SUBT_BACSU
ID SUBT_BACSU Reviewed; 381 AA.
AC P04189; O07613; P70989;
DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 3.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Subtilisin E;
DE EC=3.4.21.62;
DE Flags: Precursor;
GN Name=aprE; Synonyms=apr, aprA, sprE; OrderedLocusNames=BSU10300;
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;
RX PubMed=6427178; DOI=10.1128/jb.158.2.411-418.1984;
RA Stahl M.L., Ferrari E.;
RT "Replacement of the Bacillus subtilis subtilisin structural gene with an In
RT vitro-derived deletion mutation.";
RL J. Bacteriol. 158:411-418(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9579061; DOI=10.1099/00221287-144-4-859;
RA Noback M.A., Holsappel S., Kiewiet R., Terpstra P., Wambutt R., Wedler H.,
RA Venema G., Bron S.;
RT "The 172 kb prkA-addAB region from 83 degrees to 97 degrees of the Bacillus
RT subtilis chromosome contains several dysfunctional genes, the glyB marker,
RT many genes encoding transporter proteins, and the ubiquitous hit gene.";
RL Microbiology 144:859-875(1998).
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 SEQUENCE REVISION TO 27 AND 191.
RX PubMed=19383706; DOI=10.1099/mic.0.027839-0;
RA Barbe V., Cruveiller S., Kunst F., Lenoble P., Meurice G., Sekowska A.,
RA Vallenet D., Wang T., Moszer I., Medigue C., Danchin A.;
RT "From a consortium sequence to a unified sequence: the Bacillus subtilis
RT 168 reference genome a decade later.";
RL Microbiology 155:1758-1775(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-156.
RC STRAIN=168 / PY79;
RX PubMed=6322190; DOI=10.1073/pnas.81.4.1184;
RA Wong S.L., Price C.W., Goldfarb D.S., Doi R.H.;
RT "The subtilisin E gene of Bacillus subtilis is transcribed from a sigma 37
RT promoter in vivo.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:1184-1188(1984).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-156.
RC STRAIN=168 / PY79;
RX PubMed=3108260; DOI=10.1016/s0021-9258(18)47646-6;
RA Ikemura H., Takagi H., Inouye M.;
RT "Requirement of pro-sequence for the production of active subtilisin E in
RT Escherichia coli.";
RL J. Biol. Chem. 262:7859-7864(1987).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 113-323.
RC STRAIN=RT-5;
RX PubMed=7589571; DOI=10.1016/0014-5793(95)01145-5;
RA Kamal M., Hoeoeg J.-O., Kaiser R., Shafqat J., Razzaki T., Zaidi Z.H.,
RA Joernvall H.;
RT "Isolation, characterization and structure of subtilisin from a
RT thermostable Bacillus subtilis isolate.";
RL FEBS Lett. 374:363-366(1995).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-13.
RC STRAIN=168;
RX PubMed=2496113; DOI=10.1128/jb.171.5.2657-2665.1989;
RA Park S.S., Wong S.L., Wang L.F., Doi R.H.;
RT "Bacillus subtilis subtilisin gene (aprE) is expressed from a sigma A
RT (sigma 43) promoter in vitro and in vivo.";
RL J. Bacteriol. 171:2657-2665(1989).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-8.
RX PubMed=2447063; DOI=10.1128/jb.170.1.296-300.1988;
RA Henner D.J., Ferrari E., Perego M., Hoch J.A.;
RT "Location of the targets of the hpr-97, sacU32(Hy), and sacQ36(Hy)
RT mutations in upstream regions of the subtilisin promoter.";
RL J. Bacteriol. 170:296-300(1988).
RN [10]
RP PROTEIN SEQUENCE OF 30-54, AND SIGNAL SEQUENCE CLEAVAGE SITE.
RC STRAIN=168 / DB104;
RX PubMed=3090033; DOI=10.1016/s0021-9258(18)67507-6;
RA Wong S.L., Doi R.H.;
RT "Determination of the signal peptidase cleavage site in the
RT preprosubtilisin of Bacillus subtilis.";
RL J. Biol. Chem. 261:10176-10181(1986).
RN [11]
RP DOMAIN, AND MUTAGENESIS OF ASP-138.
RX PubMed=2657436; DOI=10.1038/339483a0;
RA Zhu X.L., Ohta Y., Jordan F., Inouye M.;
RT "Pro-sequence of subtilisin can guide the refolding of denatured subtilisin
RT in an intermolecular process.";
RL Nature 339:483-484(1989).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF MUTANT CYS-327 OF MATURE
RP SUBTILISIN IN COMPLEX WITH PROPEPTIDE AND CALCIUM IONS, AND COFACTOR.
RC STRAIN=168;
RX PubMed=9811547; DOI=10.1006/jmbi.1998.2161;
RA Jain S.C., Shinde U., Li Y., Inouye M., Berman H.M.;
RT "The crystal structure of an autoprocessed Ser221Cys-subtilisin E-
RT propeptide complex at 2.0-A resolution.";
RL J. Mol. Biol. 284:137-144(1998).
