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Protein

Cyclic GMP-AMP synthase

Gene

Mb21d1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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] (PubMed:23258413, PubMed:23647843, PubMed:23722158, PubMed:26829768). 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 (PubMed:23258413, PubMed:23647843, PubMed:23722158). 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 (PubMed:23722158). cGAMP can be transferred between cells by virtue of packaging within viral particles contributing to IFN-induction in newly infected cells in a cGAS-independent but TMEM173/STING-dependent manner (PubMed:26229117).5 Publications

Catalytic activityi

ATP + GTP = 2 diphosphate + cyclic G-P(2'-5')A-P(3'-5').1 Publication

Cofactori

Mg2+1 Publication, Mn2+1 PublicationNote: 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)DescriptionActionsGraphical viewLength
Binding sitei197GTP1 Publication1
Binding sitei199ATP1 Publication1
Metal bindingi211Magnesium; catalytic1 Publication1
Metal bindingi213Magnesium; catalytic1 Publication1
Metal bindingi307Magnesium; catalytic1 Publication1
Binding sitei307GTP1 Publication1
Binding sitei371ATP1 Publication1
Metal bindingi378Zinc; via tele nitrogen2 Publications1
Metal bindingi384Zinc2 Publications1
Metal bindingi385Zinc2 Publications1
Metal bindingi392Zinc2 Publications1
Binding sitei402ATP1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi364 – 371GTP1 Publication8
Nucleotide bindingi420 – 424ATP1 Publication5

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cyclic-GMP-AMP synthase activity Source: UniProtKB
  • DNA binding Source: UniProtKB
  • GTP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • activation of innate immune response Source: UniProtKB
  • cellular response to exogenous dsRNA Source: UniProtKB
  • cyclic nucleotide biosynthetic process Source: UniProtKB
  • defense response to virus Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • 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

BRENDAi2.7.7.86. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclic GMP-AMP synthase (EC:2.7.7.861 Publication)
Short name:
cGAMP synthase
Short name:
cGAS
Short name:
m-cGAS
Alternative name(s):
2'3'-cGAMP synthase
Mab-21 domain-containing protein 1
Gene namesi
Name:Mb21d1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:2442261. Mb21d1.

Subcellular locationi

  • Cytoplasmcytosol 1 Publication

GO - Cellular componenti

  • cytosol Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi198G → A: Abolishes stimulation of interferon production; when associated with A-199. 1 Publication1
Mutagenesisi199S → A: Abolishes stimulation of interferon production; when associated with A-199. 1 Publication1
Mutagenesisi211E → A: Abolishes ability to promote type-I interferon production. 1 Publication1
Mutagenesisi213D → A: Abolishes ability to promote type-I interferon production. 1 Publication1
Mutagenesisi272E → A: Increased DNA-binding activity. 1 Publication1
Mutagenesisi302E → A: Increased nucleotidyltransferase activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004217641 – 507Cyclic GMP-AMP synthaseAdd BLAST507

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2725-glutamyl polyglutamate1 Publication1
Modified residuei3025-glutamyl glutamate1 Publication1
Modified residuei402N6-acetyllysineBy similarity1

Post-translational modificationi

Polyglutamylated by TTLL6 at Glu-272, leading to impair DNA-binding activity. Monoglutamylated at Glu-302 by TTLL4, leading to impair the nucleotidyltransferase activity. Deglutamylated by AGBL5/CCP5 and AGBL6/CCP6.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond

Proteomic databases

EPDiQ8C6L5.
MaxQBiQ8C6L5.
PaxDbiQ8C6L5.
PRIDEiQ8C6L5.

PTM databases

iPTMnetiQ8C6L5.
PhosphoSitePlusiQ8C6L5.

Expressioni

Gene expression databases

BgeeiENSMUSG00000032344.
ExpressionAtlasiQ8C6L5. baseline and differential.
GenevisibleiQ8C6L5. MM.

Interactioni

Subunit structurei

Monomer in the absence of DNA. Homodimer when bound to DNA.1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000063331.

Structurei

Secondary structure

1507
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi147 – 157Combined sources11
Helixi161 – 184Combined sources24
Beta strandi185 – 187Combined sources3
Turni188 – 191Combined sources4
Beta strandi193 – 198Combined sources6
Turni199 – 203Combined sources5
Beta strandi207 – 209Combined sources3
Beta strandi211 – 219Combined sources9
Beta strandi222 – 228Combined sources7
Beta strandi232 – 239Combined sources8
Helixi249 – 251Combined sources3
Beta strandi252 – 257Combined sources6
Helixi259 – 274Combined sources16
Beta strandi279 – 284Combined sources6
Beta strandi293 – 314Combined sources22
Helixi320 – 322Combined sources3
Turni329 – 332Combined sources4
Helixi334 – 340Combined sources7
Beta strandi345 – 349Combined sources5
Beta strandi352 – 354Combined sources3
Helixi359 – 361Combined sources3
Beta strandi363 – 366Combined sources4
Helixi368 – 376Combined sources9
Turni382 – 385Combined sources4
Helixi394 – 411Combined sources18
Helixi413 – 415Combined sources3
Helixi420 – 433Combined sources14
Helixi437 – 440Combined sources4
Helixi442 – 444Combined sources3
Helixi445 – 462Combined sources18
Beta strandi468 – 470Combined sources3
Turni478 – 480Combined sources3
Helixi483 – 498Combined sources16
Helixi502 – 505Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni158 – 201DNA-binding1 PublicationAdd BLAST44
Regioni372 – 395DNA-binding1 PublicationAdd BLAST24

