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Protein

Peptidoglycan-recognition protein SA

Gene

PGRP-SA

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Peptidoglycan-recognition protein that plays a key role in innate immunity by binding to peptidoglycans (PGN) of Gram-positive bacteria and activating the Toll pathway upstream of spz activating enzyme SPE (PubMed:11106397, PubMed:16399077, PubMed:15448690). Has no activity against Gram-negative bacteria and fungi (PubMed:11742401). Shows some partial redundancy with PRPGP-SD in Gram-positive bacteria recognition (PubMed:11742401, PubMed:15448690). May act by forming a complex with GNBP1 that activates the proteolytic cleavage of Spatzle and the subsequent activation of Toll pathway (PubMed:14684822, PubMed:14722090, PubMed:11742401). Binds to diaminopimelic acid-type tetrapeptide PGN (DAP-type PGN) and lysine-type PGN (Lys-type PGN) (PubMed:15361936). Has some L,D-carboxypeptidase activity for DAP-type PGN, which are specific to prokaryotes, but not for Lys-type PGN (PubMed:15361936).6 Publications

Caution

Although suggested, the interaction with GNBP1 has not been experimentally demonstrated.1 Publication

Catalytic activityi

GlcNAc-MurNAc-L-alanyl-gamma-D-glutamyl-meso-diaminopimelyl-D-alanine + H2O = GlcNAc-MurNAc-L-alanyl-gamma-D-glutamyl-meso-diaminopimelate + D-alanine.1 Publication

Kineticsi

  1. KM=21.4 µM for GlcNAc-MurNAc(anhydro)-L-Ala-gamma-D-Glu-meso-DAP-D-Ala1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei182PeptidoglycanCurated1

    GO - Molecular functioni

    • muramyl dipeptide binding Source: FlyBase
    • peptidase activity Source: UniProtKB-KW
    • peptidoglycan binding Source: FlyBase
    • peptidoglycan receptor activity Source: FlyBase
    • signaling pattern recognition receptor activity Source: FlyBase
    • zinc ion binding Source: InterPro

    GO - Biological processi

    • defense response to Gram-positive bacterium Source: UniProtKB
    • immune response Source: FlyBase
    • innate immune response Source: FlyBase
    • peptidoglycan catabolic process Source: UniProtKB
    • positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria Source: UniProtKB
    • positive regulation of Toll signaling pathway Source: FlyBase
    • regulation of Toll signaling pathway Source: FlyBase
    • response to peptidoglycan Source: FlyBase
    • Toll signaling pathway Source: FlyBase

    Keywordsi

    Molecular functionHydrolase, Protease
    Biological processImmunity, Innate immunity

    Enzyme and pathway databases

    ReactomeiR-DME-6803157 Antimicrobial peptides

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Peptidoglycan-recognition protein SA (EC:3.4.17.131 Publication)
    Alternative name(s):
    Protein semmelweis
    Gene namesi
    Name:PGRP-SA
    Synonyms:seml
    ORF Names:CG11709
    OrganismiDrosophila melanogaster (Fruit fly)
    Taxonomic identifieri7227 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraHolometabolaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
    Proteomesi
    • UP000000803 Componenti: Chromosome X

    Organism-specific databases

    FlyBaseiFBgn0030310 PGRP-SA

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi37C → A: Does not affect activation of Toll pathway. 1 Publication1
    Mutagenesisi68H → A: Abolishes L,D-carboxypeptidase activity on DAP-type PGN. 1 Publication1
    Mutagenesisi70 – 71VT → AA: Strongly reduces PGN-binding and activation of Toll pathway. 1 Publication2
    Mutagenesisi74C → A: Abolishes activation of Toll pathway. 1 Publication1
    Mutagenesisi80C → Y in seml; induces susceptibility to Gram-positive bacterial infection. 1 Publication1
    Mutagenesisi90 – 91YH → AA: Strongly reduces PGN-binding and activation of Toll pathway. 1 Publication2
    Mutagenesisi96 – 98DFN → AAA: Strongly reduces PGN-binding and activation of Toll pathway. 1 Publication3
    Mutagenesisi101S → A: Increases PGN-binding and activation of Toll pathway. 1 Publication1
    Mutagenesisi126Y → A: Strongly reduces PGN-binding and activation of Toll pathway. 1 Publication1
    Mutagenesisi180I → A: Strongly reduces PGN-binding. 1 Publication1
    Mutagenesisi182T → Y: Abolishes PGN-binding and activation of Toll pathway. 1 Publication1
    Mutagenesisi184S → A or C: Abolishes PGN-binding and activation of Toll pathway. Abolishes L,D-carboxypeptidase activity on DAP-type PGN. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 261 PublicationAdd BLAST26
    ChainiPRO_000002390627 – 203Peptidoglycan-recognition protein SAAdd BLAST177

