PSTS1_MYCTU
ID PSTS1_MYCTU Reviewed; 374 AA.
AC P9WGU1; L0T854; O05868; P15712;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=Phosphate-binding protein PstS 1;
DE Short=PBP 1;
DE Short=PhoS1 {ECO:0000303|PubMed:19362712};
DE Short=PstS-1;
DE AltName: Full=38-kDa glycolipoprotein {ECO:0000303|PubMed:16622205};
DE AltName: Full=38-kDa lipoprotein {ECO:0000303|PubMed:1906192};
DE Short=P38;
DE AltName: Full=Antigen Ag78;
DE AltName: Full=Protein antigen B {ECO:0000303|PubMed:2545626};
DE Short=Pab {ECO:0000303|PubMed:2545626};
DE Flags: Precursor;
GN Name=pstS1; Synonyms=phoS1; OrderedLocusNames=Rv0934;
GN ORFNames=MTCY08D9.05c;
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 [GENOMIC DNA].
RX PubMed=2545626; DOI=10.1128/iai.57.8.2481-2488.1989;
RA Andersen A.B., Hansen E.B.;
RT "Structure and mapping of antigenic domains of protein antigen b, a 38,000-
RT molecular-weight protein of Mycobacterium tuberculosis.";
RL Infect. Immun. 57:2481-2488(1989).
RN [2]
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 [3]
RP FUNCTION IN INFECTION, SUBCELLULAR LOCATION, AND PALMITOYLATION AT CYS-24.
RC STRAIN=H37Rv;
RX PubMed=1906192; DOI=10.1016/0923-2508(91)90097-t;
RA Young D.B., Garbe T.R.;
RT "Lipoprotein antigens of Mycobacterium tuberculosis.";
RL Res. Microbiol. 142:55-65(1991).
RN [4]
RP FUNCTION, AND PHOSPHATE-BINDING.
RC STRAIN=H37Rv;
RX PubMed=8294447; DOI=10.1016/s0021-9258(17)42120-x;
RA Chang Z., Choudhary A., Lathigra R., Quiocho F.A.;
RT "The immunodominant 38-kDa lipoprotein antigen of Mycobacterium
RT tuberculosis is a phosphate-binding protein.";
RL J. Biol. Chem. 269:1956-1958(1994).
RN [5]
RP SUBCELLULAR LOCATION, AND INDUCTION BY PHOSPHATE STARVATION.
RC STRAIN=H37Rv;
RX PubMed=1612766; DOI=10.1128/iai.60.7.2998-3001.1992;
RA Espitia C., Elinos M., Hernandez-Pando R., Mancilla R.;
RT "Phosphate starvation enhances expression of the immunodominant 38-
RT kilodalton protein antigen of Mycobacterium tuberculosis: demonstration by
RT immunogold electron microscopy.";
RL Infect. Immun. 60:2998-3001(1992).
RN [6]
RP SUBCELLULAR LOCATION.
RC STRAIN=H37Rv;
RX PubMed=10426995; DOI=10.1126/science.285.5428.732;
RA Brightbill H.D., Libraty D.H., Krutzik S.R., Yang R.B., Belisle J.T.,
RA Bleharski J.R., Maitland M., Norgard M.V., Plevy S.E., Smale S.T.,
RA Brennan P.J., Bloom B.R., Godowski P.J., Modlin R.L.;
RT "Host defense mechanisms triggered by microbial lipoproteins through Toll-
RT like receptors.";
RL Science 285:732-736(1999).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=15731097; DOI=10.1128/iai.73.3.1898-1902.2005;
RA Peirs P., Lefevre P., Boarbi S., Wang X.M., Denis O., Braibant M.,
RA Pethe K., Locht C., Huygen K., Content J.;
RT "Mycobacterium tuberculosis with disruption in genes encoding the phosphate
RT binding proteins PstS1 and PstS2 is deficient in phosphate uptake and
RT demonstrates reduced in vivo virulence.";
RL Infect. Immun. 73:1898-1902(2005).