CC -!- FUNCTION: Subtilisin is an extracellular alkaline serine protease, it
CC catalyzes the hydrolysis of proteins and peptide amides.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins with broad specificity for peptide
CC bonds, and a preference for a large uncharged residue in P1.
CC Hydrolyzes peptide amides.; EC=3.4.21.62;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:9811547};
CC Note=Binds 2 calcium ions per subunit. {ECO:0000269|PubMed:9811547};
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- DOMAIN: The propeptide functions as an intramolecular chaperone which
CC is essential for the correct folding of the protease domain but is not
CC required for enzymatic function of the folded protein. It is
CC autoprocessed and degraded after completion of the folding process.
CC {ECO:0000269|PubMed:2657436}.
CC -!- MISCELLANEOUS: Secretion of subtilisin is associated with onset of
CC sporulation, and many mutations which block sporulation at early stages
CC affect expression levels of subtilisin. However, subtilisin is not
CC necessary for normal sporulation.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. {ECO:0000305}.
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DR EMBL; K01988; AAA22742.1; -; Genomic_DNA.
DR EMBL; Y14083; CAA74536.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB12870.2; -; Genomic_DNA.
DR EMBL; K01443; AAA22814.1; -; Genomic_DNA.
DR EMBL; M16639; AAA22744.1; -; Genomic_DNA.
DR EMBL; M31060; AAA22246.1; -; Genomic_DNA.
DR EMBL; M19125; AAA22245.1; -; Genomic_DNA.
DR PIR; A00972; SUBSI.
DR RefSeq; NP_388911.2; NC_000964.3.
DR RefSeq; WP_003233171.1; NZ_JNCM01000035.1.
DR RefSeq; WP_009966941.1; NZ_CM000487.1.
DR PDB; 1SCJ; X-ray; 2.00 A; A=107-381, B=36-106.
DR PDB; 3WHI; X-ray; 2.40 A; A/B=30-381.
DR PDB; 6O44; X-ray; 1.83 A; A/B=107-381.
DR PDB; 6PAK; X-ray; 1.98 A; A/B=107-381.
DR PDBsum; 1SCJ; -.
DR PDBsum; 3WHI; -.
DR PDBsum; 6O44; -.
DR PDBsum; 6PAK; -.
DR AlphaFoldDB; P04189; -.
DR BMRB; P04189; -.
DR SMR; P04189; -.
DR STRING; 224308.BSU10300; -.
DR MEROPS; I09.001; -.
DR MEROPS; S08.036; -.
DR PaxDb; P04189; -.
DR PRIDE; P04189; -.
DR EnsemblBacteria; CAB12870; CAB12870; BSU_10300.
DR GeneID; 939313; -.
DR KEGG; bsu:BSU10300; -.
DR PATRIC; fig|224308.179.peg.1106; -.
DR eggNOG; COG1404; Bacteria.
DR InParanoid; P04189; -.
DR OMA; SGQYSWI; -.
DR PhylomeDB; P04189; -.
DR BioCyc; BSUB:BSU10300-MON; -.
DR BRENDA; 3.4.21.62; 658.
DR SABIO-RK; P04189; -.
DR EvolutionaryTrace; P04189; -.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0030435; P:sporulation resulting in formation of a cellular spore; IEA:UniProtKB-KW.
DR CDD; cd07477; Peptidases_S8_Subtilisin_subset; 1.
DR Gene3D; 3.30.70.80; -; 1.
DR Gene3D; 3.40.50.200; -; 1.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR InterPro; IPR023827; Peptidase_S8_Asp-AS.
DR InterPro; IPR022398; Peptidase_S8_His-AS.
DR InterPro; IPR023828; Peptidase_S8_Ser-AS.
DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR InterPro; IPR010259; S8pro/Inhibitor_I9.
DR InterPro; IPR037045; S8pro/Inhibitor_I9_sf.
DR InterPro; IPR034202; Subtilisin_Carlsberg-like.
DR Pfam; PF05922; Inhibitor_I9; 1.
DR Pfam; PF00082; Peptidase_S8; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF52743; SSF52743; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
DR PROSITE; PS00136; SUBTILASE_ASP; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Calcium; Direct protein sequencing;
KW Hydrolase; Metal-binding; Protease; Reference proteome; Secreted;
KW Serine protease; Signal; Sporulation; Zymogen.