Sequence similaritiesi

Belongs to the mab-21 family.Curated

Phylogenomic databases

eggNOGiENOG410IE27. Eukaryota.
ENOG410XTKD. LUCA.
GeneTreeiENSGT00710000106842.
HOGENOMiHOG000293423.
HOVERGENiHBG068840.
InParanoidiQ8C6L5.
KOiK17834.
OMAiPQDSQWD.
OrthoDBiEOG091G0MHW.
TreeFamiTF331255.

Family and domain databases

InterProiIPR024810. Mab-21_dom.
[Graphical view]
PfamiPF03281. Mab-21. 1 hit.
[Graphical view]
SMARTiSM01265. Mab-21. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8C6L5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEDPRRRTTA PRAKKPSAKR APTQPSRTRA HAESCGPQRG ARSRRAERDG
60 70 80 90 100
DTTEKPRAPG PRVHPARATE LTKDAQPSAM DAAGATARPA VRVPQQQAIL
110 120 130 140 150
DPELPAVREP QPPADPEARK VVRGPSHRRG ARSTGQPRAP RGSRKEPDKL
160 170 180 190 200
KKVLDKLRLK RKDISEAAET VNKVVERLLR RMQKRESEFK GVEQLNTGSY
210 220 230 240 250
YEHVKISAPN EFDVMFKLEV PRIELQEYYE TGAFYLVKFK RIPRGNPLSH
260 270 280 290 300
FLEGEVLSAT KMLSKFRKII KEEVKEIKDI DVSVEKEKPG SPAVTLLIRN
310 320 330 340 350
PEEISVDIIL ALESKGSWPI STKEGLPIQG WLGTKVRTNL RREPFYLVPK
360 370 380 390 400
NAKDGNSFQG ETWRLSFSHT EKYILNNHGI EKTCCESSGA KCCRKECLKL
410 420 430 440 450
MKYLLEQLKK EFQELDAFCS YHVKTAIFHM WTQDPQDSQW DPRNLSSCFD
460 470 480 490 500
KLLAFFLECL RTEKLDHYFI PKFNLFSQEL IDRKSKEFLS KKIEYERNNG

FPIFDKL
Length:507
Mass (Da):58,194
Last modified:March 1, 2003 - v1
Checksum:i9FDA84DF5E4859CA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6R → I in BAE26335 (PubMed:16141072).Curated1
Sequence conflicti471P → R in BAE26335 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_173386.5.
UniGeneiMm.101559.

Genome annotation databases

EnsembliENSMUST00000070742; ENSMUSP00000063331; ENSMUSG00000032344.
GeneIDi214763.
KEGGimmu:214763.
UCSCiuc009quj.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_173386.5.
UniGeneiMm.101559.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000063331.

PTM databases

iPTMnetiQ8C6L5.
PhosphoSitePlusiQ8C6L5.

Proteomic databases

EPDiQ8C6L5.
MaxQBiQ8C6L5.
PaxDbiQ8C6L5.
PRIDEiQ8C6L5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000070742; ENSMUSP00000063331; ENSMUSG00000032344.
GeneIDi214763.
KEGGimmu:214763.
UCSCiuc009quj.2. mouse.

Organism-specific databases

CTDi115004.
MGIiMGI:2442261. Mb21d1.

Phylogenomic databases

eggNOGiENOG410IE27. Eukaryota.
ENOG410XTKD. LUCA.
GeneTreeiENSGT00710000106842.
HOGENOMiHOG000293423.
HOVERGENiHBG068840.
InParanoidiQ8C6L5.
KOiK17834.
OMAiPQDSQWD.
OrthoDBiEOG091G0MHW.
TreeFamiTF331255.

Enzyme and pathway databases

BRENDAi2.7.7.86. 3474.

Miscellaneous databases

PROiQ8C6L5.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032344.
ExpressionAtlasiQ8C6L5. baseline and differential.
GenevisibleiQ8C6L5. MM.

Family and domain databases

InterProiIPR024810. Mab-21_dom.
[Graphical view]
PfamiPF03281. Mab-21. 1 hit.
[Graphical view]
SMARTiSM01265. Mab-21. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 2, 2016
This is version 97 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

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.