ID PDEA_LISM4 Reviewed; 657 AA.
AC A0A0H3GCG4;
DT 13-APR-2016, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 1.
DT 27-MAR-2024, entry version 32.
DE RecName: Full=Cyclic-di-AMP phosphodiesterase PdeA {ECO:0000303|PubMed:23716572};
DE Short=c-di-AMP phosphodiesterase;
DE EC=3.1.4.59;
GN Name=pdeA {ECO:0000303|PubMed:23716572}; OrderedLocusNames=LMRG_02481;
OS Listeria monocytogenes serotype 1/2a (strain 10403S).
OC Bacteria; Bacillota; Bacilli; Bacillales; Listeriaceae; Listeria.
OX NCBI_TaxID=393133;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=10403S;
RG The Broad Institute Genome Sequencing Platform;
RG The Broad Institute Genome Sequencing Center for Infectious Disease;
RA Borowsky M., Borodovsky M., Young S.K., Zeng Q., Koehrsen M.,
RA Fitzgerald M., Wiedmann M., Swaminathan B., Lauer P., Portnoy D.,
RA Cossart P., Buchrieser C., Higgins D., Abouelleil A., Alvarado L.,
RA Arachchi H.M., Berlin A., Borenstein D., Brown A., Chapman S.B., Chen Z.,
RA Dunbar C.D., Engels R., Freedman E., Gearin G., Gellesch M., Goldberg J.,
RA Griggs A., Gujja S., Heilman E., Heiman D., Howarth C., Jen D., Larson L.,
RA Lui A., MacDonald J., Mehta T., Montmayeur A., Neiman D., Park D.,
RA Pearson M., Priest M., Richards J., Roberts A., Saif S., Shea T.,
RA Shenoy N., Sisk P., Stolte C., Sykes S., Walk T., White J., Yandava C.,
RA Haas B., Nusbaum C., Birren B.;
RT "The genome sequence of Listeria monocytogenes strain 10403S.";
RL Submitted (APR-2010) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, DOMAIN, AND DISRUPTION PHENOTYPE.
RC STRAIN=10403S;
RX PubMed=23716572; DOI=10.1128/mbio.00282-13;
RA Witte C.E., Whiteley A.T., Burke T.P., Sauer J.D., Portnoy D.A.,
RA Woodward J.J.;
RT "Cyclic di-AMP is critical for Listeria monocytogenes growth, cell wall
RT homeostasis, and establishment of infection.";
RL MBio 4:E00282-E00282(2013).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=10403S / JW06;
RX PubMed=25583510; DOI=10.1073/pnas.1416485112;
RA Huynh T.N., Luo S., Pensinger D., Sauer J.D., Tong L., Woodward J.J.;
RT "An HD-domain phosphodiesterase mediates cooperative hydrolysis of c-di-AMP
RT to affect bacterial growth and virulence.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:E747-E756(2015).
RN [4]
RP FUNCTION, DOMAIN, AND DISRUPTION PHENOTYPE.
RC STRAIN=10403S;
RX PubMed=25965978; DOI=10.1021/jacs.5b00275;
RA Kellenberger C.A., Chen C., Whiteley A.T., Portnoy D.A., Hammond M.C.;
RT "RNA-based fluorescent biosensors for live cell imaging of second messenger
RT cyclic di-AMP.";
RL J. Am. Chem. Soc. 137:6432-6435(2015).
CC -!- FUNCTION: Has phosphodiesterase (PDE) activity against cyclic-di-AMP
CC (c-di-AMP) (PubMed:23716572, PubMed:25965978). Overexpression decreases
CC export of c-di-AMP, leads to slightly increased susceptibility to the
CC antibiotic cefuroxime and somewhat slower growth in macrophages
CC (PubMed:23716572). There are at least 2 PDEs for c-di-AMP in this
CC bacteria (this one and pgpH); this may be the major PDE for
CC intracellular growth in host macrophages (PubMed:25583510). During host
CC infection c-di-AMP is secreted into the host cytoplasm which leads to
CC interferon-beta production and secretion by the host (Probable). c-di-
CC AMP is a second messenger that mediates growth, cell wall stability and
CC virulence (Probable). May monitor cellular heme or NO levels (By
CC similarity). {ECO:0000250|UniProtKB:P37484,
CC ECO:0000269|PubMed:23716572, ECO:0000269|PubMed:25583510,
CC ECO:0000269|PubMed:25965978, ECO:0000305|PubMed:25583510}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',3'-c-di-AMP + H2O = 5'-O-phosphonoadenylyl-(3'->5')-
CC adenosine + H(+); Xref=Rhea:RHEA:54420, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:71500, ChEBI:CHEBI:138171;
CC EC=3.1.4.59;
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000250|UniProtKB:P37484};
CC Note=Binds 1 heme (probably heme b) per subunit.
CC {ECO:0000250|UniProtKB:P37484};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P37484};
CC Note=Binds 2 Mn(2+) per subunit. {ECO:0000250|UniProtKB:P37484};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- DOMAIN: Has a GGDEF domain (residues 175-303) preceded by a PAS-like
CC domain (residues 74-137) which together may have ATPase activity (By
CC similarity). This is followed by a region with a DHH (342-498) and a
CC DHHA1 (592-645) domain which together have c-di-AMP phosphodiesterase
CC activity (PubMed:23716572, PubMed:25965978). The PAS-like domain is
CC important for heme b-binding (By similarity).
CC {ECO:0000250|UniProtKB:P37484, ECO:0000269|PubMed:23716572,
CC ECO:0000269|PubMed:25965978}.
CC -!- DISRUPTION PHENOTYPE: Disruption leads to increased resistance to pH
CC 2.5, transcription of a number of genes is induced (PubMed:23716572).
