PGLYRP3

Summary

PGLYRP3 (peptidoglycan recognition protein 3, HGNC:30014) is a protein-coding gene on chromosome 1q21.3, encoding Peptidoglycan recognition protein 3 (Q96LB9). Pattern receptor that binds to murein peptidoglycans (PGN) of Gram-positive bacteria.

This gene encodes a peptidoglycan recognition protein, which belongs to the N-acetylmuramoyl-L-alanine amidase 2 family. These proteins are part of the innate immune system and recognize peptidoglycan, a ubiquitous component of bacterial cell walls. This antimicrobial protein binds to murein peptidoglycans of Gram-positive bacteria.

Source: NCBI Gene 114771 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_052891

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30014
Approved symbol	PGLYRP3
Name	peptidoglycan recognition protein 3
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	PGRPIA, PGLYRPIalpha, PGRP-Ialpha
Ensembl gene	ENSG00000159527
Ensembl biotype	protein_coding
OMIM	608197
Entrez	114771

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000290722, ENST00000683862

RefSeq mRNA: 1 — MANE Select: NM_052891 NM_052891

CCDS: CCDS1035

Canonical transcript exons

ENST00000683862 — 8 exons

Exon	Start	End
ENSE00001046162	153303857	153304009
ENSE00001046175	153302409	153302607
ENSE00001046182	153299113	153299231
ENSE00001072538	153307066	153307267
ENSE00001615390	153304947	153305065
ENSE00003916986	153297116	153298134
ENSE00003917879	153310611	153310706
ENSE00003921133	153312643	153312952

Expression profiles

Bgee: expression breadth broad, 57 present calls, max score 93.20.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3610 / max 66.2363, expressed in 60 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14601	0.3468	57
14602	0.0142	10

Top tissues by expression

217 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	93.20	gold quality
skin of abdomen	UBERON:0001416	91.28	gold quality
skin of leg	UBERON:0001511	90.94	gold quality
esophagus mucosa	UBERON:0002469	89.27	gold quality
zone of skin	UBERON:0000014	85.56	gold quality
vagina	UBERON:0000996	72.51	gold quality
esophagus	UBERON:0001043	62.37	gold quality
tonsil	UBERON:0002372	54.19	gold quality
ectocervix	UBERON:0012249	51.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	51.63	silver quality
uterine cervix	UBERON:0000002	47.57	gold quality
amniotic fluid	UBERON:0000173	45.38	gold quality
minor salivary gland	UBERON:0001830	44.42	gold quality
penis	UBERON:0000989	44.08	gold quality
mouth mucosa	UBERON:0003729	44.00	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
saliva-secreting gland	UBERON:0001044	43.17	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
gingiva	UBERON:0001828	42.04	gold quality
epithelium of nasopharynx	UBERON:0001951	41.94	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
mammalian vulva	UBERON:0000997	41.15	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
right lung	UBERON:0002167	40.87	gold quality
bone marrow cell	CL:0002092	40.84	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.79

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• Results describe the function of mammalian antimicrobial peptidoglycan recognition proteins 3 and 4, and show that they are a new class of bactericidal and bacteriostatic proteins. (PMID:16354652)
• Data are consistent with previous reports of association of psoriasis with genes on 1q21, and suggest a role for Pglyrp3 in skin biology. (PMID:16362825)
• expression of PGlyRP3 can be regulated by dietary factors such as probiotic oligosaccharides; PPARgamma is involved in regulation of expression of PGlyRP3 in intestinal mucosa by dietary components (PMID:21451128)
• anti-inflammatory role in intestinal epithelial cells during antibacterial immune response (PMID:22099350)
• a significant induction of three PGLYRPs 2-4 in primary human corneal epithelial cells (HCECs) exposed to live or heat-killed Candida albicans, is reported. (PMID:26039076)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pglyrp3	ENSMUSG00000042244
rattus_norvegicus	LOC134485743	ENSRNOG00000045617
rattus_norvegicus	Pglyrp3	ENSRNOG00000046881
rattus_norvegicus		ENSRNOG00000082231
drosophila_melanogaster	PGRP-SA	FBGN0030310
drosophila_melanogaster	PGRP-LE	FBGN0030695
drosophila_melanogaster	PGRP-SC1b	FBGN0033327
drosophila_melanogaster	PGRP-SD	FBGN0035806
drosophila_melanogaster	PGRP-LF	FBGN0035977
drosophila_melanogaster	PGRP-SC2	FBGN0043575
drosophila_melanogaster	PGRP-SC1a	FBGN0043576
drosophila_melanogaster	PGRP-SB2	FBGN0043577
drosophila_melanogaster	PGRP-SB1	FBGN0043578
drosophila_melanogaster	PGRP-LD	FBGN0260458

Paralogs (3): PGLYRP1 (ENSG00000008438), PGLYRP2 (ENSG00000161031), PGLYRP4 (ENSG00000163218)

Protein

Protein identifiers

Peptidoglycan recognition protein 3 — Q96LB9 (reviewed: Q96LB9)

Alternative names: Peptidoglycan recognition protein I-alpha, Peptidoglycan recognition protein intermediate alpha

All UniProt accessions (1): Q96LB9

UniProt curated annotations — full annotation on UniProt →

Function. Pattern receptor that binds to murein peptidoglycans (PGN) of Gram-positive bacteria. Has bactericidal activity towards Gram-positive bacteria. May kill Gram-positive bacteria by interfering with peptidoglycan biosynthesis. Also binds to Gram-negative bacteria, and has bacteriostatic activity towards Gram-negative bacteria. Plays a role in innate immunity.

