LEP_MYCTU
ID LEP_MYCTU Reviewed; 294 AA.
AC P9WKA1; L0TAZ5; Q10789;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 41.
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=Rv2903c; ORFNames=MTCY274.34c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [4]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=22427625; DOI=10.1128/jb.00224-12;
RA Ollinger J., O'Malley T., Ahn J., Odingo J., Parish T.;
RT "Inhibition of the sole type I signal peptidase of Mycobacterium
RT tuberculosis is bactericidal under replicating and nonreplicating
RT conditions.";
RL J. Bacteriol. 194:2614-2619(2012).
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 Evidence={ECO:0000269|PubMed:22427625};
CC -!- ACTIVITY REGULATION: Inhibited by 1-(2,5-dichlorophenyl)-3-
CC (dimethylamino)propan-1-one (MD3). {ECO:0000269|PubMed:22427625}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type II
CC membrane protein {ECO:0000250}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the peptidase S26 family. {ECO:0000305}.
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DR EMBL; AL123456; CCP45705.1; -; Genomic_DNA.
DR PIR; B70927; B70927.
DR RefSeq; NP_217419.1; NC_000962.3.
DR RefSeq; WP_003414715.1; NZ_NVQJ01000006.1.
DR AlphaFoldDB; P9WKA1; -.
DR SMR; P9WKA1; -.
DR STRING; 83332.Rv2903c; -.
DR MEROPS; S26.024; -.
DR PaxDb; P9WKA1; -.
DR DNASU; 887157; -.
DR GeneID; 45426890; -.
DR GeneID; 887157; -.
DR KEGG; mtu:Rv2903c; -.
DR TubercuList; Rv2903c; -.
DR eggNOG; COG0681; Bacteria.
DR OMA; HGCNGCV; -.
DR PhylomeDB; P9WKA1; -.
DR BRENDA; 3.4.21.89; 3445.
DR BRENDA; 3.4.22.46; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005887; C:integral component of plasma membrane; HDA:MTBBASE.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0006465; P:signal peptide processing; IBA:GO_Central.
DR CDD; cd06530; S26_SPase_I; 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; IPR019756; Pept_S26A_signal_pept_1_Ser-AS.
DR InterPro; IPR019533; Peptidase_S26.
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; PS00761; SPASE_I_3; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Hydrolase; Membrane; Protease; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..294
FT /note="Signal peptidase I"
FT /id="PRO_0000109511"
FT TOPO_DOM 1..66
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 67..87
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 88..294
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..59
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 96
FT /evidence="ECO:0000305"
FT ACT_SITE 174
FT /evidence="ECO:0000305"
SQ SEQUENCE 294 AA; 31880 MW; BBCAE8ADF68F897D CRC64;
MTETTDSPSE RQPGPAEPEL SSRDPDIAGQ VFDAAPFDAA PDADSEGDSK AAKTDEPRPA
KRSTLREFAV LAVIAVVLYY VMLTFVARPY LIPSESMEPT LHGCSTCVGD RIMVDKLSYR
FGSPQPGDVI VFRGPPSWNV GYKSIRSHNV AVRWVQNALS FIGFVPPDEN DLVKRVIAVG
GQTVQCRSDT GLTVNGRPLK EPYLDPATMM ADPSIYPCLG SEFGPVTVPP GRVWVMGDNR
THSADSRAHC PLLCTDDPLP GTVPVANVIG KARLIVWPPS RWGVVRSVNP QQGR
