CTPB_BACSU
ID CTPB_BACSU Reviewed; 480 AA.
AC O35002; Q795D7;
DT 19-JAN-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Carboxy-terminal processing protease CtpB;
DE Short=C-terminal processing protease;
DE EC=3.4.21.102 {ECO:0000269|PubMed:24243021};
DE Flags: Precursor;
GN Name=ctpB; Synonyms=yvjB; OrderedLocusNames=BSU35240;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9570401; DOI=10.1046/j.1365-2958.1998.00747.x;
RA Reizer J., Hoischen C., Titgemeyer F., Rivolta C., Rabus R., Stuelke J.,
RA Karamata D., Saier M.H. Jr., Hillen W.;
RT "A novel protein kinase that controls carbon catabolite repression in
RT bacteria.";
RL Mol. Microbiol. 27:1157-1169(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Lazarevic V., Soldo B., Rivolta C., Reynolds S., Mauel C., Karamata D.;
RT "Nucleotide sequence of the 300-304 chromosomal segment of Bacillus
RT subtilis.";
RL Submitted (NOV-1997) 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 FUNCTION IN SIGMA-K ACTIVATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=168 / PY79;
RX PubMed=14526016; DOI=10.1128/jb.185.20.6051-6056.2003;
RA Pan Q., Losick R., Rudner D.Z.;
RT "A second PDZ-containing serine protease contributes to activation of the
RT sporulation transcription factor sigmaK in Bacillus subtilis.";
RL J. Bacteriol. 185:6051-6056(2003).
RN [5]
RP FUNCTION AS A SPOIVFA PROTEASE, AND DISRUPTION PHENOTYPE.
RC STRAIN=168 / PY79;
RX PubMed=16818230; DOI=10.1016/j.molcel.2006.05.019;
RA Campo N., Rudner D.Z.;
RT "A branched pathway governing the activation of a developmental
RT transcription factor by regulated intramembrane proteolysis.";
RL Mol. Cell 23:25-35(2006).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, CLEAVAGE, CLEAVAGE
RP SITES BY SPOIVB, AND MUTAGENESIS OF 36-ALA--ALA-40.
RC STRAIN=168 / PY79;
RX PubMed=17557826; DOI=10.1128/jb.00399-07;
RA Campo N., Rudner D.Z.;
RT "SpoIVB and CtpB are both forespore signals in the activation of the
RT sporulation transcription factor sigmaK in Bacillus subtilis.";
RL J. Bacteriol. 189:6021-6027(2007).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 44-480 OF WILD-TYPE AND MUTANTS
RP TYR-118; ARG-168 AND ALA-309 IN ACTIVE AND RESTING STATES AND IN COMPLEX
RP WITH PEPTIDE SUBSTRATE, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP SUBSTRATE SPECIFICITY, SUBUNIT, DOMAIN, PROTEOLYTIC AUTO-CLEAVAGE, ACTIVE
RP SITES, SITES, DISRUPTION PHENOTYPE, MUTAGENESIS OF VAL-118; ARG-168;
RP SER-309 AND GLN-338, AND PDZ DOMAIN DELETION MUTANT.
RX PubMed=24243021; DOI=10.1016/j.cell.2013.09.050;
RA Mastny M., Heuck A., Kurzbauer R., Heiduk A., Boisguerin P., Volkmer R.,
RA Ehrmann M., Rodrigues C.D., Rudner D.Z., Clausen T.;
RT "CtpB assembles a gated protease tunnel regulating cell-cell signaling
RT during spore formation in Bacillus subtilis.";
RL Cell 155:647-658(2013).
CC -!- FUNCTION: Involved in the signal transduction pathway leading to the
CC proteolytic activation of the mother cell transcription factor pro-
CC sigma-K during sporulation. The signaling serine protease CtpB triggers
CC pro-sigma-K processing by cleaving the pre-processed regulatory protein
CC SpoIVFA and is necessary for the proper timing of sigma-K activation.
CC {ECO:0000269|PubMed:14526016, ECO:0000269|PubMed:16818230,
CC ECO:0000269|PubMed:17557826, ECO:0000269|PubMed:24243021}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=The enzyme shows specific recognition of a C-terminal
CC tripeptide, Xaa-Yaa-Zaa, in which Xaa is preferably Ala or Leu, Yaa
CC is preferably Ala or Tyr, and Zaa is preferably Ala, but then cleaves
CC at a variable distance from the C-terminus. A typical cleavage is
CC -Ala-Ala-|-Arg-Ala-Ala-Lys-Glu-Asn-Tyr-Ala-Leu-Ala-Ala.;
CC EC=3.4.21.102; Evidence={ECO:0000269|PubMed:24243021};
CC -!- ACTIVITY REGULATION: Activated by peptide binding to the PDZ domain.
CC {ECO:0000269|PubMed:24243021}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:24243021}.
