LEP_ECOLI
ID LEP_ECOLI Reviewed; 324 AA.
AC P00803; P78098; Q2MAG2;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Signal peptidase I;
DE Short=SPase I;
DE EC=3.4.21.89;
DE AltName: Full=Leader peptidase I;
GN Name=lepB; OrderedLocusNames=b2568, JW2552;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6311837; DOI=10.1016/s0021-9258(17)44342-0;
RA Wolfe P.B., Wickner W., Goodman J.M.;
RT "Sequence of the leader peptidase gene of Escherichia coli and the
RT orientation of leader peptidase in the bacterial envelope.";
RL J. Biol. Chem. 258:12073-12080(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RA Nashimoto H., Saito N.;
RL Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP TOPOLOGY.
RX PubMed=16453726;
RA von Heijne G.;
RT "The distribution of positively charged residues in bacterial inner
RT membrane proteins correlates with the trans-membrane topology.";
RL EMBO J. 5:3021-3027(1986).
RN [6]
RP TOPOLOGY.
RX PubMed=2202591; DOI=10.1002/j.1460-2075.1990.tb07458.x;
RA Bilgin N., Lee J.I., Zhu H.Y., Dalbey R., von Heijne G.;
RT "Mapping of catalytically important domains in Escherichia coli leader
RT peptidase.";
RL EMBO J. 9:2717-2722(1990).
RN [7]
RP MUTAGENESIS, AND ACTIVE SITES.
RX PubMed=1618816; DOI=10.1016/s0021-9258(18)42186-2;
RA Sung M., Dalbey R.E.;
RT "Identification of potential active-site residues in the Escherichia coli
RT leader peptidase.";
RL J. Biol. Chem. 267:13154-13159(1992).
RN [8]
RP MUTAGENESIS.
RC STRAIN=HJM114, and IT41;
RX PubMed=1546969; DOI=10.1042/bj2820539;
RA Black M.T., Munn J.G.R., Allsop A.E.;
RT "On the catalytic mechanism of prokaryotic leader peptidase 1.";
RL Biochem. J. 282:539-543(1992).
RN [9]
RP MUTAGENESIS, AND ACTIVE SITES.
RX PubMed=8394311; DOI=10.1128/jb.175.16.4957-4961.1993;
RA Black M.T.;
RT "Evidence that the catalytic activity of prokaryote leader peptidase
RT depends upon the operation of a serine-lysine catalytic dyad.";
RL J. Bacteriol. 175:4957-4961(1993).
RN [10]
RP TOPOLOGY.
RX PubMed=2551889; DOI=10.1128/jb.171.10.5536-5541.1989;
RA San Millan J.L., Boyd D., Dalbey R., Wickner W., Beckwith J.;
RT "Use of phoA fusions to study the topology of the Escherichia coli inner
RT membrane protein leader peptidase.";
RL J. Bacteriol. 171:5536-5541(1989).
RN [11]
RP TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=15919996; DOI=10.1126/science.1109730;
RA Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G.;
RT "Global topology analysis of the Escherichia coli inner membrane
RT proteome.";
RL Science 308:1321-1323(2005).
RN [12]
RP SUBCELLULAR LOCATION.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=21778229; DOI=10.1074/jbc.m111.245696;
RA Fontaine F., Fuchs R.T., Storz G.;
RT "Membrane localization of small proteins in Escherichia coli.";
RL J. Biol. Chem. 286:32464-32474(2011).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 77-324.
RX PubMed=9823901; DOI=10.1038/24196;
RA Paetzel M., Dalbey R.E., Strynadka N.C.;
RT "Crystal structure of a bacterial signal peptidase in complex with a beta-
RT lactam inhibitor.";
RL Nature 396:186-190(1998).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of hydrophobic, N-terminal signal or leader sequences
CC from secreted and periplasmic proteins.; EC=3.4.21.89;
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000269|PubMed:21778229}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:21778229}.
CC -!- SIMILARITY: Belongs to the peptidase S26 family. {ECO:0000305}.
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DR EMBL; K00426; AAA24064.1; -; Genomic_DNA.
DR EMBL; D64044; BAA10915.1; -; Genomic_DNA.
DR EMBL; U00096; AAC75621.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE76744.1; -; Genomic_DNA.