RN [8]
RP FUNCTION IN INFECTION, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=16622205; DOI=10.1128/iai.74.5.2686-2696.2006;
RA Jung S.B., Yang C.S., Lee J.S., Shin A.R., Jung S.S., Son J.W.,
RA Harding C.V., Kim H.J., Park J.K., Paik T.H., Song C.H., Jo E.K.;
RT "The mycobacterial 38-kilodalton glycolipoprotein antigen activates the
RT mitogen-activated protein kinase pathway and release of proinflammatory
RT cytokines through Toll-like receptors 2 and 4 in human monocytes.";
RL Infect. Immun. 74:2686-2696(2006).
RN [9]
RP FUNCTION IN INFECTION.
RC STRAIN=H37Rv;
RX PubMed=19140873; DOI=10.1111/j.1365-3083.2008.02193.x;
RA Sanchez A., Espinosa P., Esparza M.A., Colon M., Bernal G., Mancilla R.;
RT "Mycobacterium tuberculosis 38-kDa lipoprotein is apoptogenic for human
RT monocyte-derived macrophages.";
RL Scand. J. Immunol. 69:20-28(2009).
RN [10]
RP FUNCTION IN INFECTION.
RC STRAIN=H37Rv;
RX PubMed=19362712; DOI=10.1016/j.cellimm.2009.03.008;
RA Drage M.G., Pecora N.D., Hise A.G., Febbraio M., Silverstein R.L.,
RA Golenbock D.T., Boom W.H., Harding C.V.;
RT "TLR2 and its co-receptors determine responses of macrophages and dendritic
RT cells to lipoproteins of Mycobacterium tuberculosis.";
RL Cell. Immunol. 258:29-37(2009).
RN [11]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=20933472; DOI=10.1016/j.tube.2010.09.004;
RA Vanzembergh F., Peirs P., Lefevre P., Celio N., Mathys V., Content J.,
RA Kalai M.;
RT "Effect of PstS sub-units or PknD deficiency on the survival of
RT Mycobacterium tuberculosis.";
RL Tuberculosis 90:338-345(2010).
RN [12]
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 [13]
RP BIOTECHNOLOGY.
RX PubMed=23719937; DOI=10.1002/eji.201243245;
RA Palma C., Schiavoni G., Abalsamo L., Mattei F., Piccaro G., Sanchez M.,
RA Fernandez C., Singh M., Gabriele L.;
RT "Mycobacterium tuberculosis PstS1 amplifies IFN-gamma and induces IL-17/IL-
RT 22 responses by unrelated memory CD4+ T cells via dendritic cell
RT activation.";
RL Eur. J. Immunol. 43:2386-2397(2013).
RN [14]
RP FUNCTION IN INFECTION, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RC STRAIN=H37Rv;
RX PubMed=25359607; DOI=10.1111/sji.12249;
RA Esparza M., Palomares B., Garcia T., Espinosa P., Zenteno E., Mancilla R.;
RT "PstS-1, the 38-kDa Mycobacterium tuberculosis glycoprotein, is an adhesin,
RT which binds the macrophage mannose receptor and promotes phagocytosis.";
RL Scand. J. Immunol. 81:46-55(2015).
RN [15]
RP FUNCTION IN INFECTION.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=25544271; DOI=10.1007/s10495-014-1080-2;
RA Lim Y.J., Choi J.A., Lee J.H., Choi C.H., Kim H.J., Song C.H.;
RT "Mycobacterium tuberculosis 38-kDa antigen induces endoplasmic reticulum
RT stress-mediated apoptosis via toll-like receptor 2/4.";
RL Apoptosis 20:358-370(2015).
RN [16]
RP REVIEW.
RX PubMed=20234378; DOI=10.1038/nrmicro2321;
RA Harding C.V., Boom W.H.;
RT "Regulation of antigen presentation by Mycobacterium tuberculosis: a role
RT for Toll-like receptors.";
RL Nat. Rev. Microbiol. 8:296-307(2010).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.16 ANGSTROMS) OF 25-374 IN COMPLEX WITH PHOSPHATE.
