MYCP1_MYCTU
ID MYCP1_MYCTU Reviewed; 446 AA.
AC O05461; F2GDP4; I6YD96; L0TFJ1;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Mycosin-1 {ECO:0000303|PubMed:10974545};
DE EC=3.4.21.- {ECO:0000269|PubMed:20227664};
DE AltName: Full=MycP1 protease {ECO:0000303|PubMed:20227664};
DE Flags: Precursor;
GN Name=mycP1 {ECO:0000303|PubMed:10974545};
GN OrderedLocusNames=Rv3883c {ECO:0000312|EMBL:CCP46712.1};
GN ORFNames=LH57_21150 {ECO:0000312|EMBL:AIR16677.1};
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RA Hazbon M.H., Riojas M.A., Damon A.M., Alalade R.O., Cantwell B.J.,
RA Monaco A., King S., Sohrabi A.;
RT "Phylogenetic analysis of Mycobacterial species using whole genome
RT sequences.";
RL Submitted (SEP-2014) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RC STRAIN=H37Rv;
RX PubMed=10974545; DOI=10.1016/s0378-1119(00)00277-8;
RA Brown G.D., Dave J.A., Gey van Pittius N.C., Stevens L., Ehlers M.R.,
RA Beyers A.D.;
RT "The mycosins of Mycobacterium tuberculosis H37Rv: a family of subtilisin-
RT like serine proteases.";
RL Gene 254:147-155(2000).
RN [4]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=12366866; DOI=10.1186/1471-2180-2-30;
RA Dave J.A., Gey van Pittius N.C., Beyers A.D., Ehlers M.R., Brown G.D.;
RT "Mycosin-1, a subtilisin-like serine protease of Mycobacterium
RT tuberculosis, is cell wall-associated and expressed during infection of
RT macrophages.";
RL BMC Microbiol. 2:30-30(2002).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF SER-332.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=20227664; DOI=10.1016/j.chom.2010.02.006;
RA Ohol Y.M., Goetz D.H., Chan K., Shiloh M.U., Craik C.S., Cox J.S.;
RT "Mycobacterium tuberculosis MycP1 protease plays a dual role in regulation
RT of ESX-1 secretion and virulence.";
RL Cell Host Microbe 7:210-220(2010).
RN [6]
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).
CC -!- FUNCTION: May play a dual role in regulation of ESX-1 secretion and
CC virulence. Acts as a protease that cleaves EspB. Essential for ESX-1
CC function, required for early replication in macrophages and full
CC virulence in mice. {ECO:0000269|PubMed:20227664}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10974545,
CC ECO:0000269|PubMed:12366866}; Single-pass membrane protein
CC {ECO:0000255}. Note=Cell wall-associated. {ECO:0000269|PubMed:10974545,
CC ECO:0000269|PubMed:12366866}.
CC -!- INDUCTION: Constitutively expressed during growth in culture
CC (PubMed:10974545). Induced during growth in macrophages
CC (PubMed:12366866). {ECO:0000269|PubMed:10974545,
CC ECO:0000269|PubMed:12366866}.
CC -!- DISRUPTION PHENOTYPE: Deletion mutant fails to secrete EsxA and EspB
CC and replicates poorly in mice. {ECO:0000269|PubMed:20227664}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be proteolytically processed
CC intracellularly. {ECO:0000305|PubMed:12366866}.
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DR EMBL; CP009480; AIR16677.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP46712.1; -; Genomic_DNA.
DR RefSeq; NP_218400.1; NC_000962.3.
DR RefSeq; WP_003400004.1; NZ_NVQJ01000082.1.
DR AlphaFoldDB; O05461; -.
DR SMR; O05461; -.
DR STRING; 83332.Rv3883c; -.
DR MEROPS; S08.131; -.
DR PaxDb; O05461; -.
DR PRIDE; O05461; -.
DR GeneID; 45427886; -.
DR GeneID; 886217; -.
DR KEGG; mtu:Rv3883c; -.
DR PATRIC; fig|83332.111.peg.4323; -.
DR TubercuList; Rv3883c; -.
DR eggNOG; COG1404; Bacteria.
DR HOGENOM; CLU_011263_13_1_11; -.
DR OMA; WANDYLR; -.
DR PhylomeDB; O05461; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009986; C:cell surface; IDA:MTBBASE.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:MTBBASE.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:MTBBASE.
DR GO; GO:0044003; P:modulation by symbiont of host process; IDA:MTBBASE.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IDA:MTBBASE.
DR GO; GO:0051046; P:regulation of secretion; IDA:MTBBASE.
DR Gene3D; 3.40.50.200; -; 1.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR InterPro; IPR023834; T7SS_pept_S8A_mycosin.
DR Pfam; PF00082; Peptidase_S8; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF52743; SSF52743; 1.
DR TIGRFAMs; TIGR03921; T7SS_mycosin; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Hydrolase; Membrane; Protease; Reference proteome;
KW Serine protease; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..446
FT /note="Mycosin-1"
FT /id="PRO_5007696644"
FT TRANSMEM 419..439
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 64..387
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT REGION 24..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 90
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 121
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 332
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT MUTAGEN 332
FT /note="S->A: Lack of protease activity. Has hyperactivated
FT ESX-1 secretion during macrophage infection, resulting in
FT increased innate immune signaling. Secretes full-length
FT EspB."
FT /evidence="ECO:0000269|PubMed:20227664"
SQ SEQUENCE 446 AA; 45118 MW; CFC8CAAE88152DAD CRC64;
MHRIFLITVA LALLTASPAS AITPPPIDPG ALPPDVTGPD QPTEQRVLCA SPTTLPGSGF
HDPPWSNTYL GVADAHKFAT GAGVTVAVID TGVDASPRVP AEPGGDFVDQ AGNGLSDCDA
HGTLTASIIA GRPAPTDGFV GVAPDARLLS LRQTSEAFEP VGSQANPNDP NATPAAGSIR
SLARAVVHAA NLGVGVINIS EAACYKVSRP IDETSLGASI DYAVNVKGVV VVVAAGNTGG
DCVQNPAPDP STPGDPRGWN NVQTVVTPAW YAPLVLSVGG IGQTGMPSSF SMHGPWVDVA
APAENIVALG DTGEPVNALQ GREGPVPIAG TSFAAAYVSG LAALLRQRFP DLTPAQIIHR
ITATARHPGG GVDDLVGAGV IDAVAALTWD IPPGPASAPY NVRRLPPPVV EPGPDRRPIT
AVALVAVGLT LALGLGALAR RALSRR