DR PIR; G65034; ZPECS.
DR RefSeq; NP_417063.1; NC_000913.3.
DR RefSeq; WP_000002541.1; NZ_STEB01000011.1.
DR PDB; 1B12; X-ray; 1.95 A; A/B/C/D=77-324.
DR PDB; 1KN9; X-ray; 2.40 A; A/B/C/D=77-324.
DR PDB; 1T7D; X-ray; 2.47 A; A/B=76-324.
DR PDB; 3IIQ; X-ray; 2.00 A; A/B=77-324.
DR PDB; 3S04; X-ray; 2.44 A; A/B=76-324.
DR PDB; 6B88; X-ray; 2.41 A; A/B=78-324.
DR PDBsum; 1B12; -.
DR PDBsum; 1KN9; -.
DR PDBsum; 1T7D; -.
DR PDBsum; 3IIQ; -.
DR PDBsum; 3S04; -.
DR PDBsum; 6B88; -.
DR AlphaFoldDB; P00803; -.
DR SMR; P00803; -.
DR BioGRID; 4259467; 112.
DR STRING; 511145.b2568; -.
DR BindingDB; P00803; -.
DR ChEMBL; CHEMBL4470; -.
DR DrugBank; DB06904; (5S,6S)-6-[(R)ACETOXYETH-2-YL]-PENEM-3-CARBOXYLATEPROPANE.
DR DrugBank; DB02080; 1-{2-[2-(2-Methoxyethoxy)Ethoxy]Ethoxy}-4-(1,1,3,3-Tetramethylbutyl)Benzene.
DR DrugBank; DB01934; Arylomycin A2.
DR MEROPS; S26.001; -.
DR TCDB; 9.B.391.1.3; the eukaryotic inner membrane peptidase complex (impc) family.
DR jPOST; P00803; -.
DR PaxDb; P00803; -.
DR PRIDE; P00803; -.
DR EnsemblBacteria; AAC75621; AAC75621; b2568.
DR EnsemblBacteria; BAE76744; BAE76744; BAE76744.
DR GeneID; 947040; -.
DR KEGG; ecj:JW2552; -.
DR KEGG; eco:b2568; -.
DR PATRIC; fig|1411691.4.peg.4166; -.
DR EchoBASE; EB0525; -.
DR eggNOG; COG0681; Bacteria.
DR HOGENOM; CLU_028723_1_1_6; -.
DR InParanoid; P00803; -.
DR OMA; SDSRFWG; -.
DR PhylomeDB; P00803; -.
DR BioCyc; EcoCyc:EG10530-MON; -.
DR BioCyc; MetaCyc:EG10530-MON; -.
DR BRENDA; 3.4.21.89; 2026.
DR SABIO-RK; P00803; -.
DR EvolutionaryTrace; P00803; -.
DR PRO; PR:P00803; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IDA:EcoliWiki.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:EcoCyc.
DR GO; GO:0005886; C:plasma membrane; IDA:EcoliWiki.
DR GO; GO:0004175; F:endopeptidase activity; IDA:EcoCyc.
DR GO; GO:0008233; F:peptidase activity; IDA:EcoliWiki.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IMP:EcoCyc.
DR GO; GO:0016485; P:protein processing; IMP:EcoliWiki.
DR GO; GO:0006508; P:proteolysis; IDA:EcoliWiki.
DR GO; GO:0006465; P:signal peptide processing; IDA:EcoCyc.
DR CDD; cd06530; S26_SPase_I; 1.
DR Gene3D; 2.170.230.10; -; 1.
DR InterPro; IPR036286; LexA/Signal_pep-like_sf.
DR InterPro; IPR000223; Pept_S26A_signal_pept_1.
DR InterPro; IPR019758; Pept_S26A_signal_pept_1_CS.
DR InterPro; IPR019757; Pept_S26A_signal_pept_1_Lys-AS.
DR InterPro; IPR019756; Pept_S26A_signal_pept_1_Ser-AS.
DR InterPro; IPR019533; Peptidase_S26.
DR InterPro; IPR019766; Sign_pep_all-beta_subdom.
DR PANTHER; PTHR43390; PTHR43390; 1.
DR Pfam; PF10502; Peptidase_S26; 1.
