Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2NFSIQ)

• DOT Name: Protein transport protein Sec23B (SEC23B)
• Synonyms: hSec23B; SEC23-related protein B
• Gene Name: SEC23B
• Related Disease:
  Congenital dyserythropoietic anemia type 1
  Congenital dyserythropoietic anemia type 2
  Anemia
  Autosomal recessive congenital ichthyosis 3
  Beta thalassemia
  Hypogonadotropic hypogonadism 6 with or without anosmia
  Mevalonate kinase deficiency
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Hydrops fetalis
  Cowden disease
  Familial Mediterranean fever
  Advanced cancer
  Congenital dyserythropoietic anemia
  Cowden syndrome 7
• UniProt ID: SC23B_HUMAN
• Pfam ID: PF00626 ; PF08033 ; PF04815 ; PF04811 ; PF04810
• Sequence:
  MATYLEFIQQNEERDGVRFSWNVWPSSRLEATRMVVPLACLLTPLKERPDLPPVQYEPVL
  CSRPTCKAVLNPLCQVDYRAKLWACNFCFQRNQFPPAYGGISEVNQPAELMPQFSTIEYV
  IQRGAQSPLIFLYVVDTCLEEDDLQALKESLQMSLSLLPPDALVGLITFGRMVQVHELSC
  EGISKSYVFRGTKDLTAKQIQDMLGLTKPAMPMQQARPAQPQEHPFASSRFLQPVHKIDM
  NLTDLLGELQRDPWPVTQGKRPLRSTGVALSIAVGLLEGTFPNTGARIMLFTGGPPTQGP
  GMVVGDELKIPIRSWHDIEKDNARFMKKATKHYEMLANRTAANGHCIDIYACALDQTGLL
  EMKCCANLTGGYMVMGDSFNTSLFKQTFQRIFTKDFNGDFRMAFGATLDVKTSRELKIAG
  AIGPCVSLNVKGPCVSENELGVGGTSQWKICGLDPTSTLGIYFEVVNQHNTPIPQGGRGA
  IQFVTHYQHSSTQRRIRVTTIARNWADVQSQLRHIEAAFDQEAAAVLMARLGVFRAESEE
  GPDVLRWLDRQLIRLCQKFGQYNKEDPTSFRLSDSFSLYPQFMFHLRRSPFLQVFNNSPD
  ESSYYRHHFARQDLTQSLIMIQPILYSYSFHGPPEPVLLDSSSILADRILLMDTFFQIVI
  YLGETIAQWRKAGYQDMPEYENFKHLLQAPLDDAQEILQARFPMPRYINTEHGGSQARFL
  LSKVNPSQTHNNLYAWGQETGAPILTDDVSLQVFMDHLKKLAVSSAC
• Function: Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules for their transport to the Golgi complex.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital dyserythropoietic anemia type 1	DISCBVO6	Definitive	Biomarker	[1]
Congenital dyserythropoietic anemia type 2	DIS5RDUE	Definitive	Autosomal recessive	[2]
Anemia	DISTVL0C	Strong	Genetic Variation	[3]
Autosomal recessive congenital ichthyosis 3	DISDBKJ4	Strong	CausalMutation	[4]
Beta thalassemia	DIS5RCQK	Strong	Biomarker	[5]
Hypogonadotropic hypogonadism 6 with or without anosmia	DISXWNNI	Strong	Genetic Variation	[6]
Mevalonate kinase deficiency	DISSTRVK	Strong	Genetic Variation	[7]
Thyroid cancer	DIS3VLDH	Strong	Genetic Variation	[8]
Thyroid gland carcinoma	DISMNGZ0	Strong	Genetic Variation	[8]
Thyroid tumor	DISLVKMD	Strong	Genetic Variation	[8]
Hydrops fetalis	DISD9BBF	moderate	Biomarker	[9]
Cowden disease	DISMYKCE	Supportive	Autosomal dominant	[8]
Familial Mediterranean fever	DISVP5WP	Disputed	CausalMutation	[10]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[11]
Congenital dyserythropoietic anemia	DIS6FAT6	Limited	Autosomal recessive	[12]
Cowden syndrome 7	DISJE8HT	Limited	Autosomal dominant	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein transport protein Sec23B (SEC23B).	[13]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein transport protein Sec23B (SEC23B).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein transport protein Sec23B (SEC23B).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein transport protein Sec23B (SEC23B).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein transport protein Sec23B (SEC23B).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein transport protein Sec23B (SEC23B).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein transport protein Sec23B (SEC23B).	[18]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Protein transport protein Sec23B (SEC23B).	[19]
Selenium	DM25CGV	Approved	Selenium increases the expression of Protein transport protein Sec23B (SEC23B).	[20]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Protein transport protein Sec23B (SEC23B).	[21]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Protein transport protein Sec23B (SEC23B).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein transport protein Sec23B (SEC23B).	[24]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Protein transport protein Sec23B (SEC23B).	[25]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Protein transport protein Sec23B (SEC23B).	[26]

