Q9VYX7 (PGPSA_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Peptidoglycan-recognition protein SA
EC=3.4.17.13

Alternative name(s):
Protein semmelweis

Gene names

Name:	PGRP-SA
Synonyms:	seml
ORF Names:	CG11709

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	203 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Peptidoglycan-recognition protein that plays a key role in innate immnunity by binding to peptidoglycans (PGN) of Gram-positive bacteria and activating the Toll pathway. Has no activity against on Gram-negative bacteria and fungi. Shows some partial redundancy with PRPGP-SD in Gram-positive bacteria recognition. May act by forming a complex with GNBP1 that activates the proteolytic cleavage of Spatzle and the subsequent activation of Toll pathway. Binds to diaminopimelic acid-type tetrapeptide PGN (DAP-type PGN) and lysine-type PGN (Lys-type PGN). Has some L,D-carboxypeptidase activity for DAP-type PGN, which are specific to prokaryotes, but not for Lys-type PGN. Ref.6 Ref.8 Ref.9 Ref.10
Catalytic activity	GlcNAc-MurNAc-L-alanyl-gamma-D-glutamyl-meso-diaminopimelyl-D-alanine + H2O = GlcNAc-MurNAc-L-alanyl-gamma-D-glutamyl-meso-diaminopimelate + D-alanine. Ref.12
Subcellular location	Secreted. Note: Secreted in hemolymph. Ref.6
Tissue specificity	In larvae, it is expressed in fat body. Also expressed in uninduced hemocytes and mbn-2 cells. Ref.1 Ref.6
Induction	Strongly up-regulated by PGN from B.subtilis. Regulated by both imd/Relish and Toll pathways. Ref.1 Ref.7
Sequence similarities	Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.
Caution	Although suggested (Ref.8), the interaction with GNBP1 has not been experimentally demonstrated.
Biophysicochemical properties	Kinetic parameters: KM=21.4 µM for GlcNAc-MurNAc(anhydro)-L-Ala-gamma-D-Glu-meso-DAP-D-Ala Ref.12

Ontologies

Keywords
Biological process	Immunity Innate immunity
Cellular component	Secreted
Domain	Signal
Molecular function	Hydrolase Protease
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	Toll signaling pathway Traceable author statement. Source: FlyBase defense response to Gram-positive bacterium Inferred from direct assay Ref.6. Source: UniProtKB innate immune response Non-traceable author statement Ref.1. Source: UniProtKB peptidoglycan catabolic process Non-traceable author statement Ref.1. Source: UniProtKB positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria Inferred from mutant phenotype Ref.6. Source: FlyBase proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of Toll signaling pathway Traceable author statement. Source: FlyBase response to peptidoglycan Inferred from mutant phenotype. Source: FlyBase
Cellular component	extracellular region Inferred from direct assay Ref.6. Source: UniProtKB
Molecular function	N-acetylmuramoyl-L-alanine amidase activity Inferred from electronic annotation. Source: InterPro muramyl dipeptide binding Inferred from direct assay. Source: FlyBase peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW peptidoglycan receptor activity Non-traceable author statement. Source: FlyBase protein binding Inferred from physical interaction. Source: FlyBase zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

26

Chain

27 – 203

177

Peptidoglycan-recognition protein SA

PRO_0000023906

Regions

Region

87 – 90

4

Peptidoglycan binding Probable

Region

97 – 102

6

Peptidoglycan binding Probable

Sites

Binding site

182

1

Peptidoglycan Probable

Amino acid modifications

Disulfide bond

37 ↔ 160

Ref.11 Ref.12

Disulfide bond

74 ↔ 80

Ref.11 Ref.12

Experimental info

Mutagenesis

37

1

C → A: Does not affect activation of Toll pathway. Ref.12

Mutagenesis

68

1

H → A: Abolishes L,D-carboxypeptidase activity on DAP-type PGN. Ref.12

Mutagenesis

70 – 71

2

VT → AA: Strongly reduces PGN-binding and activation of Toll pathway.

