Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJH1UNR)

• DOT Name: Polycystin-2-like protein 2 (PKD2L2)
• Synonyms: Polycystin-2L2; Polycystic kidney disease 2-like 2 protein; Polycystin-L2
• Gene Name: PKD2L2
• Related Disease: Atrial fibrillation
• UniProt ID: PK2L2_HUMAN
• Pfam ID: PF08016 ; PF20519
• Sequence:
  MAEASRWHRGGASKHKLHYRKEVEITTTLQELLLYFIFLINLCILTFGMVNPHMYYLNKV
  MSSLFLDTSVPGEERTNFKSIRSITDFWKFMEGPLLEGLYWDSWYNNQQLYNLKNSSRIY
  YENILLGVPRVRQLKVRNNTCKVYSSFQSLMSECYGKYTSANEDLSNFGLQINTEWRYST
  SNTNSPWHWGFLGVYRNGGYIFTLSKSKSETKNKFIDLRLNSWITRGTRVIFIDFSLYNA
  NVNLFCIIRLVAEFPATGGILTSWQFYSVKLLRYVSYYDYFIASCEITFCIFLFVFTTQE
  VKKIKEFKSAYFKSIWNWLELLLLLLCFVAVSFNTYYNVQIFLLLGQLLKSTEKYSDFYF
  LACWHIYYNNIIAITIFFAWIKIFKFISFNKTMSQLSSTLSRCVKDIVGFAIMFFIIFFA
  YAQLGFLVFGSQVDDFSTFQNSIFAQFRIVLGDFNFAGIQQANPILGPIYFITFIFFVFF
  VLLNMFLAIINDTYSEVKADYSIGRRLDFELGKMIKQSYKNVLEKFRLKKAQKDEDKKTK
  GSGDLAEQARREGFDENEIQNAEQMKKWKERLEKKYYSMEIQDDYQPVTQEEFRELFLYA
  VELEKELHYINLKLNQVVRKVSAL
• Function: May function as a subunit of a cation channel and play a role in fertilization.
• Tissue Specificity: According to PubMed:10602361, expressed only in testis. According to PubMed:10756092, expressed also in brain and kidney. Isoform 2 is found only in transformed lymphoblasts. Isoform 3 is found in all tissues tested.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Polycystin-2-like protein 2 (PKD2L2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Polycystin-2-like protein 2 (PKD2L2).	[3]

References

• [1] Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation.Nat Genet. 2017 Jun;49(6):946-952. doi: 10.1038/ng.3843. Epub 2017 Apr 17.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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.