# Peptidoglycan recognition protein, PGRP-S
**Peptidoglycan recognition protein S (PGRP-S)**, officially named peptidoglycan recognition protein 1 (PGLYRP1) in humans, is a short secreted pattern-recognition protein of the innate immune system that binds peptidoglycan (PGN), the conserved cell-wall polymer of bacteria, and contributes to bacterial killing in neutrophils.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC1779587/) The name "short" distinguishes it from the long (PGRP-L) and intermediate (PGRP-Iα and PGRP-Iβ) transcripts of the same mammalian family.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC1779587/)
| Key fact | Detail |
|---|---|
| Human gene and protein | PGLYRP1 (synonyms PGRP, PGRP-S, TAG7, TNFSF3L), 196 amino acids, chromosome 19[3](https://www.uniprot.org/uniprotkb?query=O75594) |
| Ligand | Peptidoglycan of Gram-positive (Lys-type) and Gram-negative (DAP-type) bacteria; affinity set by the third amino acid of the PGN stem peptide[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/) |
| Location | Granules of human neutrophils, alongside lysozyme; also colocalizes with lysozyme in neutrophil extracellular traps (NETs)[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/) |
| Antimicrobial activity | Recombinant human PGRP-S at 25 μg/mL inhibits growth of S aureus and E coli in liquid culture; activity is ablated at 150 mM NaCl[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/) |
| Knockout phenotype | PGRP-S-deficient mice are more susceptible to low-pathogenicity Gram-positive bacteria (Bacillus subtilis, Micrococcus luteus) but not to S aureus or E coli[4](https://pubmed.ncbi.nlm.nih.gov/12649138/) |
| Family | One of four mammalian PGRPs (PGRP-S, -L, -Iα, -Iβ), renamed PGLYRP-1 through PGLYRP-4 by the Human Genome Organization Gene Nomenclature Committee[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC1779587/) |
| Other activities | Forms a complex with HSPA1A that induces apoptosis and necroptosis in tumor cell lines, and a complex with S100A4 that attracts lymphocytes through CCR5 and CXCR3[3](https://www.uniprot.org/uniprotkb?query=O75594) |
## The PGRP family
Peptidoglycan recognition proteins are pattern-recognition receptors, molecules that bind conserved microbial structures absent from the host. The first PGRP was discovered in silkworms as a protein that recognized bacterial peptidoglycan, and the family was named for that activity.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC9520249/) Mammals carry a family of four PGRPs, initially named PGRP-S, PGRP-L, and PGRP-Iα and PGRP-Iβ for their short, long, and intermediate transcripts; the Human Genome Organization Gene Nomenclature Committee later changed these symbols to PGLYRP-1, PGLYRP-2, PGLYRP-3, and PGLYRP-4 respectively.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC1779587/) In this scheme PGRP-S corresponds to PGLYRP-1.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC1779587/)
The family divides functionally into amidases, which hydrolyze peptidoglycan, and non-catalytic members. The mammalian bactericidal branch comprises PGLYRP-1, present in phagocytic granules, and PGLYRP-3 and PGLYRP-4, present on skin and mucous membranes; PGLYRP-2 is the mammalian amidase.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC1779587/) Mammalian PGRP-S has been described as an antibacterial protein lacking amidase activity.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/) All four mammalian PGRPs carry a peptidoglycan-binding domain, and each binds peptidoglycan with high affinity.[6](https://onlinelibrary.wiley.com/doi/10.1002/eji.200425095)
## Expression and location
Human PGRP-S is expressed in a pattern distinct from its three siblings: it is strongly expressed mostly in polymorphonuclear cells (neutrophils), whereas PGRP-L is high in the liver and PGRP-Iα and PGRP-Iβ are restricted mainly to the esophagus.[6](https://onlinelibrary.wiley.com/doi/10.1002/eji.200425095) Gene-expression mapping found PGRP-S transcripts of 1.4 kb, 0.9 kb, and 0.5 kb in bone marrow, a 0.9 kb transcript in fetal liver, and 1.4 kb and 0.9 kb transcripts in peripheral blood leukocytes; the protein was expressed in peripheral blood polymorphonuclear leukocytes but not in monocytes, lymphocytes, or NK cells.[7](https://patents.glgoo.top/patent/WO2003029401A2/en)
Within the neutrophil, PGRP-S sits in granules together with other antimicrobial proteins such as lysozyme.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/) In mice, PGRP-S is present in neutrophil tertiary granules.[4](https://pubmed.ncbi.nlm.nih.gov/12649138/)
