General Information of Drug Off-Target (DOT) (ID: OTLIUY8Z)

DOT Name Regenerating islet-derived protein 3-gamma (REG3G)
Synonyms REG-3-gamma; Pancreatitis-associated protein 1B; PAP-1B; Pancreatitis-associated protein IB; PAP IB; Regenerating islet-derived protein III-gamma; REG III; Reg III-gamma
Gene Name REG3G
Related Disease
Alcoholic liver diseases ( )
Colitis ( )
Fatty liver disease ( )
Head and neck cancer ( )
Head and neck carcinoma ( )
High blood pressure ( )
Lung cancer ( )
Lung carcinoma ( )
Head-neck squamous cell carcinoma ( )
Chronic pancreatitis ( )
Cystitis ( )
Matthew-Wood syndrome ( )
Neoplasm ( )
Pancreatic cancer ( )
Pancreatic ductal carcinoma ( )
Pyelonephritis ( )
UniProt ID
REG3G_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00059
Sequence
MLPPMALPSVSWMLLSCLILLCQVQGEETQKELPSPRISCPKGSKAYGSPCYALFLSPKS
WMDADLACQKRPSGKLVSVLSGAEGSFVSSLVRSISNSYSYIWIGLHDPTQGSEPDGDGW
EWSSTDVMNYFAWEKNPSTILNPGHCGSLSRSTGFLKWKDYNCDAKLPYVCKFKD
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. Induced by IL17A in keratinocytes, regulates keratinocyte proliferation and differentiation after skin injury. In parallel, inhibits skin inflammation through the inhibition of inflammatory cytokines such as IL6 and TNF. Induced by IL22 in lung epithelial cells, inhibits cytokine production and regulates allergic airway inflammation. 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. Produced by nociceptor in response to endotoxins, prevents endotoxic death by targeting kynurenine pathway in microglia; [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.
Tissue Specificity Predominantly expressed in pancreas, where it may be restricted to exocrine pancreas. Moderate expression levels in testis and weak in heart, kidney and placenta.
Reactome Pathway
Antimicrobial peptides (R-HSA-6803157 )

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alcoholic liver diseases DISXEPHQ Strong Biomarker [1]
Colitis DISAF7DD Strong Altered Expression [2]
Fatty liver disease DIS485QZ Strong Altered Expression [1]
Head and neck cancer DISBPSQZ Strong Altered Expression [3]
Head and neck carcinoma DISOU1DS Strong Altered Expression [3]
High blood pressure DISY2OHH Strong Biomarker [4]
Lung cancer DISCM4YA Strong Altered Expression [5]
Lung carcinoma DISTR26C Strong Altered Expression [5]
Head-neck squamous cell carcinoma DISF7P24 moderate Altered Expression [6]
Chronic pancreatitis DISBUOMJ Limited Biomarker [7]
Cystitis DIS2D4B9 Limited Altered Expression [8]
Matthew-Wood syndrome DISA7HR7 Limited Biomarker [7]
Neoplasm DISZKGEW Limited Biomarker [7]
Pancreatic cancer DISJC981 Limited Biomarker [7]
Pancreatic ductal carcinoma DIS26F9Q Limited Biomarker [7]
Pyelonephritis DISAOX93 Limited Altered Expression [8]
------------------------------------------------------------------------------------
⏷ Show the Full List of 16 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Isoproterenol DMK7MEY Approved Isoproterenol decreases the expression of Regenerating islet-derived protein 3-gamma (REG3G). [9]
------------------------------------------------------------------------------------
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Regenerating islet-derived protein 3-gamma (REG3G). [10]
------------------------------------------------------------------------------------

References

1 Bacteria engineered to produce IL-22 in intestine induce expression of REG3G to reduce ethanol-induced liver disease in mice.Gut. 2019 Aug;68(8):1504-1515. doi: 10.1136/gutjnl-2018-317232. Epub 2018 Nov 17.
2 The AIM2 inflammasome is a central regulator of intestinal homeostasis through the IL-18/IL-22/STAT3 pathway.Cell Mol Immunol. 2017 Jan;14(1):127-142. doi: 10.1038/cmi.2016.35. Epub 2016 Aug 15.
3 Expression of REG III and prognosis in head and neck cancer.Oncol Rep. 2013 Aug;30(2):573-8. doi: 10.3892/or.2013.2521. Epub 2013 Jun 5.
4 Mitogen-activated protein kinase p38 target regenerating islet-derived 3 expression is upregulated in cardiac inflammatory response in the rat heart.Physiol Rep. 2016 Oct;4(20):e12996. doi: 10.14814/phy2.12996. Epub 2016 Oct 24.
5 REG I gene expression is linked with the poor prognosis of lung adenocarcinoma and squamous cell carcinoma patients via discrete mechanisms.Oncol Rep. 2013 Dec;30(6):2625-31. doi: 10.3892/or.2013.2739. Epub 2013 Sep 19.
6 Resveratrolinduced REG III expression enhances chemo?and radiosensitivity in head and neck cancer in xenograft mice.Oncol Rep. 2019 Jul;42(1):436-442. doi: 10.3892/or.2019.7137. Epub 2019 Apr 25.
7 Acceleration of pancreatic tumorigenesis under immunosuppressive microenvironment induced by Reg3g overexpression.Cell Death Dis. 2017 Sep 7;8(9):e3033. doi: 10.1038/cddis.2017.424.
8 Expression and Significance of the HIP/PAP and RegIII Antimicrobial Peptides during Mammalian Urinary Tract Infection.PLoS One. 2015 Dec 10;10(12):e0144024. doi: 10.1371/journal.pone.0144024. eCollection 2015.
9 Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo. Toxicol Appl Pharmacol. 2014 Jan 15;274(2):302-12.
10 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.