Gene - combatTB X

pstS1

Type: protein_coding
Name: pstS1
Locus Name: Rv0934
Product: Periplasmic phosphate-binding lipoprotein PstS1 (PBP-1) (PstS1)
Functional Category: Cell wall and cell processes
Location: 1042115..1043239 (+ strand)
Gene Length: 1124 bp
Nucleotides: TGAAAATTCGTTTGCATACGCTGTTGGCCGTGTTGACCGCTGCGCCGCTGCTGCTAGCAGCGGCGGGCTGTGGCTCGAAACCACCGAGCGGTTCGCCTGAAACGGGCGCCGGCGCCGGTACTGTCGCGACTACCCCCGCGTCGTCGCCGGTGACGTTGGCGGAGACCGGTAGCACGCTGCTCTACCCGCTGTTCAACCTGTGGGGTCCGGCCTTTCACGAGAGGTATCCGAACGTCACGATCACCGCTCAGGGCACCGGTTCTGGTGCCGGGATCGCGCAGGCCGCCGCCGGGACGGTCAACATTGGGGCCTCCGACGCCTATCTGTCGGAAGGTGATATGGCCGCGCACAAGGGGCTGATGAACATCGCGCTAGCCATCTCCGCTCAGCAGGTCAACTACAACCTGCCCGGAGTGAGCGAGCACCTCAAGCTGAACGGAAAAGTCCTGGCGGCCATGTACCAGGGCACCATCAAAACCTGGGACGACCCGCAGATCGCTGCGCTCAACCCCGGCGTGAACCTGCCCGGCACCGCGGTAGTTCCGCTGCACCGCTCCGACGGGTCCGGTGACACCTTCTTGTTCACCCAGTACCTGTCCAAGCAAGATCCCGAGGGCTGGGGCAAGTCGCCCGGCTTCGGCACCACCGTCGACTTCCCGGCGGTGCCGGGTGCGCTGGGTGAGAACGGCAACGGCGGCATGGTGACCGGTTGCGCCGAGACACCGGGCTGCGTGGCCTATATCGGCATCAGCTTCCTCGACCAGGCCAGTCAACGGGGACTCGGCGAGGCCCAACTAGGCAATAGCTCTGGCAATTTCTTGTTGCCCGACGCGCAAAGCATTCAGGCCGCGGCGGCTGGCTTCGCATCGAAAACCCCGGCGAACCAGGCGATTTCGATGATCGACGGGCCCGCCCCGGACGGCTACCCGATCATCAACTACGAGTACGCCATCGTCAACAACCGGCAAAAGGACGCCGCCACCGCGCAGACCTTGCAGGCATTTCTGCACTGGGCGATCACCGACGGCAACAAGGCCTCGTTCCTCGACCAGGTTCATTTCCAGCCGCTGCCGCCCGCGGTGGTGAAGTTGTCTGACGCGTTGATCGCGACGATTTCCAGCTAG
Drug Resistance: Check for drug resistance association at TBDREAMDB
Mutations: Check for mutants available at TARGET

