CGAP1_VIBCH
ID CGAP1_VIBCH Reviewed; 431 AA.
AC Q9KLR1;
DT 20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=3'3'-cGAMP-specific phosphodiesterase 1 {ECO:0000303|PubMed:25837739};
DE Short=3'3'-cGAMP PDE 1 {ECO:0000303|PubMed:25837739};
DE Short=V-cGAP1 {ECO:0000303|PubMed:25837739};
DE EC=3.1.4.- {ECO:0000269|PubMed:25837739, ECO:0000269|PubMed:30365951};
DE AltName: Full=5'-pApG 5'-nucleotidase {ECO:0000305|PubMed:25837739};
DE EC=3.1.3.- {ECO:0000269|PubMed:25837739};
GN OrderedLocusNames=VC_A0681 {ECO:0000312|EMBL:AAF96581.1};
OS Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC Vibrio.
OX NCBI_TaxID=243277;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
RX PubMed=10952301; DOI=10.1038/35020000;
RA Heidelberg J.F., Eisen J.A., Nelson W.C., Clayton R.A., Gwinn M.L.,
RA Dodson R.J., Haft D.H., Hickey E.K., Peterson J.D., Umayam L.A., Gill S.R.,
RA Nelson K.E., Read T.D., Tettelin H., Richardson D.L., Ermolaeva M.D.,
RA Vamathevan J.J., Bass S., Qin H., Dragoi I., Sellers P., McDonald L.A.,
RA Utterback T.R., Fleischmann R.D., Nierman W.C., White O., Salzberg S.L.,
RA Smith H.O., Colwell R.R., Mekalanos J.J., Venter J.C., Fraser C.M.;
RT "DNA sequence of both chromosomes of the cholera pathogen Vibrio
RT cholerae.";
RL Nature 406:477-483(2000).
RN [2]
RP FUNCTION AS A C-DI-GMP PHOSPHODIESTERASE, AND INDUCTION.
RC STRAIN=El Tor C6706;
RX PubMed=25343965; DOI=10.1186/s12866-014-0272-9;
RA McKee R.W., Kariisa A., Mudrak B., Whitaker C., Tamayo R.;
RT "A systematic analysis of the in vitro and in vivo functions of the HD-GYP
RT domain proteins of Vibrio cholerae.";
RL BMC Microbiol. 14:272-272(2014).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, INDUCTION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF 74-HIS-ASP-75; 288-HIS-ASP-289;
RP 291-GLY-LYS-292; 341-HIS--GLU-343; 346-ASP-GLY-347 AND TYR-350.
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
RX PubMed=25837739; DOI=10.1038/cr.2015.40;
RA Gao J., Tao J., Liang W., Zhao M., Du X., Cui S., Duan H., Kan B., Su X.,
RA Jiang Z.;
RT "Identification and characterization of phosphodiesterases that
RT specifically degrade 3'3'-cyclic GMP-AMP.";
RL Cell Res. 25:539-550(2015).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBUNIT.
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
RX PubMed=30365951; DOI=10.1016/j.jmb.2018.10.010;
RA Deng M.J., Tao J., Chao E., Ye Z.Y., Jiang Z., Yu J., Su X.D.;
RT "Novel Mechanism for Cyclic Dinucleotide Degradation Revealed by Structural
RT Studies of Vibrio Phosphodiesterase V-cGAP3.";
RL J. Mol. Biol. 430:5080-5093(2018).
CC -!- FUNCTION: Phosphodiesterase (PDE) that catalyzes the hydrolysis of
CC 3'3'-cyclic GMP-AMP (3'3'-cGAMP), leading to linear 5'-pApG
CC (PubMed:25837739, PubMed:30365951). Also displays 5'-nucleotidase
CC activity, further hydrolyzing 5'-pApG to 5'-ApG. Counteracts the
CC function of the 3'3'-cGAMP synthase DncV, and is involved in the
CC modulation of intracellular 3'3'-cGAMP levels. Enhances bacterial
CC chemotaxis and inhibits intestinal colonization in vivo. Thus exerts a
CC crucial role in regulating bacterial infectivity through catalyzing
CC 3'3'-cGAMP degradation. Is specific for 3'3'-cGAMP since it cannot
CC degrade other cGAMP linkage isomers (3'2'-, 2'3'-, and 2'2'-cGAMPs)
CC (PubMed:25837739). Is also able to hydrolyze c-di-GMP but not c-di-AMP
CC (PubMed:25343965, PubMed:25837739). {ECO:0000269|PubMed:25343965,
CC ECO:0000269|PubMed:25837739, ECO:0000269|PubMed:30365951}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',3'-cGAMP + H2O = 5'-pApG-3' + H(+); Xref=Rhea:RHEA:58800,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:71501,
CC ChEBI:CHEBI:142752; Evidence={ECO:0000269|PubMed:25837739,
CC ECO:0000269|PubMed:30365951};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58801;
CC Evidence={ECO:0000305|PubMed:25837739};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5'-pApG-3' + H2O = 5'-ApG-3' + phosphate;
CC Xref=Rhea:RHEA:58804, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:142752, ChEBI:CHEBI:142753;
CC Evidence={ECO:0000269|PubMed:25837739};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58805;
CC Evidence={ECO:0000305|PubMed:25837739};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:30365951};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:30365951};
CC Note=Requires a divalent metal cation for activity. Likely has a bi-
CC nuclear metal center. Has the highest enzyme activity with Ca(2+),
CC followed by Mg(2+). {ECO:0000269|PubMed:30365951};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8.5-10.5. {ECO:0000269|PubMed:30365951};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:30365951}.
