Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQNQAC7)

• DOT Name: GRB2-associated and regulator of MAPK protein 2 (GAREM2)
• Synonyms: GRB2-associated and regulator of MAPK1-like
• Gene Name: GAREM2
• Related Disease: Neuroblastoma
• UniProt ID: GARE2_HUMAN
• Pfam ID: PF12736
• Sequence:
  MEKLAAGLAGLRWSMGAFPLDLIVSRCRLPTLACLGPGEYAEGVSERDILLIHSCRQWTT
  VTAHTLEEGHYVIGPKIDIPLQYPGKFKLLEQARDVREPVRYFSSVEEVASVFPDRIFVM
  EAITFSVKVVSGEFSEDSEVYNFTLHAGDELTLMGQAEILCAKTTKERSRFTTLLRKLGR
  AGALAGVGGGGPASAGAAGGTGGGGARPVKGKMPCLICMNHRTNESLSLPFQCQGRFSTR
  SPLELQMQEGEHTVRAIIERVRLPVNVLVPSRPPRNPYDLHPVREGHCYKLVSIISKTVV
  LGLALRREGPAPLHFLLLTDTPRFALPQGLLAGDPRVERLVRDSASYCRERFDPDEYSTA
  VREAPAELAEDCASPRRARLCLPAPRAPGLARAPGPLAPAPAGEGDQEYVSPDWAAAPEP
  AAPPAEIPYEELWAHQGPEGLVRPPPGLDLISFGAAGPPRREPEAPPPPVPPKSEAVKEE
  CRLLNAPPVPPRGGNGSGRLSSSPPVPPRFPKLQPVHSPSSSLSYYSSGLQDGAGSRSGS
  GSPSPDTYSLYCYPCTWGDCKVGESSSRPAPGPLPSTTQPSQASRALTEPLSGRAASLLG
  ADTPVKTYHSCPPLFKPSHPQKRFAPFGALNPFSGPAYPSGPSAALSSGPRTTSGPVATS
  GPAYSPGPASPGQAYSAAPPSSCAPSSSSSSEWQEPVLEPFDPFELGQGSSPEPELLRSQ
  EPRAVGTPGPGPRLSPLGPSKAFEPEGLVLHQVPTPLSPAALQGPEAGGALFLTQGRLEG
  PPASPRDGATGFGVRDASSWQPPADLSALSLEEVSRSLRFIGLSEDVVSFFARERIDGSI
  FVQLSEDILADDFHLTKLQVKKIMQFIKGWRPKI
• Function: Probable adapter protein that may provide a link between cell surface epidermal growth factor receptor and the MAPK/ERK signaling pathway.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of GRB2-associated and regulator of MAPK protein 2 (GAREM2).	[2]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of GRB2-associated and regulator of MAPK protein 2 (GAREM2).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of GRB2-associated and regulator of MAPK protein 2 (GAREM2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of GRB2-associated and regulator of MAPK protein 2 (GAREM2).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of GRB2-associated and regulator of MAPK protein 2 (GAREM2).	[6]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of GRB2-associated and regulator of MAPK protein 2 (GAREM2).	[7]

References

• [1] A brain-specific Grb2-associated regulator of extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) (GAREM) subtype, GAREM2, contributes to neurite outgrowth of neuroblastoma cells by regulating Erk signaling.J Biol Chem. 2013 Oct 11;288(41):29934-42. doi: 10.1074/jbc.M113.492520. Epub 2013 Sep 3.
• [2] 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.
• [3] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [6] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [7] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.