Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQE226K)

• DOT Name: Ran-specific GTPase-activating protein (RANBP1)
• Synonyms: Ran-binding protein 1; RanBP1
• Gene Name: RANBP1
• Related Disease:
  Autism spectrum disorder
  DiGeorge syndrome
  HIV infectious disease
  Kidney cancer
  Kidney neoplasm
  Metastatic malignant neoplasm
  Sciatic neuropathy
  Shprintzen-Goldberg syndrome
  Velocardiofacial syndrome
  Osteosarcoma
  Myocardial infarction
• UniProt ID: RANG_HUMAN
• PDB ID: 1K5D; 1K5G
• Pfam ID: PF00638
• Sequence:
  MAAAKDTHEDHDTSTENTDESNHDPQFEPIVSLPEQEIKTLEEDEEELFKMRAKLFRFAS
  ENDLPEWKERGTGDVKLLKHKEKGAIRLLMRRDKTLKICANHYITPMMELKPNAGSDRAW
  VWNTHADFADECPKPELLAIRFLNAENAQKFKTKFEECRKEIEEREKKAGSGKNDHAEKV
  AEKLEALSVKEETKEDAEEKQ
• Function: Plays a role in RAN-dependent nucleocytoplasmic transport. Alleviates the TNPO1-dependent inhibition of RAN GTPase activity and mediates the dissociation of RAN from proteins involved in transport into the nucleus. Induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins. Promotes the disassembly of the complex formed by RAN and importin beta. Promotes dissociation of RAN from a complex with KPNA2 and CSE1L. Required for normal mitotic spindle assembly and normal progress through mitosis via its effect on RAN. Does not increase the RAN GTPase activity by itself, but increases GTP hydrolysis mediated by RANGAP1. Inhibits RCC1-dependent exchange of RAN-bound GDP by GTP.
• KEGG Pathway:
  Human T-cell leukemia virus 1 infection (hsa05166)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway: Rev-mediated nuclear export of HIV RNA (R-HSA-165054)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Strong	Altered Expression	[1]
DiGeorge syndrome	DIST1RKO	Strong	Biomarker	[2]
HIV infectious disease	DISO97HC	Strong	Biomarker	[3]
Kidney cancer	DISBIPKM	Strong	Biomarker	[4]
Kidney neoplasm	DISBNZTN	Strong	Biomarker	[4]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[5]
Sciatic neuropathy	DISMGDKX	Strong	Biomarker	[6]
Shprintzen-Goldberg syndrome	DISQH6P3	Strong	Biomarker	[2]
Velocardiofacial syndrome	DISOSBTY	Strong	Biomarker	[2]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[7]
Myocardial infarction	DIS655KI	Limited	Biomarker	[8]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Ran-specific GTPase-activating protein (RANBP1) affects the response to substance of Topotecan.	[36]
Vinblastine	DM5TVS3	Approved	Ran-specific GTPase-activating protein (RANBP1) affects the response to substance of Vinblastine.	[36]
PEITC	DMOMN31	Phase 2	Ran-specific GTPase-activating protein (RANBP1) affects the binding of PEITC.	[37]

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 Ran-specific GTPase-activating protein (RANBP1).	[9]
TAK-243	DM4GKV2	Phase 1	TAK-243 affects the sumoylation of Ran-specific GTPase-activating protein (RANBP1).	[28]

26 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 Ran-specific GTPase-activating protein (RANBP1).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ran-specific GTPase-activating protein (RANBP1).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[16]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[17]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[18]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[19]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Ran-specific GTPase-activating protein (RANBP1).	[20]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[21]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[22]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[23]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[24]
LY2835219	DM93VBZ	Approved	LY2835219 decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[23]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[26]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[29]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[31]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ran-specific GTPase-activating protein (RANBP1).	[32]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Ran-specific GTPase-activating protein (RANBP1).	[33]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Ran-specific GTPase-activating protein (RANBP1).	[34]
Z-Pro-Prolinal	DM43O2U	Investigative	Z-Pro-Prolinal increases the expression of Ran-specific GTPase-activating protein (RANBP1).	[35]

References

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