Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWU7AOO)

• DOT Name: Adhesion G protein-coupled receptor F5 (ADGRF5)
• Synonyms: G-protein coupled receptor 116
• Gene Name: ADGRF5
• Related Disease:
  Breast neoplasm
  Colorectal carcinoma
  Hereditary pulmonary alveolar proteinosis
  Kidney failure
  Neoplasm
  Postmenopausal osteoporosis
  Pulmonary disease
  Breast cancer
  Breast carcinoma
• UniProt ID: AGRF5_HUMAN
• Pfam ID: PF00002 ; PF01825 ; PF13927 ; PF01390
• Sequence:
  MKSPRRTTLCLMFIVIYSSKAALNWNYESTIHPLSLHEHEPAGEEALRQKRAVATKSPTA
  EEYTVNIEISFENASFLDPIKAYLNSLSFPIHGNNTDQITDILSINVTTVCRPAGNEIWC
  SCETGYGWPRERCLHNLICQERDVFLPGHHCSCLKELPPNGPFCLLQEDVTLNMRVRLNV
  GFQEDLMNTSSALYRSYKTDLETAFRKGYGILPGFKGVTVTGFKSGSVVVTYEVKTTPPS
  LELIHKANEQVVQSLNQTYKMDYNSFQAVTINESNFFVTPEIIFEGDTVSLVCEKEVLSS
  NVSWRYEEQQLEIQNSSRFSIYTALFNNMTSVSKLTIHNITPGDAGEYVCKLILDIFEYE
  CKKKIDVMPIQILANEEMKVMCDNNPVSLNCCSQGNVNWSKVEWKQEGKINIPGTPETDI
  DSSCSRYTLKADGTQCPSGSSGTTVIYTCEFISAYGARGSANIKVTFISVANLTITPDPI
  SVSEGQNFSIKCISDVSNYDEVYWNTSAGIKIYQRFYTTRRYLDGAESVLTVKTSTREWN
  GTYHCIFRYKNSYSIATKDVIVHPLPLKLNIMVDPLEATVSCSGSHHIKCCIEEDGDYKV
  TFHTGSSSLPAAKEVNKKQVCYKHNFNASSVSWCSKTVDVCCHFTNAANNSVWSPSMKLN
  LVPGENITCQDPVIGVGEPGKVIQKLCRFSNVPSSPESPIGGTITYKCVGSQWEEKRNDC
  ISAPINSLLQMAKALIKSPSQDEMLPTYLKDLSISIDKAEHEISSSPGSLGAIINILDLL
  STVPTQVNSEMMTHVLSTVNVILGKPVLNTWKVLQQQWTNQSSQLLHSVERFSQALQSGD
  SPPLSFSQTNVQMSSMVIKSSHPETYQQRFVFPYFDLWGNVVIDKSYLENLQSDSSIVTM
  AFPTLQAILAQDIQENNFAESLVMTTTVSHNTTMPFRISMTFKNNSPSGGETKCVFWNFR
  LANNTGGWDSSGCYVEEGDGDNVTCICDHLTSFSILMSPDSPDPSSLLGILLDIISYVGV
  GFSILSLAACLVVEAVVWKSVTKNRTSYMRHTCIVNIAASLLVANTWFIVVAAIQDNRYI
  LCKTACVAATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIAFCLGYGCPL
  AISVITLGATQPREVYTRKNVCWLNWEDTKALLAFAIPALIIVVVNITITIVVITKILRP
  SIGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTNLVFHIIFAILNVFQGL
  FILLFGCLWDLKVQEALLNKFSLSRWSSQHSKSTSLGSSTPVFSMSSPISRRFNNLFGKT
  GTYNVSTPEATSSSLENSSSASSLLN
• Function: Receptor that plays a critical role in lung surfactant homeostasis. May play a role in controlling adipocyte function.
• Reactome Pathway: Surfactant metabolism (R-HSA-5683826)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Hereditary pulmonary alveolar proteinosis	DISQC53I	Strong	Biomarker	[3]
Kidney failure	DISOVQ9P	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Postmenopausal osteoporosis	DISS0RQZ	Strong	Biomarker	[6]
Pulmonary disease	DIS6060I	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Limited	Biomarker	[7]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Adhesion G protein-coupled receptor F5 (ADGRF5).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Adhesion G protein-coupled receptor F5 (ADGRF5).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Adhesion G protein-coupled receptor F5 (ADGRF5).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Adhesion G protein-coupled receptor F5 (ADGRF5).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Adhesion G protein-coupled receptor F5 (ADGRF5).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Adhesion G protein-coupled receptor F5 (ADGRF5).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Adhesion G protein-coupled receptor F5 (ADGRF5).	[12]

References

• [1] GPR116, an adhesion G-protein-coupled receptor, promotes breast cancer metastasis via the Gq-p63RhoGEF-Rho GTPase pathway.Cancer Res. 2013 Oct 15;73(20):6206-18. doi: 10.1158/0008-5472.CAN-13-1049. Epub 2013 Sep 5.
• [2] Expression Analysis of Fibronectin Type III Domain-Containing (FNDC) Genes in Inflammatory Bowel Disease and Colorectal Cancer.Gastroenterol Res Pract. 2019 Apr 9;2019:3784172. doi: 10.1155/2019/3784172. eCollection 2019.
• [3] Epithelial Gpr116 regulates pulmonary alveolar homeostasis via Gq/11 signaling.JCI Insight. 2017 Jun 2;2(11):e93700. doi: 10.1172/jci.insight.93700. eCollection 2017 Jun 2.
• [4] Developmental vascular remodeling defects and postnatal kidney failure in mice lacking Gpr116 (Adgrf5) and Eltd1 (Adgrl4).PLoS One. 2017 Aug 14;12(8):e0183166. doi: 10.1371/journal.pone.0183166. eCollection 2017.
• [5] MiR-511-5p functions as a tumor suppressor and a predictive of prognosis in colorectal cancer by directly targeting GPR116.Eur Rev Med Pharmacol Sci. 2019 Jul;23(14):6119-6130. doi: 10.26355/eurrev_201907_18425.
• [6] Identification of gene biomarkers in patients with postmenopausal osteoporosis.Mol Med Rep. 2019 Feb;19(2):1065-1073. doi: 10.3892/mmr.2018.9752. Epub 2018 Dec 12.
• [7] High expression of GPR116 indicates poor survival outcome and promotes tumor progression in colorectal carcinoma.Oncotarget. 2017 Jul 18;8(29):47943-47956. doi: 10.18632/oncotarget.18203.
• [8] 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.
• [9] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [10] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [11] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [12] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [13] 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.