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Protein

Cyclic GMP-AMP synthase

Gene

MB21D1

Organism
Sus scrofa (Pig)
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]. 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.1 Publication

Catalytic activityi

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

Cofactori

Mg2+1 PublicationNote: Binds 1 Mg2+ ion per subunit.1 Publication

Enzyme regulationi

The enzyme activity is strongly increased by double-stranded DNA, but not by single-stranded DNA or RNA.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei186 – 1861GTP1 Publication
Binding sitei188 – 1881ATP1 Publication
Metal bindingi200 – 2001Magnesium; catalytic1 Publication
Metal bindingi202 – 2021Magnesium; catalytic1 Publication
Metal bindingi294 – 2941Magnesium; catalytic1 Publication
Binding sitei294 – 2941GTP1 Publication
Binding sitei358 – 3581ATP1 Publication
Metal bindingi365 – 3651Zinc; via tele nitrogen1 Publication
Metal bindingi371 – 3711Zinc1 Publication
Metal bindingi372 – 3721Zinc1 Publication
Metal bindingi379 – 3791Zinc1 Publication
Binding sitei389 – 3891ATP1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi351 – 3588GTP1 Publication
Nucleotide bindingi410 – 4145ATP1 Publication

GO - Molecular functioni

GO - Biological processi

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_354585. STING mediated induction of host immune responses.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclic GMP-AMP synthase (EC:2.7.7.861 Publication)
Short name:
cGAMP synthase
Short name:
cGAS
Alternative name(s):
Mab-21 domain-containing protein 1
Gene namesi
Name:MB21D1
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
ProteomesiUP000008227 Componenti: Chromosome 1

Subcellular locationi

  • Cytoplasmcytosol By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi200 – 2001E → Q: Abolishes enzyme activity and stimulation of interferon production; when associated with N-202. 1 Publication
Mutagenesisi202 – 2021D → N: Abolishes enzyme activity and stimulation of interferon production; when associated with Q-200. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 495495Cyclic GMP-AMP synthasePRO_0000423063Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei7 – 71N6-acetyllysineBy similarity
Modified residuei389 – 3891N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation

Interactioni

Subunit structurei

Monomer in the absence of DNA. Homodimer when bound to DNA.By similarity

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000025159.

Structurei

Secondary structure

1
495
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi139 – 1479Combined sources
Helixi150 – 17324Combined sources
Turni177 – 1804Combined sources
Beta strandi182 – 1843Combined sources
Turni188 – 1925Combined sources
Beta strandi200 – 2089Combined sources
Beta strandi213 – 2175Combined sources
Beta strandi221 – 2277Combined sources
Helixi238 – 2403Combined sources
Helixi248 – 26215Combined sources
Beta strandi269 – 2713Combined sources
Beta strandi281 – 2855Combined sources
Beta strandi287 – 2893Combined sources
Beta strandi291 – 30111Combined sources
Helixi307 – 3093Combined sources
Turni316 – 3194Combined sources
Helixi321 – 3288Combined sources
Beta strandi332 – 3354Combined sources
Beta strandi339 – 3446Combined sources
Helixi346 – 3483Combined sources
Beta strandi350 – 3534Combined sources
Helixi355 – 3639Combined sources
Beta strandi366 – 3683Combined sources
Turni369 – 3724Combined sources
Helixi381 – 39818Combined sources
Turni399 – 4013Combined sources
Turni404 – 4074Combined sources
Helixi410 – 42314Combined sources
Helixi427 – 4293Combined sources
Helixi432 – 4343Combined sources
Helixi435 – 45218Combined sources
Turni468 – 4703Combined sources
Helixi473 – 48816Combined sources
Helixi492 – 4943Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4JLXX-ray2.00A135-495[»]
4JLZX-ray2.27A/B135-495[»]
4KB6X-ray3.08A135-495[»]
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni147 – 19044DNA-binding1 PublicationAdd
BLAST
Regioni359 – 38224DNA-binding1 PublicationAdd
BLAST

Sequence similaritiesi

Belongs to the mab-21 family.Curated

Phylogenomic databases

GeneTreeiENSGT00710000106842.
InParanoidiI3LM39.
OMAiPQDSQWD.
OrthoDBiEOG7S21ZG.
TreeFamiTF331255.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

I3LM39-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAARRGKSTR TASEVGAAGP RASARSVNGA PTVPEAARPG ARRNGPSRAS
60 70 80 90 100
GCRREKSGPD PREKPQVRTR TARAEDQAEG PSAPSERVEP PSAQGASLLR
110 120 130 140 150
AGSCRAREAR SARELRPQAG ATELAAPARM EAPPGAWKLQ TVLEKVRLSR
160 170 180 190 200
HEISEAAEVV NWVVEHLLRR LQGGESEFKG VALLRTGSYY ERVKISAPNE
210 220 230 240 250
FDVMFKLEVP RIQLEEYCNS GAHYFVKFKR NPGGNPLEQF LEKEILSASK
260 270 280 290 300
MLSKFRKIIK EEIKNIEGVT VERKRRGSPA VTLLISKPKE ISVDIILALE
310 320 330 340 350
SKSSWPASTQ KGLPISQWLG AKVKNNLKRQ PFYLVPKHAK EGSGFQEETW
360 370 380 390 400
RLSFSHIEKD ILKNHGQSKT CCEIDGVKCC RKECLKLMKY LLEQLKKKFG
410 420 430 440 450
NRRELAKFCS YHVKTAFFHV CTQDPHDNQW HLKNLECCFD NCVAYFLQCL
460 470 480 490
KTEQLANYFI PGVNLFSRDL IDKPSKEFLS KQIEYERNNG FPVFW
Length:495
Mass (Da):55,809
Last modified:July 11, 2012 - v1
Checksum:i13E76296D97E176B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FP102323 Genomic DNA. No translation available.

Genome annotation databases

EnsembliENSSSCT00000030573; ENSSSCP00000025159; ENSSSCG00000021383.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FP102323 Genomic DNA. No translation available.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4JLXX-ray2.00A135-495[»]
4JLZX-ray2.27A/B135-495[»]
4KB6X-ray3.08A135-495[»]
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000025159.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSSSCT00000030573; ENSSSCP00000025159; ENSSSCG00000021383.

Phylogenomic databases

GeneTreeiENSGT00710000106842.
InParanoidiI3LM39.
OMAiPQDSQWD.
OrthoDBiEOG7S21ZG.
TreeFamiTF331255.

Enzyme and pathway databases

ReactomeiREACT_354585. STING mediated induction of host immune responses.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  1. Porcine genome sequencing project
    Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. 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.

Entry informationi

Entry nameiCGAS_PIG
AccessioniPrimary (citable) accession number: I3LM39
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 24, 2013
Last sequence update: July 11, 2012
Last modified: June 24, 2015
This is version 20 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.