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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 (PubMed:23722159). 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 (By similarity).By similarity1 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)DescriptionActionsGraphical viewLength
Binding sitei186GTP1 Publication1
Binding sitei188ATP1 Publication1
Metal bindingi200Magnesium; catalytic1 Publication1
Metal bindingi202Magnesium; catalytic1 Publication1
Metal bindingi294Magnesium; catalytic1 Publication1
Binding sitei294GTP1 Publication1
Binding sitei358ATP1 Publication1
Metal bindingi365Zinc; via tele nitrogen1 Publication1
Metal bindingi371Zinc1 Publication1
Metal bindingi372Zinc1 Publication1
Metal bindingi379Zinc1 Publication1
Binding sitei389ATP1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi351 – 358GTP1 Publication8
Nucleotide bindingi410 – 414ATP1 Publication5

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

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):
2'3'-cGAMP synthase
Mab-21 domain-containing protein 1
Gene namesi
Name:MB21D1
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Chromosome 1

Subcellular locationi

  • Cytoplasmcytosol By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi200E → Q: Abolishes enzyme activity and stimulation of interferon production; when associated with N-202. 1 Publication1
Mutagenesisi202D → N: Abolishes enzyme activity and stimulation of interferon production; when associated with Q-200. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004230631 – 495Cyclic GMP-AMP synthaseAdd BLAST495

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei7N6-acetyllysineBy similarity1
Modified residuei2615-glutamyl polyglutamateBy similarity1
Modified residuei389N6-acetyllysineBy similarity1

Post-translational modificationi

Polyglutamylated by TTLL6 at Glu-261, leading to impair DNA-binding activity. Deglutamylated by AGBL5/CCP5 and AGBL6/CCP6.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond

Proteomic databases

PaxDbiI3LM39.
PeptideAtlasiI3LM39.
PRIDEiI3LM39.

Expressioni

Gene expression databases

BgeeiENSSSCG00000021383.

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

1495
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi139 – 147Combined sources9
Helixi150 – 173Combined sources24
Turni177 – 180Combined sources4
Beta strandi182 – 184Combined sources3
Turni188 – 192Combined sources5
Beta strandi200 – 208Combined sources9
Beta strandi213 – 217Combined sources5
Beta strandi221 – 227Combined sources7
Helixi238 – 240Combined sources3
Helixi248 – 262Combined sources15
Beta strandi269 – 271Combined sources3
Beta strandi281 – 285Combined sources5
Beta strandi287 – 289Combined sources3
Beta strandi291 – 301Combined sources11
Helixi307 – 309Combined sources3
Turni316 – 319Combined sources4
Helixi321 – 328Combined sources8
Beta strandi332 – 335Combined sources4
Beta strandi339 – 344Combined sources6
Helixi346 – 348Combined sources3
Beta strandi350 – 353Combined sources4
Helixi355 – 363Combined sources9
Beta strandi366 – 368Combined sources3
Turni369 – 372Combined sources4
Helixi381 – 398Combined sources18
Turni399 – 401Combined sources3
Turni404 – 407Combined sources4
Helixi410 – 423Combined sources14
Helixi427 – 429Combined sources3
Helixi432 – 434Combined sources3
Helixi435 – 452Combined sources18
Turni468 – 470Combined sources3
Helixi473 – 488Combined sources16
Helixi492 – 494Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4JLXX-ray2.00A135-495[»]
4JLZX-ray2.27A/B135-495[»]
4KB6X-ray3.08A135-495[»]
SMRiI3LM39.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni147 – 190DNA-binding1 PublicationAdd BLAST44
Regioni359 – 382DNA-binding1 PublicationAdd BLAST24

Sequence similaritiesi

Belongs to the mab-21 family.Curated

Phylogenomic databases

eggNOGiENOG410IE27. Eukaryota.
ENOG410XTKD. LUCA.
GeneTreeiENSGT00710000106842.
InParanoidiI3LM39.
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.

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.
RefSeqiXP_013840602.1. XM_013985148.1.

Genome annotation databases

EnsembliENSSSCT00000030573; ENSSSCP00000025159; ENSSSCG00000021383.
GeneIDi100516408.
KEGGissc:100516408.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FP102323 Genomic DNA. No translation available.
RefSeqiXP_013840602.1. XM_013985148.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4JLXX-ray2.00A135-495[»]
4JLZX-ray2.27A/B135-495[»]
4KB6X-ray3.08A135-495[»]
SMRiI3LM39.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000025159.

Proteomic databases

PaxDbiI3LM39.
PeptideAtlasiI3LM39.
PRIDEiI3LM39.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSSSCT00000030573; ENSSSCP00000025159; ENSSSCG00000021383.
GeneIDi100516408.
KEGGissc:100516408.

Organism-specific databases

CTDi115004.

Phylogenomic databases

eggNOGiENOG410IE27. Eukaryota.
ENOG410XTKD. LUCA.
GeneTreeiENSGT00710000106842.
InParanoidiI3LM39.
KOiK17834.
OMAiPQDSQWD.
OrthoDBiEOG091G0MHW.
TreeFamiTF331255.

Gene expression databases

BgeeiENSSSCG00000021383.

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_PIG
AccessioniPrimary (citable) accession number: I3LM39
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 24, 2013
Last sequence update: July 11, 2012
Last modified: November 2, 2016
This is version 32 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

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.