PPE68_MYCTU
ID PPE68_MYCTU Reviewed; 368 AA.
AC P9WHW9; L0TFI2; Q79F92; Q7D4P4;
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=PPE family immunomodulator PPE68 {ECO:0000305};
GN Name=PPE68; OrderedLocusNames=Rv3873;
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 FUNCTION IN STIMULATION OF INTERFERON SECRETION, EXPRESSION, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=14573626; DOI=10.1128/iai.71.11.6116-6123.2003;
RA Okkels L.M., Brock I., Follmann F., Agger E.M., Arend S.M.,
RA Ottenhoff T.H.M., Oftung F., Rosenkrands I., Andersen P.;
RT "PPE protein (Rv3873) from DNA segment RD1 of Mycobacterium tuberculosis:
RT strong recognition of both specific T-cell epitopes and epitopes conserved
RT within the PPE family.";
RL Infect. Immun. 71:6116-6123(2003).
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15039340; DOI=10.1128/iai.72.4.2170-2176.2004;
RA Demangel C., Brodin P., Cockle P.J., Brosch R., Majlessi L., Leclerc C.,
RA Cole S.T.;
RT "Cell envelope protein PPE68 contributes to Mycobacterium tuberculosis RD1
RT immunogenicity independently of a 10-kilodalton culture filtrate protein
RT and ESAT-6.";
RL Infect. Immun. 72:2170-2176(2004).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=16368961; DOI=10.1128/iai.74.1.88-98.2006;
RA Brodin P., Majlessi L., Marsollier L., de Jonge M.I., Bottai D.,
RA Demangel C., Hinds J., Neyrolles O., Butcher P.D., Leclerc C., Cole S.T.,
RA Brosch R.;
RT "Dissection of ESAT-6 system 1 of Mycobacterium tuberculosis and impact on
RT immunogenicity and virulence.";
RL Infect. Immun. 74:88-98(2006).
RN [5]
RP SUBUNIT, AND INTERACTION WITH ESPG1; ECCA1 AND ESXB.
RX PubMed=17433643; DOI=10.1016/j.micres.2006.11.016;
RA Teutschbein J., Schumann G., Mollmann U., Grabley S., Cole S.T., Munder T.;
RT "A protein linkage map of the ESAT-6 secretion system 1 (ESX-1) of
RT Mycobacterium tuberculosis.";
RL Microbiol. Res. 164:253-259(2009).
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, INTERACTION WITH PE35 AND TLR2, AND SUBCELLULAR LOCATION.
RC STRAIN=H37Rv;
RX PubMed=24467650; DOI=10.1111/febs.12723;
RA Tiwari B., Soory A., Raghunand T.R.;
RT "An immunomodulatory role for the Mycobacterium tuberculosis region of
RT difference 1 locus proteins PE35 (Rv3872) and PPE68 (Rv3873).";
RL FEBS J. 281:1556-1570(2014).
RN [8]
RP BIOTECHNOLOGY.
RX PubMed=25136958; DOI=10.1371/journal.pone.0103679;
RA Mustafa A.S.;
RT "Characterization of a cross-reactive, immunodominant and HLA-promiscuous
RT epitope of Mycobacterium tuberculosis-specific major antigenic protein
RT PPE68.";
RL PLoS ONE 9:E103679-E103679(2014).
CC -!- FUNCTION: Plays a major role in RD1-associated pathogenesis, and may
CC contribute to the establishment and maintenance of M.tuberculosis
CC infection. Together with PE35, stimulates the secretion of IL-10 and
CC MCP-1 from human macrophages, via the interaction with human Toll-like
CC receptor 2 (TLR2) (PubMed:24467650). Stimulates high levels of gamma
CC interferon secretion in peripheral blood mononuclear cells isolated
CC from tuberculosis patients, as well as from healthy tuberculin purified
CC protein derivative-positive donors. Does not interfere with the
CC secretion and immunogenicity of EsxA (ESAT-6) and EsxB (CFP-10)
CC (PubMed:14573626, PubMed:15039340). {ECO:0000269|PubMed:14573626,
CC ECO:0000269|PubMed:15039340, ECO:0000269|PubMed:24467650}.