FT SIGNAL 1..29
FT /evidence="ECO:0000269|PubMed:3090033"
FT PROPEP 30..106
FT /id="PRO_0000027187"
FT CHAIN 107..381
FT /note="Subtilisin E"
FT /id="PRO_0000027188"
FT DOMAIN 38..103
FT /note="Inhibitor I9"
FT /evidence="ECO:0000255"
FT DOMAIN 111..380
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 138
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240,
FT ECO:0000269|PubMed:9811547"
FT ACT_SITE 170
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240,
FT ECO:0000269|PubMed:9811547"
FT ACT_SITE 327
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240,
FT ECO:0000269|PubMed:9811547"
FT BINDING 108
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9811547"
FT BINDING 147
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9811547"
FT BINDING 181
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9811547"
FT BINDING 183
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9811547"
FT BINDING 185
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9811547"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9811547"
FT BINDING 275
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9811547"
FT BINDING 277
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9811547"
FT BINDING 280
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9811547"
FT BINDING 303
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9811547"
FT MUTAGEN 138
FT /note="D->N: Prevents intramolecular processing to an
FT active enzyme."
FT /evidence="ECO:0000269|PubMed:2657436"
FT CONFLICT 27
FT /note="A -> V (in Ref. 2; CAA74536)"
FT /evidence="ECO:0000305"
FT CONFLICT 191
FT /note="A -> S (in Ref. 1; AAA22742, 2; CAA74536 and 7)"
FT /evidence="ECO:0000305"
FT STRAND 37..43
FT /evidence="ECO:0007829|PDB:1SCJ"
FT STRAND 45..48
FT /evidence="ECO:0007829|PDB:1SCJ"
FT HELIX 52..60
FT /evidence="ECO:0007829|PDB:1SCJ"
FT TURN 61..63
FT /evidence="ECO:0007829|PDB:1SCJ"
FT STRAND 65..69
FT /evidence="ECO:0007829|PDB:1SCJ"
FT STRAND 71..80
FT /evidence="ECO:0007829|PDB:1SCJ"
FT HELIX 82..89
FT /evidence="ECO:0007829|PDB:1SCJ"
FT STRAND 94..99
FT /evidence="ECO:0007829|PDB:1SCJ"
FT STRAND 102..105
FT /evidence="ECO:0007829|PDB:1SCJ"
FT HELIX 112..116
FT /evidence="ECO:0007829|PDB:6O44"
FT HELIX 119..125
FT /evidence="ECO:0007829|PDB:6O44"
FT STRAND 133..139
FT /evidence="ECO:0007829|PDB:6O44"
FT STRAND 150..155
FT /evidence="ECO:0007829|PDB:6O44"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:6O44"
FT HELIX 170..179
FT /evidence="ECO:0007829|PDB:6O44"
FT STRAND 182..186
FT /evidence="ECO:0007829|PDB:6O44"
FT STRAND 194..200
FT /evidence="ECO:0007829|PDB:6O44"
FT STRAND 206..209
FT /evidence="ECO:0007829|PDB:1SCJ"
FT HELIX 210..222
FT /evidence="ECO:0007829|PDB:6O44"
FT STRAND 226..230
FT /evidence="ECO:0007829|PDB:6O44"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:6O44"
FT HELIX 239..250
FT /evidence="ECO:0007829|PDB:6O44"
FT STRAND 254..258
FT /evidence="ECO:0007829|PDB:6O44"
FT TURN 274..276
FT /evidence="ECO:0007829|PDB:6O44"
FT STRAND 280..286
FT /evidence="ECO:0007829|PDB:6O44"
FT STRAND 304..307
FT /evidence="ECO:0007829|PDB:6O44"
FT STRAND 309..315
FT /evidence="ECO:0007829|PDB:6O44"
FT TURN 316..318
FT /evidence="ECO:0007829|PDB:6O44"
FT STRAND 319..323
FT /evidence="ECO:0007829|PDB:6O44"
FT HELIX 326..343
FT /evidence="ECO:0007829|PDB:6O44"
FT HELIX 349..358
FT /evidence="ECO:0007829|PDB:6O44"
FT HELIX 366..369
FT /evidence="ECO:0007829|PDB:6O44"
FT HELIX 376..379
FT /evidence="ECO:0007829|PDB:6O44"
SQ SEQUENCE 381 AA; 39479 MW; 5C8A4B0E42FCE83D CRC64;
MRSKKLWISL LFALTLIFTM AFSNMSAQAA GKSSTEKKYI VGFKQTMSAM SSAKKKDVIS
EKGGKVQKQF KYVNAAAATL DEKAVKELKK DPSVAYVEED HIAHEYAQSV PYGISQIKAP
ALHSQGYTGS NVKVAVIDSG IDSSHPDLNV RGGASFVPSE TNPYQDGSSH GTHVAGTIAA
LNNSIGVLGV APSASLYAVK VLDSTGSGQY SWIINGIEWA ISNNMDVINM SLGGPTGSTA
LKTVVDKAVS SGIVVAAAAG NEGSSGSTST VGYPAKYPST IAVGAVNSSN QRASFSSAGS
ELDVMAPGVS IQSTLPGGTY GAYNGTSMAT PHVAGAAALI LSKHPTWTNA QVRDRLESTA
TYLGNSFYYG KGLINVQAAA Q
