Details of Drug Off-Target (DOT)

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

• DOT Name: Polycystin-1-like protein 2 (PKD1L2)
• Synonyms: Polycystin-1L2; PC1-like 2 protein; Polycystic kidney disease protein 1-like 2
• Gene Name: PKD1L2
• Related Disease:
  Colorectal carcinoma
  Hypoplastic left heart syndrome 1
  Myopathy
  Neuromuscular disease
  Polycystic kidney disease
• UniProt ID: PK1L2_HUMAN
• Pfam ID: PF02140 ; PF01825 ; PF00059 ; PF08016 ; PF01477 ; PF20519 ; PF02010
• Sequence:
  MSAVGLVLLVLALRLRATTVKPEEGSFCSNSQVAFRDACYEFVPLGRTFRDAQSWCEGQG
  GHLVFIQDEGTQWFLQKHISQDREWWIGLTWNLARNGTTEGPGTWLDTSNVTYSNWHGGQ
  AAAAPDTCGHIGRGPSSEWVTSDCAQTFAFMCEFRVGQSLACEGLNATVHCGLGQVIQVQ
  DAVYGRQNPHFCTQDAGRPSDLEQGCSWANVKEEVAGQCQELQSCQVAADETYFGNLCPT
  QGSYLWVQYQCREALQLMVSSESFIFDNVTISLTWLLSPYIGNLSCIISTGDSHTFDPYN
  PPSVSSNVTHQFTSPGEFTVFAECTTSEWHVTAQRQVTVRDKMETLSVTACSGLSQSGAG
  PLCQAVFGDPLWIQVELDGGTGVTYTVLLGDITLAESTTQKGSLPYNLILDRETQKLMGP
  GRHRLEIQATGNTTTSTISRNITVHLVELLSGLQASWASDHLELGQDLLITISLAQGTPE
  ELTFEVAGLNATFSHEQVSFGEPFGICRLAVPVEGTFLVTMLVRNAFSNLSLEIGNITIT
  APSGLQEPSGMNAEGKSKDKGDMEVYIQPGPYVDPFTTVTLGWPDNDKELRFQWSCGSCW
  ALWSSCVERQLLRTDQRELVVPASCLPPPDSAVTLRLAVLRGQELENRAEQCLYVSAPWE
  LRPRVSCERNCRPVNASKDILLRVTMGEDSPVAMFSWYLDNTPTEQAEPLLDACRLRGFW
  PRSLTLLQSNTSTLLLNSSFLQSRGEVIRIRATALTRHAYGEDTYVISTVPPREVPACTI
  APEEGTVLTSFAIFCNASTALGPLEFCFCLESGSCLHCGPEPALPSVYLPLGEENNDFVL
  TVVISATNRAGDTQQTQAMAKVALGDTCVEDVAFQAAVSEKIPTALQGEGGPEQLLQLAK
  AVSSMLNQEHESQGSGQSLSIDVRQKVREHVLGSLSAVTTGLEDVQRVQELAEVLREVTC
  RSKELTPSAQWEASLALQHASEALLTVSAKARPEDQRRQAATRDLFQAVGSVLEASLSNR
  PEEPAEASSSQIATVLRLLRVMEHVQTTLLLGKLPGGLPAMLATPSISVYTNRIQPWSWQ
  GSSLRPDAADSATFMLPAASSLSSLEGGQEPVDIKIMSFPKSPFPARSHFDVSGTVGGLR
  VTSPSGQLIPVKNLSENIEILLPRHSQRHSQPTVLNLTSPEALWVNVTSGEATLGIQLHW
  RPDIALTLSLGYGYHPNKSSYDAQTHLVPMVAPDELPTWILSPQDLRFGEGVYYLTVVPE
  SDLEPAPGRDLTVGITTFLSHCVFWDEVQETWDDSGCQVGPRTSPYQTHCLCNHLTFFGS
  TFLVMSNAINIHQTAELFATFEDNPVVVTTVGCLCVVYVLVVIWARRKDAQDQAKVKVTV
  LEDNDPFAQYHYLVTVYTGHRRGAATSSKVTVTLYGLDGEREPHHLADPDTPVFERGAVD
  AFLLSTLFPLGELRSLRLWHDNSGDRPSWYVSRVLVYDLVMDRKWYFLCNSWLSINVGDC
  VLDKVFPVATEQDRKQFSHLFFMKTSAGFQDGHIWYSIFSRCARSSFTRVQRVSCCFSLL
  LCTMLTSIMFWGVPKDPAEQKMDLGKIEFTWQEVMIGLESSILMFPINLLIVQIFQNTRP
  RVAKEQNTGKWDRGSPNLTPSPQPMEDGLLTPEAVTKDVSRIVSSLFKALKVPSPALGWD
  SVNLMDINSLLALVEDVIYPQNTSGQVFWEEAKKREDPVTLTLGSSEMKEKSQCPKPKAA
  RSGPWKDSAYRQCLYLQLEHVEQELRLVGPRGFSQPHSHAQALRQLQTLKGGLGVQPGTW
  APAHASALQVSKPPQGLPWWCILVGWLLVAATSGVAAFFTMLYGLHYGRASSLRWLISMA
  VSFVESMFVTQPLKVLGFAAFFALVLKRVDDEEDTVAPLPGHLLGPDPYALFRARRNSSR