## Antimicrobial function
**Binding and growth inhibition.** Recombinant human PGRP-S binds to both Gram-positive Staphylococcus aureus, whose PGN is of the lysine (Lys) type, and Gram-negative Escherichia coli, whose PGN contains mesodiaminopimelic acid (DAP), and inhibits the growth of both, with stronger activity against S aureus.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/) In liquid culture, 25 μg/mL of the recombinant protein inhibited growth of both bacteria; adding cognate PGN at 100 μg/mL completely reversed inhibition of S aureus growth and partially (about 50%) reversed inhibition of E coli growth, indicating a PGN-dependent mechanism.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/) The protein also agglutinates intact E coli but not S aureus.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/) Its activity is salt sensitive: inhibition zones shrink as NaCl rises and disappear at 150 mM NaCl.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/)
**Binding specificity.** Using synthetic PGN fragments and surface plasmon resonance (BIAcore), the study showed that high-affinity binding requires both the glycan backbone, with N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) present, and the peptide stem; a muramyl tripeptide alone did not bind at up to 80 μM, but the same tripeptide coupled to GlcNAc-MurNAc bound with high affinity.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/) The third amino acid in the PGN stem peptide determines binding affinity and thereby antimicrobial activity.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/) Human PGRP-S binds both main PGN types, a broader ligand specificity than reported for other mammalian PGRP-S molecules, and it binds Lys-type PGN more avidly than DAP-type.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/)
**Synergy with lysozyme and NETs.** The antimicrobial effect of PGRP-S against E coli is synergistic with lysozyme, and the two proteins colocalize in neutrophil extracellular traps, the web-like structures neutrophils release on activation. This suggests the granule-derived proteins act together to kill bacteria trapped in the NETs.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/)
## Evidence from knockout mice
Mice lacking PGRP-S have increased susceptibility to intraperitoneal infection with [Gram-positive bacteria](https://www.edgepedia.org/gram-positive-bacteria) of low pathogenicity, such as [Bacillus subtilis](https://www.edgepedia.org/bacillus-subtilis) and [Micrococcus luteus](https://www.edgepedia.org/micrococcus-luteus), but not with more pathogenic Gram-positive or Gram-negative bacteria such as S aureus and E coli.[4](https://pubmed.ncbi.nlm.nih.gov/12649138/) Their neutrophils show normal phagocytic uptake of bacteria but are defective in intracellular killing and digestion of relatively nonpathogenic Gram-positive bacteria, while inflammatory responses and production of TNF-α and interleukin 6 remain normal.[4](https://pubmed.ncbi.nlm.nih.gov/12649138/) These findings led Dziarski and colleagues to propose a role for PGRP-S in preventing nonpathogenic bacteria from causing disease, an idea they compared with Alexander Fleming's earlier proposal for lysozyme.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/) The comparison of knockout and wild-type susceptibility also showed that only bacterial recognition by PGRP-S, not its effector function, is conserved from insects to mammals.[4](https://pubmed.ncbi.nlm.nih.gov/12649138/)
## Structure and ligand binding
Crystal structures of PGRP-S illuminate how one binding site accommodates several microbial molecules. The camel PGRP-S structure solved in complex with heptanoic acid at 2.15 Å resolution shows a dimeric protein with a ligand-binding cleft; analysis of multiple complexes shows that fatty acids bind at the A-B site while non-fatty-acid ligands such as peptidoglycan, lipopolysaccharide (LPS), and lipoteichoic acid (LTA) interact through the C-D interface.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC9520249/) Camel PGRP-S binds both LPS and LTA with high affinity, and in mice it markedly reduced LPS- and LTA-induced TNF-α and IL-6 production and mortality, properties noted as potentially useful for an antibiotic agent.[8](https://pubmed.ncbi.nlm.nih.gov/21454594/) In the mammalian PGRP-S binding site the chemical profile is exclusively hydrophobic.[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC3071341/)
