ID   THER_ALIAC              Reviewed;         546 AA.
AC   Q43880;
DT   26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   03-MAY-2023, entry version 93.
DE   RecName: Full=Thermolysin;
DE            EC=3.4.24.27;
DE   AltName: Full=Thermostable neutral proteinase;
DE   Flags: Precursor;
OS   Alicyclobacillus acidocaldarius subsp. acidocaldarius (Bacillus
OS   acidocaldarius).
OC   Bacteria; Bacillota; Bacilli; Bacillales; Alicyclobacillaceae;
OC   Alicyclobacillus.
OX   NCBI_TaxID=1388;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=BT1;
RX   PubMed=7789802; DOI=10.1016/0378-1119(95)00167-5;
RA   Vecerek B., Kyslik P.;
RT   "Cloning and sequencing of the neutral protease-encoding gene from a
RT   thermophilic strain of Bacillus sp.";
RL   Gene 158:147-148(1995).
CC   -!- FUNCTION: Extracellular zinc metalloprotease.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Preferential cleavage: Xaa-|-Leu > Xaa-|-Phe.; EC=3.4.24.27;
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC       Note=Binds 4 Ca(2+) ions per subunit.;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC       Note=Binds 1 zinc ion per subunit.;
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; U07824; AAC43402.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q43880; -.
DR   SMR; Q43880; -.
DR   MEROPS; M04.018; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd09597; M4_TLP; 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; IPR011096; FTP_domain.
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   PANTHER; PTHR33794; BACILLOLYSIN; 1.
DR   PANTHER; PTHR33794:SF3; NEUTRAL PROTEASE B; 1.
DR   Pfam; PF07504; FTP; 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.
PE   1: Evidence at protein level;
KW   Calcium; Hydrolase; Metal-binding; Metalloprotease; Protease; Secreted;
KW   Signal; Zinc; Zymogen.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   PROPEP          26..228
FT                   /note="Activation peptide"
FT                   /id="PRO_0000028584"
FT   CHAIN           229..546
FT                   /note="Thermolysin"
FT                   /id="PRO_0000028585"
FT   ACT_SITE        373
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   ACT_SITE        461
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
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         291
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         368
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         372
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         376
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         396
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         407
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         407
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="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         415
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         417
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         420
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         420
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         423
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
FT   BINDING         424
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
FT   BINDING         427
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
FT   BINDING         430
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   546 AA;  59770 MW;  3AC33A611BD2B071 CRC64;
     MNKRAMLGAI GLAFGLMAWP FGASAKEKSM VWNEQWKTPS FVSGSLLKGE DAPEELVYRY
     LDQEKNTFQL GGQARERLSL IGKQTDELGH TVMRFEQRYR GIPVYGAVLV AHVNDGELSS
     LSGTLIPNLD KRTLKTEAAI SIQQAEMIAK QDVADAVTKE RPAAEEGKPT RLVIYPDGET
     PRLAYEVNVR FLTPVPGNWI YMIDAADGKV LNKWNQMDEA KPGGGQPVAG TSTVGVGRGV
     LGDQKYINTT YSSYYGYYYL QDNTRGSGIF TYDGRNRTVL PGSLWADGDN QFFASYDAAA
     VDAHYYAGVV YDYYKNVHGR LSYDGSNAAI RSTVHYGRGY NNAFWNGSQM VYGDGDGQTF
     LPFSGGIDVV GHELTHAVTD YTAGLVYQNE SGAINEAMSD IFGTLVEFYA NRNPDWEIGE
     DIYTPGIAGD ALRSMSDPAK YGDPDHYSKR YTGTQDNGGV HTNSGIINKA AYLLSQGGVH
     YGVSVTGIGR DKMGKIFYRA LVYYLTPTSN FSQLRAACVQ AAADLYGSTS QEVNSVKQAF
     NAVGVY
//