LPPM_MYCTU
ID LPPM_MYCTU Reviewed; 227 AA.
AC O53505; F2GK01; I6XDJ6; L0TAE3;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 3.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Protein LppM;
DE AltName: Full=Putative lipoprotein LppM {ECO:0000303|PubMed:27568926};
DE Flags: Precursor;
GN Name=lppM; OrderedLocusNames=Rv2171;
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, AND DISRUPTION PHENOTYPE.
RC STRAIN=Beijing GC1237;
RX PubMed=20844580; DOI=10.1371/journal.ppat.1001100;
RA Brodin P., Poquet Y., Levillain F., Peguillet I., Larrouy-Maumus G.,
RA Gilleron M., Ewann F., Christophe T., Fenistein D., Jang J., Jang M.S.,
RA Park S.J., Rauzier J., Carralot J.P., Shrimpton R., Genovesio A.,
RA Gonzalo-Asensio J.A., Puzo G., Martin C., Brosch R., Stewart G.R.,
RA Gicquel B., Neyrolles O.;
RT "High content phenotypic cell-based visual screen identifies Mycobacterium
RT tuberculosis acyltrehalose-containing glycolipids involved in phagosome
RT remodeling.";
RL PLoS Pathog. 6:E1001100-E1001100(2010).
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, INDUCTION, DOMAIN, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=27220037; DOI=10.1111/cmi.12619;
RA Deboosere N., Iantomasi R., Queval C.J., Song O.R., Deloison G., Jouny S.,
RA Debrie A.S., Chamaillard M., Nigou J., Cohen-Gonsaud M., Locht C.,
RA Brodin P., Veyron-Churlet R.;
RT "LppM impact on the colonization of macrophages by Mycobacterium
RT tuberculosis.";
RL Cell. Microbiol. 0:0-0(2016).
RN [5]
RP STRUCTURE BY NMR OF 26-185, POSSIBLE FUNCTION, SUBCELLULAR LOCATION,
RP POST-TRANSLATIONAL MODIFICATION, LIPID-BINDING, AND MUTAGENESIS OF CYS-25.
RX PubMed=27568926; DOI=10.1016/j.str.2016.07.009;
RA Barthe P., Veyron-Churlet R., de Visch A., Gilleron M., Saliou J.M.,
RA Tomavo S., Nigou J., Brodin P., Cohen-Gonsaud M.;
RT "Mycobacterium tuberculosis LppM displays an original structure and domain
RT composition linked to a dual localization.";
RL Structure 24:1788-1794(2016).
CC -!- FUNCTION: A putative lipoprotein that seems to be specialized for the
CC initial steps of macrophage infection (PubMed:27220037). A non-acylated
CC fragment (residues 26-185) binds phosphatidyl-myo-inositol mannosides
CC (PIMs) (PubMed:27568926). Limits, in a TLR2-dependent fashion,
CC bacterial uptake by host (mouse); this effect may be mediated by
CC nonacylated fragment 26-185 (PubMed:27220037). Plays a TLR2-dependent
CC role in host phagosome maturation arrest (PubMed:20844580,
CC PubMed:27220037). Plays a TLR2-independent role in chemokine production
CC during the first 24 hours of mouse infection (PubMed:27220037).
CC {ECO:0000269|PubMed:27568926, ECO:0000305|PubMed:20844580,
CC ECO:0000305|PubMed:27220037}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255|PROSITE-ProRule:PRU00303};
CC Lipid-anchor {ECO:0000255|PROSITE-ProRule:PRU00303}. Membrane
CC {ECO:0000255}; Single-pass membrane protein {ECO:0000255}. Secreted,
CC cell wall {ECO:0000269|PubMed:27568926}. Secreted
CC {ECO:0000269|PubMed:27568926}. Note=Mature form (about 28 kDa) is
CC associated with the cell wall and membrane fraction, secreted form is
CC seen after 1 week axenic culture in Sauton's medium without detergent,
CC this form is about 20 kDa (PubMed:27568926). May not be acylated, cell
CC wall association is unchanged by mutation of the putatively acylated
CC residue, and the mutant's migration does not change (PubMed:27568926).
CC {ECO:0000269|PubMed:27568926}.
CC -!- INDUCTION: Constitutively expressed in culture (at protein level)
CC (PubMed:27220037). {ECO:0000269|PubMed:27220037}.
CC -!- DOMAIN: An extracytoplasmic domain (residues 26-185, without the lipid-
CC anchor, either periplasmic or extracellular) decreases phagocystosis by
CC macrophages; when added exogenously to the deletion mutant initial
CC bacteria uptake by host (mouse) decreases to wild-type levels. When
CC added exogenously however this region is not sufficient to restore
CC phagosome maturation arrest (PubMed:27220037).
CC {ECO:0000269|PubMed:27220037}.
