Details of Drug Off-Target (DOT)

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

• DOT Name: Huntingtin-interacting protein 1-related protein (HIP1R)
• Synonyms: HIP1-related protein; Huntingtin-interacting protein 12; HIP-12
• Gene Name: HIP1R
• Related Disease:
  Prostate cancer
  Prostate carcinoma
  Atrial fibrillation
  B-cell lymphoma
  Bipolar disorder
  Parkinson disease
  Schizophrenia
  Familial atrial fibrillation
  Small lymphocytic lymphoma
  Essential tremor
  Nervous system inflammation
• UniProt ID: HIP1R_HUMAN
• PDB ID: 1R0D
• Pfam ID: PF07651 ; PF16515 ; PF01608
• Sequence:
  MNSIKNVPARVLSRRPGHSLEAEREQFDKTQAISISKAINTQEAPVKEKHARRIILGTHH
  EKGAFTFWSYAIGLPLPSSSILSWKFCHVLHKVLRDGHPNVLHDCQRYRSNIREIGDLWG
  HLHDRYGQLVNVYTKLLLTKISFHLKHPQFPAGLEVTDEVLEKAAGTDVNNIFQLTVEMF
  DYMDCELKLSESVFRQLNTAIAVSQMSSGQCRLAPLIQVIQDCSHLYHYTVKLLFKLHSC
  LPADTLQGHRDRFHEQFHSLRNFFRRASDMLYFKRLIQIPRLPEGPPNFLRASALAEHIK
  PVVVIPEEAPEDEEPENLIEISTGPPAGEPVVVADLFDQTFGPPNGSVKDDRDLQIESLK
  REVEMLRSELEKIKLEAQRYIAQLKSQVNALEGELEEQRKQKQKALVDNEQLRHELAQLR
  AAQLEGERSQGLREEAERKASATEARYNKLKEKHSELVHVHAELLRKNADTAKQLTVTQQ
  SQEEVARVKEQLAFQVEQVKRESELKLEEKSDQLEKLKRELEAKAGELARAQEALSHTEQ
  SKSELSSRLDTLSAEKDALSGAVRQREADLLAAQSLVRETEAALSREQQRSSQEQGELQG
  RLAERESQEQGLRQRLLDEQFAVLRGAAAEAAGILQDAVSKLDDPLHLRCTSSPDYLVSR
  AQEALDAVSTLEEGHAQYLTSLADASALVAALTRFSHLAADTIINGGATSHLAPTDPADR
  LIDTCRECGARALELMGQLQDQQALRHMQASLVRTPLQGILQLGQELKPKSLDVRQEELG
  AVVDKEMAATSAAIEDAVRRIEDMMNQARHASSGVKLEVNERILNSCTDLMKAIRLLVTT
  STSLQKEIVESGRGAATQQEFYAKNSRWTEGLISASKAVGWGATQLVEAADKVVLHTGKY
  EELIVCSHEIAASTAQLVAASKVKANKHSPHLSRLQECSRTVNERAANVVASTKSGQEQI
  EDRDTMDFSGLSLIKLKKQEMETQVRVLELEKTLEAERMRLGELRKQHYVLAGASGSPGE
  EVAIRPSTAPRSVTTKKPPLAQKPSVAPRQDHQLDKKDGIYPAQLVNY
• Function: Component of clathrin-coated pits and vesicles, that may link the endocytic machinery to the actin cytoskeleton. Binds 3-phosphoinositides (via ENTH domain). May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis.
• Tissue Specificity: Brain, heart, kidney, pancreas, and liver, but not in lung or placenta.
• Reactome Pathway:
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Golgi Associated Vesicle Biogenesis (R-HSA-432722)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Definitive	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Definitive	Altered Expression	[1]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[2]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[3]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[4]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[5]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[6]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[2]
Small lymphocytic lymphoma	DIS30POX	moderate	Altered Expression	[7]
Essential tremor	DIS7GBKQ	Disputed	Genetic Variation	[8]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[9]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Huntingtin-interacting protein 1-related protein (HIP1R) decreases the response to substance of Arsenic trioxide.	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Huntingtin-interacting protein 1-related protein (HIP1R).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Huntingtin-interacting protein 1-related protein (HIP1R).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Huntingtin-interacting protein 1-related protein (HIP1R).	[12]
Selenium	DM25CGV	Approved	Selenium increases the expression of Huntingtin-interacting protein 1-related protein (HIP1R).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Huntingtin-interacting protein 1-related protein (HIP1R).	[14]

References

• [1] The microRNA-23b/-27b cluster suppresses prostate cancer metastasis via Huntingtin-interacting protein 1-related.Oncogene. 2016 Sep 8;35(36):4752-61. doi: 10.1038/onc.2016.6. Epub 2016 Feb 22.
• [2] Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
• [3] FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures.Oncotarget. 2016 Aug 16;7(33):52940-52956. doi: 10.18632/oncotarget.9507.
• [4] Multiple genes and factors associated with bipolar disorder converge on growth factor and stress activated kinase pathways controlling translation initiation: implications for oligodendrocyte viability.Neurochem Int. 2007 Feb;50(3):461-90. doi: 10.1016/j.neuint.2006.11.009. Epub 2007 Jan 18.
• [5] The single nucleotide polymorphism Rs12817488 is associated with Parkinson's disease in the Chinese population.J Clin Neurosci. 2015 Jun;22(6):1002-4. doi: 10.1016/j.jocn.2014.11.024. Epub 2015 Mar 26.
• [6] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [7] Gene expression signature of chronic lymphocytic leukaemia with Trisomy 12.Eur J Clin Invest. 2009 Jul;39(7):568-75. doi: 10.1111/j.1365-2362.2009.02146.x. Epub 2009 Apr 30.
• [8] Genetics of Parkinson's disease and essential tremor.Curr Opin Neurol. 2011 Aug;24(4):318-23. doi: 10.1097/WCO.0b013e3283484b87.
• [9] Kinematic gait parameters are highly sensitive measures of motor deficits and spinal cord injury in mice subjected to experimental autoimmune encephalomyelitis.Behav Brain Res. 2017 Jan 15;317:95-108. doi: 10.1016/j.bbr.2016.09.034. Epub 2016 Sep 14.
• [10] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [13] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [14] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [15] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.