Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQE8IEH)

• DOT Name: Rac GTPase-activating protein 1 (RACGAP1)
• Synonyms: Male germ cell RacGap; MgcRacGAP; Protein CYK4 homolog; CYK4; HsCYK-4
• Gene Name: RACGAP1
• Related Disease:
  Pancreatic ductal carcinoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma of esophagus
  Colorectal carcinoma
  Endometrium adenocarcinoma
  Epithelial ovarian cancer
  Gastric cancer
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Matthew-Wood syndrome
  Neoplasm
  Non-small-cell lung cancer
  Polycystic ovarian syndrome
  Squamous cell carcinoma
  Stomach cancer
  Melanoma
  Meningioma
  Prostate cancer
  Prostate carcinoma
  Bladder cancer
  Hepatitis C virus infection
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: RGAP1_HUMAN
• PDB ID: 2OVJ; 3W6R; 3WPQ; 3WPS; 4B6D; 5C2J; 5C2K
• Pfam ID: PF00130 ; PF00620
• Sequence:
  MDTMMLNVRNLFEQLVRRVEILSEGNEVQFIQLAKDFEDFRKKWQRTDHELGKYKDLLMK
  AETERSALDVKLKHARNQVDVEIKRRQRAEADCEKLERQIQLIREMLMCDTSGSIQLSEE
  QKSALAFLNRGQPSSSNAGNKRLSTIDESGSILSDISFDKTDESLDWDSSLVKTFKLKKR
  EKRRSTSRQFVDGPPGPVKKTRSIGSAVDQGNESIVAKTTVTVPNDGGPIEAVSTIETVP
  YWTRSRRKTGTLQPWNSDSTLNSRQLEPRTETDSVGTPQSNGGMRLHDFVSKTVIKPESC
  VPCGKRIKFGKLSLKCRDCRVVSHPECRDRCPLPCIPTLIGTPVKIGEGMLADFVSQTSP
  MIPSIVVHCVNEIEQRGLTETGLYRISGCDRTVKELKEKFLRVKTVPLLSKVDDIHAICS
  LLKDFLRNLKEPLLTFRLNRAFMEAAEITDEDNSIAAMYQAVGELPQANRDTLAFLMIHL
  QRVAQSPHTKMDVANLAKVFGPTIVAHAVPNPDPVTMLQDIKRQPKVVERLLSLPLEYWS
  QFMMVEQENIDPLHVIENSNAFSTPQTPDIKVSLLGPVTTPEHQLLKTPSSSSLSQRVRS
  TLTKNTPRFGSKSKSATNLGRQGNFFASPMLK
• Function: Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Required for proper attachment of the midbody to the cell membrane during cytokinesis. Sequentially binds to ECT2 and RAB11FIP3 which regulates cleavage furrow ingression and abscission during cytokinesis. Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity. Has a critical role in erythropoiesis. Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogenesis and in the RACGAP1 pathway in neuronal proliferation. Shows strong GAP (GTPase activation) activity towards CDC42 and RAC1 and less towards RHOA. Essential for the early stages of embryogenesis. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells.
• Tissue Specificity: Highly expressed in testis, thymus and placenta. Expressed at lower levels in spleen and peripheral blood lymphocytes. In testis, expression is restricted to germ cells with the highest levels of expression found in spermatocytes. Expression is regulated in a cell cycle-dependent manner and peaks during G2/M phase.
• Reactome Pathway:
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  RHOA GTPase cycle (R-HSA-8980692)
  RHOB GTPase cycle (R-HSA-9013026)
  RHOC GTPase cycle (R-HSA-9013106)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOD GTPase cycle (R-HSA-9013405)
  RAC3 GTPase cycle (R-HSA-9013423)
  Kinesins (R-HSA-983189)
  MHC class II antigen presentation (R-HSA-2132295)

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pancreatic ductal carcinoma	DIS26F9Q	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[6]
Endometrium adenocarcinoma	DISY6744	Strong	Altered Expression	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[8]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[9]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Lung cancer	DISCM4YA	Strong	Biomarker	[12]
Lung carcinoma	DISTR26C	Strong	Biomarker	[12]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[13]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[14]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[15]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[10]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[9]
Melanoma	DIS1RRCY	moderate	Biomarker	[16]
Meningioma	DISPT4TG	moderate	Altered Expression	[17]
Prostate cancer	DISF190Y	moderate	Biomarker	[18]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[18]
Bladder cancer	DISUHNM0	Limited	Biomarker	[19]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[20]
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[19]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Rac GTPase-activating protein 1 (RACGAP1) affects the response to substance of Vinblastine.	[54]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[21]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[22]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[24]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[25]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[26]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[27]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[28]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[29]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[30]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[30]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[31]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[32]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[33]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[34]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[35]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[36]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[37]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[38]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[39]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[40]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[41]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[42]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[43]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[27]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[44]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[45]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[49]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[43]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[50]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[29]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[52]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of Rac GTPase-activating protein 1 (RACGAP1).	[53]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Rac GTPase-activating protein 1 (RACGAP1).	[46]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Rac GTPase-activating protein 1 (RACGAP1).	[48]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Rac GTPase-activating protein 1 (RACGAP1).	[48]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Rac GTPase-activating protein 1 (RACGAP1).	[51]

References

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