CC -!- SUBUNIT: Homodimer (PubMed:17433643). Interacts with PE35. PE35/PPE68
CC complex interacts with human TLR2 (PubMed:24467650). Interacts in vitro
CC with EspG1, EccA1 and EsxB (PubMed:17433643).
CC {ECO:0000269|PubMed:17433643, ECO:0000269|PubMed:24467650}.
CC -!- INTERACTION:
CC P9WHW9; P9WIG7: PE35; NbExp=3; IntAct=EBI-9086224, EBI-9086211;
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000269|PubMed:14573626,
CC ECO:0000269|PubMed:15039340}. Cell membrane
CC {ECO:0000269|PubMed:14573626, ECO:0000269|PubMed:15039340}. Cell
CC surface {ECO:0000269|PubMed:24467650}. Note=Detected predominantly in
CC the membrane and cell wall fractions. {ECO:0000269|PubMed:14573626,
CC ECO:0000269|PubMed:15039340}.
CC -!- DISRUPTION PHENOTYPE: Inactivation does not abolish EsxA secretion,
CC EsxA-specific immunogenicity and enhanced virulence.
CC {ECO:0000269|PubMed:16368961}.
CC -!- BIOTECHNOLOGY: PPE68 is recognized by antigen-specific T-cell lines
CC from HLA-heterogeneous subjects. Peptide P9 is an immunodominant and
CC HLA-DR promiscuous peptide of PPE68 (amino acids 121-145), and may be
CC exploited as a peptide-based vaccine candidate against tuberculosis and
CC other mycobacterial diseases. {ECO:0000269|PubMed:25136958}.
CC -!- SIMILARITY: Belongs to the mycobacterial PPE family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46702.1; -; Genomic_DNA.
DR PIR; G70802; G70802.
DR RefSeq; WP_003399879.1; NZ_NVQJ01000074.1.
DR RefSeq; YP_178022.1; NC_000962.3.
DR AlphaFoldDB; P9WHW9; -.
DR SMR; P9WHW9; -.
DR IntAct; P9WHW9; 2.
DR MINT; P9WHW9; -.
DR STRING; 83332.Rv3873; -.
DR PaxDb; P9WHW9; -.
DR DNASU; 886201; -.
DR GeneID; 886201; -.
DR KEGG; mtu:Rv3873; -.
DR TubercuList; Rv3873; -.
DR eggNOG; COG5651; Bacteria.
DR OMA; FEPIMPM; -.
DR PhylomeDB; P9WHW9; -.
DR PHI-base; PHI:7580; -.
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:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR Gene3D; 1.20.1260.20; -; 1.
DR InterPro; IPR000030; PPE_family.
DR InterPro; IPR038332; PPE_sf.
DR Pfam; PF00823; PPE; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell wall; Membrane; Reference proteome; Secreted;
KW Virulence.
FT CHAIN 1..368
FT /note="PPE family immunomodulator PPE68"
FT /id="PRO_0000379593"
FT REGION 255..280
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 312..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 353..368
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 368 AA; 37330 MW; D78F44095F658CA2 CRC64;
MLWHAMPPEL NTARLMAGAG PAPMLAAAAG WQTLSAALDA QAVELTARLN SLGEAWTGGG
SDKALAAATP MVVWLQTAST QAKTRAMQAT AQAAAYTQAM ATTPSLPEIA ANHITQAVLT
ATNFFGINTI PIALTEMDYF IRMWNQAALA MEVYQAETAV NTLFEKLEPM ASILDPGASQ
STTNPIFGMP SPGSSTPVGQ LPPAATQTLG QLGEMSGPMQ QLTQPLQQVT SLFSQVGGTG
GGNPADEEAA QMGLLGTSPL SNHPLAGGSG PSAGAGLLRA ESLPGAGGSL TRTPLMSQLI
EKPVAPSVMP AAAAGSSATG GAAPVGAGAM GQGAQSGGST RPGLVAPAPL AQEREEDDED
DWDEEDDW
