PGLYRP1

Description

The PGLYRP1 (peptidoglycan recognition protein 1) is a protein-coding gene located on chromosome 19.

Peptidoglycan recognition protein 1, PGLYRP1, also known as TAG7, is an antibacterial and pro-inflammatory innate immunity protein that in humans is encoded by the PGLYRP1 gene. PGLYRP1 was discovered independently by two laboratories in 1998. Håkan Steiner and coworkers, using a differential display screen, identified and cloned Peptidoglycan Recognition Protein (PGRP) in a moth (Trichoplusia ni) and based on this sequence discovered and cloned mouse and human PGRP orthologs. Sergei Kiselev and coworkers discovered and cloned a protein from a mouse adenocarcinoma with the same sequence as mouse PGRP, which they named Tag7. Human PGRP was a founding member of a family of four PGRP genes found in humans that were named PGRP-S, PGRP-L, PGRP-Iα, and PGRP-Iβ (for short, long, and intermediate size transcripts, by analogy to insect PGRPs). Their gene symbols were subsequently changed to PGLYRP1 (peptidoglycan recognition protein 1), PGLYRP2 (peptidoglycan recognition protein 2), PGLYRP3 (peptidoglycan recognition protein 3), and PGLYRP4 (peptidoglycan recognition protein 4), respectively, by the Human Genome Organization Gene Nomenclature Committee, and this nomenclature is currently also used for other mammalian PGRPs. In 2005, Roy Mariuzza and coworkers crystallized human PGLYRP1 and solved its structure. PGLYRP1 has the highest level of expression of all mammalian PGRPs. PGLYRP1 is highly constitutively expressed in the bone marrow and in the tertiary granules of polymorphonuclear leukocytes (neutrophils and eosinophils), and to a lesser extent in activated macrophages and fetal liver. PGLYRP1 is also expressed in lactating mammary gland, and to a much lower level in corneal epithelium in the eye, in the inflamed skin, spleen, thymus, and in epithelial cells in the respiratory and intestinal tracts.

PGLYRP1 is an innate immunity protein that plays a crucial role in antimicrobial and antitumor defense systems. It acts as a pattern receptor that binds to murein peptidoglycans (PGN) of Gram-positive bacteria, leading to bactericidal activity. It forms a complex with heat shock protein HSPA1A and triggers programmed cell death (apoptosis and necroptosis) in tumor cell lines by activating the TNFR1 receptor on the target cell membrane. PGLYRP1, when complexed with the Ca(2+)-binding protein S100A4, acts as a chemoattractant, inducing lymphocyte movement by acting as a ligand for the chemotactic receptors CCR5 and CXCR3 present on immune cells. Furthermore, PGLYRP1 promotes lymphocyte activation, enabling them to kill virus-infected and tumor cells by modulating their target-cell specificity. The induction of cytotoxicity on the monocyte surface requires interaction with the TREM1 receptor.

PGLYRP1 is also known as PGLYRP, PGRP, PGRP-S, PGRPS, TAG7, TNFSF3L.

Associated Diseases

WES Whole Exome Sequencing