RC STRAIN=H37Rv;
RX PubMed=12842040; DOI=10.1016/s0969-2126(03)00109-6;
RA Vyas N.K., Vyas M.N., Quiocho F.A.;
RT "Crystal structure of M tuberculosis ABC phosphate transport receptor:
RT specificity and charge compensation dominated by ion-dipole interactions.";
RL Structure 11:765-774(2003).
CC -!- FUNCTION: Functions in inorganic phosphate uptake, although probably
CC not the main uptake protein under phosphate starvation
CC (PubMed:15731097, PubMed:20933472). Binds phosphate; probably able to
CC bind both H(2)PO(4)(-) and HPO(4)(2-) (PubMed:8294447,
CC PubMed:12842040). Part of the ABC transporter complex PstSACB involved
CC in phosphate import (Probable). {ECO:0000269|PubMed:12842040,
CC ECO:0000269|PubMed:15731097, ECO:0000269|PubMed:20933472,
CC ECO:0000269|PubMed:8294447, ECO:0000305}.
CC -!- FUNCTION: A host TLR2 agonist (toll-like receptor), shown
CC experimentally for human and mouse (PubMed:1906192, PubMed:19362712).
CC Requires both host TLR1 and TLR2 as coreceptors to elicit host response
CC in mouse (TLR6 may also play a role) neither CD14 or CD36 function as
CC accessory receptors (PubMed:19362712). Protein purified from culture
CC filtrate induces host (human) monocytes to produce TNF-alpha, IL-6 and
CC IL-12 p40 (IL12B) via ERK1/2 (MAPK3 and MAPK1) and p38 MAPK pathways;
CC MEK inhibitors U0126 and PD98059 and p38 inhibitor SB203580 block most
CC cytokine production (PubMed:16622205). Host ERK1/2 and p38 MAPK
CC activation is mediated mainly by TLR2, but also partially by TLR4, and
CC unlike the case for lipoprotein LpqH the protein moiety of PstS1 seems
CC to be the antigenic agent (PubMed:16622205). Greater activation of
CC ERK1/2 and p38 MAPK is seen in patients with active pulmonary
CC tuberculosis than in tuberculin-negative patients (PubMed:16622205).
CC Induces apoptosis when incubated with human monocyte-derived
CC macrophages via TLR2 (PubMed:19140873). Protein purified from culture
CC filtrate acts via TLR2 and TLR4 to induce host macrophage (shown for
CC mouse) endoplasmic reticulum stress-mediated apoptosis via MAPK (at
CC least JNK), C-C motif chemokine 2 (MCP-1, Ccl2) and ZC3H12
CC endoribonucleases (MCPIP, Zc3h12) (PubMed:25544271). Functions as an
CC adhesin, binds to human and mouse macrophages via mannose residues,
CC binds to the mouse macrophage mannose receptor (possibly Mrc1) and
CC mediates bacterial phagocytosis (PubMed:25359607).
CC {ECO:0000269|PubMed:16622205, ECO:0000269|PubMed:1906192,
CC ECO:0000269|PubMed:19140873, ECO:0000269|PubMed:19362712,
CC ECO:0000269|PubMed:25359607, ECO:0000269|PubMed:25544271}.
CC -!- SUBUNIT: The ABC transporter complex is composed of two ATP-binding
CC proteins (PstB), two transmembrane proteins (PstC and PstA) and a
CC solute-binding protein (PstS). {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor
CC {ECO:0000305|PubMed:1906192}. Cell surface {ECO:0000269|PubMed:1612766,
CC ECO:0000269|PubMed:25359607}. Secreted, cell wall
CC {ECO:0000269|PubMed:10426995}. Secreted {ECO:0000305|PubMed:16622205,
CC ECO:0000305|PubMed:1906192}. Note=A soluble cell wall-associated
CC protein (PubMed:10426995). Also found in culture filtrate in increasing
CC quantities during growth (PubMed:1906192, PubMed:16622205).
