PGPH_BACSU
ID PGPH_BACSU Reviewed; 711 AA.
AC P46344; P46345; P46346;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Cyclic-di-AMP phosphodiesterase PgpH {ECO:0000303|PubMed:26240071};
DE Short=c-di-AMP phosphodiesterase;
DE EC=3.1.4.59 {ECO:0000250|UniProtKB:A0A0H3GGY3};
GN Name=pgpH {ECO:0000303|PubMed:26240071}; Synonyms=yqfF;
GN OrderedLocusNames=BSU25330;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=168 / JH642;
RX PubMed=8969508; DOI=10.1099/13500872-142-11-3103;
RA Mizuno M., Masuda S., Takemaru K., Hosono S., Sato T., Takeuchi M.,
RA Kobayashi Y.;
RT "Systematic sequencing of the 283 kb 210 degrees-232 degrees region of the
RT Bacillus subtilis genome containing the skin element and many sporulation
RT genes.";
RL Microbiology 142:3103-3111(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ED40;
RA Kim K., Hwang S., Suh J., Song B.-H., Hong S., Kim J.;
RT "Nucleotide sequence upstream of the cdd locus in Bacillus subtilis.";
RL Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9384377; DOI=10.1038/36786;
RA Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA Yoshikawa H., Danchin A.;
RT "The complete genome sequence of the Gram-positive bacterium Bacillus
RT subtilis.";
RL Nature 390:249-256(1997).
RN [4]
RP PROBABLE FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=168;
RX PubMed=26240071; DOI=10.1128/jb.00564-15;
RA Gundlach J., Mehne F.M., Herzberg C., Kampf J., Valerius O., Kaever V.,
RA Stuelke J.;
RT "An essential poison: synthesis and degradation of cyclic di-AMP in
RT Bacillus subtilis.";
RL J. Bacteriol. 197:3265-3274(2015).
CC -!- FUNCTION: Probably has phosphodiesterase (PDE) activity against cyclic-
CC di-AMP (c-di-AMP); may be the major c-di-AMP PDE in the cell
CC (PubMed:26240071). In B.subtilis c-di-AMP is a second messenger that
CC mediates growth, DNA repair and cell wall homeostasis; it is toxic when
CC present in excess (PubMed:26240071). {ECO:0000269|PubMed:26240071}.
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; Evidence={ECO:0000250|UniProtKB:A0A0H3GGY3};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:A0A0H3GGY3};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: In strain 168 grown in minimal medium and
CC glutamate, 3.5-fold increase in c-di-AMP levels, while a double pgpH-
CC gdpP mutant has 4.2-fold increased levels of in c-di-AMP; double
CC mutants die on solid medium after 2 days (PubMed:26240071).
CC {ECO:0000269|PubMed:26240071}.
CC -!- SIMILARITY: Belongs to the PgpH phosphodiesterase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA70040.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAA70041.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAA70042.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; D84432; BAA12478.1; -; Genomic_DNA.
DR EMBL; U29177; AAA70040.1; ALT_FRAME; Genomic_DNA.
DR EMBL; U29177; AAA70041.1; ALT_FRAME; Genomic_DNA.
DR EMBL; U29177; AAA70042.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AL009126; CAB14462.1; -; Genomic_DNA.
DR PIR; E69953; E69953.
DR RefSeq; NP_390411.1; NC_000964.3.
DR RefSeq; WP_010886570.1; NZ_JNCM01000036.1.
DR AlphaFoldDB; P46344; -.
DR SMR; P46344; -.
DR IntAct; P46344; 38.
DR STRING; 224308.BSU25330; -.
DR jPOST; P46344; -.
DR PaxDb; P46344; -.
DR PRIDE; P46344; -.
DR EnsemblBacteria; CAB14462; CAB14462; BSU_25330.
DR GeneID; 937877; -.
DR KEGG; bsu:BSU25330; -.
DR PATRIC; fig|224308.43.peg.2641; -.
DR eggNOG; COG1480; Bacteria.
DR InParanoid; P46344; -.
DR OMA; DFIRTHH; -.
DR PhylomeDB; P46344; -.
DR BioCyc; BSUB:BSU25330-MON; -.
DR BRENDA; 3.1.4.59; 658.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 CDD; cd00077; HDc; 1.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR006674; HD_domain.
DR InterPro; IPR006675; HDIG_dom.
DR InterPro; IPR011624; Metal-dep_PHydrolase_7TM_extra.
DR InterPro; IPR011621; Metal-dep_PHydrolase_7TM_intra.
DR Pfam; PF07698; 7TM-7TMR_HD; 1.
DR Pfam; PF07697; 7TMR-HDED; 1.
DR Pfam; PF01966; HD; 1.
DR SMART; SM00471; HDc; 1.
DR TIGRFAMs; TIGR00277; HDIG; 1.
DR PROSITE; PS51831; HD; 1.
PE 3: Inferred from homology;
KW Cell membrane; Hydrolase; Manganese; Membrane; Metal-binding;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..711
FT /note="Cyclic-di-AMP phosphodiesterase PgpH"
FT /id="PRO_0000049797"
FT TRANSMEM 275..295
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 311..331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 336..356
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 360..380
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 384..404
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 413..433
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 448..468
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 501..643
FT /note="HD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01175"
FT REGION 114..133
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 504
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3GGY3"
FT BINDING 504
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3GGY3"
FT BINDING 533
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3GGY3"
FT BINDING 534
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3GGY3"
FT BINDING 534
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3GGY3"
FT BINDING 570
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3GGY3"
FT BINDING 594
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3GGY3"
FT BINDING 595
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3GGY3"
FT BINDING 621
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3GGY3"
FT BINDING 638
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3GGY3"
FT BINDING 638
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3GGY3"
SQ SEQUENCE 711 AA; 79167 MW; 1E424AB385D6E3B4 CRC64;
MLKKKAKTKS SSKKWSSFKN ARSMHVLLYL LLAAIMFALL FVHVKPETLD LDLFSVSDKT
IYAPATVEDQ KATEEKKQAA EDAVEDQYTL KKEYTDNRID LVSSIFDSIS EVKKSSEEGS
KSPSEKSMVK SVKDKLTSDV NDSISEDSIK TLLKADSEDF SFVRDTVITA VNTVMSSEIP
SDKLSDAKDK VEKELKSNSI PSKYLGAATE IGRFAIIPNY VFDPKATEAK RQEASDNVQQ
VQIKQGQVLV EENDLIDREV YRKLELTGLL NNSNLFKPIS GLLIMIGLFI ATLVYYFEKQ
KQNLKFKNQS ILLFSIITTL LLVIMEVVSL FQKMEYNNIG YLVPIAAGAI LIKLLMNERI
AILGSIILAI CGSMMFNQGV TGTFNYVIGI YYLISGISGV LFLGKHNARS KILQTGLFVA
FINMVVVLSL LLIQNTALSG LEIGTLMLMG VVSGFASSVL IIGLMPFFET GFGILSTMRL
LELSNPNHPL LRKILTETPG TYHHSVMVAN LSEAACEAVG ANGLLARVGA YYHDLGKTKR
PQYFIENQMN IDNPHDKLSP QLSKNIIISH TTDGANMLRS YKFPKELVDI AEQHHGTSLL
KFFYYKAKEK GDQITEEEFR YPGPKPQSKE AAIISVADSV EAAVRSMHNP NPERIEKLVR
GIISDKLQDG QFSECDLTFK ELDTIAKTLC ATLKGIFHSR IEYPEATKKV K