Mutagenesis

74

1

C → A: Abolishes activation of Toll pathway. Ref.12

Mutagenesis

80

1

C → Y in seml; induces susceptibility to Gram-positive bacterial infection. Ref.6

Mutagenesis

90 – 91

2

YH → AA: Strongly reduces PGN-binding and activation of Toll pathway.

Mutagenesis

96 – 98

3

DFN → AAA: Strongly reduces PGN-binding and activation of Toll pathway. Ref.12

Mutagenesis

101

1

S → A: Increases PGN-binding and activation of Toll pathway. Ref.12

Mutagenesis

126

1

Y → A: Strongly reduces PGN-binding and activation of Toll pathway. Ref.12

Mutagenesis

180

1

I → A: Strongly reduces PGN-binding. Ref.12

Mutagenesis

182

1

T → Y: Abolishes PGN-binding and activation of Toll pathway. Ref.12

Mutagenesis

184

1

S → A or C: Abolishes PGN-binding and activation of Toll pathway. Abolishes L,D-carboxypeptidase activity on DAP-type PGN. Ref.12

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

203

Helix Strand Turn

Details...

Helix

44 – 46

3

Beta strand

59 – 68

10

Helix

76 – 93

18

Beta strand

101 – 106

6

Beta strand

112 – 116

5

Beta strand

123 – 125

3

Beta strand

129 – 139

11

Beta strand

142 – 144

3

Helix

148 – 163

16

Beta strand

166 – 175

10

Helix

176 – 178

3

Beta strand

180 – 182

3

Helix

187 – 193

7

Sequences

	Sequence		Length	Mass (Da)
	Q9VYX7 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: D200A6EA79C66731	FASTA	203	22,260
	10 20 30 40 50 60 MQPVRFGSPW IMAIGLVLLL LAFVSAGKSR QRSPANCPTI KLKRQWGGKP SLGLHYQVRP 70 80 90 100 110 120 IRYVVIHHTV TGECSGLLKC AEILQNMQAY HQNELDFNDI SYNFLIGNDG IVYEGTGWGL 130 140 150 160 170 180 RGAHTYGYNA IGTGIAFIGN FVDKLPSDAA LQAAKDLLAC GVQQGELSED YALIAGSQVI 190 200 STQSPGLTLY NEIQEWPHWL SNP