CC -!- PTM: A shorter form (about 20 kDa) is secreted; upon overexpression of
CC the whole protein in M.smegmatis the C-terminus of the short form is
CC about residue 187, suggesting it is generated by cleavage of the
CC protein before its C-terminal transmembrane domain (PubMed:27568926).
CC {ECO:0000305|PubMed:27568926}.
CC -!- DISRUPTION PHENOTYPE: Grows normally in liquid culture. Traffics into
CC host (human and mouse) acidified compartments early after phagocytosis,
CC suggesting it no longer arrests phagosome maturation as well as wild-
CC type (PubMed:20844580, PubMed:27220037). Grows normally in mouse
CC macrophages at 7 days post-infection (PubMed:20844580). Initial uptake
CC (2 hours post-infection) by host (mouse) macrophages is higher than
CC wild-type, but decreased growth in host (mouse) macrophages from 1 to 3
CC days post-infection, wild-type growth at 4 days (PubMed:27220037).
CC Initial uptake of bacteria is the same in TLR2-/TLR2- mice
CC (PubMed:27220037). Decreased host (mouse) induction of pro-inflammatory
CC chemokines gamma IP-10 (Cxcl10), MCP-1 (Ccl2) and MIP-1-alpha (Ccl3);
CC decreased induction is not TLR2-dependent (PubMed:27220037).
CC {ECO:0000269|PubMed:20844580, ECO:0000269|PubMed:27220037}.
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DR EMBL; AL123456; CCP44948.1; -; Genomic_DNA.
DR RefSeq; NP_216687.1; NC_000962.3.
DR RefSeq; WP_003411238.1; NZ_NVQJ01000083.1.
DR PDB; 2NC8; NMR; -; A=26-185.
DR PDBsum; 2NC8; -.
DR AlphaFoldDB; O53505; -.
DR SMR; O53505; -.
DR STRING; 83332.Rv2171; -.
DR PaxDb; O53505; -.
DR PRIDE; O53505; -.
DR GeneID; 45426147; -.
DR GeneID; 887522; -.
DR KEGG; mtu:Rv2171; -.
DR PATRIC; fig|83332.111.peg.2417; -.
DR TubercuList; Rv2171; -.
DR eggNOG; ENOG50332S7; Bacteria.
DR OMA; TRSFAGW; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0052170; P:suppression by symbiont of host innate immune response; IDA:MTBBASE.
PE 1: Evidence at protein level;
KW 3D-structure; Cell wall; Lipid-binding; Lipoprotein; Membrane; Palmitate;
KW Reference proteome; Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..24
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT CHAIN 25..227
FT /note="Protein LppM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT /id="PRO_5004158821"
FT TRANSMEM 190..210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 26..185
FT /note="Important for bacterial uptake by host macrophages"
FT /evidence="ECO:0000269|PubMed:27220037"
FT LIPID 25
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT LIPID 25
FT /note="S-diacylglycerol cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT MUTAGEN 25
FT /note="C->A,S: Remains cell wall associated, no difference
FT in gel migration, upon overexpression in M.smegmatis."
FT /evidence="ECO:0000269|PubMed:27568926"
FT STRAND 27..35
FT /evidence="ECO:0007829|PDB:2NC8"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:2NC8"
FT STRAND 39..48
FT /evidence="ECO:0007829|PDB:2NC8"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:2NC8"
FT STRAND 70..77
FT /evidence="ECO:0007829|PDB:2NC8"
FT STRAND 80..91
FT /evidence="ECO:0007829|PDB:2NC8"
FT HELIX 94..106
FT /evidence="ECO:0007829|PDB:2NC8"
FT STRAND 109..115
FT /evidence="ECO:0007829|PDB:2NC8"
FT STRAND 118..126
FT /evidence="ECO:0007829|PDB:2NC8"
FT STRAND 136..142
FT /evidence="ECO:0007829|PDB:2NC8"
FT STRAND 147..156
FT /evidence="ECO:0007829|PDB:2NC8"
FT STRAND 159..164
FT /evidence="ECO:0007829|PDB:2NC8"
FT STRAND 166..177
FT /evidence="ECO:0007829|PDB:2NC8"
SQ SEQUENCE 227 AA; 23846 MW; CA3BCD0106256301 CRC64;
MARTRRRGML AIAMLLMLVP LATGCLRVRA SITISPDDLV SGEIIAAAKP KNSKDTGPAL
DGDVPFSQKV AVSNYDSDGY VGSQAVFSDL TFAELPQLAN MNSDAAGVNL SLRRNGNIVI
LEGRADLTSV SDPDADVELT VAFPAAVTST NGDRIEPEVV QWKLKPGVVS TMSAQARYTD
PNTRSFTGAG IWLGIAAFAA AGVVAVLAWI DRDRSPRLTA SGDPPTS