Function

Functions in inorganic phosphate uptake, although probably not the main uptake protein under phosphate starvation (PubMed:15731097, PubMed:20933472). Binds phosphate; probably able to bind both H(2)PO(4)(-) and HPO(4)(2-) (PubMed:8294447, PubMed:12842040). Part of the ABC transporter complex PstSACB involved in phosphate import (Probable). {ECO:0000269|PubMed:12842040, ECO:0000269|PubMed:15731097, ECO:0000269|PubMed:20933472, ECO:0000269|PubMed:8294447, ECO:0000305}.; FUNCTION: A host TLR2 agonist (toll-like receptor), shown experimentally for human and mouse (PubMed:1906192, PubMed:19362712). Requires both host TLR1 and TLR2 as coreceptors to elicit host response in mouse (TLR6 may also play a role) neither CD14 or CD36 function as accessory receptors (PubMed:19362712). Protein purified from culture filtrate induces host (human) monocytes to produce TNF-alpha, IL-6 and IL-12 p40 (IL12B) via ERK1/2 (MAPK3 and MAPK1) and p38 MAPK pathways; MEK inhibitors U0126 and PD98059 and p38 inhibitor SB203580 block most cytokine production (PubMed:16622205). Host ERK1/2 and p38 MAPK activation is mediated mainly by TLR2, but also partially by TLR4, and unlike the case for lipoprotein LpqH the protein moiety of PstS1 seems to be the antigenic agent (PubMed:16622205). Greater activation of ERK1/2 and p38 MAPK is seen in patients with active pulmonary tuberculosis than in tuberculin-negative patients (PubMed:16622205). Induces apoptosis when incubated with human monocyte-derived macrophages via TLR2 (PubMed:19140873). Protein purified from culture filtrate acts via TLR2 and TLR4 to induce host macrophage (shown for mouse) endoplasmic reticulum stress-mediated apoptosis via MAPK (at least JNK), C-C motif chemokine 2 (MCP-1, Ccl2) and ZC3H12 endoribonucleases (MCPIP, Zc3h12) (PubMed:25544271). Functions as an adhesin, binds to human and mouse macrophages via mannose residues, binds to the mouse macrophage mannose receptor (possibly Mrc1) and mediates bacterial phagocytosis (PubMed:25359607). {ECO:0000269|PubMed:16622205, ECO:0000269|PubMed:1906192, ECO:0000269|PubMed:19140873, ECO:0000269|PubMed:19362712, ECO:0000269|PubMed:25359607, ECO:0000269|PubMed:25544271}.

Family

PstS family

GO

cellular response to phosphate starvation GO:0016036 biological_process
phosphate ion transport GO:0006817 biological_process
plasma membrane GO:0005886 cellular_component
ATP-binding cassette (ABC) transporter complex GO:0043190 cellular_component
phosphate ion transmembrane transport GO:0035435 biological_process
cytosol GO:0005829 cellular_component
extracellular region GO:0005576 cellular_component
cell wall GO:0005618 cellular_component
phosphate ion binding GO:0042301 molecular_function
pathogenesis GO:0009405 biological_process
cell adhesion GO:0007155 biological_process
cell surface GO:0009986 cellular_component

InterPro

UniProt: P9WGU1
GenBank: Rv0934
EnsemblBacteria: Rv0934
Mycobrowser: Rv0934

Summary

Name: Phosphate-binding protein PstS 1 (PBP 1) (PhoS1) (PstS-1) (38-kDa glycolipoprotein) (38-kDa lipoprotein) (P38) (Antigen Ag78) (Protein antigen B) (Pab)
Family: PstS family
Protein Sequence: MKIRLHTLLAVLTAAPLLLAAAGCGSKPPSGSPETGAGAGTVATTPASSPVTLAETGSTLLYPLFNLWGPAFHERYPNVTITAQGTGSGAGIAQAAAGTVNIGASDAYLSEGDMAAHKGLMNIALAISAQQVNYNLPGVSEHLKLNGKVLAAMYQGTIKTWDDPQIAALNPGVNLPGTAVVPLHRSDGSGDTFLFTQYLSKQDPEGWGKSPGFGTTVDFPAVPGALGENGNGGMVTGCAETPGCVAYIGISFLDQASQRGLGEAQLGNSSGNFLLPDAQSIQAAAAGFASKTPANQAISMIDGPAPDGYPIINYEYAIVNNRQKDAATAQTLQAFLHWAITDGNKASFLDQVHFQPLPPAVVKLSDALIATISS
Mass: 38,243 Da
Length: 374 Aa

Rv0934 doesn't seem to be a targeted by any drug.

