Q9GNK5 (PGPLC_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Peptidoglycan-recognition protein LC

Alternative name(s):
Immune response deficient 7 protein

Gene names

Name:	PGRP-LC
Synonyms:	ird7, PGRPLC
ORF Names:	CG4432

Organism

Drosophila melanogaster (Fruit fly)

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	520 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Major activator of the imd/Relish pathway and is likely to encode a pattern recognition molecule for the humoral immune response. Required for Relish processing and nuclear translocation following proteolytic cleavage. Involved in the response to lipopolysaccharide (LPS) and peptidoglycan of Gram-negative bacteria. The different isoforms probably display different recognition capabilities to various microbial patterns. Isoform a and isoform x mediate the induction by LPS and Gram-negative bacteria, while isoform x mediates the induction by peptidoglycan. Ref.2 Ref.3 Ref.8
Subcellular location	Membrane; Single-pass type II membrane protein Ref.1 Ref.2.
Tissue specificity	Expressed in the fat body and hemocytes. Ref.1
Developmental stage	Expressed during larval and pupal stages. Ref.2
Sequence similarities	Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.

Ontologies

Keywords
Biological process	Immunity Innate immunity
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal-anchor Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	antibacterial humoral response Inferred from direct assay Ref.3. Source: UniProtKB defense response to Gram-negative bacterium Inferred from mutant phenotype. Source: FlyBase defense response to virus Inferred from mutant phenotype. Source: FlyBase innate immune response Non-traceable author statement. Source: FlyBase peptidoglycan catabolic process Inferred from electronic annotation. Source: InterPro peptidoglycan recognition protein signaling pathway Inferred from mutant phenotype. Source: FlyBase phagocytosis Traceable author statement. Source: FlyBase positive regulation of biosynthetic process of antibacterial peptides active against Gram-negative bacteria Inferred from mutant phenotype. Source: FlyBase
Cellular component	integral to plasma membrane Inferred from direct assay. Source: FlyBase
Molecular function	Gram-negative bacterial cell surface binding Inferred from direct assay Ref.3. Source: UniProtKB N-acetylmuramoyl-L-alanine amidase activity Inferred from electronic annotation. Source: InterPro peptidoglycan binding Inferred from direct assay. Source: FlyBase peptidoglycan receptor activity Traceable author statement. Source: UniProtKB protein dimerization activity Inferred from direct assay. Source: FlyBase zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ome	Q9VUH1	1	EBI-144264,EBI-191212

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform a Ref.1 (identifier: Q9GNK5-1) Also known as: B; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform x Ref.2 (identifier: Q9GNK5-2) Also known as: A; The sequence of this isoform differs from the canonical sequence as follows:      324-520: SKIRDDDDYR...ASFANWTHWS → TDLDVIDNST...KKWPHWSHEI
Isoform y Ref.3 (identifier: Q9GNK5-3) Also known as: C; The sequence of this isoform differs from the canonical sequence as follows:      324-520: SKIRDDDDYR...ASFANWTHWS → TNDPEIHVDG...KTWPDLHMTQ
Sequence annotation (Features)
	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
	Sequence conflict	373	1	T → K in AAQ16306. Ref.3
	Sequence conflict	338	1	I → V in AAS65052. Ref.4
	Sequence conflict	355	1	L → F in AAS65052. Ref.4

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 520

520

Peptidoglycan-recognition protein LC

PRO_0000220624

Regions

Topological domain

1 – 291

291

Cytoplasmic Potential

Transmembrane

292 – 312

21

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

313 – 520

208

Extracellular Potential

Amino acid modifications

Glycosylation

389

1

N-linked (GlcNAc...) Ref.9

Glycosylation

515

1

N-linked (GlcNAc...) Ref.9

Disulfide bond

390 ↔ 396

Ref.8 Ref.9 UniProtKB Q96PD5

Natural variations

Alternative sequence

324 – 520

197

SKIRD…WTHWS → TDLDVIDNSTLVILKVAEWG GRPAKRMLDAQQLPINRVVI SHTAAEGCESREVCSARVNV VQSFHMDSWGWDHIGYNFLV GGDGRVYEGRGWDYVGAHTK GYNRGSIGISFIGTFTTRKP NERQLEACQLLLQEGVRLKK LTTNYRLYGHRQLSATESPG EELYKIIKKWPHWSHEI in isoform x. Ref.2 Ref.3

VSP_050759

Alternative sequence

324 – 520

197

SKIRD…WTHWS → TNDPEIHVDGKLVVISIKGW GGMPTRGNLKPLKLPVSKVI ISETPPEICTTQDSCSYWTR VTQSRHMDTFNWSQVGYNFL VGGDGRIYEGRGWNYMGDHT RDNNNNSIGITFLGTFRRQE PTPKSLEACQLLIAQGVRLK KLKPDYQLLGHRQITGTLMP GEELYRIIQTWNNWYNLTKT WPDLHMTQ in isoform y.

VSP_050760

Secondary structure

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520

Helix Strand Turn

Details...

