Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8585HU)

• DOT Name: Apelin receptor (APLNR)
• Synonyms: Angiotensin receptor-like 1; G-protein coupled receptor APJ; G-protein coupled receptor HG11
• Gene Name: APLNR
• UniProt ID: APJ_HUMAN
• PDB ID: 2LOT; 2LOU; 2LOV; 2LOW; 5VBL; 6KNM; 7SUS; 7W0L; 7W0M; 7W0N; 7W0O; 7W0P
• Pfam ID: PF00001
• Sequence:
  MEEGGDFDNYYGADNQSECEYTDWKSSGALIPAIYMLVFLLGTTGNGLVLWTVFRSSREK
  RRSADIFIASLAVADLTFVVTLPLWATYTYRDYDWPFGTFFCKLSSYLIFVNMYASVFCL
  TGLSFDRYLAIVRPVANARLRLRVSGAVATAVLWVLAALLAMPVMVLRTTGDLENTTKVQ
  CYMDYSMVATVSSEWAWEVGLGVSSTTVGFVVPFTIMLTCYFFIAQTIAGHFRKERIEGL
  RKRRRLLSIIVVLVVTFALCWMPYHLVKTLYMLGSLLHWPCDFDLFLMNIFPYCTCISYV
  NSCLNPFLYAFFDPRFRQACTSMLCCGQSRCAGTSHSSSGEKSASYSSGHSQGPGPNMGK
  GGEQMHEKSIPYSQETLVVD
• Function: Receptor for apelin receptor early endogenous ligand (APELA) and apelin (APLN) hormones coupled to G proteins that inhibit adenylate cyclase activity. Plays a key role in early development such as gastrulation, blood vessels formation and heart morphogenesis by acting as a receptor for APELA hormone. May promote angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis. Promotes sinus venosus (SV)-derived endothelial cells migration into the developing heart to promote coronary blood vessel development. Also plays a role in various processes in adults such as regulation of blood vessel formation, blood pressure, heart contractility and heart failure ; (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection; may be involved in the development of AIDS dementia.
• Tissue Specificity: Expressed in heart, brain, kidney, stomach, spleen, thymus, lung, ovary, small intestine and colon, adipose tissues and pancreas . Expressed in glial cells, astrocytes and neuronal subpopulations . Expressed in embryonic (ESCs) and induced (iPSCs) pluripotent stem cells .
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Apelin sig.ling pathway (hsa04371)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

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 Apelin receptor (APLNR).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Apelin receptor (APLNR).	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Apelin receptor (APLNR).	[3]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Apelin receptor (APLNR).	[2]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Apelin receptor (APLNR).	[4]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Apelin receptor (APLNR).	[5]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Apelin receptor (APLNR).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Apelin receptor (APLNR).	[7]

References

• [1] 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.
• [2] 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.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [5] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [6] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [7] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.