ABC transporters mtu02010
mtu02010
Environmental Information Processing; Membrane transport

Two-component system mtu02020
mtu02020
Environmental Information Processing; Signal transduction

Tuberculosis mtu05152
mtu05152
Human Diseases; Infectious disease: bacterial

Crystal structure of M tuberculosis ABC phosphate transport receptor: specificity and charge compensation dominated by ion-dipole interactions.: Structure. 2003 Jul;11(7):765-74.
Regulation of antigen presentation by Mycobacterium tuberculosis: a role for Toll-like receptors.: Nat Rev Microbiol. 2010 Apr;8(4):296-307. doi: 10.1038/nrmicro2321.
Mycobacterium tuberculosis 38-kDa antigen induces endoplasmic reticulum stress-mediated apoptosis via toll-like receptor 2/4.: Apoptosis. 2015 Mar;20(3):358-70. doi: 10.1007/s10495-014-1080-2.
PstS-1, the 38-kDa Mycobacterium tuberculosis glycoprotein, is an adhesin, which binds the macrophage mannose receptor and promotes phagocytosis.: Scand J Immunol. 2015 Jan;81(1):46-55. doi: 10.1111/sji.12249.
Mycobacterium tuberculosis PstS1 amplifies IFN-gamma and induces IL-17/IL-22 responses by unrelated memory CD4+ T cells via dendritic cell activation.: Eur J Immunol. 2013 Sep;43(9):2386-97. doi: 10.1002/eji.201243245. Epub 2013 Jul 15.
Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry.: Mol Cell Proteomics. 2011 Dec;10(12):M111.011627. doi: 10.1074/mcp.M111.011445. Epub 2011 Oct 3.
Effect of PstS sub-units or PknD deficiency on the survival of Mycobacterium tuberculosis.: Tuberculosis (Edinb). 2010 Nov;90(6):338-45. doi: 10.1016/j.tube.2010.09.004. Epub 2010 Oct 8.
TLR2 and its co-receptors determine responses of macrophages and dendritic cells to lipoproteins of Mycobacterium tuberculosis.: Cell Immunol. 2009;258(1):29-37. doi: 10.1016/j.cellimm.2009.03.008. Epub 2009 Apr 11.
Mycobacterium tuberculosis 38-kDa lipoprotein is apoptogenic for human monocyte-derived macrophages.: Scand J Immunol. 2009 Jan;69(1):20-8. doi: 10.1111/j.1365-3083.2008.02193.x.
The mycobacterial 38-kilodalton glycolipoprotein antigen activates the mitogen-activated protein kinase pathway and release of proinflammatory cytokines through Toll-like receptors 2 and 4 in human monocytes.: Infect Immun. 2006 May;74(5):2686-96. doi: 10.1128/IAI.74.5.2686-2696.2006.
Mycobacterium tuberculosis with disruption in genes encoding the phosphate binding proteins PstS1 and PstS2 is deficient in phosphate uptake and demonstrates reduced in vivo virulence.: Infect Immun. 2005 Mar;73(3):1898-902. doi: 10.1128/IAI.73.3.1898-1902.2005.
Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors.: Science. 1999 Jul 30;285(5428):732-6. doi: 10.1126/science.285.5428.732.
Phosphate starvation enhances expression of the immunodominant 38-kilodalton protein antigen of Mycobacterium tuberculosis: demonstration by immunogold electron microscopy.: Infect Immun. 1992 Jul;60(7):2998-3001.
The immunodominant 38-kDa lipoprotein antigen of Mycobacterium tuberculosis is a phosphate-binding protein.: J Biol Chem. 1994 Jan 21;269(3):1956-8.
Lipoprotein antigens of Mycobacterium tuberculosis.: Res Microbiol. 1991 Jan;142(1):55-65.
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.: Nature. 1998 Jun 11;393(6685):537-44. doi: 10.1038/31159.
Structure and mapping of antigenic domains of protein antigen b, a 38,000-molecular-weight protein of Mycobacterium tuberculosis.: Infect Immun. 1989 Aug;57(8):2481-8.