Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6W8CWP)

• DOT Name: Protein transport protein Sec24B (SEC24B)
• Synonyms: SEC24-related protein B
• Gene Name: SEC24B
• Related Disease:
  Neural tube defect
  Pneumocystis pneumonia
• UniProt ID: SC24B_HUMAN
• PDB ID: 3EH1
• Pfam ID: PF00626 ; PF08033 ; PF04815 ; PF04811 ; PF04810
• Sequence:
  MSAPAGSSHPAASARIPPKFGGAAVSGAAAPAGPGAGPAPHQQNGPAQNQMQVPSGYGLH
  HQNYIAPSGHYSQGPGKMTSLPLDTQCGDYYSALYTVPTQNVTPNTVNQQPGAQQLYSRG
  PPAPHIVGSTLGSFQGAASSASHLHTSASQPYSSFVNHYNSPAMYSASSSVASQGFPSTC
  GHYAMSTVSNAAYPSVSYPSLPAGDTYGQMFTSQNAPTVRPVKDNSFSGQNTAISHPSPL
  PPLPSQQHHQQQSLSGYSTLTWSSPGLPSTQDNLIRNHTGSLAVANNNPTITVADSLSCP
  VMQNVQPPKSSPVVSTVLSGSSGSSSTRTPPTANHPVEPVTSVTQPSELLQQKGVQYGEY
  VNNQASSAPTPLSSTSDDEEEEEEDEEAGVDSSSTTSSASPMPNSYDALEGGSYPDMLSS
  SASSPAPDPAPEPDPASAPAPASAPAPVVPQPSKMAKPFGYGYPTLQPGYQNATAPLISG
  VQPSNPVYSGFQQYPQQYPGVNQLSSSIGGLSLQSSPQPESLRPVNLTQERNILPMTPVW
  APVPNLNADLKKLNCSPDSFRCTLTNIPQTQALLNKAKLPLGLLLHPFRDLTQLPVITSN
  TIVRCRSCRTYINPFVSFIDQRRWKCNLCYRVNDVPEEFMYNPLTRSYGEPHKRPEVQNS
  TVEFIASSDYMLRPPQPAVYLFVLDVSHNAVEAGYLTILCQSLLENLDKLPGDSRTRIGF
  MTFDSTIHFYNLQEGLSQPQMLIVSDIDDVFLPTPDSLLVNLYESKELIKDLLNALPNMF
  TNTRETHSALGPALQAAFKLMSPTGGRVSVFQTQLPSLGAGLLQSREDPNQRSSTKVVQH
  LGPATDFYKKLALDCSGQQTAVDLFLLSSQYSDLASLACMSKYSAGCIYYYPSFHYTHNP
  SQAEKLQKDLKRYLTRKIGFEAVMRIRCTKGLSMHTFHGNFFVRSTDLLSLANINPDAGF
  AVQLSIEESLTDTSLVCFQTALLYTSSKGERRIRVHTLCLPVVSSLADVYAGVDVQAAIC
  LLANMAVDRSVSSSLSDARDALVNAVVDSLSAYGSTVSNLQHSALMAPSSLKLFPLYVLA
  LLKQKAFRTGTSTRLDDRVYAMCQIKSQPLVHLMKMIHPNLYRIDRLTDEGAVHVNDRIV
  PQPPLQKLSAEKLTREGAFLMDCGSVFYIWVGKGCDNNFIEDVLGYTNFASIPQKMTHLP
  ELDTLSSERARSFITWLRDSRPLSPILHIVKDESPAKAEFFQHLIEDRTEAAFSYYEFLL
  HVQQQICK
• 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. Plays a central role in cargo selection within the COPII complex and together with SEC24A may have a different specificity compared to SEC24C and SEC24D. May package preferentially cargos with cytoplasmic DxE or LxxLE motifs and may also recognize conformational epitopes.
• KEGG Pathway:
  Protein processing in endoplasmic reticulum (hsa04141)
  Pathogenic Escherichia coli infection (hsa05130)
• Reactome Pathway:
  COPII-mediated vesicle transport (R-HSA-204005)
  MHC class II antigen presentation (R-HSA-2132295)
  Cargo concentration in the ER (R-HSA-5694530)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  Antigen Presentation (R-HSA-983170)
  Regulation of cholesterol biosynthesis by SREBP (SREBF) (R-HSA-1655829)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neural tube defect	DIS5J95E	Definitive	Genetic Variation	[1]
Pneumocystis pneumonia	DISFSOM3	Limited	Genetic Variation	[2]

2 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 Sec24B (SEC24B).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protein transport protein Sec24B (SEC24B).	[12]

13 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 Sec24B (SEC24B).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein transport protein Sec24B (SEC24B).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein transport protein Sec24B (SEC24B).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Protein transport protein Sec24B (SEC24B).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein transport protein Sec24B (SEC24B).	[8]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Protein transport protein Sec24B (SEC24B).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Protein transport protein Sec24B (SEC24B).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein transport protein Sec24B (SEC24B).	[10]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Protein transport protein Sec24B (SEC24B).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein transport protein Sec24B (SEC24B).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein transport protein Sec24B (SEC24B).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein transport protein Sec24B (SEC24B).	[15]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Protein transport protein Sec24B (SEC24B).	[16]

References

• [1] Mutations in the COPII vesicle component gene SEC24B are associated with human neural tube defects.Hum Mutat. 2013 Aug;34(8):1094-101. doi: 10.1002/humu.22338. Epub 2013 May 13.
• [2] Planar cell polarity defects and defective Vangl2 trafficking in mutants for the COPII gene Sec24b.Development. 2010 Apr;137(7):1067-73. doi: 10.1242/dev.041434.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 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.
• [7] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [8] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [9] 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.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [16] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.