CGAP2_VIBCH
ID CGAP2_VIBCH Reviewed; 522 AA.
AC Q9KMV8;
DT 20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=3'3'-cGAMP-specific phosphodiesterase 2 {ECO:0000303|PubMed:25837739};
DE Short=3'3'-cGAMP PDE 2 {ECO:0000303|PubMed:25837739};
DE Short=V-cGAP2 {ECO:0000303|PubMed:25837739};
DE EC=3.1.4.- {ECO:0000269|PubMed:25837739, ECO:0000269|PubMed:30365951};
GN OrderedLocusNames=VC_A0210 {ECO:0000312|EMBL:AAF96122.1};
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 382-HIS-ASP-383.
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). Counteracts the function of the
CC 3'3'-cGAMP synthase DncV, and is involved in the modulation of
CC intracellular 3'3'-cGAMP levels. Enhances bacterial chemotaxis and
CC inhibits intestinal colonization in vivo. Thus exerts a crucial role in
CC regulating bacterial infectivity through catalyzing 3'3'-cGAMP
CC degradation. Is specific for 3'3'-cGAMP since it cannot degrade other
CC 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 -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
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 Mn(2+).
CC {ECO:0000269|PubMed:30365951};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 9.0-11.0. {ECO:0000269|PubMed:30365951};
CC -!- SUBUNIT: Homodimer. {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 mutant lacking both VC_A0681 and VC_A0210 shows enhanced bacterial
CC infectivity, and the triple one (VC_A0681, VC_A0210 and VC_A0931) has
CC the highest infectivity, which demonstrates that V-cGAPs play non-
CC redundant roles in cGAMP degradation. {ECO:0000269|PubMed:25837739}.
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DR EMBL; AE003853; AAF96122.1; -; Genomic_DNA.
DR PIR; H82486; H82486.
DR RefSeq; NP_232609.1; NC_002506.1.
DR AlphaFoldDB; Q9KMV8; -.
DR SMR; Q9KMV8; -.
DR STRING; 243277.VC_A0210; -.
DR PRIDE; Q9KMV8; -.
DR DNASU; 2612328; -.
DR EnsemblBacteria; AAF96122; AAF96122; VC_A0210.
DR KEGG; vch:VC_A0210; -.
DR PATRIC; fig|243277.26.peg.2844; -.
DR eggNOG; COG0784; Bacteria.
DR eggNOG; COG3437; Bacteria.
DR HOGENOM; CLU_000445_92_10_6; -.
DR OMA; WINLLYM; -.
DR BioCyc; VCHO:VCA0210-MON; -.
DR PHI-base; PHI:3228; -.
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 GO; GO:0000160; P:phosphorelay signal transduction system; IEA:InterPro.
DR CDD; cd00077; HDc; 1.
DR InterPro; IPR011006; CheY-like_superfamily.
DR InterPro; IPR021800; DUF3369.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR037522; HD_GYP_dom.
DR InterPro; IPR001789; Sig_transdc_resp-reg_receiver.
DR Pfam; PF11849; DUF3369; 1.
DR SMART; SM00471; HDc; 1.
DR SUPFAM; SSF52172; SSF52172; 1.
DR PROSITE; PS51832; HD_GYP; 1.
DR PROSITE; PS50110; RESPONSE_REGULATORY; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Manganese; Metal-binding; Phosphoprotein; Reference proteome.
FT CHAIN 1..522
FT /note="3'3'-cGAMP-specific phosphodiesterase 2"
FT /id="PRO_0000435353"
FT DOMAIN 36..160
FT /note="Response regulatory"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169"
FT DOMAIN 325..522
FT /note="HD-GYP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01176"
FT ACT_SITE 386
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT BINDING 382
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT BINDING 383
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT BINDING 383
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT BINDING 411
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT BINDING 437
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT BINDING 438
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT BINDING 466
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9KL18"
FT MOD_RES 91
FT /note="4-aspartylphosphate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169"
FT MUTAGEN 382..383
FT /note="HD->AA: Loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:25837739"
SQ SEQUENCE 522 AA; 59713 MW; 4E11AAD179AE3106 CRC64;
MKWFKYGDGM DLFADMRQEA AGEKERVVMH SQEPWCVLLV DDDEQMHQIT RLALTGFKFQ
NRPLELISVL SGLEARKVMA ERSDIALALV DVVMETEHAG LDLVRYIREE LQNRQVRLVL
RTGQAGQAPE DRVIKEYEID DYKEKTELTT QKLRTLLYSM LRAYRDLCLI EDQKLGLSHV
IEASANVQNT KSLQSYATAV LNQLTSLLKL HASAFYCVAT PCPDSEKCNA LTVATTAERV
ELYVESPFKG LPEDVQRRCK EVLSQRTTRD YGDAYVFFKQ DERGVDSVLY VGFEQELSEL
DRKLLEIYMY NIGLTFENIN LMVDLRETSK ELVYNLANAV EARSRETGAH VQRVALYCER
LAHLYGLAES EADMIKNASP LHDVGKVAIP DSILHKPGKL DAQEWAIMQK HVEYGVEILN
RSKRRLMQVA KEIAATHHEK WDGSGYPNRL QGDDIPISGR ITAIADVFDA LGAKRSYKDP
WTDEQIREEL MAQKGRHFEP KLVELLLEHW DEFIAIRASL PD
