Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMTJBQ1)

• DOT Name: Protein transport protein Sec24C (SEC24C)
• Synonyms: SEC24-related protein C
• Gene Name: SEC24C
• Related Disease:
  Bipolar disorder
  Colorectal carcinoma
  DiGeorge syndrome
  Hepatitis C virus infection
  Major depressive disorder
  Mood disorder
  Schizophrenia
  Velocardiofacial syndrome
  Isolated congenital microcephaly
• UniProt ID: SC24C_HUMAN
• PDB ID: 3EH2; 6PU1; 8CL3
• Pfam ID: PF00626 ; PF08033 ; PF04815 ; PF04811 ; PF04810
• Sequence:
  MNVNQSVPPVPPFGQPQPIYPGYHQSSYGGQSGSTAPAIPYGAYNGPVPGYQQTPPQGMS
  RAPPSSGAPPASTAQAPCGQAAYGQFGQGDVQNGPSSTVQMQRLPGSQPFGSPLAPVGNQ
  PPVLQPYGPPPTSAQVATQLSGMQISGAVAPAPPSSGLGFGPPTSLASASGSFPNSGLYG
  SYPQGQAPPLSQAQGHPGIQTPQRSAPSQASSFTPPASGGPRLPSMTGPLLPGQSFGGPS
  VSQPNHVSSPPQALPPGTQMTGPLGPLPPMHSPQQPGYQPQQNGSFGPARGPQSNYGGPY
  PAAPTFGSQPGPPQPLPPKRLDPDAIPSPIQVIEDDRNNRGTEPFVTGVRGQVPPLVTTN
  FLVKDQGNASPRYIRCTSYNIPCTSDMAKQAQVPLAAVIKPLARLPPEEASPYVVDHGES
  GPLRCNRCKAYMCPFMQFIEGGRRFQCCFCSCINDVPPQYFQHLDHTGKRVDAYDRPELS
  LGSYEFLATVDYCKNNKFPSPPAFIFMIDVSYNAIRTGLVRLLCEELKSLLDFLPREGGA
  EESAIRVGFVTYNKVLHFYNVKSSLAQPQMMVVSDVADMFVPLLDGFLVNVNESRAVITS
  LLDQIPEMFADTRETETVFVPVIQAGMEALKAAECAGKLFLFHTSLPIAEAPGKLKNRDD
  RKLINTDKEKTLFQPQTGAYQTLAKECVAQGCCVDLFLFPNQYVDVATLSVVPQLTGGSV
  YKYASFQVENDQERFLSDLRRDVQKVVGFDAVMRVRTSTGIRAVDFFGAFYMSNTTDVEL
  AGLDGDKTVTVEFKHDDRLNEESGALLQCALLYTSCAGQRRLRIHNLALNCCTQLADLYR
  NCETDTLINYMAKFAYRGVLNSPVKAVRDTLITQCAQILACYRKNCASPSSAGQLILPEC
  MKLLPVYLNCVLKSDVLQPGAEVTTDDRAYVRQLVTSMDVTETNVFFYPRLLPLTKSPVE
  STTEPPAVRASEERLSNGDIYLLENGLNLFLWVGASVQQGVVQSLFSVSSFSQITSGLSV
  LPVLDNPLSKKVRGLIDSLRAQRSRYMKLTVVKQEDKMEMLFKHFLVEDKSLSGGASYVD
  FLCHMHKEIRQLLS
• 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 SEC24D may have a different specificity compared to SEC24A and SEC24B. May more specifically package GPI-anchored proteins through the cargo receptor TMED10. May also be specific for IxM motif-containing cargos like the SNAREs GOSR2 and STX5.
• Tissue Specificity: Ubiquitous.
• 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 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
DiGeorge syndrome	DIST1RKO	Strong	GermlineModifyingMutation	[3]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[4]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[1]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[5]
Schizophrenia	DISSRV2N	Strong	Biomarker	[1]
Velocardiofacial syndrome	DISOSBTY	Strong	GermlineModifyingMutation	[3]
Isolated congenital microcephaly	DISUXHZ6	moderate	Biomarker	[6]

8 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 Sec24C (SEC24C).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein transport protein Sec24C (SEC24C).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein transport protein Sec24C (SEC24C).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein transport protein Sec24C (SEC24C).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein transport protein Sec24C (SEC24C).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Protein transport protein Sec24C (SEC24C).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein transport protein Sec24C (SEC24C).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein transport protein Sec24C (SEC24C).	[14]

References

• [1] Construction and analysis of the protein-protein interaction networks for schizophrenia, bipolar disorder, and major depression.BMC Bioinformatics. 2011;12 Suppl 13(Suppl 13):S20. doi: 10.1186/1471-2105-12-S13-S20. Epub 2011 Nov 30.
• [2] OLFM4, KNG1 and Sec24C identified by proteomics and immunohistochemistry as potential markers of early colorectal cancer stages.Clin Proteomics. 2017 Mar 24;14:9. doi: 10.1186/s12014-017-9143-3. eCollection 2017.
• [3] Histone Modifier Genes Alter Conotruncal Heart Phenotypes in 22q11.2 Deletion Syndrome.Am J Hum Genet. 2015 Dec 3;97(6):869-77. doi: 10.1016/j.ajhg.2015.10.013. Epub 2015 Nov 19.
• [4] Sec24C-Dependent Transport of Claudin-1 Regulates Hepatitis C Virus Entry.J Virol. 2017 Aug 24;91(18):e00629-17. doi: 10.1128/JVI.00629-17. Print 2017 Sep 15.
• [5] The serotonin transporter is an exclusive client of the coat protein complex II (COPII) component SEC24C.J Biol Chem. 2011 May 6;286(18):16482-90. doi: 10.1074/jbc.M111.230037. Epub 2011 Mar 17.
• [6] The COPII cargo adapter SEC24C is essential for neuronal homeostasis.J Clin Invest. 2018 Aug 1;128(8):3319-3332. doi: 10.1172/JCI98194. Epub 2018 Jun 25.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.