Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIM4TYI)

• DOT Name: Rho GTPase-activating protein 36 (ARHGAP36)
• Gene Name: ARHGAP36
• Related Disease: Medulloblastoma
• UniProt ID: RHG36_HUMAN
• Pfam ID: PF00620
• Sequence:
  MGGCIPFLKAARALCPRIMPPLLLLSAFIFLVSVLGGAPGHNPDRRTKMVSIHSLSELER
  LKLQETAYHELVARHFLSEFKPDRALPIDRPNTLDKWFLILRGQQRAVSHKTFGISLEEV
  LVNEFTRRKHLELTATMQVEEATGQAAGRRRGNVVRRVFGRIRRFFSRRRNEPTLPREFT
  RRGRRGAVSVDSLAELEDGALLLQTLQLSKISFPIGQRLLGSKRKMSLNPIAKQIPQVVE
  ACCQFIEKHGLSAVGIFTLEYSVQRVRQLREEFDQGLDVVLDDNQNVHDVAALLKEFFRD
  MKDSLLPDDLYMSFLLTATLKPQDQLSALQLLVYLMPPCHSDTLERLLKALHKITENCED
  SIGIDGQLVPGNRMTSTNLALVFGSALLKKGKFGKRESRKTKLGIDHYVASVNVVRAMID
  NWDVLFQVPPHIQRQVAKRVWKSSPEALDFIRRRNLRKIQSARIKMEEDALLSDPVETSA
  EARAAVLAQSKPSDEGSSEEPAVPSGTARSHDDEEGAGNPPIPEQDRPLLRVPREKEAKT
  GVSYFFP
• Function: GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.
• Tissue Specificity: Detected in the outer root sheath of hair follicles at the level of the stem cell bulge, during the anagen and telogen phases of hair growth (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Rho GTPase-activating protein 36 (ARHGAP36).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Rho GTPase-activating protein 36 (ARHGAP36).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Rho GTPase-activating protein 36 (ARHGAP36).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Rho GTPase-activating protein 36 (ARHGAP36).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Rho GTPase-activating protein 36 (ARHGAP36).	[6]

References

• [1] Bimodal antagonism of PKA signalling by ARHGAP36.Nat Commun. 2016 Oct 7;7:12963. doi: 10.1038/ncomms12963.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.