CC -!- INTERACTION:
CC O35002; O35002: ctpB; NbExp=5; IntAct=EBI-5246793, EBI-5246793;
CC O35002; P26936: spoIVFA; NbExp=2; IntAct=EBI-5246793, EBI-5254757;
CC -!- SUBCELLULAR LOCATION: Forespore intermembrane space
CC {ECO:0000269|PubMed:17557826}. Note=Is expressed in both the mother
CC cell and forespore compartments but that synthesis in the forespore is
CC both necessary and sufficient for the proper timing of pro-sigma-K
CC processing.
CC -!- DEVELOPMENTAL STAGE: Is expressed in the forespore under the control of
CC sigma-G, and in the mother cell under the control of sigma-E.
CC {ECO:0000269|PubMed:14526016, ECO:0000269|PubMed:17557826}.
CC -!- DOMAIN: The PDZ domain functions as a gatekeeper to the protease tunnel
CC and defines resting and active conformations of the protease.
CC {ECO:0000269|PubMed:24243021}.
CC -!- PTM: Is cleaved by SpoIVB in vitro and in vivo but this cleavage does
CC not appear to be necessary for CtpB activation. CtpB can also cleave
CC itself in vivo. {ECO:0000269|PubMed:17557826,
CC ECO:0000269|PubMed:24243021}.
CC -!- DISRUPTION PHENOTYPE: Pro-sigma-K processing is delayed by
CC approximately 30 minutes, and sporulation efficiency is reduced
CC approximately two-fold. {ECO:0000269|PubMed:14526016,
CC ECO:0000269|PubMed:16818230, ECO:0000269|PubMed:24243021}.
CC -!- SIMILARITY: Belongs to the peptidase S41A family. {ECO:0000305}.
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DR EMBL; AF017113; AAC67263.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB15541.1; -; Genomic_DNA.
DR PIR; E70042; E70042.
DR RefSeq; NP_391404.1; NC_000964.3.
DR RefSeq; WP_003228041.1; NZ_JNCM01000033.1.
DR PDB; 4C2C; X-ray; 1.90 A; A=44-480.
DR PDB; 4C2D; X-ray; 2.70 A; A/B/C/D=44-480.
DR PDB; 4C2E; X-ray; 1.80 A; A/B=44-480.
DR PDB; 4C2F; X-ray; 2.40 A; A=44-480.
DR PDB; 4C2G; X-ray; 1.90 A; A=44-480, C=29-40.
DR PDB; 4C2H; X-ray; 1.95 A; A/B=44-480.
DR PDBsum; 4C2C; -.
DR PDBsum; 4C2D; -.
DR PDBsum; 4C2E; -.
DR PDBsum; 4C2F; -.
DR PDBsum; 4C2G; -.
DR PDBsum; 4C2H; -.
DR AlphaFoldDB; O35002; -.
DR SMR; O35002; -.
DR IntAct; O35002; 3.
DR STRING; 224308.BSU35240; -.
DR MEROPS; S41.007; -.
DR TCDB; 9.B.174.1.1; the two tunnel gated c-terminal processing protease (ctp) family.
DR PaxDb; O35002; -.
DR PRIDE; O35002; -.
DR EnsemblBacteria; CAB15541; CAB15541; BSU_35240.
DR GeneID; 936678; -.
DR KEGG; bsu:BSU35240; -.
DR PATRIC; fig|224308.179.peg.3814; -.
DR eggNOG; COG0793; Bacteria.
DR eggNOG; COG3409; Bacteria.
DR InParanoid; O35002; -.
DR OMA; DPHSSYY; -.
DR PhylomeDB; O35002; -.
DR BioCyc; BSUB:BSU35240-MON; -.
DR BRENDA; 3.4.21.102; 658.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0030288; C:outer membrane-bounded periplasmic space; IBA:GO_Central.
DR GO; GO:0004175; F:endopeptidase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0042277; F:peptide binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0006518; P:peptide metabolic process; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IMP:UniProtKB.
DR GO; GO:0030435; P:sporulation resulting in formation of a cellular spore; IDA:UniProtKB.
DR CDD; cd07560; Peptidase_S41_CPP; 1.
DR Gene3D; 1.10.101.10; -; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR041489; PDZ_6.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR004447; Peptidase_S41A.
DR InterPro; IPR002477; Peptidoglycan-bd-like.
DR InterPro; IPR036365; PGBD-like_sf.
DR InterPro; IPR036366; PGBDSf.
DR InterPro; IPR005151; Tail-specific_protease.
DR Pfam; PF17820; PDZ_6; 1.
DR Pfam; PF03572; Peptidase_S41; 1.
DR Pfam; PF01471; PG_binding_1; 1.
DR SMART; SM00228; PDZ; 1.
DR SMART; SM00245; TSPc; 1.
DR SUPFAM; SSF47090; SSF47090; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF52096; SSF52096; 1.
DR TIGRFAMs; TIGR00225; prc; 1.
