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Q8C6L5

- CGAS_MOUSE

UniProt

Q8C6L5 - CGAS_MOUSE

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Protein
Cyclic GMP-AMP synthase
Gene
Mb21d1
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.3 Publications

Catalytic activityi

ATP + GTP = 2 diphosphate + cyclic 3',5'-AMP-GMP.1 Publication

Cofactori

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

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei197 – 1971GTP
Binding sitei199 – 1991ATP
Metal bindingi211 – 2111Magnesium; catalytic
Metal bindingi213 – 2131Magnesium; catalytic
Metal bindingi307 – 3071Magnesium; catalytic
Binding sitei307 – 3071GTP
Binding sitei371 – 3711ATP
Metal bindingi378 – 3781Zinc
Metal bindingi384 – 3841Zinc
Metal bindingi385 – 3851Zinc
Metal bindingi392 – 3921Zinc
Binding sitei402 – 4021ATP

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi364 – 3718GTP
Nucleotide bindingi420 – 4245ATP

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. DNA binding Source: UniProtKB-KW
  3. GTP binding Source: UniProtKB-KW
  4. cyclic-GMP-AMP synthase activity Source: UniProtKB
  5. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. activation of innate immune response Source: UniProtKB
  2. cellular response to exogenous dsRNA Source: UniProtKB
  3. cyclic nucleotide biosynthetic process Source: UniProtKB
  4. defense response to virus Source: UniProtKB-KW
  5. innate immune response Source: UniProtKB-KW
  6. positive regulation of defense response to virus by host Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Nucleotidyltransferase, Transferase

Keywords - Biological processi

Antiviral defense, Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, DNA-binding, GTP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_196457. STING mediated induction of host immune responses.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclic GMP-AMP synthase (EC:2.7.7.86)
Short name:
cGAMP synthase
Short name:
cGAS
Short name:
m-cGAS
Alternative name(s):
Mab-21 domain-containing protein 1
Gene namesi
Name:Mb21d1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:2442261. Mb21d1.

Subcellular locationi

Cytoplasmcytosol 1 Publication

GO - Cellular componenti

  1. cytosol Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi211 – 2111E → A: Abolishes ability to promote type-I interferon production. 1 Publication
Mutagenesisi213 – 2131D → A: Abolishes ability to promote type-I interferon production. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 507507Cyclic GMP-AMP synthase
PRO_0000421764Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine By similarity
Modified residuei402 – 4021N6-acetyllysine By similarity

Keywords - PTMi

Acetylation

Proteomic databases

PRIDEiQ8C6L5.

Expressioni

Gene expression databases

ArrayExpressiQ8C6L5.
GenevestigatoriQ8C6L5.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi147 – 15711
Helixi161 – 18424
Beta strandi185 – 1873
Turni188 – 1914
Beta strandi193 – 1986
Turni199 – 2035
Beta strandi207 – 2093
Beta strandi211 – 2199
Beta strandi222 – 2287
Beta strandi232 – 2398
Helixi249 – 2513
Beta strandi252 – 2576
Helixi259 – 27416
Beta strandi279 – 2846
Beta strandi293 – 31422
Helixi320 – 3223
Turni329 – 3324
Helixi334 – 3407
Beta strandi345 – 3495
Beta strandi352 – 3543
Helixi359 – 3613
Beta strandi363 – 3664
Helixi368 – 3769
Turni382 – 3854
Helixi394 – 41118
Helixi413 – 4153
Helixi420 – 43314
Helixi437 – 4404
Helixi442 – 4443
Helixi445 – 46218
Beta strandi468 – 4703
Turni478 – 4803
Helixi483 – 49816
Helixi502 – 5054

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliQ8C6L5.
SMRiQ8C6L5. Positions 147-506.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni158 – 20144DNA-binding
Add
BLAST
Regioni372 – 39524DNA-binding
Add
BLAST

Sequence similaritiesi

Belongs to the mab-21 family.

Phylogenomic databases

GeneTreeiENSGT00710000106842.
HOVERGENiHBG068840.
InParanoidiQ8C6L5.
KOiK17834.
OMAiPQDSQWD.
OrthoDBiEOG7S21ZG.
TreeFamiTF331255.

