Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTZ0FXP)

• DOT Name: SEC23-interacting protein (SEC23IP)
• Synonyms: p125
• Gene Name: SEC23IP
• Related Disease:
  Attention deficit hyperactivity disorder
  Hepatocellular carcinoma
• UniProt ID: S23IP_HUMAN
• Pfam ID: PF02862 ; PF00536 ; PF02825
• Sequence:
  MAERKPNGGSGGASTSSSGTNLLFSSSATEFSFNVPFIPVTQASASPASLLLPGEDSTDV
  GEEDSFLGQTSIHTSAPQTFSYFSQVSSSSDPFGNIGQSPLTTAATSVGQSGFPKPLTAL
  PFTTGSQDVSNAFSPSISKAQPGAPPSSLMGINSYLPSQPSSLPPSYFGNQPQGIPQPGY
  NPYRHTPGSSRANPYIAPPQLQQCQTPGPPAHPPPSGPPVQMYQMPPGSLPPVPSSVQSP
  AQQQVPARPGAPSVQVPSPFLLQNQYEPVQPHWFYCKEVEYKQLWMPFSVFDSLNLEEIY
  NSVQPDPESVVLGTDGGRYDVYLYDRIRKAAYWEEEPAEVRRCTWFYKGDTDSRFIPYTE
  EFSEKLEAEYKKAVTTNQWHRRLEFPSGETIVMHNPKVIVQFQPSSVPDEWGTTQDGQTR
  PRVVKRGIDDNLDEIPDGEMPQVDHLVFVVHGIGPVCDLRFRSIIECVDDFRVVSLKLLR
  THFKKSLDDGKVSRVEFLPVHWHSSLGGDATGVDRNIKKITLPSIGRFRHFTNETLLDIL
  FYNSPTYCQTIVEKVGMEINHLHALFMSRNPDFKGGVSVAGHSLGSLILFDILSNQKDLN
  LSKCPGPLAVANGVVKQLHFQEKQMPEEPKLTLDESYDLVVENKEVLTLQETLEALSLSE
  YFSTFEKEKIDMESLLMCTVDDLKEMGIPLGPRKKIANFVEHKAAKLKKAASEKKAVAAT
  STKGQEQSAQKTKDMASLPSESNEPKRKLPVGACVSSVCVNYESFEVGAGQVSVAYNSLD
  FEPEIFFALGSPIAMFLTIRGVDRIDENYSLPTCKGFFNIYHPLDPVAYRLEPMIVPDLD
  LKAVLIPHHKGRKRLHLELKESLSRMGSDLKQGFISSLKSAWQTLNEFARAHTSSTQLQE
  ELEKVANQIKEEEEKQVVEAEKVVESPDFSKDEDYLGKVGMLNGGRRIDYVLQEKPIESF
  NEYLFALQSHLCYWESEDTALLLLKEIYRTMNISPEQPQH
• Function: Plays a role in the organization of endoplasmic reticulum exit sites. Specifically binds to phosphatidylinositol 3-phosphate (PI(3)P), phosphatidylinositol 4-phosphate (PI(4)P) and phosphatidylinositol 5-phosphate (PI(5)P).
• Tissue Specificity: Ubiquitously expressed with stronger levels detected in heart, liver and skeletal muscle.
• Reactome Pathway: COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of SEC23-interacting protein (SEC23IP).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of SEC23-interacting protein (SEC23IP).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SEC23-interacting protein (SEC23IP).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SEC23-interacting protein (SEC23IP).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of SEC23-interacting protein (SEC23IP).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SEC23-interacting protein (SEC23IP).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of SEC23-interacting protein (SEC23IP).	[9]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of SEC23-interacting protein (SEC23IP).	[10]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of SEC23-interacting protein (SEC23IP).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of SEC23-interacting protein (SEC23IP).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of SEC23-interacting protein (SEC23IP).	[14]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of SEC23-interacting protein (SEC23IP).	[15]

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 decreases the phosphorylation of SEC23-interacting protein (SEC23IP).	[12]

References

• [1] Exome chip analyses in adult attention deficit hyperactivity disorder.Transl Psychiatry. 2016 Oct 18;6(10):e923. doi: 10.1038/tp.2016.196.
• [2] Significance of DNA polymerase delta catalytic subunit p125 induced by mutant p53 in the invasive potential of human hepatocellular carcinoma.Oncology. 2010;79(3-4):229-37. doi: 10.1159/000322374. Epub 2011 Mar 3.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [11] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [12] 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.
• [13] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.