Details of Drug Off-Target (DOT)

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

DOT Name Cadherin-related family member 2 (CDHR2)
Synonyms Protocadherin LKC; PC-LKC; Protocadherin-24
Gene Name CDHR2
Related Disease
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Hepatocellular carcinoma ( )
Hereditary nonpolyposis colon cancer ( )
Liver cancer ( )
Congenital contractural arachnodactyly ( )
Neoplasm ( )
UniProt ID
CDHR2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5CZR; 7N86
Pfam ID
PF00028
Sequence
MAQLWLSCFLLPALVVSVAANVAPKFLANMTSVILPEDLPVGAQAFWLVAEDQDNDPLTY
GMSGPNAYFFAVTPKTGEVKLASALDYETLYTFKVTISVSDPYIQVQREMLVIVEDRNDN
APVFQNTAFSTSINETLPVGSVVFSVLAVDKDMGSAGMVVYSIEKVIPSTGDSEHLFRIL
ANGSIVLNGSLSYNNKSAFYQLELKACDLGGMYHNTFTIQCSLPVFLSISVVDQPDLDPQ
FVREFYSASVAEDAAKGTSVLTVEAVDGDKGINDPVIYSISYSTRPGWFDIGADGVIRVN
GSLDREQLLEADEEVQLQVTATETHLNIYGQEAKVSIWVTVRVMDVNDHKPEFYNCSLPA
CTFTPEEAQVNFTGYVDEHASPRIPIDDLTMVVYDPDKGSNGTFLLSLGGPDAEAFSVSP
ERAVGSASVQVLVRVSALVDYERQTAMAVQVVATDSVSQNFSVAMVTIHLRDINDHRPTF
PQSLYVLTVPEHSATGSVVTDSIHATDPDTGAWGQITYSLLPGNGADLFQVDPVSGTVTV
RNGELLDRESQAVYYLTLQATDGGNLSSSTTLQIHLLDINDNAPVVSGSYNIFVQEEEGN
VSVTIQAHDNDEPGTNNSRLLFNLLPGPYSHNFSLDPDTGLLRNLGPLDREAIDPALEGR
IVLTVLVSDCGEPVLGTKVNVTITVEDINDNLPIFNQSSYNFTVKEEDPGVLVGVVKAWD
ADQTEANNRISFSLSGSGANYFMIRGLVLGAGWAEGYLRLPPDVSLDYETQPVFNLTVSA
ENPDPQGGETIVDVCVNVKDVNDNPPTLDVASLRGIRVAENGSQHGQVAVVVASDVDTSA
QLEIQLVNILCTKAGVDVGSLCWGWFSVAANGSVYINQSKAIDYEACDLVTLVVRACDLA
TDPGFQAYSNNGSLLITIEDVNDNAPYFLPENKTFVIIPELVLPNREVASVRARDDDSGN
NGVILFSILRVDFISKDGATIPFQGVFSIFTSSEADVFAGSIQPVTSLDSTLQGTYQVTV
QARDRPSLGPFLEATTTLNLFTVDQSYRSRLQFSTPKEEVGANRQAINAALTQATRTTVY
IVDIQDIDSAARARPHSYLDAYFVFPNGSALTLDELSVMIRNDQDSLTQLLQLGLVVLGS
QESQESDLSKQLISVIIGLGVALLLVLVIMTMAFVCVRKSYNRKLQAMKAAKEARKTAAG
VMPSAPAIPGTNMYNTERANPMLNLPNKDLGLEYLSPSNDLDSVSVNSLDDNSVDVDKNS
QEIKEHRPPHTPPEPDPEPLSVVLLGRQAGASGQLEGPSYTNAGLDTTDL
Function
Intermicrovillar adhesion molecule that forms, via its extracellular domain, calcium-dependent heterophilic complexes with CDHR5 on adjacent microvilli. Thereby, controls the packing of microvilli at the apical membrane of epithelial cells. Through its cytoplasmic domain, interacts with microvillus cytoplasmic proteins to form the intermicrovillar adhesion complex/IMAC. This complex plays a central role in microvilli and epithelial brush border differentiation. May also play a role in cell-cell adhesion and contact inhibition in epithelial cells.
Tissue Specificity
Highly expressed in liver, kidney and colon. Moderately expressed in small intestine. Down-regulated in a number of liver and colon cancers . Expressed in duodenum with higher expression in enterocytes along the villus axis and lower expression in crypts (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colon cancer DISVC52G Strong Altered Expression [1]
Colon carcinoma DISJYKUO Strong Altered Expression [1]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [2]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [3]
Hereditary nonpolyposis colon cancer DISPA49R Strong Biomarker [2]
Liver cancer DISDE4BI Strong Biomarker [1]
Congenital contractural arachnodactyly DISOM1K7 Limited Biomarker [4]
Neoplasm DISZKGEW Limited Biomarker [3]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Cadherin-related family member 2 (CDHR2). [5]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of Cadherin-related family member 2 (CDHR2). [6]
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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 decreases the methylation of Cadherin-related family member 2 (CDHR2). [7]
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References

1 Protocadherin LKC, a new candidate for a tumor suppressor of colon and liver cancers, its association with contact inhibition of cell proliferation.Carcinogenesis. 2002 Jul;23(7):1139-48. doi: 10.1093/carcin/23.7.1139.
2 Loss of expression of -protocadherin and protocadherin-24 in sporadic and hereditary nonpolyposis colorectal cancers.Hum Pathol. 2019 Feb;84:299-308. doi: 10.1016/j.humpath.2018.09.019. Epub 2018 Oct 5.
3 Cadherin Related Family Member 2 Acts As A Tumor Suppressor By Inactivating AKT In Human Hepatocellular Carcinoma.J Cancer. 2019 Jan 29;10(4):864-873. doi: 10.7150/jca.27663. eCollection 2019.
4 Discovery and Qualification of Serum Protein Biomarker Candidates for Cholangiocarcinoma Diagnosis.J Proteome Res. 2019 Sep 6;18(9):3305-3316. doi: 10.1021/acs.jproteome.9b00242. Epub 2019 Jul 31.
5 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
6 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
7 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.