Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFC725Z)

• DOT Name: Catenin alpha-1 (CTNNA1)
• Synonyms: Alpha E-catenin; Cadherin-associated protein; Renal carcinoma antigen NY-REN-13
• Gene Name: CTNNA1
• Related Disease:
  CTNNA1-related diffuse gastric and lobular breast cancer syndrome
  Metabolic disorder
  Neural tube defect
  Ovarian neoplasm
  Patterned macular dystrophy 2
  Adult glioblastoma
  Age-related macular degeneration
  Astrocytoma
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cardiac failure
  Childhood myelodysplastic syndrome
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Congestive heart failure
  Desmoid tumour
  Gastric cancer
  Gastrointestinal stromal tumour
  Glioblastoma multiforme
  Haematological malignancy
  Leber congenital amaurosis 1
  leukaemia
  Leukemia
  Lung carcinoma
  Myelodysplastic syndrome
  Neoplasm of esophagus
  Non-alcoholic fatty liver disease
  Pancreatic tumour
  Patterned dystrophy of the retinal pigment epithelium
  Renal cell carcinoma
  Signet ring cell carcinoma
  Squamous cell carcinoma
  Stomach cancer
  Urinary bladder neoplasm
  Schwannoma
  Patterned macular dystrophy
  Acute myelogenous leukaemia
  Advanced cancer
  Asthma
  Childhood kidney Wilms tumor
  Cutaneous squamous cell carcinoma
  Thyroid gland papillary carcinoma
  Wilms tumor
  Hereditary nonpolyposis colon cancer
• UniProt ID: CTNA1_HUMAN
• PDB ID: 1H6G; 4EHP; 4IGG; 6UPV; 6V2O; 6V2P; 7UTJ
• Pfam ID: PF01044
• Sequence:
  MTAVHAGNINFKWDPKSLEIRTLAVERLLEPLVTQVTTLVNTNSKGPSNKKRGRSKKAHV
  LAASVEQATENFLEKGDKIAKESQFLKEELVAAVEDVRKQGDLMKAAAGEFADDPCSSVK
  RGNMVRAARALLSAVTRLLILADMADVYKLLVQLKVVEDGILKLRNAGNEQDLGIQYKAL
  KPEVDKLNIMAAKRQQELKDVGHRDQMAAARGILQKNVPILYTASQACLQHPDVAAYKAN
  RDLIYKQLQQAVTGISNAAQATASDDASQHQGGGGGELAYALNNFDKQIIVDPLSFSEER
  FRPSLEERLESIISGAALMADSSCTRDDRRERIVAECNAVRQALQDLLSEYMGNAGRKER
  SDALNSAIDKMTKKTRDLRRQLRKAVMDHVSDSFLETNVPLLVLIEAAKNGNEKEVKEYA
  QVFREHANKLIEVANLACSISNNEEGVKLVRMSASQLEALCPQVINAALALAAKPQSKLA
  QENMDLFKEQWEKQVRVLTDAVDDITSIDDFLAVSENHILEDVNKCVIALQEKDVDGLDR
  TAGAIRGRAARVIHVVTSEMDNYEPGVYTEKVLEATKLLSNTVMPRFTEQVEAAVEALSS
  DPAQPMDENEFIDASRLVYDGIRDIRKAVLMIRTPEELDDSDFETEDFDVRSRTSVQTED
  DQLIAGQSARAIMAQLPQEQKAKIAEQVASFQEEKSKLDAEVSKWDDSGNDIIVLAKQMC
  MIMMEMTDFTRGKGPLKNTSDVISAAKKIAEAGSRMDKLGRTIADHCPDSACKQDLLAYL
  QRIALYCHQLNICSKVKAEVQNLGGELVVSGVDSAMSLIQAAKNLMNAVVQTVKASYVAS
  TKYQKSQGMASLNLPAVSWKMKAPEKKPLVKREKQDETQTKIKRASQKKHVNPVQALSEF
  KAMDSI
• Function: Associates with the cytoplasmic domain of a variety of cadherins. The association of catenins to cadherins produces a complex which is linked to the actin filament network, and which seems to be of primary importance for cadherins cell-adhesion properties. Can associate with both E- and N-cadherins. Originally believed to be a stable component of E-cadherin/catenin adhesion complexes and to mediate the linkage of cadherins to the actin cytoskeleton at adherens junctions. In contrast, cortical actin was found to be much more dynamic than E-cadherin/catenin complexes and CTNNA1 was shown not to bind to F-actin when assembled in the complex suggesting a different linkage between actin and adherens junctions components. The homodimeric form may regulate actin filament assembly and inhibit actin branching by competing with the Arp2/3 complex for binding to actin filaments. Involved in the regulation of WWTR1/TAZ, YAP1 and TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation. May play a crucial role in cell differentiation.
• Tissue Specificity: Expressed ubiquitously in normal tissues.
• KEGG Pathway:
  Hippo sig.ling pathway (hsa04390)
  Adherens junction (hsa04520)
  Leukocyte transendothelial migration (hsa04670)
  Bacterial invasion of epithelial cells (hsa05100)
  Pathways in cancer (hsa05200)
  Endometrial cancer (hsa05213)
  Gastric cancer (hsa05226)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
• Reactome Pathway:
  VEGFR2 mediated vascular permeability (R-HSA-5218920)
  Myogenesis (R-HSA-525793)
  RHO GTPases activate IQGAPs (R-HSA-5626467)
  Regulation of CDH11 function (R-HSA-9762292)
  Regulation of CDH19 Expression and Function (R-HSA-9764302)
  CDH11 homotypic and heterotypic interactions (R-HSA-9833576)
  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
CTNNA1-related diffuse gastric and lobular breast cancer syndrome	DISUOJ70	Definitive	Autosomal dominant	[1]
Metabolic disorder	DIS71G5H	Definitive	Biomarker	[2]
Neural tube defect	DIS5J95E	Definitive	Genetic Variation	[3]
Ovarian neoplasm	DISEAFTY	Definitive	Genetic Variation	[4]
Patterned macular dystrophy 2	DISP4RA9	Definitive	Autosomal dominant	[5]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[6]
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[5]
