Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI76XGK)

• DOT Name: Cilia- and flagella-associated protein 53 (CFAP53)
• Synonyms: Coiled-coil domain-containing protein 11
• Gene Name: CFAP53
• Related Disease:
  Heterotaxy, visceral, 6, autosomal
  Visceral heterotaxy
  Situs inversus
• UniProt ID: CFA53_HUMAN
• PDB ID: 7UNG; 8J07
• Pfam ID: PF13868
• Sequence:
  MYSQRFGTVQREVKGPTPKVVIVRSKPPKGQGAEHHLERIRRSHQKHNAILASIKSSERD
  RLKAEWDQHNDCKILDSLVRARIKDAVQGFIINIEERRNKLRELLALEENEYFTEMQLKK
  ETIEEKKDRMREKTKLLKEKNEKERQDFVAEKLDQQFRERCEELRVELLSIHQKKVCEER
  KAQIAFNEELSRQKLVEEQMFSKLWEEDRLAKEKREAQEARRQKELMENTRLGLNAQITS
  IKAQRQATQLLKEEEARLVESNNAQIKHENEQDMLKKQKAKQETRTILQKALQERIEHIQ
  QEYRDEQDLNMKLVQRALQDLQEEADKKKQKREDMIREQKIYHKYLAQRREEEKAQEKEF
  DRILEEDKAKKLAEKDKELRLEKEARRQLVDEVMCTRKLQVQEKLQREAKEQEERAMEQK
  HINESLKELNCEEKENFARRQRLAQEYRKQLQMQIAYQQQSQEAEKEEKRREFEAGVAAN
  KMCLDKVQEVLSTHQVLPQNIHPMRKACPSKLPP
• Function: Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. May play a role in the beating of primary cilia and thereby be involved in the establishment of organ laterality during embryogenesis.
• Tissue Specificity: Expressed in skin fibroblasts (at protein level). Expressed in airway epithelial cells .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Heterotaxy, visceral, 6, autosomal	DIS4MD97	Strong	Autosomal recessive	[1]
Visceral heterotaxy	DIS1DV90	Strong	Genetic Variation	[2]
Situs inversus	DISFA7AJ	Supportive	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cilia- and flagella-associated protein 53 (CFAP53).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cilia- and flagella-associated protein 53 (CFAP53).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cilia- and flagella-associated protein 53 (CFAP53).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cilia- and flagella-associated protein 53 (CFAP53).	[8]

3 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 Cilia- and flagella-associated protein 53 (CFAP53).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cilia- and flagella-associated protein 53 (CFAP53).	[7]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the acetylation of Cilia- and flagella-associated protein 53 (CFAP53).	[9]

References

• [1] A human laterality disorder associated with recessive CCDC11 mutation. J Med Genet. 2012 Jun;49(6):386-90. doi: 10.1136/jmedgenet-2011-100457. Epub 2012 May 10.
• [2] Roles of the cilium-associated gene CCDC11 in left-right patterning and in laterality disorders in humans. Int J Dev Biol. 2017;61(3-4-5):267-276. doi: 10.1387/ijdb.160442yc.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.