CC -!- INDUCTION: Expression is up-regulated by 3'3'-cGAMP production (at both
CC mRNA and protein levels) (PubMed:25837739). Transcripts are more
CC abundant in biofilm cells than in planktonic cells (PubMed:25343965).
CC {ECO:0000269|PubMed:25343965, ECO:0000269|PubMed:25837739}.
CC -!- DISRUPTION PHENOTYPE: Significant increase in the ability to colonize
CC the small intestine compared to the wild-type strain. No defect in
CC biofilm formation. Enforced DncV expression in mutant cells lacking
CC this gene causes an enhanced inhibition of chemotaxis. The double
CC mutants lacking both VC_A0681 and VC_A0210 or both VC_A0681 and
CC VC_A0931 show enhanced bacterial infectivity, and the triple one
CC (VC_A0681, VC_A0210 and VC_A0931) has the highest infectivity, which
CC demonstrates that V-cGAPs play non-redundant roles in cGAMP
CC degradation. {ECO:0000269|PubMed:25837739}.
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DR EMBL; AE003853; AAF96581.1; -; Genomic_DNA.
DR PIR; G82430; G82430.
DR RefSeq; NP_233069.1; NC_002506.1.
DR AlphaFoldDB; Q9KLR1; -.
DR SMR; Q9KLR1; -.
DR STRING; 243277.VC_A0681; -.
DR PRIDE; Q9KLR1; -.
DR DNASU; 2612204; -.
DR EnsemblBacteria; AAF96581; AAF96581; VC_A0681.
DR KEGG; vch:VC_A0681; -.
DR PATRIC; fig|243277.26.peg.3306; -.
DR eggNOG; COG2206; Bacteria.
DR HOGENOM; CLU_040286_2_0_6; -.
DR OMA; FYIIKSH; -.
DR BioCyc; VCHO:VCA0681-MON; -.
DR PHI-base; PHI:3227; -.
DR Proteomes; UP000000584; Chromosome 2.
DR GO; GO:0004112; F:cyclic-nucleotide phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009214; P:cyclic nucleotide catabolic process; IDA:UniProtKB.
DR CDD; cd00077; HDc; 2.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR006674; HD_domain.
DR InterPro; IPR037522; HD_GYP_dom.
DR InterPro; IPR006675; HDIG_dom.
DR Pfam; PF01966; HD; 2.
DR SMART; SM00471; HDc; 2.
DR TIGRFAMs; TIGR00277; HDIG; 1.
DR PROSITE; PS51831; HD; 1.
DR PROSITE; PS51832; HD_GYP; 1.
PE 1: Evidence at protein level;
KW Calcium; Hydrolase; Magnesium; Metal-binding; Reference proteome.
FT CHAIN 1..431
FT /note="3'3'-cGAMP-specific phosphodiesterase 1"
FT /id="PRO_0000435352"
FT DOMAIN 39..155
FT /note="HD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01175"
FT DOMAIN 231..427
FT /note="HD-GYP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01176"
FT ACT_SITE 292
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT BINDING 288
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT BINDING 289
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT BINDING 289
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT BINDING 317
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT BINDING 341
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT BINDING 342
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT BINDING 370
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT MUTAGEN 74..75
FT /note="HD->AA: Reduced enzymatic activity."
FT /evidence="ECO:0000269|PubMed:25837739"
FT MUTAGEN 288..289
FT /note="HD->AA: Loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:25837739"
FT MUTAGEN 291..292
FT /note="GK->AA: Reduced enzymatic activity."
FT /evidence="ECO:0000269|PubMed:25837739"
FT MUTAGEN 341..343
FT /note="HHE->AAA: Reduced enzymatic activity."
FT /evidence="ECO:0000269|PubMed:25837739"
FT MUTAGEN 346..347
FT /note="DG->AA: Reduced enzymatic activity."
FT /evidence="ECO:0000269|PubMed:25837739"
FT MUTAGEN 350
FT /note="Y->A: Loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:25837739"
SQ SEQUENCE 431 AA; 49305 MW; 16287AF1B5E037C4 CRC64;
MRWSEIGCTM KSVNIEWNVN LRQAFFCIAR ALDSVGVDDI NHGHRVGYMA YSCAQAMEWS
EEECQLVFAL GLIHDCGVAQ KRDFYRLLEN MQPDNTQQHC VRGNELLSNC PPLAPFADAI
LYHHTPWDEL KNIAISDRNK RFAALIFLAD RVDYLKELYP RDEYGNVTQE ARNQVCLEIG
RLSGSLFERD LVRTMQHLLS KEFIWFSMEH HHIEAMGHNL PSTPFFEQKL GVEEIMSIAM
LMANVVDAKS QFTFQHSQKV AELCQHLAKE LGLNVEMQKA LYLTGLVHDI GKLHTPEEIL
HKPGKLNESE YLCIQRHSTD SRYTLQMVFG QSVVCEWAGN HHERLDGSGY PRGLQGAAID
LPSRIIAIAD VFQALTQARP YRGSMSLNEV MNIMRHEVSC GRLDSQVFDV IVRNSQQYYQ
LSIAESPTEW A
