PPE18_MYCTU
ID PPE18_MYCTU Reviewed; 391 AA.
AC L7N675; I6Y9X0;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2013, sequence version 1.
DT 03-AUG-2022, entry version 56.
DE RecName: Full=PPE family protein PPE18 {ECO:0000305};
GN Name=PPE18 {ECO:0000312|EMBL:CCP43952.1};
GN OrderedLocusNames=Rv1196 {ECO:0000312|EMBL:CCP43952.1};
GN ORFNames=LH57_06560 {ECO:0000312|EMBL:AIR13943.1};
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 INDUCTION.
RC STRAIN=H37Rv;
RX PubMed=19651861; DOI=10.1128/iai.01495-08;
RA Goldstone R.M., Goonesekera S.D., Bloom B.R., Sampson S.L.;
RT "The transcriptional regulator Rv0485 modulates the expression of a pe and
RT ppe gene pair and is required for Mycobacterium tuberculosis virulence.";
RL Infect. Immun. 77:4654-4667(2009).
RN [4]
RP FUNCTION, INTERACTION WITH TLR2, SUBCELLULAR LOCATION, AND DOMAIN.
RC STRAIN=H37Rv;
RX PubMed=19880448; DOI=10.4049/jimmunol.0901367;
RA Nair S., Ramaswamy P.A., Ghosh S., Joshi D.C., Pathak N., Siddiqui I.,
RA Sharma P., Hasnain S.E., Mande S.C., Mukhopadhyay S.;
RT "The PPE18 of Mycobacterium tuberculosis interacts with TLR2 and activates
RT IL-10 induction in macrophage.";
RL J. Immunol. 183:6269-6281(2009).
RN [5]
RP FUNCTION, AND DOMAIN.
RX PubMed=21451109; DOI=10.4049/jimmunol.1000773;
RA Nair S., Pandey A.D., Mukhopadhyay S.;
RT "The PPE18 protein of Mycobacterium tuberculosis inhibits NF-kappaB/rel-
RT mediated proinflammatory cytokine production by upregulating and
RT phosphorylating suppressor of cytokine signaling 3 protein.";
RL J. Immunol. 186:5413-5424(2011).
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).
RN [7]
RP FUNCTION IN VIRULENCE, AND DISRUPTION PHENOTYPE.
RX PubMed=23300718; DOI=10.1371/journal.pone.0052601;
RA Bhat K.H., Ahmed A., Kumar S., Sharma P., Mukhopadhyay S.;
RT "Role of PPE18 protein in intracellular survival and pathogenicity of
RT Mycobacterium tuberculosis in mice.";
RL PLoS ONE 7:E52601-E52601(2012).
CC -!- FUNCTION: Could be a crucial virulence factor for intracellular
CC survival of M.tuberculosis (PubMed:23300718). Favors development of
CC Th2-type response, and down-regulates the pro-inflammatory and Th1-type
CC response (PubMed:19880448, PubMed:21451109). Specifically interacts
CC with the human Toll-like receptor 2 (TLR2), leading to an early and
CC sustained activation of p38 MAPK, which induces IL-10 production and
CC activates Th2-type immune response (PubMed:19880448). Also inhibits
CC pro-inflammatory cytokines IL-12p40 and TNF-alpha production. Acts by
CC up-regulating the expression as well as tyrosine phosphorylation of
CC suppressor of cytokine signaling 3 (SOCS-3), leading to the inhibition
CC of phosphorylation of I-kappa-B-alpha, thereby preventing nuclear
CC translocation of the NF-kappa-B/REL subunits and expression of NF-
CC kappa-B regulated genes like IL-12 and TNF-alpha. Induction of SOCS-3
CC probably depends on the activation of p38 MAPK (PubMed:21451109).
CC {ECO:0000269|PubMed:19880448, ECO:0000269|PubMed:21451109,
CC ECO:0000269|PubMed:23300718}.
CC -!- SUBUNIT: Interacts with human TLR2. {ECO:0000269|PubMed:19880448}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall
CC {ECO:0000269|PubMed:19880448}. Cell surface
CC {ECO:0000269|PubMed:19880448}.
CC -!- INDUCTION: Expression is positively regulated by Rv0485.
CC {ECO:0000269|PubMed:19651861}.
CC -!- DOMAIN: The N-terminal region is responsible for interaction with TLR2
CC (PubMed:19880448). It is also important in mediating tyrosine
CC phosphorylation of SOCS-3 (PubMed:21451109).
CC {ECO:0000269|PubMed:19880448, ECO:0000269|PubMed:21451109}.
CC -!- DISRUPTION PHENOTYPE: Mice infected with the ppe18 deleted strain have
CC reduced infection burden in lung, liver and spleen and have better
CC survival rates compared to mice infected with the wild-type train.
CC {ECO:0000269|PubMed:23300718}.
CC -!- SIMILARITY: Belongs to the mycobacterial PPE family. {ECO:0000305}.
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DR EMBL; CP009480; AIR13943.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP43952.1; -; Genomic_DNA.
DR RefSeq; WP_003898765.1; NZ_NVQJ01000025.1.
DR RefSeq; YP_177795.1; NC_000962.3.
DR AlphaFoldDB; L7N675; -.
DR SMR; L7N675; -.
DR STRING; 83332.Rv1196; -.
DR PaxDb; L7N675; -.
DR PRIDE; L7N675; -.
DR DNASU; 886073; -.
DR GeneID; 886073; -.
DR KEGG; mtu:Rv1196; -.
DR PATRIC; fig|83332.111.peg.1337; -.
DR TubercuList; Rv1196; -.
DR eggNOG; COG5651; Bacteria.
DR HOGENOM; CLU_000243_0_0_11; -.
DR OMA; ANNHVSM; -.
DR PhylomeDB; L7N675; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0052572; P:response to host immune response; IBA:GO_Central.
DR Gene3D; 1.20.1260.20; -; 1.
DR InterPro; IPR022171; PPE_C.
DR InterPro; IPR000030; PPE_family.
DR InterPro; IPR038332; PPE_sf.
DR Pfam; PF00823; PPE; 1.
DR Pfam; PF12484; PPE-SVP; 1.
PE 1: Evidence at protein level;
KW Cell wall; Reference proteome; Secreted; Virulence.
FT CHAIN 1..391
FT /note="PPE family protein PPE18"
FT /id="PRO_0000438002"
SQ SEQUENCE 391 AA; 39158 MW; E409396B3ABDC0F8 CRC64;
MVDFGALPPE INSARMYAGP GSASLVAAAQ MWDSVASDLF SAASAFQSVV WGLTVGSWIG
SSAGLMVAAA SPYVAWMSVT AGQAELTAAQ VRVAAAAYET AYGLTVPPPV IAENRAELMI
LIATNLLGQN TPAIAVNEAE YGEMWAQDAA AMFGYAAATA TATATLLPFE EAPEMTSAGG
LLEQAAAVEE ASDTAAANQL MNNVPQALQQ LAQPTQGTTP SSKLGGLWKT VSPHRSPISN
MVSMANNHMS MTNSGVSMTN TLSSMLKGFA PAAAAQAVQT AAQNGVRAMS SLGSSLGSSG
LGGGVAANLG RAASVGSLSV PQAWAAANQA VTPAARALPL TSLTSAAERG PGQMLGGLPV
GQMGARAGGG LSGVLRVPPR PYVMPHSPAA G
