ID   NPRE_BACCL              Reviewed;         544 AA.
AC   P23384;
DT   01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1991, sequence version 1.
DT   02-SEP-2026, entry version 110.
DE   RecName: Full=Bacillolysin;
DE            EC=3.4.24.28;
DE   AltName: Full=Thermostable neutral protease;
DE   Flags: Precursor;
GN   Name=npr;
OS   Bacillus caldolyticus.
OC   Bacteria; Bacillati; Bacillota; Bacilli; Caryophanales; Anoxybacillaceae;
OC   Geobacillus; Geobacillus thermoleovorans group.
OX   NCBI_TaxID=1394;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1905714; DOI=10.1128/jb.173.13.4107-4115.1991;
RA   van den Burg B., Enequist H.G., van de Haar M.E., Eijsink V.G.H.,
RA   Stulp B.K., Venema G.;
RT   "A highly thermostable neutral protease from Bacillus caldolyticus: cloning
RT   and expression of the gene in Bacillus subtilis and characterization of the
RT   gene product.";
RL   J. Bacteriol. 173:4107-4115(1991).
CC   -!- FUNCTION: Extracellular zinc metalloprotease.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Similar, but not identical, to that of thermolysin.;
CC         EC=3.4.24.28;
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC       Note=Binds 4 Ca(2+) ions per subunit. {ECO:0000250};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Temperature dependence:
CC         Thermostable.;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- SIMILARITY: Belongs to the peptidase M4 family. {ECO:0000305}.
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DR   EMBL; M63575; AAA22623.1; -; Genomic_DNA.
DR   PIR; A42464; A42464.
DR   SMR; P23384; -.
DR   MEROPS; M04.018; -.
DR   CDD; cd09597; M4_TLP; 1.
DR   FunFam; 1.10.390.10:FF:000012; Thermolysin; 1.
DR   Gene3D; 3.10.170.10; -; 1.
DR   Gene3D; 3.10.450.40; -; 1.
DR   Gene3D; 3.10.450.490; -; 1.
DR   Gene3D; 1.10.390.10; Neutral Protease Domain 2; 1.
DR   InterPro; IPR025711; PepSY.
DR   InterPro; IPR023612; Peptidase_M4.
DR   InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR   InterPro; IPR001570; Peptidase_M4_C_domain.
DR   InterPro; IPR013856; Peptidase_M4_domain.
DR   InterPro; IPR050728; Zinc_Metalloprotease_M4.
DR   PANTHER; PTHR33794; BACILLOLYSIN; 1.
DR   PANTHER; PTHR33794:SF3; NEUTRAL PROTEASE B; 1.
DR   Pfam; PF03413; PepSY; 1.
DR   Pfam; PF01447; Peptidase_M4; 1.
DR   Pfam; PF02868; Peptidase_M4_C; 1.
DR   PRINTS; PR00730; THERMOLYSIN.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR   AlphaFoldDB; P23384; -.
PE   1: Evidence at protein level;
KW   Calcium; Hydrolase; Metal-binding; Metalloprotease; Protease; Secreted;
KW   Signal; Zinc; Zymogen.
FT   SIGNAL          1..25
FT   PROPEP          26..225
FT                   /note="Activation peptide"
FT                   /id="PRO_0000028600"
FT   CHAIN           226..544
FT                   /note="Bacillolysin"
FT                   /id="PRO_0000028601"
FT   ACT_SITE        371
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   ACT_SITE        459
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         285
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         287
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         289
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         366
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         370
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         374
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         394
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         405
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         405
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         411
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         413
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         413
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         415
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         418
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         418
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         421
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
FT   BINDING         422
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
FT   BINDING         425
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
FT   BINDING         428
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   544 AA;  59413 MW;  C551E67ACCA356FD CRC64;
     MNKRAMLGAI GLAFGLMAWP FGASAKGKSM VWNEQWKTPS FVSGSLLGRC SQELVYRYLD
     QEKNTFQLGG QARERLSLIG NKLDELGHTV MRFEQAIAAS LCMGAVLVAH VNDGELSSLS
     GTLIPNLDKR TLKTEAAISI QQAEMIAKQD VADRVTKERP AAEEGKPTRL VIYPDEETPR
     LAYEVNVRFL TPVPGNWIYM IDAADGKVLN KWNQMDEAKP GGAQPVAGTS TVGVGRGVLG
     DQKYINTTYS SYYGYYYLQD NTRGSGIFTY DGRNRTVLPG SLWADGDNQF FASYDAAAVD
     AHYYAGVVYD YYKNVHGRLS YDGSNAAIRS TVHYGRGYNN AFWNGSQMVY GDGDGQTFLP
     FSGGIDVVGH ELTHAVTDYT AGLVYQNESG AINEAMSDIF GTLVEFYANR NPDWEIGEDI
     YTPGVAGDAL RSMSDPAKYG DPDHYSKRYT GTQDNGGVHT NSGIINKAAY LLSQGGVHYG
     VSVTGIGRDK MGKIFYRALV YYLTPTSNFS QLRAACVQAA ADLYGSTSQE VNSVKQAFNA
     VGVY
//