CC {ECO:0000269|PubMed:10426995, ECO:0000269|PubMed:16622205,
CC ECO:0000269|PubMed:1906192}.
CC -!- INDUCTION: Transcription slightly induced by phosphate starvation, part
CC of the pstB3-pstS2-pstC1-pstA2 operon (PubMed:20933472). Strongly
CC induced by phosphate starvation (at protein level) (PubMed:1612766).
CC Also shown to be only slightly induced by phosphate starvation; results
CC may depend on growth media (at protein level) (PubMed:20933472).
CC {ECO:0000269|PubMed:1612766, ECO:0000269|PubMed:20933472}.
CC -!- PTM: Glycosylated, probably with mannose residues; treatment with
CC alpha-D-mannosidase abolishes its interaction with concanavalin A.
CC {ECO:0000269|PubMed:25359607}.
CC -!- DISRUPTION PHENOTYPE: No growth phenotype in phosphate-rich medium (3.6
CC mM Pi), decreased phosphate uptake in phosphate-depleted medium
CC (PubMed:15731097). Grows faster than wild-type in restricted (Sauton)
CC phosphate-free medium, even after nutrient starvation
CC (PubMed:20933472). Decreased growth in infected BALB/c and C57BL/6 mice
CC for up to 5 months after infection (PubMed:15731097).
CC {ECO:0000269|PubMed:15731097, ECO:0000269|PubMed:20933472}.
CC -!- BIOTECHNOLOGY: When used as a vaccine has immunostimulatory properties;
CC it stimulates the differentiation of unrelated antigen memory CD4+ T-
CC cells to produce IFN-gamma, IL-17 and IL-22.
CC {ECO:0000269|PubMed:23719937}.
CC -!- SIMILARITY: Belongs to the PstS family. {ECO:0000305}.
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DR EMBL; M30046; AAA25374.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP43682.1; -; Genomic_DNA.
DR PIR; F70584; F70584.
DR RefSeq; WP_003900236.1; NZ_NVQJ01000001.1.
DR RefSeq; YP_177770.1; NC_000962.3.
DR PDB; 1PC3; X-ray; 2.16 A; A/B=25-374.
DR PDB; 7DM1; X-ray; 2.10 A; A/B=25-374.
DR PDB; 7DM2; X-ray; 2.40 A; A=25-374.
DR PDBsum; 1PC3; -.
DR PDBsum; 7DM1; -.
DR PDBsum; 7DM2; -.
DR AlphaFoldDB; P9WGU1; -.
DR SMR; P9WGU1; -.
DR STRING; 83332.Rv0934; -.
DR PaxDb; P9WGU1; -.
DR ABCD; P9WGU1; 4 sequenced antibodies.
DR DNASU; 885724; -.
DR GeneID; 45424900; -.
DR GeneID; 885724; -.
DR KEGG; mtu:Rv0934; -.
DR TubercuList; Rv0934; -.
DR eggNOG; COG0226; Bacteria.
DR OMA; NEGMSAQ; -.
DR PhylomeDB; P9WGU1; -.
DR Reactome; R-HSA-9637628; Modulation by Mtb of host immune system.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0043190; C:ATP-binding cassette (ABC) transporter complex; IEA:InterPro.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; IDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; IDA:MTBBASE.
DR GO; GO:0042301; F:phosphate ion binding; IDA:MTBBASE.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0016036; P:cellular response to phosphate starvation; IEP:MTBBASE.
DR GO; GO:0035435; P:phosphate ion transmembrane transport; IEA:InterPro.
DR GO; GO:0006817; P:phosphate ion transport; IMP:MTBBASE.
DR InterPro; IPR005673; ABC_phos-bd_PstS.
DR InterPro; IPR024370; PBP_domain.
DR Pfam; PF12849; PBP_like_2; 1.
DR PIRSF; PIRSF002756; PstS; 1.
DR TIGRFAMs; TIGR00975; 3a0107s03; 1.
