Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYZ1NV8)

• DOT Name: Rhophilin-1 (RHPN1)
• Synonyms: GTP-Rho-binding protein 1
• Gene Name: RHPN1
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Polycystic ovarian syndrome
  Uveal Melanoma
  Head-neck squamous cell carcinoma
  Neoplasm
• UniProt ID: RHPN1_HUMAN
• Pfam ID: PF03097 ; PF02185 ; PF00595
• Sequence:
  MILEERPDGAGAGEESPRLQGCDSLTQIQCGQLQSRRAQIHQQIDKELQMRTGAENLYRA
  TSNNRVRETVALELSYVNSNLQLLKEELEELSGGVDPGRHGSEAVTVPMIPLGLKETKEL
  DWSTPLKELISVHFGEDGASYEAEIRELEALRQAMRTPSRNESGLELLTAYYNQLCFLDA
  RFLTPARSLGLFFHWYDSLTGVPAQQRALAFEKGSVLFNIGALHTQIGARQDRSCTEGAR
  RAMEAFQRAAGAFSLLRENFSHAPSPDMSAASLCALEQLMMAQAQECVFEGLSPPASMAP
  QDCLAQLRLAQEAAQVAAEYRLVHRTMAQPPVHDYVPVSWTALVHVKAEYFRSLAHYHVA
  MALCDGSPATEGELPTHEQVFLQPPTSSKPRGPVLPQELEERRQLGKAHLKRAILGQEEA
  LRLHALCRVLREVDLLRAVISQTLQRSLAKYAELDREDDFCEAAEAPDIQPKTHQKPEAR
  MPRLSQGKGPDIFHRLGPLSVFSAKNRWRLVGPVHLTRGEGGFGLTLRGDSPVLIAAVIP
  GSQAAAAGLKEGDYIVSVNGQPCRWWRHAEVVTELKAAGEAGASLQVVSLLPSSRLPSLG
  DRRPVLLGPRGLLRSQREHGCKTPASTWASPRPLLNWSRKAQQGKTGGCPQPCAPVKPAP
  PSSLKHPGWP
• Function: Has no enzymatic activity. May serve as a target for Rho, and interact with some cytoskeletal component upon Rho binding or relay a Rho signal to other molecules.
• Reactome Pathway:
  RHOA GTPase cycle (R-HSA-8980692)
  RHO GTPases Activate Rhotekin and Rhophilins (R-HSA-5666185)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[3]
Uveal Melanoma	DISA7ZGL	Strong	Biomarker	[4]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[5]
Neoplasm	DISZKGEW	moderate	Altered Expression	[5]

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 Rhophilin-1 (RHPN1).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Rhophilin-1 (RHPN1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Rhophilin-1 (RHPN1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Rhophilin-1 (RHPN1).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Rhophilin-1 (RHPN1).	[10]

References

• [1] Co-expression of key gene modules and pathways of human breast cancer cell lines.Biosci Rep. 2019 Jul 18;39(7):BSR20181925. doi: 10.1042/BSR20181925. Print 2019 Jul 31.
• [2] c-Myc induced the regulation of long non-coding RNA RHPN1-AS1 on breast cancer cell proliferation via inhibiting P53.Mol Genet Genomics. 2019 Oct;294(5):1219-1229. doi: 10.1007/s00438-019-01572-w. Epub 2019 May 14.
• [3] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [4] The Long Non-Coding RNA RHPN1-AS1 Promotes Uveal Melanoma Progression.Int J Mol Sci. 2017 Jan 23;18(1):226. doi: 10.3390/ijms18010226.
• [5] Knockdown of LncRNA RHPN1-AS1 Inhibits Cell Migration, Invasion and Proliferation in Head and Neck Squamous Cell Carcinoma.J Cancer. 2019 Jul 5;10(17):4000-4008. doi: 10.7150/jca.29029. eCollection 2019.
• [6] 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.
• [7] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [8] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.