Q9KL18 · CGAP3_VIBCH
- Protein3'3'-cGAMP-specific phosphodiesterase 3
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids460 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Phosphodiesterase (PDE) that catalyzes the hydrolysis of 3'3'-cyclic GMP-AMP (3'3'-cGAMP), leading to linear 5'-pApG (PubMed:25837739, PubMed:30365951).
Counteracts the function of the 3'3'-cGAMP synthase DncV, and is involved in the modulation of intracellular 3'3'-cGAMP levels. Enhances bacterial chemotaxis and inhibits intestinal colonization in vivo. Thus exerts a crucial role in regulating bacterial infectivity through catalyzing 3'3'-cGAMP degradation. Is specific for 3'3'-cGAMP since it cannot degrade other cGAMP linkage isomers (3'2'-, 2'3'-, and 2'2'-cGAMPs); is also able to hydrolyze c-di-GMP but not c-di-AMP (PubMed:25837739).
Counteracts the function of the 3'3'-cGAMP synthase DncV, and is involved in the modulation of intracellular 3'3'-cGAMP levels. Enhances bacterial chemotaxis and inhibits intestinal colonization in vivo. Thus exerts a crucial role in regulating bacterial infectivity through catalyzing 3'3'-cGAMP degradation. Is specific for 3'3'-cGAMP since it cannot degrade other cGAMP linkage isomers (3'2'-, 2'3'-, and 2'2'-cGAMPs); is also able to hydrolyze c-di-GMP but not c-di-AMP (PubMed:25837739).
Catalytic activity
- 3',3'-cGAMP + H2O = 5'-pApG-3' + H+This reaction proceeds in the forward direction.
Cofactor
Note: Requires a divalent metal cation for activity. Likely has a bi-nuclear metal center. Has the highest enzyme activity with Mn2+, and when incubated with Ni2+, its activity is about 60% lower than that observed with Mn2+.
pH Dependence
Optimum pH is 10.0.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 317 | a divalent metal cation 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 318 | a divalent metal cation 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 318 | a divalent metal cation 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Active site | 321 | Proton donor | ||||
Sequence: K | ||||||
Binding site | 346 | a divalent metal cation 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 370 | a divalent metal cation 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 371 | a divalent metal cation 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 399 | a divalent metal cation 1 (UniProtKB | ChEBI) | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | cyclic-nucleotide phosphodiesterase activity | |
Molecular Function | metal ion binding | |
Biological Process | cyclic nucleotide catabolic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name3'3'-cGAMP-specific phosphodiesterase 3
- EC number
- Short names3'3'-cGAMP PDE 3 ; V-cGAP3
Gene names
Organism names
- Strain
- Taxonomic lineageBacteria > Pseudomonadota > Gammaproteobacteria > Vibrionales > Vibrionaceae > Vibrio
Accessions
- Primary accessionQ9KL18
Proteomes
Phenotypes & Variants
Disruption phenotype
Significant increase in the ability to colonize the small intestine compared to the wild-type strain. No defect in biofilm formation. Enforced DncV expression in mutant cells lacking this gene causes an enhanced inhibition of chemotaxis. The double mutant lacking both VC_A0681 and VC_A0931 shows enhanced bacterial infectivity, and the triple one (VC_A0681, VC_A0210 and VC_A0931) has the highest infectivity, which demonstrates that V-cGAPs play non-redundant roles in cGAMP degradation.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 13 | Large decrease in enzymatic activity. | ||||
Sequence: L → D or H | ||||||
Mutagenesis | 17 | Large decrease in enzymatic activity. | ||||
Sequence: L → H, K, or T | ||||||
Mutagenesis | 21 | Large decrease in enzymatic activity. | ||||
Sequence: L → D or H | ||||||
Mutagenesis | 317-318 | Loss of enzymatic activity. | ||||
Sequence: HD → AA | ||||||
Mutagenesis | 321 | Almost loss of activity. | ||||
Sequence: K → A, C, D, N, R, S, T, or V |
Miscellaneous
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000435354 | 1-460 | 3'3'-cGAMP-specific phosphodiesterase 3 | |||
Sequence: MSVAQNTFPLSELMISLTTALDMTEGQPPEHCIRCCWIGMHIGMQLELSEPELHDLFFTLLLKDAGCSSNAARICELYATDDLTFKRRYKTVGTSLSSVINFIVKNTGSEQSWTERILTTIDILKNGNDYAQELIQTRCTRGADVARELRFSEAVAQGIHSLDEHWNGQGRPEQRKGEAIPLFSRIALLAQVFDVFQMEHSIEEALQEIMARSGVWFDPKLVEVVEQLVENPRFLSGLKATDISQRVMNLPPAQAHLPLDDAYLECIVTAFGKIVDAKSPYTAGHSERVAVYTDLIARQLAISDADRIWLRRAALLHDIGKLGVSNAILDKPGKLDEAEWRAVQAHAAYTEQILYKLSPFKTLARMAGAHHEKLDGTGYPRGVNGDEISLMTRIITTADIFDALSAERPYRAAMPIDKALAIMEENLHTAIDPECFAALKKALNLLPDEYTQLPHSSDKT |
Expression
Induction
Expression is up-regulated by 3'3'-cGAMP production (at both mRNA and protein levels).
Interaction
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 28-189 | HD | ||||
Sequence: PPEHCIRCCWIGMHIGMQLELSEPELHDLFFTLLLKDAGCSSNAARICELYATDDLTFKRRYKTVGTSLSSVINFIVKNTGSEQSWTERILTTIDILKNGNDYAQELIQTRCTRGADVARELRFSEAVAQGIHSLDEHWNGQGRPEQRKGEAIPLFSRIALL | ||||||
Domain | 260-455 | HD-GYP | ||||
Sequence: DDAYLECIVTAFGKIVDAKSPYTAGHSERVAVYTDLIARQLAISDADRIWLRRAALLHDIGKLGVSNAILDKPGKLDEAEWRAVQAHAAYTEQILYKLSPFKTLARMAGAHHEKLDGTGYPRGVNGDEISLMTRIITTADIFDALSAERPYRAAMPIDKALAIMEENLHTAIDPECFAALKKALNLLPDEYTQLPH |
Domain
Consists of two tandem domains of about 15% identity and similar three-dimensional topology that interact to form a pseudo-dimeric structure. The N-terminal domain (residues 1-258) plays an important regulatory role in facilitating the catalytic function of the C-terminal domain (residues 259-460). The N-terminal domain alone does not show any activity. The C-terminal domain alone is much less active comparing to the full-length protein. The full-length protein is 13 times more active than the C-terminal domain alone.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length460
- Mass (Da)51,291
- Last updated2000-10-01 v1
- ChecksumE160C15151DC3D2F
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AE003853 EMBL· GenBank· DDBJ | AAF96828.1 EMBL· GenBank· DDBJ | Genomic DNA |