PGPLE_DROME
ID PGPLE_DROME Reviewed; 345 AA.
AC Q9VXN9;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Peptidoglycan-recognition protein LE;
GN Name=PGRP-LE; ORFNames=CG8995;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=11106397; DOI=10.1073/pnas.97.25.13772;
RA Werner T., Liu G., Kang D., Ekengren S., Steiner H., Hultmark D.;
RT "A family of peptidoglycan recognition proteins in the fruit fly Drosophila
RT melanogaster.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:13772-13777(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP FUNCTION.
RX PubMed=12359879; DOI=10.1073/pnas.212301199;
RA Takehana A., Katsuyama T., Yano T., Oshima Y., Takada H., Aigaki T.,
RA Kurata S.;
RT "Overexpression of a pattern-recognition receptor, peptidoglycan-
RT recognition protein-LE, activates imd/relish-mediated antibacterial defense
RT and the prophenoloxidase cascade in Drosophila larvae.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13705-13710(2002).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15538387; DOI=10.1038/sj.emboj.7600466;
RA Takehana A., Yano T., Mita S., Kotani A., Oshima Y., Kurata S.;
RT "Peptidoglycan recognition protein (PGRP)-LE and PGRP-LC act
RT synergistically in Drosophila immunity.";
RL EMBO J. 23:4690-4700(2004).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 173-345 IN COMPLEX WITH
RP PEPTIDOGLYCAN FRAGMENT, SUBUNIT, AND MUTAGENESIS OF GLU-231; SER-232 AND
RP ARG-254.
RX PubMed=16428381; DOI=10.1074/jbc.m513030200;
RA Lim J.-H., Kim M.-S., Kim H.-E., Yano T., Oshima Y., Aggarwal K.,
RA Goldman W.E., Silverman N., Kurata S., Oh B.-H.;
RT "Structural basis for preferential recognition of diaminopimelic acid-type
RT peptidoglycan by a subset of peptidoglycan recognition proteins.";
RL J. Biol. Chem. 281:8286-8295(2006).
CC -!- FUNCTION: Peptidoglycan-recognition protein that plays a key role in
CC innate immunity by binding to murein peptidoglycans (PGN) of Gram-
CC negative bacteria and activating the imd/Relish pathway. Has no
CC activity against on Gram-positive bacteria. Binds to diaminopimelic
CC acid-type PGN (DAP-type PGN), an activator of the imd/Relish pathway.
CC Functions synergistically with PGRP-LC in producing resistance to
CC E.coli and B.megaterium infections, which have the DAP-type
CC peptidoglycan. Acts both upstream and in parallel with PGRP-LC in the
CC imd/Relish pathway, and is required for infection-dependent activation
CC of melanization. Required for Relish processing and nuclear
CC translocation following proteolytic cleavage. Its localization suggests
CC a role in the recognition and subsequent activation of the signaling at
CC the first point of contact with invading bacteria.
CC {ECO:0000269|PubMed:12359879, ECO:0000269|PubMed:15538387}.
CC -!- SUBUNIT: Monomer. Peptidoglycan binding induces oligomerization.
CC {ECO:0000269|PubMed:16428381}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15538387}.
CC Note=However, no signal sequence are predicted by sequence analysis
CC tools.
CC -!- TISSUE SPECIFICITY: Expressed in hemolymph. Localizes at the lumenal
CC surface of the trachea (at protein level).
CC {ECO:0000269|PubMed:15538387}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in 0-5 hours embryos and in adult
CC females, suggesting that it is expressed maternally.
CC {ECO:0000269|PubMed:11106397}.
CC -!- SIMILARITY: Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.
CC {ECO:0000305}.
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DR EMBL; AF313391; AAG32064.1; -; mRNA.
DR EMBL; AE014298; AAF48519.1; -; Genomic_DNA.
DR EMBL; AY058258; AAL13487.1; -; mRNA.
DR RefSeq; NP_001245695.1; NM_001258766.3.
DR RefSeq; NP_573078.1; NM_132850.4.
DR PDB; 2CB3; X-ray; 2.40 A; A/B/C/D=173-345.
DR PDBsum; 2CB3; -.
DR AlphaFoldDB; Q9VXN9; -.
DR SMR; Q9VXN9; -.
DR BioGRID; 58882; 148.
DR IntAct; Q9VXN9; 2.
DR STRING; 7227.FBpp0300347; -.
DR GlyGen; Q9VXN9; 5 sites.
DR PaxDb; Q9VXN9; -.
DR DNASU; 32534; -.
DR EnsemblMetazoa; FBtr0074183; FBpp0073968; FBgn0030695.
DR EnsemblMetazoa; FBtr0307978; FBpp0300347; FBgn0030695.
DR GeneID; 32534; -.
DR KEGG; dme:Dmel_CG8995; -.
DR CTD; 32534; -.
DR FlyBase; FBgn0030695; PGRP-LE.
DR VEuPathDB; VectorBase:FBgn0030695; -.
DR eggNOG; ENOG502S2KY; Eukaryota.
DR GeneTree; ENSGT00940000166535; -.
DR HOGENOM; CLU_804788_0_0_1; -.
DR InParanoid; Q9VXN9; -.
DR OMA; HSWLAQM; -.
DR OrthoDB; 1110472at2759; -.
DR PhylomeDB; Q9VXN9; -.
DR Reactome; R-DME-209171; Peptidoglycans (PGN) bind to a peptidoglycan recognition protein receptor, PGRP-LC/LE.
DR Reactome; R-DME-209266; Peptidoglycan bound PGRP-LC/LE oligomerises.