## Roles beyond antibacterial defense
Human PGRP-S was originally identified and characterized as a novel cytokine named Tag7.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/) According to its UniProt annotation, it forms an equimolar complex with the heat shock protein [HSPA1A](https://www.edgepedia.org/hspa1a) that induces programmed cell death through apoptosis and necroptosis in tumor cell lines by activating the TNFR1 receptor, and a complex with the calcium-binding protein S100A4 that acts as a chemoattractant for lymphocytes through the chemotactic receptors CCR5 and CXCR3.[3](https://www.uniprot.org/uniprotkb?query=O75594) Recombinant human PGLYRP1 has also been shown to inhibit intracellular survival of [Listeria monocytogenes](https://www.edgepedia.org/listeria-monocytogenes) in macrophages.[10](https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.582803/full)
## Evolutionary context
PGRPs are conserved from insects to mammals, but the gene repertoires differ sharply. A birth-and-death evolutionary analysis found that four rounds of gene duplication plus a single domain duplication generated the variety of present vertebrate PGRPs, whereas in invertebrates more than ten times as many duplications are needed to explain the present repertoire; gene death in vertebrates appears almost absent while it is frequent in invertebrates.[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC3071341/) In Drosophila, short extracellular PGRPs such as PGRP-SA and PGRP-SD bind Lys-type peptidoglycan of Gram-positive bacteria and activate the Toll pathway, and insect PGRP-S ligation leads to prophenoloxidase-mediated melanization, antimicrobial peptide induction, or amidase-mediated cleavage of PGN.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/) • [11](https://www.uniprot.org/uniprotkb/Q9VS97/entry) The InterPro database classifies the PGRP-S family as entry IPR017331, with members carrying an [N-acetylmuramoyl-L-alanine amidase domain](https://www.edgepedia.org/n-acetylmuramoyl-l-alanine-amidase-domain) and a metazoa/bacteria PGRP family domain.[12](https://www.rcsb.org/annotations/2RKQ)
## References
1. [Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity, Blood (2005), PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC1895263/)
2. [The peptidoglycan recognition proteins (PGRPs), Protein & Cell / PMC (2005)](https://pmc.ncbi.nlm.nih.gov/articles/PMC1779587/)
3. [PGLYRP1 – Peptidoglycan recognition protein 1, Homo sapiens, UniProtKB O75594](https://www.uniprot.org/uniprotkb?query=O75594)
4. [Dziarski R, Platt KA, Gelius E, Steiner H, Gupta D (2003). Defect in neutrophil killing and increased susceptibility to infection with nonpathogenic gram-positive bacteria in PGRP-S-deficient mice. Blood 102:689-697, PubMed](https://pubmed.ncbi.nlm.nih.gov/12649138/)
5. [Ligand recognition by peptidoglycan recognition protein-S (PGRP-S): structure of the complex of camel PGRP-S with heptanoic acid at 2.15 Å resolution, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC9520249/)
6. [Girardin SE et al. (2004). Mini-review: The role of peptidoglycan recognition in innate immunity. European Journal of Immunology](https://onlinelibrary.wiley.com/doi/10.1002/eji.200425095)
7. [WO2003029401A2 – Peptidoglycan recognition protein encoding nucleic acids and methods of use thereof, Google Patents](https://patents.glgoo.top/patent/WO2003029401A2/en)
8. [Structural insights into recognition of pathogen-associated molecular patterns and inhibition of proinflammatory cytokines by camel PGRP-S, PubMed](https://pubmed.ncbi.nlm.nih.gov/21454594/)
9. [Evolutionary origin of peptidoglycan recognition proteins in vertebrate innate immune system, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3071341/)
10. [Human Short Peptidoglycan Recognition Protein PGLYRP1/Tag-7/PGRP-S Inhibits Listeria monocytogenes Intracellular Survival in Macrophages, Frontiers in Cellular and Infection Microbiology (2020)](https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.582803/full)
11. [PGRP-SD – Peptidoglycan-recognition protein SD, Drosophila melanogaster, UniProtKB Q9VS97](https://www.uniprot.org/uniprotkb/Q9VS97/entry)
12. [Annotations: 2RKQ, RCSB PDB (InterPro classification IPR017331)](https://www.rcsb.org/annotations/2RKQ)
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*Topic: Encyclopedia › Life and health › Biological foundations › Immunology and immune-system biology › Pattern-recognition and innate signaling receptors*
*Initially written Oct 21, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license