DR PROSITE; PS51257; PROKAR_LIPOPROTEIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell adhesion; Cell membrane; Cell wall; Glycoprotein;
KW Lipoprotein; Membrane; Palmitate; Phosphate transport; Reference proteome;
KW Secreted; Signal; Transport; Virulence.
FT SIGNAL 1..23
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT CHAIN 24..374
FT /note="Phosphate-binding protein PstS 1"
FT /id="PRO_0000031854"
FT REGION 25..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 58..60
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:12842040"
FT BINDING 88
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:12842040"
FT BINDING 106
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:12842040"
FT BINDING 185..191
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:12842040"
FT LIPID 24
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303,
FT ECO:0000305|PubMed:1906192"
FT LIPID 24
FT /note="S-diacylglycerol cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT STRAND 51..57
FT /evidence="ECO:0007829|PDB:7DM1"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:7DM1"
FT HELIX 62..75
FT /evidence="ECO:0007829|PDB:7DM1"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:7DM1"
FT HELIX 88..97
FT /evidence="ECO:0007829|PDB:7DM1"
FT STRAND 99..107
FT /evidence="ECO:0007829|PDB:7DM1"
FT HELIX 111..116
FT /evidence="ECO:0007829|PDB:7DM1"
FT STRAND 120..134
FT /evidence="ECO:0007829|PDB:7DM1"
FT HELIX 147..154
FT /evidence="ECO:0007829|PDB:7DM1"
FT HELIX 164..167
FT /evidence="ECO:0007829|PDB:7DM1"
FT STRAND 181..187
FT /evidence="ECO:0007829|PDB:7DM1"
FT HELIX 190..202
FT /evidence="ECO:0007829|PDB:7DM1"
FT TURN 204..211
FT /evidence="ECO:0007829|PDB:7DM1"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:7DM1"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:7DM1"
FT HELIX 230..240
FT /evidence="ECO:0007829|PDB:7DM1"
FT STRAND 244..249
FT /evidence="ECO:0007829|PDB:7DM1"
FT HELIX 250..252
FT /evidence="ECO:0007829|PDB:7DM1"
FT HELIX 253..258
FT /evidence="ECO:0007829|PDB:7DM1"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:7DM1"
FT HELIX 278..288
FT /evidence="ECO:0007829|PDB:7DM1"
FT TURN 289..291
FT /evidence="ECO:0007829|PDB:7DM1"
FT STRAND 310..322
FT /evidence="ECO:0007829|PDB:7DM1"
FT HELIX 326..340
FT /evidence="ECO:0007829|PDB:7DM1"
FT HELIX 342..344
FT /evidence="ECO:0007829|PDB:7DM1"
FT HELIX 346..349
FT /evidence="ECO:0007829|PDB:7DM1"
FT TURN 350..353
FT /evidence="ECO:0007829|PDB:7DM1"
FT HELIX 359..369
FT /evidence="ECO:0007829|PDB:7DM1"
SQ SEQUENCE 374 AA; 38243 MW; 6334968191FF38AA CRC64;
MKIRLHTLLA VLTAAPLLLA AAGCGSKPPS GSPETGAGAG TVATTPASSP VTLAETGSTL
LYPLFNLWGP AFHERYPNVT ITAQGTGSGA GIAQAAAGTV NIGASDAYLS EGDMAAHKGL
MNIALAISAQ QVNYNLPGVS EHLKLNGKVL AAMYQGTIKT WDDPQIAALN PGVNLPGTAV
VPLHRSDGSG DTFLFTQYLS KQDPEGWGKS PGFGTTVDFP AVPGALGENG NGGMVTGCAE
TPGCVAYIGI SFLDQASQRG LGEAQLGNSS GNFLLPDAQS IQAAAAGFAS KTPANQAISM
IDGPAPDGYP IINYEYAIVN NRQKDAATAQ TLQAFLHWAI TDGNKASFLD QVHFQPLPPA
VVKLSDALIA TISS