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Disulfide bondi37 ↔ 160
    Disulfide bondi74 ↔ 80

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    PaxDbiQ9VYX7
    PRIDEiQ9VYX7

    Expressioni

    Tissue specificityi

    In larvae, it is expressed in fat body. Also expressed in uninduced hemocytes and mbn-2 cells.2 Publications

    Inductioni

    Strongly up-regulated by PGN from B.subtilis. Regulated by both imd/Relish and Toll pathways.2 Publications

    Gene expression databases

    BgeeiFBgn0030310
    ExpressionAtlasiQ9VYX7 baseline and differential
    GenevisibleiQ9VYX7 DM

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    GNBP1Q9NHB04EBI-15721239,EBI-15721168

    Protein-protein interaction databases

    BioGridi58509, 1 interactor
    DIPiDIP-60775N
    IntActiQ9VYX7, 1 interactor
    STRINGi7227.FBpp0073358

    Structurei

    Secondary structure

    1203
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi43 – 46Combined sources4
    Beta strandi59 – 68Combined sources10
    Helixi76 – 93Combined sources18
    Beta strandi101 – 106Combined sources6
    Beta strandi112 – 116Combined sources5
    Beta strandi123 – 125Combined sources3
    Turni129 – 131Combined sources3
    Beta strandi132 – 139Combined sources8
    Beta strandi142 – 144Combined sources3
    Helixi148 – 163Combined sources16
    Beta strandi166 – 175Combined sources10
    Helixi176 – 178Combined sources3
    Beta strandi180 – 182Combined sources3
    Helixi187 – 193Combined sources7

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1S2JX-ray2.20A/B1-203[»]
    1SXRX-ray1.56A/B27-203[»]
    ProteinModelPortaliQ9VYX7
    SMRiQ9VYX7
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9VYX7

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni87 – 90Peptidoglycan bindingCurated4
    Regioni97 – 102Peptidoglycan bindingCurated6

    Sequence similaritiesi

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiENOG410IYTD Eukaryota
    ENOG4111PQD LUCA
    InParanoidiQ9VYX7
    KOiK01446
    OMAiHTYGYNK
    OrthoDBiEOG091G0O6Z
    PhylomeDBiQ9VYX7

    Family and domain databases

    CDDicd06583 PGRP, 1 hit
    Gene3Di3.40.80.10, 1 hit
    InterProiView protein in InterPro
    IPR036505 Amidase/PGRP_sf
    IPR002502 Amidase_domain
    IPR017331 Peptidoglycan_recognition
    IPR015510 PGRP
    IPR006619 PGRP_domain_met/bac
    PANTHERiPTHR11022 PTHR11022, 1 hit
    PfamiView protein in Pfam
    PF01510 Amidase_2, 1 hit
    PIRSFiPIRSF037945 PGRPs, 1 hit
    SMARTiView protein in SMART
    SM00644 Ami_2, 1 hit
    SM00701 PGRP, 1 hit
    SUPFAMiSSF55846 SSF55846, 1 hit

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q9VYX7-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MQPVRFGSPW IMAIGLVLLL LAFVSAGKSR QRSPANCPTI KLKRQWGGKP
    60 70 80 90 100
    SLGLHYQVRP IRYVVIHHTV TGECSGLLKC AEILQNMQAY HQNELDFNDI
    110 120 130 140 150
    SYNFLIGNDG IVYEGTGWGL RGAHTYGYNA IGTGIAFIGN FVDKLPSDAA
    160 170 180 190 200
    LQAAKDLLAC GVQQGELSED YALIAGSQVI STQSPGLTLY NEIQEWPHWL

    SNP
    Length:203
    Mass (Da):22,260
    Last modified:May 1, 2000 - v1
    Checksum:iD200A6EA79C66731
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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
    RefSeqiNP_001285128.1, NM_001298199.1
    NP_572727.1, NM_132499.3
    UniGeneiDm.14186

    Genome annotation databases

    EnsemblMetazoaiFBtr0073509; FBpp0073358; FBgn0030310
    FBtr0340296; FBpp0309257; FBgn0030310
    GeneIDi32099
    KEGGidme:Dmel_CG11709

    Similar proteinsi

    Entry informationi

    Entry nameiPGPSA_DROME
    AccessioniPrimary (citable) accession number: Q9VYX7
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2005
    Last sequence update: May 1, 2000
    Last modified: May 23, 2018
    This is version 136 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programDrosophila annotation project

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Drosophila
      Drosophila: entries, gene names and cross-references to FlyBase
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

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