Helix

358 – 361

4

Beta strand

375 – 384

10

Helix

393 – 409

17

Beta strand

419 – 422

4

Beta strand

428 – 432

5

Turn

433 – 435

3

Beta strand

440 – 442

3

Helix

444 – 447

4

Beta strand

451 – 457

7

Beta strand

460 – 462

3

Helix

466 – 481

16

Beta strand

484 – 493

10

Helix

494 – 497

4

Helix

502 – 504

3

Helix

507 – 511

5

Turn

512 – 515

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform a (B) [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 3215F8380857DFC1	FASTA	520	56,046
	10 20 30 40 50 60 MPFSNETEMS QCSNAKRRVN DPLTGPKNCS TSSTDSGVIL NDNVAAFRPE KETKDRGTGE 70 80 90 100 110 120 GQFQSKSEEK TESKRISVEH TVNITTENVG KTSSPAVSIR STTISVVSID DNAIDSSSID 130 140 150 160 170 180 SDSEAEAEDY TVQKLGHQVT YPPNSSHLRD LNQGLTVISR HVAPGEAAVP PPNPLEAGIV 190 200 210 220 230 240 AKQILNGNLA VATPTSPAGG ATQGIGSIAL TNSTDVTFGD KHFYEGPVTI QQFLIDNRDK 250 260 270 280 290 300 WKPGEGPAGG QDNPAFNGGP STNGSAPGSK HEDPAQTPPI CPFLPNTVGR KAVTVTVVFV 310 320 330 340 350 360 TLTFLLGIVL ATTTNLFGKT LNQSKIRDDD DYRQNIPINS TIDLDNIGGG LILRFVERQQ 370 380 390 400 410 420 WLAQPPQKEI PDLELPVGLV IALPTNSENC STQAICVLRV RLLQTYDIES SQKCDIAYNF 430 440 450 460 470 480 LIGGDGNVYV GRGWNKMGAH MNNINYDSQS LSFAYIGSFK TIQPSAKQLS VTRLLLERGV 490 500 510 520 KLGKIAPSYR FTASSKLMPS VTDFKADALY ASFANWTHWS
	Isoform x (A) [UniParc]. Checksum: A0459DE723A8C720	FASTA	500	54,094
	10 20 30 40 50 60 MPFSNETEMS QCSNAKRRVN DPLTGPKNCS TSSTDSGVIL NDNVAAFRPE KETKDRGTGE 70 80 90 100 110 120 GQFQSKSEEK TESKRISVEH TVNITTENVG KTSSPAVSIR STTISVVSID DNAIDSSSID 130 140 150 160 170 180 SDSEAEAEDY TVQKLGHQVT YPPNSSHLRD LNQGLTVISR HVAPGEAAVP PPNPLEAGIV 190 200 210 220 230 240 AKQILNGNLA VATPTSPAGG ATQGIGSIAL TNSTDVTFGD KHFYEGPVTI QQFLIDNRDK 250 260 270 280 290 300 WKPGEGPAGG QDNPAFNGGP STNGSAPGSK HEDPAQTPPI CPFLPNTVGR KAVTVTVVFV 310 320 330 340 350 360 TLTFLLGIVL ATTTNLFGKT LNQTDLDVID NSTLVILKVA EWGGRPAKRM LDAQQLPINR 370 380 390 400 410 420 VVISHTAAEG CESREVCSAR VNVVQSFHMD SWGWDHIGYN FLVGGDGRVY EGRGWDYVGA 430 440 450 460 470 480 HTKGYNRGSI GISFIGTFTT RKPNERQLEA CQLLLQEGVR LKKLTTNYRL YGHRQLSATE 490 500 SPGEELYKII KKWPHWSHEI
	Isoform y (C) [UniParc]. Checksum: 0969EE0AF556F549	FASTA	511	55,545
	10 20 30 40 50 60 MPFSNETEMS QCSNAKRRVN DPLTGPKNCS TSSTDSGVIL NDNVAAFRPE KETKDRGTGE 70 80 90 100 110 120 GQFQSKSEEK TESKRISVEH TVNITTENVG KTSSPAVSIR STTISVVSID DNAIDSSSID 130 140 150 160 170 180 SDSEAEAEDY TVQKLGHQVT YPPNSSHLRD LNQGLTVISR HVAPGEAAVP PPNPLEAGIV 190 200 210 220 230 240 AKQILNGNLA VATPTSPAGG ATQGIGSIAL TNSTDVTFGD KHFYEGPVTI QQFLIDNRDK 250 260 270 280 290 300 WKPGEGPAGG QDNPAFNGGP STNGSAPGSK HEDPAQTPPI CPFLPNTVGR KAVTVTVVFV 310 320 330 340 350 360 TLTFLLGIVL ATTTNLFGKT LNQTNDPEIH VDGKLVVISI KGWGGMPTRG NLKPLKLPVS 370 380 390 400 410 420 KVIISETPPE ICTTQDSCSY WTRVTQSRHM DTFNWSQVGY NFLVGGDGRI YEGRGWNYMG 430 440 450 460 470 480 DHTRDNNNNS IGITFLGTFR RQEPTPKSLE ACQLLIAQGV RLKKLKPDYQ LLGHRQITGT 490 500 510 LMPGEELYRI IQTWNNWYNL TKTWPDLHMT Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A family of peptidoglycan recognition proteins in the fruit fly Drosophila melanogaster." Werner T., Liu G., Kang D., Ekengren S., Steiner H., Hultmark D. Proc. Natl. Acad. Sci. U.S.A. 97:13772-13777(2000) [PubMed: 11106397] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; X AND Y), SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Strain: Berkeley and Canton-S. Tissue: Embryo, Head, Larva and Pupae.
[2]	"Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila." Choe K.-M., Werner T., Stoeven S., Hultmark D., Anderson K.V. Science 296:359-362(2002) [PubMed: 11872802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM X), FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE. Strain: Berkeley. Tissue: Larva and Pupae.
[3]	"Functional diversity of the Drosophila PGRP-LC gene cluster in the response to lipopolysaccharide and peptidoglycan." Werner T., Borge-Renberg K., Mellroth P., Steiner H., Hultmark D. J. Biol. Chem. 278:26319-26322(2003) [PubMed: 12777387] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM Y), FUNCTION. Strain: Canton-S.
[4]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[5]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING. Strain: Berkeley.
[6]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed: 12537569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM X). Strain: Berkeley. Tissue: Larva and Pupae.
[7]	Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M., Park S., Wan K.H., Yu C., Celniker S.E. Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM X). Strain: Berkeley.
[8]	"Structure of the ectodomain of Drosophila peptidoglycan-recognition protein LCa suggests a molecular mechanism for pattern recognition." Chang C.-I., Ihara K., Chelliah Y., Mengin-Lecreulx D., Wakatsuki S., Deisenhofer J. Proc. Natl. Acad. Sci. U.S.A. 102:10279-10284(2005) [PubMed: 16006509] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 355-520, DISULFIDE BOND, FUNCTION.
[9]	"Structure of tracheal cytotoxin in complex with a heterodimeric pattern-recognition receptor." Chang C.-I., Chelliah Y., Borek D., Mengin-Lecreulx D., Deisenhofer J. Science 311:1761-1764(2006) [PubMed: 16556841] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 355-520 IN COMPLEX WITH PEPTIDOGLYCAN FRAGMENT, DISULFIDE BOND, GLYCOSYLATION AT ASN-389 AND ASN-515.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF207539 mRNA. Translation: AAG23733.1.
AF500096 mRNA. Translation: AAM18530.1.
AY327466 mRNA. Translation: AAQ16306.1.
AE014296 Genomic DNA. Translation: AAF50302.3.
AE014296 Genomic DNA. Translation: AAN11957.1.
AE014296 Genomic DNA. Translation: AAS65052.1.
AY119048 mRNA. Translation: AAM50908.1.
BT025958 mRNA. Translation: ABG02202.1.

