Details of Drug Off-Target (DOT)

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

• DOT Name: Protein transport protein Sec24A (SEC24A)
• Synonyms: SEC24-related protein A
• Gene Name: SEC24A
• UniProt ID: SC24A_HUMAN
• PDB ID: 2NUP; 2NUT; 3EGD; 3EGX; 5VNE; 5VNF; 5VNG; 5VNH; 5VNI; 5VNJ; 5VNK; 5VNL; 5VNM; 5VNN; 5VNO
• Pfam ID: PF00626 ; PF08033 ; PF04815 ; PF04811 ; PF04810
• Sequence:
  MSQPGIPASGGAPASLQAQNGAALASGSPYTNGPVQNALLSSQESVSQGYNFQLPGSYPH
  PIPAKTLNPVSGQSNYGGSQGSGQTLNRPPVASNPVTPSLHSGPAPRMPLPASQNPATTP
  MPSSSFLPEANLPPPLNWQYNYPSTASQTNHCPRASSQPTVSGNTSLTTNHQYVSSGYPS
  LQNSFIKSGPSVPPLVNPPLPTTFQPGAPHGPPPAGGPPPVRALTPLTSSYRDVPQPLFN
  SAVNQEGITSNTNNGSMVVHSSYDEIEGGGLLATPQLTNKNPKMSRSVGYSYPSLPPGYQ
  NTTPPGATGVPPSSLNYPSGPQAFTQTPLGANHLTTSMSGLSLQPEGLRVVNLLQERNML
  PSTPLKPPVPNLHEDIQKLNCNPELFRCTLTSIPQTQALLNKAKLPLGLLLHPFKDLVQL
  PVVTSSTIVRCRSCRTYINPFVSFLDQRRWKCNLCYRVNDVPEEFLYNPLTRVYGEPHRR
  PEVQNATIEFMAPSEYMLRPPQPPVYLFVFDVSHNAVETGYLNSVCQSLLDNLDLLPGNT
  RTKIGFITFDSTIHFYGLQESLSQPQMLIVSDIEDVFIPMPENLLVNLNESKELVQDLLK
  TLPQMFTKTLETQSALGPALQAAFKLMSPTGGRMSVFQTQLPTLGVGALKPREEPNHRSS
  AKDIHMTPSTDFYKKLALDCSGQQVAVDLFLLSGQYSDLASLGCISRYSAGSVYYYPSYH
  HQHNPVQVQKLQKELQRYLTRKIGFEAVMRIRCTKGLSIHTFHGNFFVRSTDLLSLPNVN
  PDAGYAVQMSVEESLTDTQLVSFQSALLYTSSKGERRIRVHTLCLPVVSTLNDVFLGADV
  QAISGLLANMAVDRSMTASLSDARDALVNAVIDSLSAYRSSVLSNQQPGLMVPFSLRLFP
  LFVLALLKQKSFQTGTNARLDERIFAMCQVKNQPLVYLMLTTHPSLYRVDNLSDEGALNI
  SDRTIPQPPILQLSVEKLSRDGAFLMDAGSVLMLWVGKNCTQNFLSQVLGVQNYASIPQP
  MTDLPELDTPESARIIAFISWLREQRPFFPILYVIRDESPMKANFLQNMIEDRTESALSY
  YEFLLHIQQQVNK
• 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 SEC24B 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

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein transport protein Sec24A (SEC24A).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein transport protein Sec24A (SEC24A).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein transport protein Sec24A (SEC24A).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein transport protein Sec24A (SEC24A).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein transport protein Sec24A (SEC24A).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein transport protein Sec24A (SEC24A).	[6]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Protein transport protein Sec24A (SEC24A).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein transport protein Sec24A (SEC24A).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein transport protein Sec24A (SEC24A).	[9]

References

• [1] Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Toxicol Sci. 2023 Sep 28;195(2):169-183. doi: 10.1093/toxsci/kfad076.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [9] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.