PPE17_MYCTU
ID PPE17_MYCTU Reviewed; 346 AA.
AC P9WI27; L0T8M7; Q79FR6; Q7D8Q2;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 33.
DE RecName: Full=PPE family protein PPE17 {ECO:0000305};
GN Name=PPE17; OrderedLocusNames=Rv1168c;
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 INDUCTION, AND PUTATIVE FUNCTION AS A CANDIDATE FOR SERODIAGNOSIS.
RX PubMed=18400969; DOI=10.1128/cvi.00485-07;
RA Khan N., Alam K., Nair S., Valluri V.L., Murthy K.J.R., Mukhopadhyay S.;
RT "Association of strong immune responses to PPE protein Rv1168c with active
RT tuberculosis.";
RL Clin. Vaccine Immunol. 15:974-980(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 FUNCTION IN HIV-1 ACTIVATION, INTERACTION WITH HOST TLR2, SUBCELLULAR
RP LOCATION, AND DOMAIN.
RX PubMed=22427668; DOI=10.1074/jbc.m111.327825;
RA Bhat K.H., Chaitanya C.K., Parveen N., Varman R., Ghosh S.,
RA Mukhopadhyay S.;
RT "Proline-proline-glutamic acid (PPE) protein Rv1168c of Mycobacterium
RT tuberculosis augments transcription from HIV-1 long terminal repeat
RT promoter.";
RL J. Biol. Chem. 287:16930-16946(2012).
RN [5]
RP SUBCELLULAR LOCATION, INDUCTION, AND DOMAIN.
RX PubMed=23469198; DOI=10.1371/journal.pone.0057517;
RA Dona V., Ventura M., Sali M., Cascioferro A., Provvedi R., Palu G.,
RA Delogu G., Manganelli R.;
RT "The PPE domain of PPE17 is responsible for its surface localization and
RT can be used to express heterologous proteins on the mycobacterial
RT surface.";
RL PLoS ONE 8:e57517-e57517(2013).
RN [6]
RP FUNCTION AS A CANDIDATE FOR SERODIAGNOSIS.
RX PubMed=26364913; DOI=10.1016/j.meegid.2015.09.005;
RA Abraham P.R., Udgata A., Latha G.S., Mukhopadhyay S.;
RT "The Mycobacterium tuberculosis PPE protein Rv1168c induces stronger B cell
RT response than Rv0256c in active TB patients.";
RL Infect. Genet. Evol. 40:339-345(2016).
RN [7]
RP FUNCTION IN PRO-INFLAMMATORY-TYPE RESPONSE.
RX PubMed=27481848; DOI=10.4049/jimmunol.1501816;
RA Udgata A., Qureshi R., Mukhopadhyay S.;
RT "Transduction of functionally contrasting signals by two Mycobacterial PPE
RT proteins downstream of TLR2 receptors.";
RL J. Immunol. 197:1776-1787(2016).
RN [8]
RP FUNCTION AS A CANDIDATE FOR SERODIAGNOSIS.
RX PubMed=28651002; DOI=10.1371/journal.pone.0179965;
RA Abraham P.R., Pathak N., Pradhan G., Sumanlatha G., Mukhopadhyay S.;
RT "The N-terminal domain of Mycobacterium tuberculosis PPE17 (Rv1168c)
RT protein plays a dominant role in inducing antibody responses in active TB
RT patients.";
RL PLoS ONE 12:e0179965-e0179965(2017).
RN [9]
RP FUNCTION AS A CANDIDATE FOR SERODIAGNOSIS.
RX PubMed=30475863; DOI=10.1371/journal.pone.0207787;
RA Abraham P.R., Devalraju K.P., Jha V., Valluri V.L., Mukhopadhyay S.;
RT "PPE17 (Rv1168c) protein of Mycobacterium tuberculosis detects individuals
RT with latent TB infection.";
RL PLoS ONE 13:e0207787-e0207787(2018).
RN [10]
RP EXPRESSION, AND REFOLDING.
RX PubMed=30666076;
RA Najafi A., Tafaghodi M., Sankian M., Amini Y., Ghazvini K.;
RT "Cloning, expression, and refolding of PPE17 protein of Mycobacterium
RT tuberculosis as a promising vaccine candidate.";
RL Iran. J. Med. Sci. 44:53-59(2019).
CC -!- FUNCTION: Induces pro-inflammatory responses (PubMed:22427668,
CC PubMed:27481848). Induces host TLR1/2 heterodimerization, which causes
CC an increased recruitment of IRAK1, MYD88, and protein kinase C epsilon
CC (PRKCE) to the downstream TLR-signaling complex that translocates PRKCE
CC into the nucleus in an IRAK1-dependent manner. PRKCE-mediated
CC phosphorylation allowed the nuclear IRAK3 to be exported to the
CC cytoplasm, leading to increased activation of ERK1/2, stabilization of
CC MAPK phosphatase 1 (MKP1), and induction of TNF-alpha with concomitant
CC down-regulation of MAP kinase p38 (PubMed:27481848).