Family and domain databases

InterProiIPR024810. Mab-21_dom.
[Graphical view]
PfamiPF03281. Mab-21. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8C6L5-1 [UniParc]FASTAAdd to Basket

« Hide

MEDPRRRTTA PRAKKPSAKR APTQPSRTRA HAESCGPQRG ARSRRAERDG    50
DTTEKPRAPG PRVHPARATE LTKDAQPSAM DAAGATARPA VRVPQQQAIL 100
DPELPAVREP QPPADPEARK VVRGPSHRRG ARSTGQPRAP RGSRKEPDKL 150
KKVLDKLRLK RKDISEAAET VNKVVERLLR RMQKRESEFK GVEQLNTGSY 200
YEHVKISAPN EFDVMFKLEV PRIELQEYYE TGAFYLVKFK RIPRGNPLSH 250
FLEGEVLSAT KMLSKFRKII KEEVKEIKDI DVSVEKEKPG SPAVTLLIRN 300
PEEISVDIIL ALESKGSWPI STKEGLPIQG WLGTKVRTNL RREPFYLVPK 350
NAKDGNSFQG ETWRLSFSHT EKYILNNHGI EKTCCESSGA KCCRKECLKL 400
MKYLLEQLKK EFQELDAFCS YHVKTAIFHM WTQDPQDSQW DPRNLSSCFD 450
KLLAFFLECL RTEKLDHYFI PKFNLFSQEL IDRKSKEFLS KKIEYERNNG 500
FPIFDKL 507
Length:507
Mass (Da):58,194
Last modified:March 1, 2003 - v1
Checksum:i9FDA84DF5E4859CA
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti6 – 61R → I in BAE26335. 1 Publication
Sequence conflicti471 – 4711P → R in BAE26335. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS40702.1.
RefSeqiNP_775562.2. NM_173386.4.
UniGeneiMm.101559.

Genome annotation databases

EnsembliENSMUST00000070742; ENSMUSP00000063331; ENSMUSG00000032344.
GeneIDi214763.
KEGGimmu:214763.
UCSCiuc009quj.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS40702.1.
RefSeqi NP_775562.2. NM_173386.4.
UniGenei Mm.101559.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4K8V X-ray 2.00 A/B/C/D 147-507 [» ]
4K96 X-ray 2.08 A/B 147-507 [» ]
4K97 X-ray 2.41 A 147-507 [» ]
4K98 X-ray 1.94 A 147-507 [» ]
4K99 X-ray 1.95 A 147-507 [» ]
4K9A X-ray 2.26 A 147-507 [» ]
4K9B X-ray 2.26 A 147-507 [» ]
4LEY X-ray 2.50 A/B/C/D 142-507 [» ]
4LEZ X-ray 2.36 A/C 142-507 [» ]
4O6A X-ray 1.86 A/B 147-507 [» ]
ProteinModelPortali Q8C6L5.
SMRi Q8C6L5. Positions 147-506.
ModBasei Search...
MobiDBi Search...

Proteomic databases

PRIDEi Q8C6L5.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000070742 ; ENSMUSP00000063331 ; ENSMUSG00000032344 .
GeneIDi 214763.
KEGGi mmu:214763.
UCSCi uc009quj.1. mouse.

Organism-specific databases

CTDi 115004.
MGIi MGI:2442261. Mb21d1.

Phylogenomic databases

GeneTreei ENSGT00710000106842.
HOVERGENi HBG068840.
InParanoidi Q8C6L5.
KOi K17834.
OMAi PQDSQWD.
OrthoDBi EOG7S21ZG.
TreeFami TF331255.

Enzyme and pathway databases

Reactomei REACT_196457. STING mediated induction of host immune responses.

Miscellaneous databases

NextBioi 374454.
PROi Q8C6L5.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q8C6L5.
Genevestigatori Q8C6L5.

Family and domain databases

InterProi IPR024810. Mab-21_dom.
[Graphical view ]
Pfami PF03281. Mab-21. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.

Entry informationi

Entry nameiCGAS_MOUSE
AccessioniPrimary (citable) accession number: Q8C6L5
Secondary accession number(s): Q3ULW3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 6, 2013
Last sequence update: March 1, 2003
Last modified: September 3, 2014
This is version 78 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3

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