LPRA_MYCTU
ID LPRA_MYCTU Reviewed; 244 AA.
AC P9WK55; L0T656; Q11049;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Lipoprotein LprA;
DE Flags: Precursor;
GN Name=lprA; OrderedLocusNames=Rv1270c; ORFNames=MTCY50.12;
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 IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15294983; DOI=10.4049/jimmunol.173.4.2660;
RA Gehring A.J., Dobos K.M., Belisle J.T., Harding C.V., Boom W.H.;
RT "Mycobacterium tuberculosis LprG (Rv1411c): a novel TLR-2 ligand that
RT inhibits human macrophage class II MHC antigen processing.";
RL J. Immunol. 173:2660-2668(2004).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, EXPRESSION IN M.SMEGMATIS, GLYCOSYLATION,
RP AND MUTAGENESIS OF CYS-25.
RC STRAIN=H37Rv;
RX PubMed=16785538; DOI=10.4049/jimmunol.177.1.422;
RA Pecora N.D., Gehring A.J., Canaday D.H., Boom W.H., Harding C.V.;
RT "Mycobacterium tuberculosis LprA is a lipoprotein agonist of TLR2 that
RT regulates innate immunity and APC function.";
RL J. Immunol. 177:422-429(2006).
RN [4]
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 [5]
RP FUNCTION, LIPID-BINDING, PALMITOYLATION AT CYS-25, AND DIACYLGLYCEROL AT
RP CYS-25.
RC STRAIN=H37Rv;
RX PubMed=20694006; DOI=10.1038/nsmb.1869;
RA Drage M.G., Tsai H.C., Pecora N.D., Cheng T.Y., Arida A.R., Shukla S.,
RA Rojas R.E., Seshadri C., Moody D.B., Boom W.H., Sacchettini J.C.,
RA Harding C.V.;
RT "Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated
RT glycolipid agonists of Toll-like receptor 2.";
RL Nat. Struct. Mol. Biol. 17:1088-1095(2010).
RN [6]
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 [7]
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).
CC -!- FUNCTION: Constitutes a host TLR2 agonist (toll-like receptor), shown
CC experimentally for human and mouse (PubMed:19362712). In host cells
CC full-length (acylated) protein acts as a TLR2 agonist, inducing human
CC and murine macrophages to produce cytokines, inducing murine dendritic
CC cell maturation and cytokine production and inhibiting antibody
CC processing in murine macrophages (PubMed:16785538). Binds diacylated
CC phosphatidyl-myo-inositol mannosides (PIMs) (PubMed:20694006). Does not
CC induce murine macrophage apoptosis or necrosis (PubMed:16785538). Non-
CC acylated protein does not act as a TLR2 agonist (PubMed:20694006).
CC Requires only host TLR2 as receptors to elicit host response in mouse,
CC although TLR6 may play a redundant role, also requires CD14 and CD16 as
CC accessory receptors (PubMed:19362712). {ECO:0000269|PubMed:16785538,
CC ECO:0000269|PubMed:19362712, ECO:0000269|PubMed:20694006}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255|PROSITE-
CC ProRule:PRU00303}; Lipid-anchor {ECO:0000255|PROSITE-ProRule:PRU00303}.
CC Note=May be shed from the cell surface in infected host cells.
CC {ECO:0000305|PubMed:16785538}.
CC -!- PTM: Modified by Lgt on Cys-25 with an S-linked diacylglycerol, signal
CC peptide is removed by LspA, Cys-25 is further modifed with an amide
CC group on the amino group by Lnt yielding a triacylated protein
CC (PubMed:20694006). Upon expression in M.smegmatis non-glycosylated form
CC and glycosylated forms are detected (by concanavalin A binding); when
CC only the mature sequence is expressed from mutated protein only the
CC non-glycosylated form is detected (PubMed:16785538).
CC {ECO:0000250|UniProtKB:P9WK47, ECO:0000269|PubMed:16785538,
CC ECO:0000305|PubMed:20694006}.
CC -!- SIMILARITY: Belongs to the LppX/LprAFG lipoprotein family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP44026.1; -; Genomic_DNA.
DR PIR; F70754; F70754.
DR RefSeq; NP_215786.1; NC_000962.3.
DR RefSeq; WP_003406562.1; NZ_NVQJ01000030.1.
DR AlphaFoldDB; P9WK55; -.
DR SMR; P9WK55; -.
DR STRING; 83332.Rv1270c; -.
DR PaxDb; P9WK55; -.
DR DNASU; 887017; -.
DR GeneID; 887017; -.
DR KEGG; mtu:Rv1270c; -.
DR TubercuList; Rv1270c; -.
DR eggNOG; ENOG50338Y0; Bacteria.
DR OMA; GNTIEMS; -.
DR PhylomeDB; P9WK55; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0048018; F:receptor ligand activity; IDA:MTBBASE.
DR GO; GO:0042785; P:evasion of host immune response via regulation of host cytokine network; IDA:MTBBASE.
DR CDD; cd16334; LppX-like; 1.
DR InterPro; IPR029046; LolA/LolB/LppX.
DR InterPro; IPR009830; LppX/LprAFG.
DR Pfam; PF07161; LppX_LprAFG; 1.
DR SUPFAM; SSF89392; SSF89392; 1.
DR PROSITE; PS51257; PROKAR_LIPOPROTEIN; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Lipid-binding; Lipoprotein; Membrane;
KW Palmitate; Reference proteome; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT CHAIN 25..244
FT /note="Lipoprotein LprA"
FT /id="PRO_0000018135"
FT LIPID 25
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303,
FT ECO:0000305|PubMed:20694006"
FT LIPID 25
FT /note="S-diacylglycerol cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303,
FT ECO:0000305|PubMed:20694006"
FT MUTAGEN 25
FT /note="C->M: When expressed from this site no longer acts
FT as a TLR2 agonist, suggests active protein is acylated. No
FT glycosylated form detected."
FT /evidence="ECO:0000269|PubMed:16785538"
SQ SEQUENCE 244 AA; 24874 MW; 566C3A1459622BD8 CRC64;
MKHPPCSVVA AATAILAVVL AIGGCSTEGD AGKASDTAAT ASNGDAAMLL KQATDAMRKV
TGMHVRLAVT GDVPNLRVTK LEGDISNTPQ TVATGSATLL VGNKSEDAKF VYVDGHLYSD
LGQPGTYTDF GNGASIYNVS VLLDPNKGLA NLLANLKDAS VAGSQQADGV ATTKITGNSS
ADDIATLAGS RLTSEDVKTV PTTVWIASDG SSHLVQIQIA PTKDTSVTLT MSDWGKQVTA
TKPV