CC {ECO:0000269|PubMed:22427668, ECO:0000269|PubMed:27481848}.
CC -!- FUNCTION: During M.tuberculosis and HIV-1 co-infection, can stimulate
CC transcription from the long terminal repeat (LTR) of HIV-1 in
CC monocyte/macrophage cells. Interaction with human TLR2 activates the
CC NF-kappa-B transcription factor, which binds to the promoter region of
CC the HIV-1 and induces HIV-1 gene expression.
CC {ECO:0000269|PubMed:22427668}.
CC -!- SUBUNIT: Interacts with LRR motifs 15-20 of host Toll-like receptor 2
CC (TLR2). {ECO:0000269|PubMed:22427668}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000269|PubMed:22427668,
CC ECO:0000269|PubMed:23469198}. Cell surface
CC {ECO:0000269|PubMed:23469198}. Note=Not secreted but surface exposed.
CC Mainly localized in the cell wall fraction regardless of PE11 co-
CC expression. {ECO:0000269|PubMed:23469198}.
CC -!- INDUCTION: Up-regulated under microaerophilic and anaerobic conditions,
CC nutrient starvation and in the presence of palmitic acid
CC (PubMed:18400969). Coexpressed with PE11 (PubMed:23469198).
CC {ECO:0000269|PubMed:18400969, ECO:0000269|PubMed:23469198}.
CC -!- DOMAIN: The N-terminal domain is essential for interaction with TLR2
CC and activation of HIV-1 LTR (PubMed:22427668). The PPE region contains
CC the information necessary for targeting and anchorage to the cell wall
CC (PubMed:23469198). {ECO:0000269|PubMed:22427668,
CC ECO:0000269|PubMed:23469198}.
CC -!- MISCELLANEOUS: Shows a strong immunoreactivity toward tuberculosis (TB)
CC patient sera compared to that of BCG-vaccinated controls. Could be an
CC attractive candidate for serodiagnosis to discriminate patients with
CC active tuberculosis from BCG-vaccinated individuals. Could diagnose
CC both pulmonary and extrapulmonary tuberculosis cases (PubMed:18400969,
CC PubMed:26364913, PubMed:28651002). Can also be used as a novel
CC serodiagnostic marker to detect latent tuberculosis infection (LTBI)
CC (PubMed:30475863). Antibody responses elicited in TB patients are
CC directed mostly towards the N-terminal domain of PPE17, suggesting that
CC the N-terminal domain of PPE17 protein is immunodominant and could be
CC used as a better serodiagnostic marker than the full-length PPE17
CC protein (PubMed:28651002). Antibodies directed against N-terminal
CC domain of PPE17 in active TB patients do not significantly cross-react
CC with N-terminal domains of other PPE proteins (PubMed:28651002).
CC {ECO:0000269|PubMed:18400969, ECO:0000269|PubMed:26364913,
CC ECO:0000269|PubMed:28651002, ECO:0000269|PubMed:30475863}.
CC -!- SIMILARITY: Belongs to the mycobacterial PPE family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43924.1; -; Genomic_DNA.
DR PIR; H70874; H70874.
DR RefSeq; WP_003898751.1; NZ_NVQJ01000025.1.
DR RefSeq; YP_177791.1; NC_000962.3.
DR AlphaFoldDB; P9WI27; -.
DR SMR; P9WI27; -.
DR STRING; 83332.Rv1168c; -.
DR PaxDb; P9WI27; -.
DR DNASU; 885990; -.
DR GeneID; 45425140; -.
DR GeneID; 885990; -.
DR KEGG; mtu:Rv1168c; -.
DR TubercuList; Rv1168c; -.
DR eggNOG; COG5651; Bacteria.
DR PhylomeDB; P9WI27; -.
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..346
FT /note="PPE family protein PPE17"
FT /id="PRO_0000379109"
FT REGION 6..159
FT /note="PPE"
FT /evidence="ECO:0000305"
SQ SEQUENCE 346 AA; 35821 MW; 6DC0844DA6EB9C68 CRC64;
MDFTIFPPEF NSLNIQGSAR PFLVAANAWK NLSNELSYAA SRFESEINGL ITSWRGPSST
IMAAAVAPFR AWIVTTASLA ELVADHISVV AGAYEAAHAA HVPLPVIETN RLTRLALATT
NIFGIHTPAI FALDALYAQY WSQDGEAMNL YATMAAAAAR LTPFSPPAPI ANPGALARLY
ELIGSVSETV GSFAAPATKN LPSKLWTLLT KGTYPLTAAR ISSIPVEYVL AFVEGSNMGQ
MMGNLAMRSL TPTLKGPLEL LPNAVRPAVS ATLGNADTIG GLSVPPSWVA DKSITPLAKA
VPTSAPGGPS GTSWAQLGLA SLAGGAVGAV AARTRSGVIL RSPAAG