DR PRINTS; PR00727; LEADERPTASE.
DR SUPFAM; SSF51306; SSF51306; 1.
DR TIGRFAMs; TIGR02227; sigpep_I_bact; 1.
DR PROSITE; PS00501; SPASE_I_1; 1.
DR PROSITE; PS00760; SPASE_I_2; 1.
DR PROSITE; PS00761; SPASE_I_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell inner membrane; Cell membrane; Disulfide bond;
KW Hydrolase; Membrane; Protease; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..324
FT /note="Signal peptidase I"
FT /id="PRO_0000109506"
FT TOPO_DOM 1..3
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 4..22
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 23..58
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 59..77
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 78..324
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT ACT_SITE 91
FT ACT_SITE 146
FT MOD_RES 1
FT /note="Blocked amino end (Met)"
FT /evidence="ECO:0000269|PubMed:6311837"
FT DISULFID 171..177
FT MUTAGEN 62
FT /note="E->V: Indifferent."
FT MUTAGEN 78
FT /note="R->E,N,L: Indifferent."
FT MUTAGEN 91
FT /note="S->A: Loss of activity."
FT MUTAGEN 125
FT /note="H->N: Indifferent."
FT MUTAGEN 128
FT /note="R->Q: Small effect."
FT MUTAGEN 130
FT /note="D->A: Indifferent."
FT MUTAGEN 144
FT /note="Y->F: Indifferent."
FT MUTAGEN 146
FT /note="K->M,D,G,S: Loss of activity."
FT MUTAGEN 147
FT /note="R->Q: Small effect."
FT MUTAGEN 154
FT /note="D->A: Loss of activity."
FT MUTAGEN 154
FT /note="D->N: Indifferent."
FT MUTAGEN 159
FT /note="D->N: Small effect."
FT MUTAGEN 171
FT /note="C->A: Indifferent."
FT MUTAGEN 177
FT /note="C->A: Indifferent."
FT MUTAGEN 236
FT /note="H->N: Indifferent."
FT MUTAGEN 269
FT /note="Y->F: Indifferent."
FT MUTAGEN 274
FT /note="D->A: Indifferent."
FT MUTAGEN 276
FT /note="R->Q: Small effect."
FT MUTAGEN 281
FT /note="D->A: Indifferent."
FT MUTAGEN 283
FT /note="R->Q: Small effect."
FT CONFLICT 42..43
FT /note="AG -> R (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="T -> N (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 183
FT /note="V -> A (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
FT STRAND 82..86
FT /evidence="ECO:0007829|PDB:1B12"
FT TURN 91..95
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 100..112
FT /evidence="ECO:0007829|PDB:1B12"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 119..123
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 131..135
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 142..150
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 155..159
FT /evidence="ECO:0007829|PDB:1B12"
FT TURN 160..163
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 164..168
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:1T7D"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 189..198
FT /evidence="ECO:0007829|PDB:1B12"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 205..211
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:1T7D"
FT STRAND 221..231
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 234..240
FT /evidence="ECO:0007829|PDB:1B12"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 268..272
FT /evidence="ECO:0007829|PDB:1B12"
FT HELIX 282..285
FT /evidence="ECO:0007829|PDB:1B12"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 293..304
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 310..312
FT /evidence="ECO:0007829|PDB:1B12"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:3IIQ"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:1B12"
SQ SEQUENCE 324 AA; 35960 MW; 9419710D7212E660 CRC64;
MANMFALILV IATLVTGILW CVDKFFFAPK RRERQAAAQA AAGDSLDKAT LKKVAPKPGW
LETGASVFPV LAIVLIVRSF IYEPFQIPSG SMMPTLLIGD FILVEKFAYG IKDPIYQKTL
IETGHPKRGD IVVFKYPEDP KLDYIKRAVG LPGDKVTYDP VSKELTIQPG CSSGQACENA
LPVTYSNVEP SDFVQTFSRR NGGEATSGFF EVPKNETKEN GIRLSERKET LGDVTHRILT
VPIAQDQVGM YYQQPGQQLA TWIVPPGQYF MMGDNRDNSA DSRYWGFVPE ANLVGRATAI
WMSFDKQEGE WPTGLRLSRI GGIH
