Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBRNIJ3)

• DOT Name: Protein transport protein Sec23A (SEC23A)
• Synonyms: hSec23A; SEC23-related protein A
• Gene Name: SEC23A
• Related Disease:
  Cataract
  Prostate cancer
  Colorectal carcinoma
  Congenital dyserythropoietic anemia type 2
  Prostate carcinoma
  Craniolenticulosutural dysplasia
  Advanced cancer
  Cutaneous melanoma
  Familial medullary thyroid carcinoma
  Medullary thyroid gland carcinoma
  Melanoma
  Metastatic malignant neoplasm
  Neoplasm
  Osteoarthritis
• UniProt ID: SC23A_HUMAN
• PDB ID: 2NUP; 2NUT; 2YRC; 2YRD; 3EFO; 3EG9; 3EGD; 3EGX; 5KYN; 5KYU; 5KYW; 5KYX; 5KYY; 5VNE; 5VNF; 5VNG; 5VNH; 5VNI; 5VNJ; 5VNK; 5VNL; 5VNM; 5VNN; 5VNO
• Pfam ID: PF00626 ; PF08033 ; PF04815 ; PF04811 ; PF04810
• Sequence:
  MTTYLEFIQQNEERDGVRFSWNVWPSSRLEATRMVVPVAALFTPLKERPDLPPIQYEPVL
  CSRTTCRAVLNPLCQVDYRAKLWACNFCYQRNQFPPSYAGISELNQPAELLPQFSSIEYV
  VLRGPQMPLIFLYVVDTCMEDEDLQALKESMQMSLSLLPPTALVGLITFGRMVQVHELGC
  EGISKSYVFRGTKDLSAKQLQEMLGLSKVPLTQATRGPQVQQPPPSNRFLQPVQKIDMNL
  TDLLGELQRDPWPVPQGKRPLRSSGVALSIAVGLLECTFPNTGARIMMFIGGPATQGPGM
  VVGDELKTPIRSWHDIDKDNAKYVKKGTKHFEALANRAATTGHVIDIYACALDQTGLLEM
  KCCPNLTGGYMVMGDSFNTSLFKQTFQRVFTKDMHGQFKMGFGGTLEIKTSREIKISGAI
  GPCVSLNSKGPCVSENEIGTGGTCQWKICGLSPTTTLAIYFEVVNQHNAPIPQGGRGAIQ
  FVTQYQHSSGQRRIRVTTIARNWADAQTQIQNIAASFDQEAAAILMARLAIYRAETEEGP
  DVLRWLDRQLIRLCQKFGEYHKDDPSSFRFSETFSLYPQFMFHLRRSSFLQVFNNSPDES
  SYYRHHFMRQDLTQSLIMIQPILYAYSFSGPPEPVLLDSSSILADRILLMDTFFQILIYH
  GETIAQWRKSGYQDMPEYENFRHLLQAPVDDAQEILHSRFPMPRYIDTEHGGSQARFLLS
  KVNPSQTHNNMYAWGQESGAPILTDDVSLQVFMDHLKKLAVSSAA
• 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. Required for the translocation of insulin-induced glucose transporter SLC2A4/GLUT4 to the cell membrane.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• 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

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cataract	DISUD7SL	Definitive	Genetic Variation	[1]
Prostate cancer	DISF190Y	Definitive	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Congenital dyserythropoietic anemia type 2	DIS5RDUE	Strong	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]
Craniolenticulosutural dysplasia	DISZDFEE	Supportive	Autosomal recessive	[5]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[6]
Cutaneous melanoma	DIS3MMH9	Limited	Biomarker	[6]
Familial medullary thyroid carcinoma	DIS01PWX	Limited	Altered Expression	[7]
Medullary thyroid gland carcinoma	DISHBL3K	Limited	Altered Expression	[7]
Melanoma	DIS1RRCY	Limited	Biomarker	[6]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[6]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]
Osteoarthritis	DIS05URM	Limited	Biomarker	[8]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Protein transport protein Sec23A (SEC23A) affects the response to substance of Fluorouracil.	[19]

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 Sec23A (SEC23A).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein transport protein Sec23A (SEC23A).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein transport protein Sec23A (SEC23A).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein transport protein Sec23A (SEC23A).	[12]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Protein transport protein Sec23A (SEC23A).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein transport protein Sec23A (SEC23A).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein transport protein Sec23A (SEC23A).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Protein transport protein Sec23A (SEC23A).	[10]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein transport protein Sec23A (SEC23A).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein transport protein Sec23A (SEC23A).	[17]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR decreases the expression of Protein transport protein Sec23A (SEC23A).	[18]

References

• [1] Mutations in SEC24D, encoding a component of the COPII machinery, cause a syndromic form of osteogenesis imperfecta. Am J Hum Genet. 2015 Mar 5;96(3):432-9. doi: 10.1016/j.ajhg.2015.01.002. Epub 2015 Feb 12.
• [2] miR-375 induces docetaxel resistance in prostate cancer by targeting SEC23A and YAP1.Mol Cancer. 2016 Nov 10;15(1):70. doi: 10.1186/s12943-016-0556-9.
• [3] MicroRNA-21 promotes proliferation, migration, and invasion of colorectal cancer, and tumor growth associated with down-regulation of sec23a expression.BMC Cancer. 2016 Aug 5;16:605. doi: 10.1186/s12885-016-2628-z.
• [4] Functions of the COPII gene paralogs SEC23A and SEC23B are interchangeable in vivo.Proc Natl Acad Sci U S A. 2018 Aug 14;115(33):E7748-E7757. doi: 10.1073/pnas.1805784115. Epub 2018 Jul 31.
• [5] Cranio-lenticulo-sutural dysplasia is caused by a SEC23A mutation leading to abnormal endoplasmic-reticulum-to-Golgi trafficking. Nat Genet. 2006 Oct;38(10):1192-7. doi: 10.1038/ng1876. Epub 2006 Sep 17.
• [6] Sec23a mediates miR-200c augmented oligometastatic to polymetastatic progression.EBioMedicine. 2018 Nov;37:47-55. doi: 10.1016/j.ebiom.2018.10.002. Epub 2018 Oct 6.
• [7] MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib.Oncotarget. 2016 May 24;7(21):30461-78. doi: 10.18632/oncotarget.8458.
• [8] Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance.Mol Cell Proteomics. 2009 Jan;8(1):172-89. doi: 10.1074/mcp.M800292-MCP200. Epub 2008 Sep 9.
• [9] Proteomics investigations of drug-induced hepatotoxicity in HepG2 cells. Toxicol Sci. 2011 Mar;120(1):109-22.
• [10] Gene expression changes associated with cytotoxicity identified using cDNA arrays. Funct Integr Genomics. 2000 Sep;1(2):114-26.
• [11] 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.
• [12] 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.
• [13] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [14] 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.
• [15] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [16] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [17] 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.
• [18] Cytotoxic Effects of Environmental Toxins on Human Glial Cells. Neurotox Res. 2017 Feb;31(2):245-258. doi: 10.1007/s12640-016-9678-5. Epub 2016 Oct 29.
• [19] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.