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 147-507 IN COMPLEXES WITH DNA; GMP; GTP; ATP; CYCLIC GMP-AMP; MAGNESIUM AND ZINC IONS, FUNCTION, COFACTOR, CATALYTIC ACTIVITY, DNA-BINDING.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
KC294567 mRNA. Translation: AGB51854.1.
AK054330 mRNA. Translation: BAC35733.1.
AK145268 mRNA. Translation: BAE26335.1.
AC158987 Genomic DNA. No translation available.
CH466522 Genomic DNA. Translation: EDL26396.1.
BC052196 mRNA. Translation: AAH52196.1.
BC145651 mRNA. Translation: AAI45652.1.
BC145653 mRNA. Translation: AAI45654.1.
RefSeqNP_775562.2. NM_173386.4.
UniGeneMm.101559.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4K8VX-ray2.00A/B/C/D147-507[»]
4K96X-ray2.08A/B147-507[»]
4K97X-ray2.41A147-507[»]
4K98X-ray1.94A147-507[»]
4K99X-ray1.95A147-507[»]
4K9AX-ray2.26A147-507[»]
4K9BX-ray2.26A147-507[»]
4LEYX-ray2.50A/B/C/D142-507[»]
4LEZX-ray2.36A/C142-507[»]
4O6AX-ray1.86A/B147-507[»]
ProteinModelPortalQ8C6L5.
SMRQ8C6L5. Positions 147-507.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PRIDEQ8C6L5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000070742; ENSMUSP00000063331; ENSMUSG00000032344.
GeneID214763.
KEGGmmu:214763.
UCSCuc009quj.1. mouse.

Organism-specific databases

CTD115004.
MGIMGI:2442261. Mb21d1.

Phylogenomic databases

GeneTreeENSGT00710000106842.
HOVERGENHBG068840.
InParanoidQ8C6L5.
KOK17834.
OMAPQDSQWD.
OrthoDBEOG7S21ZG.
TreeFamTF331255.

Gene expression databases

ArrayExpressQ8C6L5.
GenevestigatorQ8C6L5.

Family and domain databases

InterProIPR024810. Mab-21_dom.
IPR024805. MB21D1.
[Graphical view]
PANTHERPTHR10656:SF4. PTHR10656:SF4. 1 hit.
PfamPF03281. Mab-21. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio374454.
PROQ8C6L5.
SOURCESearch...

Entry information

Entry nameCGAS_MOUSE
AccessionPrimary (citable) accession number: Q8C6L5
Secondary accession number(s): Q3ULW3
Entry history
Integrated into UniProtKB/Swiss-Prot: March 6, 2013
Last sequence update: March 1, 2003
Last modified: April 16, 2014
This is version 74 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

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