Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2U42AC)

• DOT Name: Protein transport protein Sec31A (SEC31A)
• Synonyms: ABP125; ABP130; SEC31-like protein 1; SEC31-related protein A; Web1-like protein
• Gene Name: SEC31A
• Related Disease:
  Lung adenocarcinoma
  Non-small-cell lung cancer
  Meningioma
  B-cell lymphoma
  Lymphoma
  Neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies
  T-lymphoblastic lymphoma
• UniProt ID: SC31A_HUMAN
• PDB ID: 3WXA; 7SUL
• Pfam ID: PF12931
• Sequence:
  MKLKEVDRTAMQAWSPAQNHPIYLATGTSAQQLDATFSTNASLEIFELDLSDPSLDMKSC
  ATFSSSHRYHKLIWGPYKMDSKGDVSGVLIAGGENGNIILYDPSKIIAGDKEVVIAQNDK
  HTGPVRALDVNIFQTNLVASGANESEIYIWDLNNFATPMTPGAKTQPPEDISCIAWNRQV
  QHILASASPSGRATVWDLRKNEPIIKVSDHSNRMHCSGLAWHPDVATQMVLASEDDRLPV
  IQMWDLRFASSPLRVLENHARGILAIAWSMADPELLLSCGKDAKILCSNPNTGEVLYELP
  TNTQWCFDIQWCPRNPAVLSAASFDGRISVYSIMGGSTDGLRQKQVDKLSSSFGNLDPFG
  TGQPLPPLQIPQQTAQHSIVLPLKKPPKWIRRPVGASFSFGGKLVTFENVRMPSHQGAEQ
  QQQQHHVFISQVVTEKEFLSRSDQLQQAVQSQGFINYCQKKIDASQTEFEKNVWSFLKVN
  FEDDSRGKYLELLGYRKEDLGKKIALALNKVDGANVALKDSDQVAQSDGEESPAAEEQLL
  GEHIKEEKEESEFLPSSGGTFNISVSGDIDGLITQALLTGNFESAVDLCLHDNRMADAII
  LAIAGGQELLARTQKKYFAKSQSKITRLITAVVMKNWKEIVESCDLKNWREALAAVLTYA
  KPDEFSALCDLLGTRLENEGDSLLQTQACLCYICAGNVEKLVACWTKAQDGSHPLSLQDL
  IEKVVILRKAVQLTQAMDTSTVGVLLAAKMSQYANLLAAQGSIAAALAFLPDNTNQPNIM
  QLRDRLCRAQGEPVAGHESPKIPYEKQQLPKGRPGPVAGHHQMPRVQTQQYYPHGENPPP
  PGFIMHGNVNPNAAGQLPTSPGHMHTQVPPYPQPQPYQPAQPYPFGTGGSAMYRPQQPVA
  PPTSNAYPNTPYISSASSYTGQSQLYAAQHQASSPTSSPATSFPPPPSSGASFQHGGPGA
  PPSSSAYALPPGTTGTLPAASELPASQRTGPQNGWNDPPALNRVPKKKKMPENFMPPVPI
  TSPIMNPLGDPQSQMLQQQPSAPVPLSSQSSFPQPHLPGGQPFHGVQQPLGQTGMPPSFS
  KPNIEGAPGAPIGNTFQHVQSLPTKKITKKPIPDEHLILKTTFEDLIQRCLSSATDPQTK
  RKLDDASKRLEFLYDKLREQTLSPTITSGLHNIARSIETRNYSEGLTMHTHIVSTSNFSE
  TSAFMPVLKVVLTQANKLGV
• 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.
• Tissue Specificity: Abundantly and ubiquitously expressed.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway:
  MHC class II antigen presentation (R-HSA-2132295)
  XBP1(S) activates chaperone genes (R-HSA-381038)
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  Antigen Presentation (R-HSA-983170)
  COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[1]
Meningioma	DISPT4TG	moderate	Biomarker	[2]
B-cell lymphoma	DISIH1YQ	Limited	Biomarker	[3]
Lymphoma	DISN6V4S	Limited	Genetic Variation	[4]
Neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies	DISH2WII	Limited	Autosomal recessive	[5]
T-lymphoblastic lymphoma	DISGFZXW	Limited	Biomarker	[6]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Protein transport protein Sec31A (SEC31A) affects the response to substance of Fluorouracil.	[26]
Mitoxantrone	DMM39BF	Approved	Protein transport protein Sec31A (SEC31A) affects the response to substance of Mitoxantrone.	[26]

16 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 Sec31A (SEC31A).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein transport protein Sec31A (SEC31A).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein transport protein Sec31A (SEC31A).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein transport protein Sec31A (SEC31A).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein transport protein Sec31A (SEC31A).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein transport protein Sec31A (SEC31A).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein transport protein Sec31A (SEC31A).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein transport protein Sec31A (SEC31A).	[16]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protein transport protein Sec31A (SEC31A).	[17]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Protein transport protein Sec31A (SEC31A).	[18]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Protein transport protein Sec31A (SEC31A).	[19]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Protein transport protein Sec31A (SEC31A).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Protein transport protein Sec31A (SEC31A).	[20]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein transport protein Sec31A (SEC31A).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein transport protein Sec31A (SEC31A).	[24]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein transport protein Sec31A (SEC31A).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Protein transport protein Sec31A (SEC31A).	[13]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Protein transport protein Sec31A (SEC31A).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein transport protein Sec31A (SEC31A).	[21]
TAK-243	DM4GKV2	Phase 1	TAK-243 affects the sumoylation of Protein transport protein Sec31A (SEC31A).	[22]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein transport protein Sec31A (SEC31A).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Protein transport protein Sec31A (SEC31A).	[14]

References

• [1] SEC31A-ALK Fusion Gene in Lung Adenocarcinoma.Cancer Res Treat. 2016 Jan;48(1):398-402. doi: 10.4143/crt.2014.254. Epub 2015 Feb 17.
• [2] Meningioma protein-protein interaction network.Arch Iran Med. 2014 Apr;17(4):262-72.
• [3] Anaplastic lymphoma kinase-positive large B-cell lymphoma: an underrecognized aggressive lymphoma.Adv Hematol. 2012;2012:529572. doi: 10.1155/2012/529572. Epub 2012 Feb 26.
• [4] Fusion of the SEC31L1 and ALK genes in an inflammatory myofibroblastic tumor.Int J Cancer. 2006 Mar 1;118(5):1181-6. doi: 10.1002/ijc.21490.
• [5] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [6] JAK2 rearrangements, including the novel SEC31A-JAK2 fusion, are recurrent in classical Hodgkin lymphoma.Blood. 2011 Apr 14;117(15):4056-64. doi: 10.1182/blood-2010-06-291310. Epub 2011 Feb 15.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] 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.
• [9] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [10] 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.
• [11] 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.
• [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] Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood. Toxicol Appl Pharmacol. 2017 Apr 15;321:57-66. doi: 10.1016/j.taap.2017.02.019. Epub 2017 Feb 24.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [18] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [19] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [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] 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.
• [22] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [23] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [24] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [25] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [26] 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.