CC Grows as well as wild-type in culture and in macrophages
CC (PubMed:23716572). Double pdeA-pgpH mutants have slightly defective
CC growth in culture and in macrophages (PubMed:25583510). Single mutant
CC secretes as much c-di-AMP as wild-type (PubMed:23716572,
CC PubMed:25583510). Double pdeA-pgpH mutant secretes about 4-fold more
CC (PubMed:25583510). Single mutant induces 3.5-fold more interferon-beta
CC (IFN-beta) transcription by macrophages (PubMed:23716572,
CC PubMed:25583510). Double pdeA-pgpH mutants induces about 10-fold more
CC IFN-beta (PubMed:25583510). Double mutant is 10(3)-fold less virulent
CC in mice, suggesting increased bacterial c-di-AMP is detrimental to
CC growth within the host (PubMed:25583510). Single mutant has
CC approximately 2-fold increased intracellular levels of c-di-AMP
CC (PubMed:25965978). {ECO:0000269|PubMed:23716572,
CC ECO:0000269|PubMed:25583510, ECO:0000269|PubMed:25965978}.
CC -!- SIMILARITY: Belongs to the GdpP/PdeA phosphodiesterase family.
CC {ECO:0000305}.
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DR EMBL; CP002002; AEO05072.1; -; Genomic_DNA.
DR RefSeq; WP_003721675.1; NC_017544.1.
DR AlphaFoldDB; A0A0H3GCG4; -.
DR SMR; A0A0H3GCG4; -.
DR KEGG; lmt:LMRG_02481; -.
DR HOGENOM; CLU_018278_0_0_9; -.
DR Proteomes; UP000001288; Chromosome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0106409; F:cyclic-di-AMP phosphodiesterase activity; IEA:UniProtKB-EC.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR Gene3D; 3.10.310.30; -; 1.
DR Gene3D; 3.90.1640.10; inorganic pyrophosphatase (n-terminal core); 1.
DR Gene3D; 3.30.450.20; PAS domain; 1.
DR InterPro; IPR001667; DDH_dom.
DR InterPro; IPR038763; DHH_sf.
DR InterPro; IPR003156; DHHA1_dom.
DR InterPro; IPR049553; GdpP-like_PAS.
DR InterPro; IPR014528; GdpP/PdeA.
DR InterPro; IPR000160; GGDEF_dom.
DR PANTHER; PTHR47618; BIFUNCTIONAL OLIGORIBONUCLEASE AND PAP PHOSPHATASE NRNA; 1.
DR PANTHER; PTHR47618:SF2; CYCLIC-DI-AMP PHOSPHODIESTERASE GDPP; 1.
DR Pfam; PF01368; DHH; 1.
DR Pfam; PF02272; DHHA1; 1.
DR Pfam; PF21370; GdpP_PAS; 1.
DR PIRSF; PIRSF026583; YybT; 1.
DR SMART; SM00267; GGDEF; 1.
DR SUPFAM; SSF64182; DHH phosphoesterases; 1.
DR PROSITE; PS50887; GGDEF; 1.
PE 3: Inferred from homology;
KW Cell membrane; Heme; Hydrolase; Iron; Manganese; Membrane; Metal-binding;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..657
FT /note="Cyclic-di-AMP phosphodiesterase PdeA"
FT /id="PRO_0000436052"
FT TRANSMEM 13..35
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 37..53
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 175..303
FT /note="GGDEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00095"
FT REGION 74..137
FT /note="PAS-like"
FT /evidence="ECO:0000305|PubMed:23716572"
FT REGION 342..498
FT /note="DHH"
FT /evidence="ECO:0000305|PubMed:23716572"
FT REGION 592..645
FT /note="DHHA1"
FT /evidence="ECO:0000305|PubMed:23716572"
FT BINDING 347
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P37484"
FT BINDING 351
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P37484"
FT BINDING 353
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P37484"
FT BINDING 422
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P37484"
FT BINDING 422
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P37484"
FT BINDING 446
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P37484"
FT BINDING 501
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P37484"
SQ SEQUENCE 657 AA; 74847 MW; CB9995594BD7DA07 CRC64;
MSGYFQKRML KYPLYGLIAA TIILSVITFF FSWWLSALVV VGGIILTVAM FYFEYRLNED
VQLYVSNLTY RIKRSEEEAL VEMPMGILLY DEHYKIEWVN PFMSKYFDKA ELIGESLEEV
GPEFLDVITG NDEKGIMSIA WRDHRFDTIV KRKERILYLY DRTEYYDLNK KFQANKSVFA
VIFLDNYDEW AQGMDDRRRS ALNNLVTSML TNWAREHRIY LKRISTDRFM AFLTEEMLKR
LEEEKFQILD RIRERTSKQN IPLTLSIGIG YKEDDLIQLA DLAQSSLDLA LGRGGDQVVI
KQPEGKVRFY GGKTNPMEKR TRVRARVISQ ALQELITQSD QVFVMGHRYP DMDVIGSSLG
VMRIAEMNDR NAYVVVEPGK MSPDVKRLMN EIEEYPNVIK NIVTPQVALE NITEKSLLVV
VDTHKPSMVI NKELLDSATN VVVVDHHRRS EEFVGSPVLV YIEPYASSTA ELITELFEYQ
PDLEQVGKIE ATALLSGIVV DTKNFTLRTG SRTFDAASYL RSLGADTILV QQFLKEDITT
FTQRSRLVES LEIYHDGMAI ATGHEDEEFG TVIAAQAADT MLSMEGVQAS FVITLRPDKL
IGISARSLGQ INVQVIMEKL GGGGHLSNAA TQLKDVTIAE AEKQLISAID AYWKGET
//