  DVYQPPLTAAIEKMKTTHLKEQKAFALIREILAYLGFLWMLLLVAYGQRDPSAYHLNRHL
  QHSFTRGFSGVLGFREFFKWANTTLVSNLYGHPPGFITDGNSKLVGSAQIRQVRVQESSC
  PLAQQPQAYLNGCRAPYSLDAEDMADYGEGWNATTLSEWQYQSQDQRQGYPIWGKLTVYR
  GGGYVVPLGTDRQSTSRILRYLFDNTWLDALTRAVFVESTVYNANVNLFCIVTLTLETSA
  LGTFFTHAALQSLRLYPFTDGWHPFVVAAELIYFLFLLYYMVVQGKRMSKETWGYFCSKW
  NLLELAIILASWSALAVFVKRAVLAERDLQRCRNHREEGISFSETAAADAALGYIIAFLV
  LLSTVKLWHLLRLNPKMNMITAALRRAWGDISGFMIVILTMLLAYSIASNLIFGWKLRSY
  KTLFDAAETMVSLQLGIFNYEEVLDYSPVLGSFLIGSCIVFMTFVVLNLFISVILVAFSE
  EQKYYQLSEEGEIVDLLLMKILSFLGIKSKREEPGSSREQPGSLSQTRHSRPAQALPKD
• Function: May function as an ion-channel regulator. May function as a G-protein-coupled receptor.
• Tissue Specificity: Expressed in all tissues tested including brain, placenta, mammary gland, testis, lung and liver. Highest expression in skeletal muscle. Isoform 2 is expressed in heart and kidney.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[1]
Hypoplastic left heart syndrome 1	DISW3OY8	Strong	Genetic Variation	[2]
Myopathy	DISOWG27	Strong	Biomarker	[3]
Neuromuscular disease	DISQTIJZ	Strong	Altered Expression	[3]
Polycystic kidney disease	DISWS3UY	Strong	Biomarker	[3]

1 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-1-like protein 2 (PKD1L2).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Polycystin-1-like protein 2 (PKD1L2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Polycystin-1-like protein 2 (PKD1L2).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Polycystin-1-like protein 2 (PKD1L2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Polycystin-1-like protein 2 (PKD1L2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Polycystin-1-like protein 2 (PKD1L2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Polycystin-1-like protein 2 (PKD1L2).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Polycystin-1-like protein 2 (PKD1L2).	[11]

References

• [1] A copy number variation in PKD1L2 is associated with colorectal cancer predisposition in korean population.Int J Cancer. 2017 Jan 1;140(1):86-94. doi: 10.1002/ijc.30421. Epub 2016 Oct 3.
• [2] Genome-Wide Association Studies and Meta-Analyses for Congenital Heart Defects.Circ Cardiovasc Genet. 2017 Jun;10(3):e001449. doi: 10.1161/CIRCGENETICS.116.001449.
• [3] Upregulation of PKD1L2 provokes a complex neuromuscular disease in the mouse.Hum Mol Genet. 2009 Oct 1;18(19):3553-66. doi: 10.1093/hmg/ddp304. Epub 2009 Jul 4.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [10] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.