Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQW6R3Z)

• DOT Name: SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1)
• Synonyms: Endophilin-3-interacting protein
• Gene Name: SGIP1
• Related Disease:
  Major depressive disorder
  Obesity
• UniProt ID: SGIP1_HUMAN
• PDB ID: 5AWR; 5AWS; 5AWT; 5AWU; 6A9Y
• Pfam ID: PF10291
• Sequence:
  MMEGLKKRTRKAFGIRKKEKDTDSTGSPDRDGIQPSPHEPPYNSKAECAREGGKKVSKKS
  NGAPNGFYAEIDWERYNSPELDEEGYSIRPEEPGSTKGKHFYSSSESEEEEESHKKFNIK
  IKPLQSKDILKNAATVDELKASIGNIALSPSPVRKSPRRSPGAIKRNLSSEEVARPRRST
  PTPELISKKPPDDTTALAPLFGPPLESAFDEQKTEVLLDQPEIWGSGQPINPSMESPKLT
  RPFPTGTPPPLPPKNVPATPPRTGSPLTIGPGNDQSATEVKIEKLPSINDLDSIFGPVLS
  PKSVAVNAEEKWVHFSDTSPEHVTPELTPREKVVSPPATPDNPADSPAPGPLGPPGPTGP
  PGPPGPPRNVLSPLNLEEVQKKVAEQTFIKDDYLETISSPKDFGLGQRATPPPPPPPTYR
  TVVSSPGPGSGPGPGTTSGASSPARPATPLVPCRSTTPPPPPPRPPSRPKLPPGKPGVGD
  VSRPFSPPIHSSSPPPIAPLARAESTSSISSTNSLSAATTPTVENEQPSLVWFDRGKFYL
  TFEGSSRGPSPLTMGAQDTLPVAAAFTETVNAYFKGADPSKCIVKITGEMVLSFPAGITR
  HFANNPSPAALTFRVINFSRLEHVLPNPQLLCCDNTQNDANTKEFWVNMPNLMTHLKKVS
  EQKPQATYYNVDMLKYQVSAQGIQSTPLNLAVNWRCEPSSTDLRIDYKYNTDAMTTAVAL
  NNVQFLVPIDGGVTKLQAVLPPAVWNAEQQRILWKIPDISQKSENGGVGSLLARFQLSEG
  PSKPSPLVVQFTSEGSTLSGCDIELVGAGYRFSLIKKRFAAGKYLADN
• Function: May function in clathrin-mediated endocytosis. Has both a membrane binding/tubulating activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a preference for membranes enriched in phosphatidylserine and phosphoinositides and is required for the endocytosis of the transferrin receptor. May also bind tubulin. May play a role in the regulation of energy homeostasis.
• Tissue Specificity: Specifically expressed in brain.
• Reactome Pathway:
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[1]
Obesity	DIS47Y1K	Strong	Biomarker	[2]

9 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 SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1).	[7]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1).	[9]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1).	[8]

References

• [1] Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.Nat Neurosci. 2019 Mar;22(3):343-352. doi: 10.1038/s41593-018-0326-7. Epub 2019 Feb 4.
• [2] Genetic association studies of obesity in Africa: a systematic review.Obes Rev. 2015 Mar;16(3):259-72. doi: 10.1111/obr.12260. Epub 2015 Feb 2.
• [3] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] 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.
• [9] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [10] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.