O09049 · REG3G_MOUSE
- ProteinRegenerating islet-derived protein 3-gamma
- GeneReg3g
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids174 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Bactericidal C-type lectin which acts exclusively against Gram-positive bacteria and mediates bacterial killing by binding to surface-exposed carbohydrate moieties of peptidoglycan. Restricts bacterial colonization of the intestinal epithelial surface and consequently limits activation of adaptive immune responses by the microbiota.
Acts as a hormone in response to different stimuli like anti-inflammatory signals, such as IL17A, or gut microbiome. Is secreted by different cell types to activate its receptor EXTL3 and induce cell specific signaling pathways (PubMed:22727489, PubMed:27830702, PubMed:36240758).
Induced by IL17A in keratinocytes, regulates keratinocyte proliferation and differentiation after skin injury (PubMed:22727489).
In parallel, inhibits skin inflammation through the inhibition of inflammatory cytokines such as IL6 and TNF (PubMed:27830702).
Induced by IL22 in lung epithelial cells, inhibits cytokine production and regulates allergic airway inflammation (PubMed:28811323).
Induced in small intestine by inulin-enriched diet and Lactobacillus gasseri enriched microbiome, plays a role in the improvement of gut barrier function, the regulation of energy balance and glucose levels. Modulates microbiota composition in duodenal contents (PubMed:36240758).
Produced by nociceptor in response to endotoxins, prevents endotoxic death by targeting kynurenine pathway in microglia (PubMed:35263589).
Induced by IL17A in keratinocytes, regulates keratinocyte proliferation and differentiation after skin injury (PubMed:22727489).
In parallel, inhibits skin inflammation through the inhibition of inflammatory cytokines such as IL6 and TNF (PubMed:27830702).
Induced by IL22 in lung epithelial cells, inhibits cytokine production and regulates allergic airway inflammation (PubMed:28811323).
Induced in small intestine by inulin-enriched diet and Lactobacillus gasseri enriched microbiome, plays a role in the improvement of gut barrier function, the regulation of energy balance and glucose levels. Modulates microbiota composition in duodenal contents (PubMed:36240758).
Produced by nociceptor in response to endotoxins, prevents endotoxic death by targeting kynurenine pathway in microglia (PubMed:35263589).
Regenerating islet-derived protein 3-gamma 16.5 kDa form
Has bacteriostatic activity.
Regenerating islet-derived protein 3-gamma 15 kDa form
Has bactericidal activity against L.monocytogenes and methicillin-resistant S.aureus.
Activity regulation
Regenerating islet-derived protein 3-gamma 15 kDa form
Lipopolysaccharide inhibits pore-forming activity, explaining why is bactericidal for Gram-positive but not Gram-negative bacteria.
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameRegenerating islet-derived protein 3-gamma
- Short namesREG-3-gamma
- Alternative names
- Cleaved into 2 chains
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionO09049
Proteomes
Organism-specific databases
Phenotypes & Variants
Disruption phenotype
Mutant mice are born at normal Mendelian ratios. They appear healthy and show no signs of enteropathy, but exhibit marked increase in the number of mucosa-associated bacteria, predominantly Gram-positive, relative to cohoused wild-type littermates in distal small intestine (PubMed:21998396).
Nociceptor-specific deficient mice exhibit high mortality rates in response to endotoxin accompanied by increased kynurenine pathway and impaired ATP production in the brain (PubMed:35263589).
Nociceptor-specific deficient mice exhibit high mortality rates in response to endotoxin accompanied by increased kynurenine pathway and impaired ATP production in the brain (PubMed:35263589).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 19 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, propeptide, chain, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-26 | |||||
Sequence: MLPRITITIMSWMLLSCLMLLSQVQG | ||||||
Propeptide | PRO_0000422753 | 27-37 | ||||
Sequence: EVAKKDAPSSR | ||||||
Chain | PRO_0000017435 | 27-174 | Regenerating islet-derived protein 3-gamma 16.5 kDa form | |||
Sequence: EVAKKDAPSSRSSCPKGSRAYGSYCYALFSVSKNWYDADMACQKRPSGHLVSVLSGAEASFLSSMIKSSGNSGQYVWIGLHDPTLGYEPNRGGWEWSNADVMNYINWETNPSSSSGNHCGTLSRASGFLKWRENYCNLELPYVCKFKA | ||||||
Chain | PRO_0000422754 | 38-174 | Regenerating islet-derived protein 3-gamma 15 kDa form | |||
Sequence: SSCPKGSRAYGSYCYALFSVSKNWYDADMACQKRPSGHLVSVLSGAEASFLSSMIKSSGNSGQYVWIGLHDPTLGYEPNRGGWEWSNADVMNYINWETNPSSSSGNHCGTLSRASGFLKWRENYCNLELPYVCKFKA | ||||||
Disulfide bond | 40↔51 | |||||
Sequence: CPKGSRAYGSYC | ||||||
Disulfide bond | 68↔170 | |||||
Sequence: CQKRPSGHLVSVLSGAEASFLSSMIKSSGNSGQYVWIGLHDPTLGYEPNRGGWEWSNADVMNYINWETNPSSSSGNHCGTLSRASGFLKWRENYCNLELPYVC | ||||||
Disulfide bond | 145↔162 | |||||
Sequence: CGTLSRASGFLKWRENYC |
Post-translational modification
Proteolytic processing by trypsin removes an inhibitory N-terminal propeptide and is essential for peptidoglycan binding and antibacterial activity.