DR PROSITE; PS50106; PDZ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Hydrolase; Protease;
KW Reference proteome; Serine protease; Signal; Sporulation.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..480
FT /note="Carboxy-terminal processing protease CtpB"
FT /id="PRO_0000390777"
FT DOMAIN 92..182
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 113..116
FT /note="Peptide binding"
FT /evidence="ECO:0000269|PubMed:24243021"
FT ACT_SITE 309
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:24243021"
FT ACT_SITE 334
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:24243021"
FT ACT_SITE 338
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:24243021"
FT SITE 36..37
FT /note="Cleavage; by SpoIVB, and cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:24243021"
FT SITE 40..41
FT /note="Cleavage; by SpoIVB"
FT SITE 42..43
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:24243021"
FT SITE 168
FT /note="Crucial for substrate binding and protease
FT activation"
FT /evidence="ECO:0000269|PubMed:24243021"
FT MUTAGEN 36..40
FT /note="AAVPA->RAVPR: No cleavage by SpoIVB. No effect on
FT pro-sigma-K processing."
FT /evidence="ECO:0000269|PubMed:17557826"
FT MUTAGEN 92..182
FT /note="Missing: Constitutively active protease with higher
FT activity than wild-type protease and total loss of
FT substrate specificity."
FT /evidence="ECO:0000269|PubMed:24243021"
FT MUTAGEN 118
FT /note="V->Y: Loss of peptide binding to the PDZ domain, but
FT still has residual protease activity. Less than residual
FT protease activity; when associated with A/F-168."
FT /evidence="ECO:0000269|PubMed:24243021"
FT MUTAGEN 168
FT /note="R->A,F: 3- to 5-fold weaker affinity for PDZ ligands
FT and reduced proteolytic activity against pre-processed
FT SpoIVFA substrate. Less than residual protease activity;
FT when associated with Y-118."
FT /evidence="ECO:0000269|PubMed:24243021"
FT MUTAGEN 309
FT /note="S->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:24243021"
FT MUTAGEN 338
FT /note="Q->E: Loss of activity."
FT /evidence="ECO:0000269|PubMed:24243021"
FT HELIX 46..65
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:4C2E"
FT HELIX 72..85
FT /evidence="ECO:0007829|PDB:4C2E"
FT TURN 86..88
FT /evidence="ECO:0007829|PDB:4C2G"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:4C2E"
FT HELIX 97..108
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:4C2D"
FT STRAND 115..121
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 124..130
FT /evidence="ECO:0007829|PDB:4C2E"
FT HELIX 135..139
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 146..150
FT /evidence="ECO:0007829|PDB:4C2E"
FT HELIX 160..167
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 174..180
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 186..193
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 195..198
FT /evidence="ECO:0007829|PDB:4C2C"
FT STRAND 202..209
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 212..219
FT /evidence="ECO:0007829|PDB:4C2E"
FT HELIX 226..239
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 245..248
FT /evidence="ECO:0007829|PDB:4C2E"
FT HELIX 257..264
FT /evidence="ECO:0007829|PDB:4C2E"
FT TURN 265..267
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 284..287
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 299..303
FT /evidence="ECO:0007829|PDB:4C2E"
FT HELIX 310..320
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 336..342
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 344..346
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 348..357
FT /evidence="ECO:0007829|PDB:4C2E"
FT TURN 365..367
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 372..374
FT /evidence="ECO:0007829|PDB:4C2E"
FT HELIX 379..383
FT /evidence="ECO:0007829|PDB:4C2E"
FT HELIX 399..410
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:4C2E"
FT HELIX 424..436
FT /evidence="ECO:0007829|PDB:4C2E"
FT STRAND 443..445
FT /evidence="ECO:0007829|PDB:4C2C"
FT HELIX 447..462
FT /evidence="ECO:0007829|PDB:4C2E"
FT HELIX 464..466
FT /evidence="ECO:0007829|PDB:4C2E"
FT HELIX 468..476
FT /evidence="ECO:0007829|PDB:4C2E"
SQ SEQUENCE 480 AA; 52798 MW; 902B082C85B5CEC4 CRC64;
MNQKIMAVIA AGSMLFGGAG VYAGINLLEM DKPQTAAVPA TAQADSERDK AMDKIEKAYE
LISNEYVEKV DREKLLEGAI QGMLSTLNDP YSVYMDKQTA KQFSDSLDSS FEGIGAEVGM
EDGKIIIVSP FKKSPAEKAG LKPNDEIISI NGESMAGKDL NHAVLKIRGK KGSSVSMKIQ
RPGTKKQLSF RIKRAEIPLE TVFASEKKVQ GHSVGYIAIS TFSEHTAEDF AKALRELEKK
EIEGLVIDVR GNPGGYLQSV EEILKHFVTK DQPYIQIAER NGDKKRYFST LTHKKAYPVN
VITDKGSASA SEILAGALKE AGHYDVVGDT SFGKGTVQQA VPMGDGSNIK LTLYKWLTPN
GNWIHKKGIE PTIAIKQPDY FSAGPLQLKE PLKVDMNNED VKHAQVLLKG LSFDPGREDG
YFSKDMKKAV MAFQDQNKLN KTGVIDTRTA ETLNQQIEKK KSDEKNDLQL QTALKSLFVN