References

• [1] Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II. Nat Genet. 2009 Aug;41(8):936-40. doi: 10.1038/ng.405. Epub 2009 Jun 28.
• [2] Congenital dyserythropoietic anemia type II (CDAII) is caused by mutations in the SEC23B gene. Hum Mutat. 2009 Sep;30(9):1292-8. doi: 10.1002/humu.21077.
• [3] The BMP-SMAD pathway mediates the impaired hepatic iron metabolism associated with the ERFE-A260S variant.Am J Hematol. 2019 Nov;94(11):1227-1235. doi: 10.1002/ajh.25613. Epub 2019 Aug 30.
• [4] Two founder mutations in the SEC23B gene account for the relatively high frequency of CDA II in the Italian population.Am J Hematol. 2011 Sep;86(9):727-32. doi: 10.1002/ajh.22096.
• [5] Bone marrow transplantation in a case of severe, type II congenital dyserythropoietic anaemia (CDA II).Bone Marrow Transplant. 2001 Jan;27(2):213-5. doi: 10.1038/sj.bmt.1702764.
• [6] Hypomorphic mutations of SEC23B gene account for mild phenotypes of congenital dyserythropoietic anemia type II.Blood Cells Mol Dis. 2013 Jun;51(1):17-21. doi: 10.1016/j.bcmd.2013.02.003. Epub 2013 Mar 1.
• [7] A novel missense mutation in MVK associated with MK deficiency and dyserythropoietic anemia.Pediatrics. 2010 Apr;125(4):e964-8. doi: 10.1542/peds.2009-1774. Epub 2010 Mar 1.
• [8] Germline Heterozygous Variants in SEC23B Are Associated with Cowden Syndrome and Enriched in Apparently Sporadic Thyroid Cancer. Am J Hum Genet. 2015 Nov 5;97(5):661-76. doi: 10.1016/j.ajhg.2015.10.001. Epub 2015 Oct 29.
• [9] CDAII presenting as hydrops foetalis: molecular characterization of two cases.Blood Cells Mol Dis. 2010 Jun 15;45(1):20-2. doi: 10.1016/j.bcmd.2010.03.005. Epub 2010 Apr 9.
• [10] Retrospective cohort study of 205 cases with congenital dyserythropoietic anemia type II: definition of clinical and molecular spectrum and identification of new diagnostic scores.Am J Hematol. 2014 Oct;89(10):E169-75. doi: 10.1002/ajh.23800. Epub 2014 Jul 22.
• [11] The Functional Role of SEC23 in Vesicle Transportation, Autophagy and Cancer.Int J Biol Sci. 2019 Sep 7;15(11):2419-2426. doi: 10.7150/ijbs.37008. eCollection 2019.
• [12] PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels. Nat Genet. 2019 Nov;51(11):1560-1565. doi: 10.1038/s41588-019-0528-2.
• [13] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [18] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [19] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [20] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [21] 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.
• [22] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [23] 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.
• [24] 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.
• [25] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [26] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.