REG3A
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.
Function
Regenerating islet-derived protein 3-alpha 15 kDa form
Bactericidal C-type lectin which acts exclusively against Gram-positive bacteria and mediates bacterial killing by binding to surface-exposed carbohydrate moieties of peptidoglycan (PubMed:16931762). Binds membrane phospholipids and kills bacteria by forming a hexameric membrane-permeabilizing oligomeric pore (PubMed:24256734).
Acts as a hormone in response to different stimuli like anti-inflammatory signals, such as IL17A, or gut microbiome. Secreted by different cell types to activate its receptor EXTL3 and induce cell specific signaling pathways (PubMed:19158046, PubMed:22727489, PubMed:27830702, PubMed:34099862). Induced by IL17A in keratinocytes, regulates keratinocyte proliferation and differentiation after skin injury via activation of EXTL3-PI3K-AKT signaling pathway (PubMed:22727489). In parallel, inhibits skin inflammation through the inhibition of inflammatory cytokines such as IL6 and TNF (PubMed:27830702). In pancreas, is able to permealize beta-cells membrane and stimulate their proliferation (PubMed:19158046).
Regenerating islet-derived protein 3-alpha 16.5 kDa form
Has bacteriostatic activity.
Post-translational modifications
Proteolytic processing by trypsin removes an inhibitory N-terminal propeptide and is essential for peptidoglycan binding and antibacterial activity.
Tissue Specificity
Expressed by keratinocytes (PubMed:27830702). Highly expressed in epidermal keratinocytes of psoriasis patients (at protein level) (PubMed:22727489). Constitutively expressed in intestine. Low expression is found in healthy pancreas. Overexpressed during the acute phase of pancreatitis and in some patients with chronic pancreatitis (PubMed:1469087).
Cellular localization
- Secreted
- Found in the apical region of pancreatic acinar cells.
Alternative names
HIP, PAP, PAP1, REG3A, Regenerating islet-derived protein 3-alpha, REG-3-alpha, Hepatointestinal pancreatic protein, Human proislet peptide, Pancreatitis-associated protein 1, Regenerating islet-derived protein III-alpha, HIP/PAP, Reg III-alpha