Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1KJDAT)

• DOT Name: Polycystin-2-like protein 1 (PKD2L1)
• Synonyms: Polycystin-2L1; Polycystic kidney disease 2-like 1 protein; Polycystin-2 homolog; Polycystin-L; Polycystin-L1
• Gene Name: PKD2L1
• UniProt ID: PK2L1_HUMAN
• PDB ID: 3TE3; 4GIF; 6DU8
• Pfam ID: PF18109 ; PF08016 ; PF20519
• Sequence:
  MNAVGSPEGQELQKLGSGAWDNPAYSGPPSPHGTLRVCTISSTGPLQPQPKKPEDEPQET
  AYRTQVSSCCLHICQGIRGLWGTTLTENTAENRELYIKTTLRELLVYIVFLVDICLLTYG
  MTSSSAYYYTKVMSELFLHTPSDTGVSFQAISSMADFWDFAQGPLLDSLYWTKWYNNQSL
  GHGSHSFIYYENMLLGVPRLRQLKVRNDSCVVHEDFREDILSCYDVYSPDKEEQLPFGPF
  NGTAWTYHSQDELGGFSHWGRLTSYSGGGYYLDLPGSRQGSAEALRALQEGLWLDRGTRV
  VFIDFSVYNANINLFCVLRLVVEFPATGGAIPSWQIRTVKLIRYVSNWDFFIVGCEVIFC
  VFIFYYVVEEILELHIHRLRYLSSIWNILDLVVILLSIVAVGFHIFRTLEVNRLMGKLLQ
  QPNTYADFEFLAFWQTQYNNMNAVNLFFAWIKIFKYISFNKTMTQLSSTLARCAKDILGF
  AVMFFIVFFAYAQLGYLLFGTQVENFSTFIKCIFTQFRIILGDFDYNAIDNANRILGPAY
  FVTYVFFVFFVLLNMFLAIINDTYSEVKEELAGQKDELQLSDLLKQGYNKTLLRLRLRKE
  RVSDVQKVLQGGEQEIQFEDFTNTLRELGHAEHEITELTATFTKFDRDGNRILDEKEQEK
  MRQDLEEERVALNTEIEKLGRSIVSSPQGKSGPEAARAGGWVSGEEFYMLTRRVLQLETV
  LEGVVSQIDAVGSKLKMLERKGWLAPSPGVKEQAIWKHPQPAPAVTPDPWGVQGGQESEV
  PYKREEEALEERRLSRGEIPTLQRS
• Function: Pore-forming subunit of a heterotetrameric, non-selective cation channel that is permeable to Ca(2+). Pore-forming subunit of a calcium-permeant ion channel formed by PKD1L2 and PKD1L1 in primary cilia, where it controls cilium calcium concentration, but does not affect cytoplasmic calcium concentration. The channel formed by PKD1L2 and PKD1L1 in primary cilia regulates sonic hedgehog/SHH signaling and GLI2 transcription. Pore-forming subunit of a channel formed by PKD1L2 and PKD1L3 that contributes to sour taste perception in gustatory cells. The heteromeric channel formed by PKD1L2 and PKD1L3 is activated by low pH, but opens only when the extracellular pH rises again. May play a role in the perception of carbonation taste. May play a role in the sensory perception of water, via a mechanism that activates the channel in response to dilution of salivary bicarbonate and changes in salivary pH.
• Tissue Specificity: Detected in taste bud cells in fungiform papillae (at protein level) . Ubiquitous . Expressed in adult heart, skeletal muscle, brain, spleen, testis, retina and liver . Isoform 4 appears to be expressed only in transformed lymphoblasts.
• KEGG Pathway: Taste transduction (hsa04742)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Polycystin-2-like protein 1 (PKD2L1).	[1]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Polycystin-2-like protein 1 (PKD2L1).	[2]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Polycystin-2-like protein 1 (PKD2L1).	[3]

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 Polycystin-2-like protein 1 (PKD2L1).	[4]

References

• [1] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [2] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [3] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [4] 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.