Subunit / interactions. Monomer. Homodimer; disulfide-linked. Heterodimer with PGLYRP4; disulfide-linked.

Subcellular location. Secreted.

Tissue specificity. Detected in skin epidermis, eccrine sweat glands and ducts, ciliary body epithelial cells of the eye, in small intestine, colon, stomach and in mature epithelial cells of the tongue (at protein level). Highly expressed in skin and esophagus, expressed also in tonsils and thymus and to a much lesser extent in the stomach, descending colon, rectum and brain.

Post-translational modifications. N-glycosylated.

Induction. Up-regulated by exposure to Gram-positive and Gram-negative bacteria.

Similarity. Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.

RefSeq proteins (1): NP_443123* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002502	Amidase_domain	Domain
IPR006619	PGRP_domain_met/bac	Domain
IPR015510	PGRP	Family
IPR036505	Amidase/PGRP_sf	Homologous_superfamily

Pfam: PF01510

UniProt features (30 total): strand 9, helix 5, disulfide bond 3, binding site 3, sequence variant 2, domain 2, turn 2, signal peptide 1, chain 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1SK4	X-RAY DIFFRACTION	1.65
2APH	X-RAY DIFFRACTION	2.1
1TWQ	X-RAY DIFFRACTION	2.3
1SK3	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LB9-F1	87.87	0.71

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 231; 235; 242

Disulfide bonds (3): 194–238, 214–220, 178–300

Glycosylation sites (1): 113

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6803157	Antimicrobial peptides

MSigDB gene sets: 86 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NATURAL_KILLER_CELL_DIFFERENTIATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_DETECTION_OF_OTHER_ORGANISM, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM

GO Biological Process (12): immune response (GO:0006955), peptidoglycan catabolic process (GO:0009253), detection of bacterium (GO:0016045), killing of cells of another organism (GO:0031640), negative regulation of type II interferon production (GO:0032689), obsolete negative regulation of natural killer cell differentiation involved in immune response (GO:0032827), defense response to bacterium (GO:0042742), innate immune response (GO:0045087), defense response to Gram-positive bacterium (GO:0050830), biological process involved in interaction with host (GO:0051701), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), immune system process (GO:0002376)

GO Molecular Function (6): zinc ion binding (GO:0008270), N-acetylmuramoyl-L-alanine amidase activity (GO:0008745), peptidoglycan immune receptor activity (GO:0016019), peptidoglycan binding (GO:0042834), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), membrane (GO:0016020), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to bacterium	2
cellular anatomical structure	2
immune system process	1
response to stimulus	1
peptidoglycan metabolic process	1
glycosaminoglycan catabolic process	1
detection of other organism	1
cell killing	1
disruption of cell in another organism	1
negative regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
defense response	1
immune response	1
defense response to symbiont	1
defense response to bacterium	1
biological process involved in symbiotic interaction	1
antimicrobial humoral response	1
biological_process	1
transition metal ion binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
peptidoglycan muralytic activity	1
pattern recognition receptor activity	1
peptidoglycan binding	1
glycosaminoglycan binding	1
protein dimerization activity	1
binding	1
cellular_component	1

Protein interactions and networks

STRING

478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGLYRP3	LCE3B	Q5TA77	767
PGLYRP3	LCE3C	Q5T5A8	725
PGLYRP3	LCE1A	Q5T7P2	719
PGLYRP3	LORICRIN	P23490	601
PGLYRP3	IVL	P07476	523
PGLYRP3	THSD7B	Q9C0I4	454
PGLYRP3	DEFB115	Q30KQ5	445
PGLYRP3	SNTG2	Q9NY99	438
PGLYRP3	BPIFC	Q8NFQ6	428
PGLYRP3	CRNN	Q9UBG3	427
PGLYRP3	DEFB113	Q30KQ7	421
PGLYRP3	WFDC12	Q8WWY7	412
PGLYRP3	NOD2	Q9HC29	390
PGLYRP3	PGLYRP2	Q96PD5	388
PGLYRP3	NOD1	Q9Y239	381

IntAct

44 interactions, top by confidence:

A	B	Type	Score
PGLYRP3	HSD17B14	psi-mi:“MI:0915”(physical association)	0.560
KRT34	PGLYRP3	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	PGLYRP3	psi-mi:“MI:0915”(physical association)	0.560
PGLYRP3	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
PGLYRP3	CTSD	psi-mi:“MI:0915”(physical association)	0.560
PGLYRP3	GRN	psi-mi:“MI:0915”(physical association)	0.560
PGLYRP3	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
PGLYRP3	NEFL	psi-mi:“MI:0915”(physical association)	0.560
PRKN	PGLYRP3	psi-mi:“MI:0915”(physical association)	0.560
PGLYRP3	PRPS1	psi-mi:“MI:0915”(physical association)	0.560
PGLYRP3	WFS1	psi-mi:“MI:0915”(physical association)	0.560
PGLYRP3	CCT5	psi-mi:“MI:0915”(physical association)	0.560
PGLYRP3	KIF1B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (14): DHTKD1 (Affinity Capture-MS), MICA (Affinity Capture-MS), DHTKD1 (Affinity Capture-MS), MICA (Affinity Capture-MS), PGLYRP3 (Two-hybrid), PGLYRP3 (Two-hybrid), PGLYRP3 (Two-hybrid), PGLYRP3 (Two-hybrid), DHTKD1 (Affinity Capture-MS), PGLYRP3 (Affinity Capture-MS), P4HB (Affinity Capture-MS), ART5 (Affinity Capture-MS), B4GALT5 (Affinity Capture-MS), TRIM68 (Affinity Capture-MS)

ESM2 similar proteins: A1A547, A6QPN6, D2GZV9, E1BPW0, O18956, O75356, O75594, O93295, P10852, P15396, P22413, P49961, P55772, P57110, P70665, P82450, P97535, P97687, Q0V8L2, Q0VB07, Q53H76, Q58CQ9, Q5E9H0, Q5R5M5, Q5RBQ5, Q5RFU0, Q67BJ4, Q6P6S9, Q6YGZ1, Q71RP1, Q794F9, Q8K0L2, Q8TE60, Q8VI78, Q95194, Q96LB8, Q96LB9, Q99JP7, Q99MZ4, Q9HAT2

Diamond homologs: A1A547, B5T255, C0HK98, C0HK99, D1L2U8, O75594, O76537, O88593, P00806, P20331, Q0VB07, Q3ZFI3, Q70PR8, Q70PU1, Q70PU2, Q70PW6, Q70PY2, Q765P2, Q765P3, Q765P4, Q866Y3, Q8INK6, Q8SPP7, Q8VCS0, Q96LB8, Q96LB9, Q96PD5, Q9GK12, Q9GNK5, Q9JLN4, Q9V4X2, Q9VS97, Q9VV96, Q9VXN9, Q9VYX7, Q9XTN0, Q8SXQ7, Q95T64, O05071, Q9GN97

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

59 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	2
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1195 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153298131:TTTT:T	acceptor_gain	1.0000
1:153298135:C:CC	acceptor_gain	1.0000
1:153299233:T:C	acceptor_gain	1.0000
1:153299233:T:TC	acceptor_gain	1.0000
1:153299239:C:CT	acceptor_gain	1.0000
1:153299240:A:T	acceptor_gain	1.0000
1:153302407:A:AC	donor_gain	1.0000
1:153302408:C:CC	donor_gain	1.0000
1:153302608:C:CC	acceptor_gain	1.0000
1:153304011:T:C	acceptor_gain	1.0000
1:153304946:CCTAT:C	donor_gain	1.0000
1:153307064:A:AC	donor_gain	1.0000
1:153307065:C:CC	donor_gain	1.0000
1:153310606:CTTA:C	donor_loss	1.0000
1:153310607:TTACC:T	donor_loss	1.0000
1:153310608:TACC:T	donor_loss	1.0000
1:153310609:A:AC	donor_gain	1.0000
1:153310609:ACC:A	donor_gain	1.0000
1:153310610:C:CC	donor_gain	1.0000
1:153310610:CCC:C	donor_gain	1.0000
1:153298130:CTTTT:C	acceptor_gain	0.9900
1:153298132:TTT:T	acceptor_gain	0.9900
1:153298133:TT:T	acceptor_gain	0.9900
1:153298134:TC:T	acceptor_loss	0.9900
1:153298135:C:CA	acceptor_loss	0.9900
1:153299107:CCTTA:C	donor_loss	0.9900
1:153299108:CTTA:C	donor_loss	0.9900
1:153299110:T:TG	donor_loss	0.9900
1:153299111:ACC:A	donor_loss	0.9900
1:153299112:CCTA:C	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000084932 (1:153298739 G>A), RS1000404741 (1:153298798 AC>A), RS1000592250 (1:153306048 C>T), RS1000694210 (1:153299884 T>C), RS1000815628 (1:153306101 G>A,T), RS1001025186 (1:153306341 C>T), RS1001093702 (1:153311789 T>C), RS1001234679 (1:153303329 T>C), RS1001336328 (1:153297416 C>T), RS1001406820 (1:153297738 G>A), RS1001441878 (1:153311500 G>A), RS1001711781 (1:153303597 T>C), RS1001933479 (1:153312209 G>C,T), RS1002385995 (1:153312556 C>A), RS1002418004 (1:153308897 G>A,T)

Disease associations

OMIM: gene MIM:608197 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008916_87	Asthma	2.000000e-13
GCST012298_14	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	7.000000e-06
GCST012301_8	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
sodium arsenite	increases expression	1
zinc sulfide	increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	affects cotreatment, increases expression	1
Lead	decreases expression	1
Selenium	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.