Astrocytoma	DISL3V18	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[7]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[7]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[8]
Cardiac failure	DISDC067	Strong	Biomarker	[9]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Posttranslational Modification	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Colon cancer	DISVC52G	Strong	Genetic Variation	[12]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[13]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[9]
Desmoid tumour	DISGX357	Strong	Genetic Variation	[14]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[15]
Gastrointestinal stromal tumour	DIS6TJYS	Strong	Biomarker	[16]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[6]
Haematological malignancy	DISCDP7W	Strong	Posttranslational Modification	[10]
Leber congenital amaurosis 1	DISY2B33	Strong	Genetic Variation	[17]
leukaemia	DISS7D1V	Strong	Posttranslational Modification	[18]
Leukemia	DISNAKFL	Strong	Posttranslational Modification	[18]
Lung carcinoma	DISTR26C	Strong	Biomarker	[19]
Myelodysplastic syndrome	DISYHNUI	Strong	Posttranslational Modification	[10]
Neoplasm of esophagus	DISOLKAQ	Strong	ModifyingMutation	[20]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[21]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[22]
Patterned dystrophy of the retinal pigment epithelium	DIST5BD5	Strong	Biomarker	[5]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[11]
Signet ring cell carcinoma	DISVCUCR	Strong	Genetic Variation	[23]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[24]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[15]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[25]
Schwannoma	DISTTVLA	moderate	Biomarker	[26]
Patterned macular dystrophy	DISWIXVD	Supportive	Autosomal dominant	[5]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[27]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[28]
Asthma	DISW9QNS	Limited	Altered Expression	[29]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Genetic Variation	[30]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Altered Expression	[31]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Genetic Variation	[32]
Wilms tumor	DISB6T16	Limited	Genetic Variation	[30]
Hereditary nonpolyposis colon cancer	DISPA49R	No Known	Autosomal dominant	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	Catenin alpha-1 (CTNNA1) affects the response to substance of Mitomycin.	[54]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Catenin alpha-1 (CTNNA1).	[33]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Catenin alpha-1 (CTNNA1).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Catenin alpha-1 (CTNNA1).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Catenin alpha-1 (CTNNA1).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Catenin alpha-1 (CTNNA1).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Catenin alpha-1 (CTNNA1).	[38]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Catenin alpha-1 (CTNNA1).	[39]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Catenin alpha-1 (CTNNA1).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Catenin alpha-1 (CTNNA1).	[41]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Catenin alpha-1 (CTNNA1).	[35]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Catenin alpha-1 (CTNNA1).	[42]
Selenium	DM25CGV	Approved	Selenium increases the expression of Catenin alpha-1 (CTNNA1).	[43]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Catenin alpha-1 (CTNNA1).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Catenin alpha-1 (CTNNA1).	[46]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Catenin alpha-1 (CTNNA1).	[47]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Catenin alpha-1 (CTNNA1).	[49]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Catenin alpha-1 (CTNNA1).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Catenin alpha-1 (CTNNA1).	[51]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Catenin alpha-1 (CTNNA1).	[46]
Manganese	DMKT129	Investigative	Manganese decreases the expression of Catenin alpha-1 (CTNNA1).	[52]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Catenin alpha-1 (CTNNA1).	[53]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Catenin alpha-1 (CTNNA1).	[46]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion increases the expression of Catenin alpha-1 (CTNNA1).	[46]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Catenin alpha-1 (CTNNA1).	[45]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Catenin alpha-1 (CTNNA1).	[48]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Catenin alpha-1 (CTNNA1).	[48]

References

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