Details of Drug Off-Target (DOT)

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

• DOT Name: Endophilin-A2 (SH3GL1)
• Synonyms: EEN fusion partner of MLL; Endophilin-2; Extra eleven-nineteen leukemia fusion gene protein; EEN; SH3 domain protein 2B; SH3 domain-containing GRB2-like protein 1
• Gene Name: SH3GL1
• UniProt ID: SH3G1_HUMAN
• Pfam ID: PF03114 ; PF00018
• Sequence:
  MSVAGLKKQFYKASQLVSEKVGGAEGTKLDDDFKEMEKKVDVTSKAVTEVLARTIEYLQP
  NPASRAKLTMLNTVSKIRGQVKNPGYPQSEGLLGECMIRHGKELGGESNFGDALLDAGES
  MKRLAEVKDSLDIEVKQNFIDPLQNLCEKDLKEIQHHLKKLEGRRLDFDYKKKRQGKIPD
  EELRQALEKFEESKEVAETSMHNLLETDIEQVSQLSALVDAQLDYHRQAVQILDELAEKL
  KRRMREASSRPKREYKPKPREPFDLGEPEQSNGGFPCTTAPKIAASSSFRSSDKPIRTPS
  RSMPPLDQPSCKALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYV
  EVLVPLPQ
• Function: Implicated in endocytosis. May recruit other proteins to membranes with high curvature.
• Tissue Specificity: Ubiquitous. Higher expression in pancreas, placenta, prostate, testis and uterus.
• KEGG Pathway: Endocytosis (hsa04144)
• Reactome Pathway:
  Negative regulation of MET activity (R-HSA-6807004)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  InlB-mediated entry of Listeria monocytogenes into host cell (R-HSA-8875360)
  EGFR downregulation (R-HSA-182971)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Endophilin-A2 (SH3GL1).	[1]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Endophilin-A2 (SH3GL1).	[2]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Endophilin-A2 (SH3GL1).	[3]
BAICALEIN	DM4C7E6	Phase 2	BAICALEIN decreases the expression of Endophilin-A2 (SH3GL1).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Endophilin-A2 (SH3GL1).	[6]
biochanin A	DM0HPWY	Investigative	biochanin A increases the expression of Endophilin-A2 (SH3GL1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Endophilin-A2 (SH3GL1).	[5]

References

• [1] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [2] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [3] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [4] MiR-3663-3p participates in the anti-hepatocellular carcinoma proliferation activity of baicalein by targeting SH3GL1 and negatively regulating EGFR/ERK/NF-B signaling. Toxicol Appl Pharmacol. 2021 Jun 1;420:115522. doi: 10.1016/j.taap.2021.115522. Epub 2021 Apr 8.
• [5] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [6] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [7] Mechanisms of the growth inhibitory effects of the isoflavonoid biochanin A on LNCaP cells and xenografts. Prostate. 2002 Aug 1;52(3):201-12.