Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCY73U9)

• DOT Name: Ras and Rab interactor 2 (RIN2)
• Synonyms: Ras association domain family 4; Ras inhibitor JC265; Ras interaction/interference protein 2
• Gene Name: RIN2
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Lung cancer
  Lung carcinoma
  RIN2 syndrome
  Acute lymphocytic leukaemia
  Bardet biedl syndrome
  Barrett esophagus
  Breast cancer
  Breast carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Cerebral palsy
  Childhood acute lymphoblastic leukemia
  Familial multiple trichoepithelioma
  Glioma
  Hepatocellular carcinoma
  Liver cancer
  Myelodysplastic syndrome
  Neoplasm
  Mental disorder
  Psychotic disorder
  Spastic cerebral palsy
  Choriocarcinoma
  Connective tissue disorder
  Megalencephaly
  Neural tube defect
• UniProt ID: RIN2_HUMAN
• Pfam ID: PF00788 ; PF02204
• Sequence:
  MTAWTMGARGLDKRGSFFKLIDTIASEIGELKQEMVRTDVNLENGLEPAETHSMVRHKDG
  GYSEEEDVKTCARDSGYDSLSNRLSILDRLLHTHPIWLQLSLSEEEAAEVLQAQPPGIFL
  VHKSTKMQKKVLSLRLPCEFGAPLKEFAIKESTYTFSLEGSGISFADLFRLIAFYCISRD
  VLPFTLKLPYAISTAKSEAQLEELAQMGLNFWSSPADSKPPNLPPPHRPLSSDGVCPASL
  RQLCLINGVHSIKTRTPSELECSQTNGALCFINPLFLKVHSQDLSGGLKRPSTRTPNANG
  TERTRSPPPRPPPPAINSLHTSPRLARTETQTSMPETVNHNKHGNVALPGTKPTPIPPPR
  LKKQASFLEAEGGAKTLSGGRPGAGPELELGTAGSPGGAPPEAAPGDCTRAPPPSSESRP
  PCHGGRQRLSDMSISTSSSDSLEFDRSMPLFGYEADTNSSLEDYEGESDQETMAPPIKSK
  KKRSSSFVLPKLVKSQLQKVSGVFSSFMTPEKRMVRRIAELSRDKCTYFGCLVQDYVSFL
  QENKECHVSSTDMLQTIRQFMTQVKNYLSQSSELDPPIESLIPEDQIDVVLEKAMHKCIL
  KPLKGHVEAMLKDFHMADGSWKQLKENLQLVRQRNPQELGVFAPTPDFVDVEKIKVKFMT
  MQKMYSPEKKVMLLLRVCKLIYTVMENNSGRMYGADDFLPVLTYVIAQCDMLELDTEIEY
  MMELLDPSLLHGEGGYYLTSAYGALSLIKNFQEEQAARLLSSETRDTLRQWHKRRTTNRT
  IPSVDDFQNYLRVAFQEVNSGCTGKTLLVRPYITTEDVCQICAEKFKVGDPEEYSLFLFV
  DETWQQLAEDTYPQKIKAELHSRPQPHIFHFVYKRIKNDPYGIIFQNGEEDLTTS
• Function: Ras effector protein. May function as an upstream activator and/or downstream effector for RAB5B in endocytic pathway. May function as a guanine nucleotide exchange (GEF) of RAB5B, required for activating the RAB5 proteins by exchanging bound GDP for free GTP.
• Tissue Specificity: Widely expressed. Expressed in heart, kidney, lung placenta. Expressed at low level in skeletal muscle, spleen and peripheral blood.
• Reactome Pathway: RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Genetic Variation	[1]
Glioblastoma multiforme	DISK8246	Definitive	Genetic Variation	[1]
Lung cancer	DISCM4YA	Definitive	Biomarker	[2]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[2]
RIN2 syndrome	DIS6K4SH	Definitive	Autosomal recessive	[3]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[4]
Bardet biedl syndrome	DISTBNZW	Strong	Genetic Variation	[5]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[8]
Cerebral palsy	DIS82ODL	Strong	Genetic Variation	[9]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[4]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Biomarker	[6]
Glioma	DIS5RPEH	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[8]
Liver cancer	DISDE4BI	Strong	Biomarker	[8]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[11]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[12]
Mental disorder	DIS3J5R8	moderate	Genetic Variation	[13]
Psychotic disorder	DIS4UQOT	moderate	Genetic Variation	[13]
Spastic cerebral palsy	DISORE14	moderate	Genetic Variation	[14]
Choriocarcinoma	DISDBVNL	Limited	Biomarker	[15]
Connective tissue disorder	DISKXBS3	Limited	Genetic Variation	[16]
Megalencephaly	DISYW5SV	Limited	Genetic Variation	[17]
Neural tube defect	DIS5J95E	Limited	Genetic Variation	[18]

4 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 Ras and Rab interactor 2 (RIN2).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ras and Rab interactor 2 (RIN2).	[31]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Ras and Rab interactor 2 (RIN2).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ras and Rab interactor 2 (RIN2).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ras and Rab interactor 2 (RIN2).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras and Rab interactor 2 (RIN2).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ras and Rab interactor 2 (RIN2).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ras and Rab interactor 2 (RIN2).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ras and Rab interactor 2 (RIN2).	[24]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ras and Rab interactor 2 (RIN2).	[25]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Ras and Rab interactor 2 (RIN2).	[20]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Ras and Rab interactor 2 (RIN2).	[26]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Ras and Rab interactor 2 (RIN2).	[26]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Ras and Rab interactor 2 (RIN2).	[27]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Ras and Rab interactor 2 (RIN2).	[28]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ras and Rab interactor 2 (RIN2).	[29]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Ras and Rab interactor 2 (RIN2).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras and Rab interactor 2 (RIN2).	[32]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ras and Rab interactor 2 (RIN2).	[35]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ras and Rab interactor 2 (RIN2).	[36]

References

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