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 [GENOMIC DNA / MRNA], PROTEIN SEQUENCE OF N-TERMINUS, PGN-BINDING, TISSUE SPECIFICITY, INDUCTION.
[2]	"The evolution of parasite recognition genes in the innate immune system: purifying selection on Drosophila melanogaster peptidoglycan recognition proteins." Jiggins F.M., Hurst G.D.D. J. Mol. Evol. 57:598-605(2003) [PubMed: 14738318] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: DI7, Draveil, KY024, KY038, Loua, Monty5, P.bourg, S30, Tahiti, Texas and ZW141.
[3]	"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.
[4]	"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. Strain: Berkeley.
[5]	"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]. Strain: Berkeley. Tissue: Testis.
[6]	"Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein." Michel T., Reichhart J.-M., Hoffmann J.A., Royet J. Nature 414:756-759(2001) [PubMed: 11742401] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-80.
[7]	"The Toll and Imd pathways are the major regulators of the immune response in Drosophila." De Gregorio E., Spellman P.T., Tzou P., Rubin G.M., Lemaitre B. EMBO J. 21:2568-2579(2002) [PubMed: 12032070] [Abstract] Cited for: INDUCTION.
[8]	"Dual activation of the Drosophila toll pathway by two pattern recognition receptors." Gobert V., Gottar M., Matskevich A.A., Rutschmann S., Royet J., Belvin M., Hoffmann J.A., Ferrandon D. Science 302:2126-2130(2003) [PubMed: 14684822] [Abstract] Cited for: FUNCTION.
[9]	"In vivo RNA interference analysis reveals an unexpected role for GNBP1 in the defense against Gram-positive bacterial infection in Drosophila adults." Pili-Floury S., Leulier F., Takahashi K., Saigo K., Samain E., Ueda R., Lemaitre B. J. Biol. Chem. 279:12848-12853(2004) [PubMed: 14722090] [Abstract] Cited for: FUNCTION.
[10]	"Function of the Drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria." Bischoff V., Vignal C., Boneca I.G., Michel T., Hoffmann J.A., Royet J. Nat. Immunol. 5:1175-1180(2004) [PubMed: 15448690] [Abstract] Cited for: FUNCTION.
[11]	"Crystal structure of the Drosophila peptidoglycan recognition protein (PGRP)-SA at 1.56 A resolution." Reiser J.-B., Teyton L., Wilson I.A. J. Mol. Biol. 340:909-917(2004) [PubMed: 15223330] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 27-203, DISULFIDE BONDS.
[12]	"A Drosophila pattern recognition receptor contains a peptidoglycan docking groove and unusual L,D-carboxypeptidase activity." Chang C.-I., Pili-Floury S., Herve M., Parquet C., Chelliah Y., Lemaitre B., Mengin-Lecreulx D., Deisenhofer J. PLoS Biol. 2:1293-1302(2004) [PubMed: 15361936] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), ENZYME ACTIVITY, DISULFIDE BONDS, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF CYS-37; HIS-68; 70-VAL-THR-71; CYS-74; 96-ASP--ASN-98; 90-TYR-HIS-91; SER-101; TYR-126; ILE-180; THR-182 AND SER-184.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF207540 Genomic DNA. Translation: AAG23734.1.
AF207541 mRNA. Translation: AAG23735.1.
AJ556551 Genomic DNA. Translation: CAD89116.1.
AJ556552 Genomic DNA. Translation: CAD89117.1.
AJ556553 Genomic DNA. Translation: CAD89118.1.
AJ556554 Genomic DNA. Translation: CAD89119.1.
AJ556555 Genomic DNA. Translation: CAD89120.1.
AJ556556 Genomic DNA. Translation: CAD89121.1.
AJ556557 Genomic DNA. Translation: CAD89122.1.
AJ556558 Genomic DNA. Translation: CAD89123.1.
AJ556559 Genomic DNA. Translation: CAD89124.1.
AJ556560 Genomic DNA. Translation: CAD89125.1.
AJ556561 Genomic DNA. Translation: CAD89126.1.
AE014298 Genomic DNA. Translation: AAF48056.1.
AY075293 mRNA. Translation: AAL68160.1.

RefSeq

NP_572727.1. NM_132499.2.

UniGene

Dm.14186.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1S2J	X-ray	2.20	A/B	1-203	[»]
1SXR	X-ray	1.56	A/B	27-203	[»]

ProteinModelPortal

Q9VYX7.

SMR

Q9VYX7. Positions 37-203.

ModBase

Search...

Protein-protein interaction databases

STRING

Q9VYX7.

Proteomic databases

PRIDE

Q9VYX7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblMetazoa

FBtr0073509; FBpp0073358; FBgn0030310.

GeneID

32099.

KEGG

dme:Dmel_CG11709.

NMPDR

fig|7227.3.peg.17441.

Organism-specific databases

CTD

32099.

FlyBase

FBgn0030310. PGRP-SA.

Phylogenomic databases

eggNOG

inNOG10934.

GeneTree

EMGT00050000009248.

InParanoid

Q9VYX7.

OMA

SQVISTQ.

OrthoDB

EOG4R4XK1.

PhylomeDB

Q9VYX7.

Gene expression databases

Bgee

Q9VYX7.

GermOnline

CG11709. Drosophila melanogaster.

Family and domain databases

InterPro

IPR002502. Amidase_domain.
IPR017331. Peptidoglycan_recognition.
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]

PIRSF

PIRSF037945. PGRPs. 1 hit.

SMART

SM00644. Ami_2. 1 hit.
SM00701. PGRP. 1 hit.
[Graphical view]

SUPFAM

SSF55846. Amidase_2. 1 hit.

ProtoNet

Search...

Other

NextBio

776832.

Entry information

Entry name

PGPSA_DROME

Accession

Primary (citable) accession number: Q9VYX7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2005
Last sequence update:	May 1, 2000
Last modified:	January 25, 2012
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project