DR Reactome; R-DME-214397; Assembly of the PGN:PGRP-LC/LE receptor 'signalling complex'.
DR Reactome; R-DME-214399; Activated IkappaB kinase (IKK) complex, Phospho IRD5:KEY dimer, phosphorylates REL in the PGN:PGRP-LC/LE receptor 'signalling complex'.
DR Reactome; R-DME-214411; REL binds to DREDD in the PGN:PGRP-LC/LE receptor 'signalling complex'.
DR Reactome; R-DME-214416; Phosphorylated REL is cleaved by and dissociates from DREDD.
DR SignaLink; Q9VXN9; -.
DR BioGRID-ORCS; 32534; 0 hits in 3 CRISPR screens.
DR EvolutionaryTrace; Q9VXN9; -.
DR GenomeRNAi; 32534; -.
DR PRO; PR:Q9VXN9; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0030695; Expressed in adult midgut (Drosophila) and 27 other tissues.
DR ExpressionAtlas; Q9VXN9; baseline and differential.
DR Genevisible; Q9VXN9; DM.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0042834; F:peptidoglycan binding; ISS:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0042742; P:defense response to bacterium; IMP:FlyBase.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:FlyBase.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IMP:FlyBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:FlyBase.
DR GO; GO:0045087; P:innate immune response; NAS:UniProtKB.
DR GO; GO:0061057; P:peptidoglycan recognition protein signaling pathway; IDA:FlyBase.
DR GO; GO:0045089; P:positive regulation of innate immune response; IMP:FlyBase.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IGI:FlyBase.
DR CDD; cd06583; PGRP; 1.
DR Gene3D; 3.40.80.10; -; 1.
DR InterPro; IPR036505; Amidase/PGRP_sf.
DR InterPro; IPR002502; Amidase_domain.
DR InterPro; IPR015510; PGRP.
DR InterPro; IPR006619; PGRP_domain_met/bac.
DR PANTHER; PTHR11022; PTHR11022; 1.
DR Pfam; PF01510; Amidase_2; 1.
DR SMART; SM00644; Ami_2; 1.
DR SMART; SM00701; PGRP; 1.
DR SUPFAM; SSF55846; SSF55846; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Glycoprotein; Immunity; Innate immunity; Reference proteome;
KW Secreted.
FT CHAIN 1..345
FT /note="Peptidoglycan-recognition protein LE"
FT /id="PRO_0000220626"
FT DOMAIN 198..324
FT /note="N-acetylmuramoyl-L-alanine amidase"
FT /evidence="ECO:0000255"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 124..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..22
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 206
FT /ligand="peptidoglycan"
FT /ligand_id="ChEBI:CHEBI:8005"
FT BINDING 229..240
FT /ligand="peptidoglycan"
FT /ligand_id="ChEBI:CHEBI:8005"
FT BINDING 254
FT /ligand="peptidoglycan"
FT /ligand_id="ChEBI:CHEBI:8005"
FT BINDING 261..267
FT /ligand="peptidoglycan"
FT /ligand_id="ChEBI:CHEBI:8005"
FT BINDING 314..322
FT /ligand="peptidoglycan"
FT /ligand_id="ChEBI:CHEBI:8005"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 231
FT /note="E->L: Loss of peptidoglycan-induced
FT oligomerization."
FT /evidence="ECO:0000269|PubMed:16428381"
FT MUTAGEN 232
FT /note="S->E: Loss of peptidoglycan-induced oligomerization.
FT Strongly reduced affinity for peptidoglycan."
FT /evidence="ECO:0000269|PubMed:16428381"
FT MUTAGEN 254
FT /note="R->T: Strongly reduced affinity for peptidoglycan."
FT /evidence="ECO:0000269|PubMed:16428381"
FT HELIX 180..183
FT /evidence="ECO:0007829|PDB:2CB3"
FT STRAND 197..206
FT /evidence="ECO:0007829|PDB:2CB3"
FT HELIX 215..231
FT /evidence="ECO:0007829|PDB:2CB3"
FT STRAND 241..244
FT /evidence="ECO:0007829|PDB:2CB3"
FT STRAND 250..254
FT /evidence="ECO:0007829|PDB:2CB3"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:2CB3"
FT TURN 264..266
FT /evidence="ECO:0007829|PDB:2CB3"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:2CB3"
FT STRAND 270..277
FT /evidence="ECO:0007829|PDB:2CB3"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:2CB3"
FT HELIX 286..301
FT /evidence="ECO:0007829|PDB:2CB3"
FT STRAND 304..313
FT /evidence="ECO:0007829|PDB:2CB3"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:2CB3"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:2CB3"
FT HELIX 325..331
FT /evidence="ECO:0007829|PDB:2CB3"
SQ SEQUENCE 345 AA; 39426 MW; 66CC484B54705AD7 CRC64;
MSESGIKKLS QERTREWLAS QEDEELESIA ESSVVDSLDY DYTEEEEDAD QNTSEEISTM
TLGTQIATKK HSIISDTIRD LMNSINSIQT LGNVNISNST NVHIGNVTNI NGNIQIIADG
LTQNRRDRRH VSPPRDNAPK TPTHFEDDYQ DESEERVRSD VFIRRQKFKI PKELSAIIPR
SSWLAQKPMD EPLPLQLPVK YVVILHTATE SSEKRAINVR LIRDMQCFHI ESRGWNDIAY
NFLVGCDGNI YEGRGWKTVG AHTLGYNRIS LGISFIGCFM KELPTADALN MCRNLLARGV
EDGHISTDYR LICHCQCNST ESPGRRLYEE IQTWPHFYNI EEEEQ
