Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7WLL0X)

• DOT Name: Dynein regulatory complex protein 1 (DRC1)
• Synonyms: Coiled-coil domain-containing protein 164
• Gene Name: DRC1
• Related Disease:
  Primary ciliary dyskinesia 1
  Primary ciliary dyskinesia 21
  Rothmund-Thomson syndrome
  Primary ciliary dyskinesia
• UniProt ID: DRC1_HUMAN
• PDB ID: 8J07
• Pfam ID: PF14772 ; PF14775
• Sequence:
  MNPPGSLEALDPNVDEHLSTQILAPSVHSDNSQERIQARRLRIAARLEARRREALGEYLD
  GKKESEEDQSKSYKQKEESRLKLAKLLLCGTELVTNIQVAIDIREIHRRVEEEEIKRQRI
  EKLENEVKTSQDKFDEITSKWEEGKQKRIPQELWEMLNTQQLHCAGLLEDKNKLISELQQ
  ELKTKDDQYVKDLKKQSDDICLLLERMEEQVKNVMKTFREELYNIEKAFEVERQELLASN
  KKKWEQALQAHNAKELEYLNNRMKKVEDYEKQLNRQRIWDCEEYNMIKIKLEQDVQILEQ
  QLQQRKAIYQLNQEKLEYNLQVLKKRDEESTVIKSQQKRKINRLHDILNNLRSKYAKQIK
  QFQEENQSLTSDYKRLVMQFKELQKAMRHFALIDDEKFWEIWLMNEEEAKDLIARAFDVD
  RIIHTHHLGLPWAAPDFWFLNNVGPISQQPQKSATQIVEEMLMRSEEEEAEEAAAEPESY
  LDLPKQISEKTTKRILMLLCDESGFLIESKLLSLLLPLEQNECYLLRLDAIFSALGIESE
  DDLYKLVNFFLKYRAHRLSSSLQIKPCSQASMEKASMEETSTRSELELAEQTEMEGEKEE
  SLVEGEKEEEEETPPSPWVIHPNDVLKILEAFVMGLKKPRDSRAPLRVQKNVRDNSKDSE
  YWQALTTVIPSSKQNLWDALYTALEKYHLVLTQRAKLLLENSSLEQQNTELQALLQQYLN
  SKINSELQVPPTQVLRVPTK
• Function: Component of the nexin-dynein regulatory complex (N-DRC) a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Plays a critical role in the assembly of N-DRC and also stabilizes the assembly of multiple inner dynein arms and radial spokes. Coassembles with CCDC65/DRC2 to form a central scaffold needed for assembly of the N-DRC and its attachment to the outer doublet microtubules.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Primary ciliary dyskinesia 1	DISPGX6H	Strong	Autosomal recessive	[1]
Primary ciliary dyskinesia 21	DISHNOT3	Strong	Autosomal recessive	[2]
Rothmund-Thomson syndrome	DISGVBCV	Strong	Biomarker	[3]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Dynein regulatory complex protein 1 (DRC1).	[4]

2 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 Dynein regulatory complex protein 1 (DRC1).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Dynein regulatory complex protein 1 (DRC1).	[6]

References

• [1] The nexin-dynein regulatory complex subunit DRC1 is essential for motile cilia function in algae and humans. Nat Genet. 2013 Mar;45(3):262-8. doi: 10.1038/ng.2533. Epub 2013 Jan 27.
• [2] Copy number variation in DRC1 is the major cause of primary ciliary dyskinesia in the Japanese population. Mol Genet Genomic Med. 2020 Mar;8(3):e1137. doi: 10.1002/mgg3.1137. Epub 2020 Jan 20.
• [3] Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome.Cell. 2005 Jun 17;121(6):887-98. doi: 10.1016/j.cell.2005.05.015.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] 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.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.