RefSeq

NP_001163396.1. NM_001169925.1.
NP_648298.1. NM_140041.3.
NP_729468.2. NM_168324.3.
NP_996030.1. NM_206308.2.

UniGene

Dm.1437.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Z6I	X-ray	2.50	A	355-520	[»]
2F2L	X-ray	2.10	A	355-520	[»]
			X	418-434	[»]

ProteinModelPortal

Q9GNK5.

SMR

Q9GNK5. Positions 355-520.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9GNK5. 1 interaction.

MINT

MINT-948537.

STRING

Q9GNK5.

Proteomic databases

PRIDE

Q9GNK5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblMetazoa

FBtr0089491; FBpp0088492; FBgn0035976.
FBtr0308349; FBpp0300668; FBgn0035976.

GeneID

39063.

KEGG

dme:Dmel_CG4432.

NMPDR

fig|7227.3.peg.9019.

Organism-specific databases

CTD

39063.

FlyBase

FBgn0035976. PGRP-LC.

Phylogenomic databases

eggNOG

inNOG10677.

GeneTree

EMGT00050000009248.

InParanoid

Q9GNK5.

OMA

QLSATES.

OrthoDB

EOG4CRJFK.

PhylomeDB

Q9GNK5.

Gene expression databases

ArrayExpress

Q9GNK5.

Bgee

Q9GNK5.

GermOnline

CG4432. Drosophila melanogaster.

Family and domain databases

InterPro

IPR002502. Amidase_domain.
IPR015510. PGRP.
IPR006619. PGRP_domain_met/bac.
[Graphical view]

Gene3D

G3DSA:3.40.80.10. Amidase_2. 1 hit.

KO

K01446.

PANTHER

PTHR11022. PGRPs. 1 hit.

Pfam

PF01510. Amidase_2. 1 hit.
[Graphical view]

SMART

SM00701. PGRP. 1 hit.
[Graphical view]

SUPFAM

SSF55846. Amidase_2. 1 hit.

ProtoNet

Search...

Other

NextBio

811728.

Entry information

Entry name

PGPLC_DROME

Accession

Primary (citable) accession number: Q9GNK5
Secondary accession number(s): Q1EBX6 , Q7YW58, Q8T5Q2, Q9VSV9

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	March 1, 2001
Last modified:	January 25, 2012
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project