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I3LM39 (CGAS_PIG) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 10. 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:
Cyclic GMP-AMP synthase

Short name=cGAMP synthase
Short name=cGAS
EC=2.7.7.86
Alternative name(s):
Mab-21 domain-containing protein 1
Gene names
Name:MB21D1
OrganismSus scrofa (Pig) [Reference proteome]
Taxonomic identifier9823 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus

Protein attributes

Sequence length495 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.2

Catalytic activity

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

Cofactor

Binds 1 Mg2+ per subunit. Ref.2

Enzyme regulation

The enzyme activity is strongly increased by double-stranded DNA, but not by single-stranded DNA or RNA. Ref.2

Subcellular location

Cytoplasmcytosol By similarity.

Sequence similarities

Belongs to the mab-21 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 495495Cyclic GMP-AMP synthase
PRO_0000423063

Regions

Nucleotide binding351 – 3588GTP
Nucleotide binding410 – 4145ATP
Region147 – 19044DNA-binding
Region359 – 38224DNA-binding

Sites

Metal binding2001Magnesium; catalytic
Metal binding2021Magnesium; catalytic
Metal binding2941Magnesium; catalytic
Metal binding3651Zinc
Metal binding3711Zinc
Metal binding3721Zinc
Metal binding3791Zinc
Binding site1861GTP
Binding site1881ATP
Binding site2941GTP
Binding site3581ATP
Binding site3891ATP

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue71N6-acetyllysine By similarity
Modified residue3891N6-acetyllysine By similarity

Experimental info

Mutagenesis2001E → Q: Abolishes enzyme activity and stimulation of interferon production; when associated with N-202. Ref.2
Mutagenesis2021D → N: Abolishes enzyme activity and stimulation of interferon production; when associated with Q-200. Ref.2

Secondary structure

.................................................................. 495
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
I3LM39 [UniParc].

Last modified July 11, 2012. Version 1.
Checksum: 13E76296D97E176B

FASTA49555,809
        10         20         30         40         50         60 
MAARRGKSTR TASEVGAAGP RASARSVNGA PTVPEAARPG ARRNGPSRAS GCRREKSGPD 

        70         80         90        100        110        120 
PREKPQVRTR TARAEDQAEG PSAPSERVEP PSAQGASLLR AGSCRAREAR SARELRPQAG 

       130        140        150        160        170        180 
ATELAAPARM EAPPGAWKLQ TVLEKVRLSR HEISEAAEVV NWVVEHLLRR LQGGESEFKG 

       190        200        210        220        230        240 
VALLRTGSYY ERVKISAPNE FDVMFKLEVP RIQLEEYCNS GAHYFVKFKR NPGGNPLEQF 

       250        260        270        280        290        300 
LEKEILSASK MLSKFRKIIK EEIKNIEGVT VERKRRGSPA VTLLISKPKE ISVDIILALE 

       310        320        330        340        350        360 
SKSSWPASTQ KGLPISQWLG AKVKNNLKRQ PFYLVPKHAK EGSGFQEETW RLSFSHIEKD 

       370        380        390        400        410        420 
ILKNHGQSKT CCEIDGVKCC RKECLKLMKY LLEQLKKKFG NRRELAKFCS YHVKTAFFHV 

       430        440        450        460        470        480 
CTQDPHDNQW HLKNLECCFD NCVAYFLQCL KTEQLANYFI PGVNLFSRDL IDKPSKEFLS 

       490 
KQIEYERNNG FPVFW 

« Hide

References

« Hide 'large scale' references
[1]Porcine genome sequencing project
Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]"Structural mechanism of cytosolic DNA sensing by cGAS."
Civril F., Deimling T., de Oliveira Mann C.C., Ablasser A., Moldt M., Witte G., Hornung V., Hopfner K.P.
Nature 498:332-337(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 135-495 IN COMPLEXES WITH MAGNESIUM IONS, ZINC IONS; ATP; GTP; UTP AND DNA, COFACTOR, FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, DNA-BINDING, MUTAGENESIS OF GLU-200 AND ASP-202.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
FP102323 Genomic DNA. No translation available.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4JLXX-ray2.00A135-495[»]
4JLZX-ray2.27A/B135-495[»]
4KB6X-ray3.08A135-495[»]
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSSSCT00000030573; ENSSSCP00000025159; ENSSSCG00000021383.

Phylogenomic databases

GeneTreeENSGT00710000106842.
OMAPQDSQWD.
OrthoDBEOG7S21ZG.
TreeFamTF331255.

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...

Entry information

Entry nameCGAS_PIG
AccessionPrimary (citable) accession number: I3LM39
Entry history
Integrated into UniProtKB/Swiss-Prot: July 24, 2013
Last sequence update: July 11, 2012
Last modified: February 19, 2014
This is version 10 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