Keywords
- PTM
Proteomic databases
Expression
Tissue specificity
Predominantly expressed in the small intestine, including Paneth cells (at protein level). Hardly detectable in the colon (at protein level) (PubMed:16504538, PubMed:16931762, PubMed:17635956, PubMed:21998396).
Highly expressed in the lung epithelium during methicillin-resistant S.aureus infection and allergic airway inflammation (at protein level) (PubMed:28811323).
Skin injury increases its epidermal expression (PubMed:22727489, PubMed:23401489, PubMed:27830702).
Also expressed in the pancreas (PubMed:9055810).
Expressed by nocireceptors (PubMed:35263589).
Highly expressed in the lung epithelium during methicillin-resistant S.aureus infection and allergic airway inflammation (at protein level) (PubMed:28811323).
Skin injury increases its epidermal expression (PubMed:22727489, PubMed:23401489, PubMed:27830702).
Also expressed in the pancreas (PubMed:9055810).
Expressed by nocireceptors (PubMed:35263589).
Induction
Up-regulated in Paneth cells by intestinal microbiota (at protein level) (PubMed:16931762).
MyD88-mediated signals are essential for its induction in intestinal epithelial cells (PubMed:17635956).
Induction in the lung is dependent on IL6ST-induced STAT3 signaling (PubMed:23401489).
IL17A and IL33 induces its expression in primary keratinocytes and skin wounds (PubMed:22727489, PubMed:27830702).
IL22 induces its expression in lung epithelial cells (PubMed:28811323).
Feeding with a fermentable fiber-enriched inulin diet increases expression in intestine (PubMed:36240758).
Expressed by nociceptors in response to LPS (PubMed:35263589).
MyD88-mediated signals are essential for its induction in intestinal epithelial cells (PubMed:17635956).
Induction in the lung is dependent on IL6ST-induced STAT3 signaling (PubMed:23401489).
IL17A and IL33 induces its expression in primary keratinocytes and skin wounds (PubMed:22727489, PubMed:27830702).
IL22 induces its expression in lung epithelial cells (PubMed:28811323).
Feeding with a fermentable fiber-enriched inulin diet increases expression in intestine (PubMed:36240758).
Expressed by nociceptors in response to LPS (PubMed:35263589).
Developmental stage
In mid-small intestine, very low levels at birth. Expression levels rise dramatically during the weaning period (P17-P22) and remain high into adulthood in conventionally raised but not germfree animals.
Gene expression databases
Interaction
Subunit
Regenerating islet-derived protein 3-gamma 15 kDa form
Forms a hexameric membrane-permeabilizing oligomeric pore on membrane phospholipids. The hexamer is formed by three dimers related by helical symmetry. Forms filaments, filamentation traps pore complexes and limits damage to host cells. Interacts with EXTL3.
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 47-171 | C-type lectin | ||||
Sequence: YGSYCYALFSVSKNWYDADMACQKRPSGHLVSVLSGAEASFLSSMIKSSGNSGQYVWIGLHDPTLGYEPNRGGWEWSNADVMNYINWETNPSSSSGNHCGTLSRASGFLKWRENYCNLELPYVCK | ||||||
Region | 103-118 | Sufficient to activate EXTL3 | ||||
Sequence: WIGLHDPTLGYEPNRG | ||||||
Motif | 114-116 | EPN | ||||
Sequence: EPN |
Domain
The EPN motif is essential for recognition of the peptidoglycan carbohydrate backbone and for efficient bacterial killing with Glu-114 playing a key role in peptidoglycan binding and bactericidal activity.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length174
- Mass (Da)19,307
- Last updated1997-07-01 v1
- Checksum5575E9E56A4D8CEF
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D63361 EMBL· GenBank· DDBJ | BAA18930.1 EMBL· GenBank· DDBJ | mRNA | ||
D63362 EMBL· GenBank· DDBJ | BAA18931.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC061139 EMBL· GenBank· DDBJ | AAH61139.1 EMBL· GenBank· DDBJ | mRNA |