Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTE5ZR6)

• DOT Name: Nectin-1 (NECTIN1)
• Synonyms: Herpes virus entry mediator C; Herpesvirus entry mediator C; HveC; Herpesvirus Ig-like receptor; HIgR; Nectin cell adhesion molecule 1; Poliovirus receptor-related protein 1; CD antigen CD111
• Gene Name: NECTIN1
• Related Disease:
  Cleft lip
  Obsessive compulsive disorder
  Tourette syndrome
  Type-1/2 diabetes
  Adult glioblastoma
  Advanced cancer
  Autoimmune disease
  Brain neoplasm
  Breast carcinoma
  Cleft lip and alveolus
  Cleft lip/palate
  Cleft lip/palate-ectodermal dysplasia syndrome
  Cleft palate
  Ectodermal dysplasia
  Endometriosis
  Erectile dysfunction
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Isolated cleft lip
  Isolated cleft palate
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Pancreatic adenocarcinoma
  Polycythemia vera
  Squamous cell carcinoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid gland papillary carcinoma
  Thyroid tumor
  Arteriosclerosis
  Atherosclerosis
  Bacterial infection
  Herpes simplex infection
  High blood pressure
  Intellectual disability
  Adenocarcinoma
  Breast cancer
  Colorectal carcinoma
  Corpus callosum, agenesis of
  Gastric cancer
  Matthew-Wood syndrome
  Nervous system disease
  Neuroblastoma
  Pancreatic ductal carcinoma
  Stomach cancer
• UniProt ID: NECT1_HUMAN
• PDB ID: 3ALP; 3SKU; 3U82; 3U83; 4FMF; 4MYW
• Pfam ID: PF08205 ; PF13927 ; PF07686
• Sequence:
  MARMGLAGAAGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLHCSFANPLPSV
  KITQVTWQKSTNGSKQNVAIYNPSMGVSVLAPYRERVEFLRPSFTDGTIRLSRLELEDEG
  VYICEFATFPTGNRESQLNLTVMAKPTNWIEGTQAVLRAKKGQDDKVLVATCTSANGKPP
  SVVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHQQSLACIVNYHMDRFKESLT
  LNVQYEPEVTIEGFDGNWYLQRMDVKLTCKADANPPATEYHWTTLNGSLPKGVEAQNRTL
  FFKGPINYSLAGTYICEATNPIGTRSGQVEVNITEFPYTPSPPEHGRRAGPVPTAIIGGV
  AGSILLVLIVVGGIVVALRRRRHTFKGDYSTKKHVYGNGYSKAGIPQHHPPMAQNLQYPD
  DSDDEKKAGPLGGSSYEEEEEEEEGGGGGERKVGGPHPKYDEDAKRPYFTVDEAEARQDG
  YGDRTLGYQYDPEQLDLAENMVSQNDGSFISKKEWYV
• Function: Promotes cell-cell contacts by forming homophilic or heterophilic trans-dimers. Heterophilic interactions have been detected between NECTIN1 and NECTIN3 and between NECTIN1 and NECTIN4. Has some neurite outgrowth-promoting activity; (Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1, herpes simplex virus 2/HHV-2, and pseudorabies virus/PRV.
• KEGG Pathway:
  Virion - Herpesvirus (hsa03266)
  Cell adhesion molecules (hsa04514)
  Adherens junction (hsa04520)
  Herpes simplex virus 1 infection (hsa05168)
• Reactome Pathway:
  Nectin/Necl trans heterodimerization (R-HSA-420597)
  Adherens junctions interactions (R-HSA-418990)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cleft lip	DISV3XW6	Definitive	Genetic Variation	[1]
Obsessive compulsive disorder	DIS1ZMM2	Definitive	Genetic Variation	[2]
Tourette syndrome	DISX9D54	Definitive	Genetic Variation	[2]
Type-1/2 diabetes	DISIUHAP	Definitive	Genetic Variation	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[5]
Autoimmune disease	DISORMTM	Strong	Biomarker	[6]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Cleft lip and alveolus	DISD651B	Strong	SusceptibilityMutation	[8]
Cleft lip/palate	DIS14IG3	Strong	Genetic Variation	[9]
Cleft lip/palate-ectodermal dysplasia syndrome	DISHCH8Y	Strong	Autosomal recessive	[10]
Cleft palate	DIS6G5TF	Strong	Genetic Variation	[11]
Ectodermal dysplasia	DISLRS4M	Strong	Genetic Variation	[12]
Endometriosis	DISX1AG8	Strong	Biomarker	[13]
Erectile dysfunction	DISD8MTH	Strong	Biomarker	[12]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[11]
Isolated cleft palate	DISV80CD	Strong	Genetic Variation	[11]
Lung cancer	DISCM4YA	Strong	Biomarker	[16]
Lung carcinoma	DISTR26C	Strong	Biomarker	[16]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[17]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Biomarker	[18]
Polycythemia vera	DISB5FPO	Strong	Biomarker	[19]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[20]
Thyroid cancer	DIS3VLDH	Strong	Altered Expression	[21]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[21]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Altered Expression	[21]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[21]
Arteriosclerosis	DISK5QGC	moderate	Biomarker	[22]
Atherosclerosis	DISMN9J3	moderate	Biomarker	[22]
Bacterial infection	DIS5QJ9S	moderate	Genetic Variation	[23]
Herpes simplex infection	DISL1SAV	moderate	Altered Expression	[24]
High blood pressure	DISY2OHH	moderate	Biomarker	[25]
Intellectual disability	DISMBNXP	Disputed	Biomarker	[26]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[27]
Breast cancer	DIS7DPX1	Limited	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[5]
Corpus callosum, agenesis of	DISO9P40	Limited	Biomarker	[28]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[29]
Matthew-Wood syndrome	DISA7HR7	Limited	Altered Expression	[30]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[31]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[32]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Altered Expression	[30]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[29]

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nectin-1 (NECTIN1).	[33]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nectin-1 (NECTIN1).	[34]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Nectin-1 (NECTIN1).	[35]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Nectin-1 (NECTIN1).	[36]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nectin-1 (NECTIN1).	[37]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Nectin-1 (NECTIN1).	[38]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Nectin-1 (NECTIN1).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nectin-1 (NECTIN1).	[39]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Nectin-1 (NECTIN1).	[40]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Nectin-1 (NECTIN1).	[41]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Nectin-1 (NECTIN1).	[42]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Nectin-1 (NECTIN1).	[43]

References

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• [22] A functional variant in the CARD4 gene and risk of premature coronary heart disease.Int J Immunogenet. 2006 Aug;33(4):307-11. doi: 10.1111/j.1744-313X.2006.00618.x.
• [23] Functional polymorphisms of innate immunity receptors are not risk factors for the non-SBP type bacterial infections in cirrhosis.Liver Int. 2018 Jul;38(7):1242-1252. doi: 10.1111/liv.13664. Epub 2018 Jan 17.
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