Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL9LPSI)

• DOT Name: Calcium-activated chloride channel regulator 1 (CLCA1)
• Synonyms: EC 3.4.-.-; Calcium-activated chloride channel family member 1; hCLCA1; Calcium-activated chloride channel protein 1; CaCC-1; hCaCC-1
• Gene Name: CLCA1
• UniProt ID: CLCA1_HUMAN
• PDB ID: 6PYO; 6PYX
• EC Number: 3.4.-.-
• Pfam ID: PF08434 ; PF13519
• Sequence:
  MGPFKSSVFILILHLLEGALSNSLIQLNNNGYEGIVVAIDPNVPEDETLIQQIKDMVTQA
  SLYLLEATGKRFYFKNVAILIPETWKTKADYVRPKLETYKNADVLVAESTPPGNDEPYTE
  QMGNCGEKGERIHLTPDFIAGKKLAEYGPQGRAFVHEWAHLRWGVFDEYNNDEKFYLSNG
  RIQAVRCSAGITGTNVVKKCQGGSCYTKRCTFNKVTGLYEKGCEFVLQSRQTEKASIMFA
  QHVDSIVEFCTEQNHNKEAPNKQNQKCNLRSTWEVIRDSEDFKKTTPMTTQPPNPTFSLL
  QIGQRIVCLVLDKSGSMATGNRLNRLNQAGQLFLLQTVELGSWVGMVTFDSAAHVQNELI
  QINSGSDRDTLAKRLPAAASGGTSICSGLRSAFTVIRKKYPTDGSEIVLLTDGEDNTISG
  CFNEVKQSGAIIHTVALGPSAAQELEELSKMTGGLQTYASDQVQNNGLIDAFGALSSGNG
  AVSQRSIQLESKGLTLQNSQWMNGTVIVDSTVGKDTLFLITWTMQPPQILLWDPSGQKQG
  GFVVDKNTKMAYLQIPGIAKVGTWKYSLQASSQTLTLTVTSRASNATLPPITVTSKTNKD
  TSKFPSPLVVYANIRQGASPILRASVTALIESVNGKTVTLELLDNGAGADATKDDGVYSR
  YFTTYDTNGRYSVKVRALGGVNAARRRVIPQQSGALYIPGWIENDEIQWNPPRPEINKDD
  VQHKQVCFSRTSSGGSFVASDVPNAPIPDLFPPGQITDLKAEIHGGSLINLTWTAPGDDY
  DHGTAHKYIIRISTSILDLRDKFNESLQVNTTALIPKEANSEEVFLFKPENITFENGTDL
  FIAIQAVDKVDLKSEISNIARVSLFIPPQTPPETPSPDETSAPCPNIHINSTIPGIHILK
  IMWKWIGELQLSIA
• Function: May be involved in mediating calcium-activated chloride conductance. May play critical roles in goblet cell metaplasia, mucus hypersecretion, cystic fibrosis and AHR. May be involved in the regulation of mucus production and/or secretion by goblet cells. Involved in the regulation of tissue inflammation in the innate immune response. May play a role as a tumor suppressor. Induces MUC5AC.
• Tissue Specificity: Highly expressed in small intestine and colon namely in intestinal basal crypt epithelia and goblet cells, and appendix. Weakly expressed in uterus, testis and kidney. Expressed in the airways epithelium of both asthmatic and healthy patients. Expressed in the bronchial epithelium, especially in mucus-producing goblet cells. Expressed in normal turbinate mucosa and nasal polyp. Expressed in.
• KEGG Pathway:
  Renin secretion (hsa04924)
  Pancreatic secretion (hsa04972)
• Reactome Pathway: Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ergotidine	DM78IME	Approved	Ergotidine increases the expression of Calcium-activated chloride channel regulator 1 (CLCA1).	[1]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Calcium-activated chloride channel regulator 1 (CLCA1).	[2]

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 affects the methylation of Calcium-activated chloride channel regulator 1 (CLCA1).	[3]

References

• [1] Histamine induces MUC5AC expression via a hCLCA1 pathway. Pharmacology. 2007;80(4):219-26. doi: 10.1159/000104419. Epub 2007 Jul 5.
• [2] Resveratrol inhibits mucus overproduction and MUC5AC expression in a murine model of asthma. Mol Med Rep. 2016 Jan;13(1):287-94. doi: 10.3892/mmr.2015.4520. Epub 2015 Nov 6.
• [3] 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.