Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6U09OL)

• DOT Name: Scinderin (SCIN)
• Synonyms: Adseverin
• Gene Name: SCIN
• Related Disease:
  Acute megakaryoblastic leukemia
  Acute myelogenous leukaemia
  Adenoma
  Advanced cancer
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Castration-resistant prostate carcinoma
  Colorectal carcinoma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Bladder cancer
  Gastric cancer
  Lung cancer
  Lung carcinoma
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Hepatocellular carcinoma
  Melanoma
• UniProt ID: SCIN_HUMAN
• PDB ID: 3FG6; 5A1K; 5A1M
• Pfam ID: PF00626
• Sequence:
  MARELYHEEFARAGKQAGLQVWRIEKLELVPVPQSAHGDFYVGDAYLVLHTAKTSRGFTY
  HLHFWLGKECSQDESTAAAIFTVQMDDYLGGKPVQNRELQGYESNDFVSYFKGGLKYKAG
  GVASGLNHVLTNDLTAKRLLHVKGRRVVRATEVPLSWDSFNKGDCFIIDLGTEIYQWCGS
  SCNKYERLKANQVATGIRYNERKGRSELIVVEEGSEPSELIKVLGEKPELPDGGDDDDII
  ADISNRKMAKLYMVSDASGSMRVTVVAEENPFSMAMLLSEECFILDHGAAKQIFVWKGKD
  ANPQERKAAMKTAEEFLQQMNYSKNTQIQVLPEGGETPIFKQFFKDWRDKDQSDGFGKVY
  VTEKVAQIKQIPFDASKLHSSPQMAAQHNMVDDGSGKVEIWRVENNGRIQVDQNSYGEFY
  GGDCYIILYTYPRGQIIYTWQGANATRDELTTSAFLTVQLDRSLGGQAVQIRVSQGKEPV
  HLLSLFKDKPLIIYKNGTSKKGGQAPAPPTRLFQVRRNLASITRIVEVDVDANSLNSNDV
  FVLKLPQNSGYIWVGKGASQEEEKGAEYVASVLKCKTLRIQEGEEPEEFWNSLGGKKDYQ
  TSPLLETQAEDHPPRLYGCSNKTGRFVIEEIPGEFTQDDLAEDDVMLLDAWEQIFIWIGK
  DANEVEKKESLKSAKMYLETDPSGRDKRTPIVIIKQGHEPPTFTGWFLGWDSSKW
• Function: Ca(2+)-dependent actin filament-severing protein that has a regulatory function in exocytosis by affecting the organization of the microfilament network underneath the plasma membrane. Severing activity is inhibited by phosphatidylinositol 4,5-bis-phosphate (PIP2). In vitro, also has barbed end capping and nucleating activities in the presence of Ca(2+). Required for megakaryocyte differentiation, maturation, polyploidization and apoptosis with the release of platelet-like particles. Plays a role in osteoclastogenesis (OCG) and actin cytoskeletal organization in osteoclasts. Regulates chondrocyte proliferation and differentiation. Inhibits cell proliferation and tumorigenesis. Signaling is mediated by MAPK, p38 and JNK pathways.
• Tissue Specificity: Expressed in megakaryocytes.
• KEGG Pathway:
  Fc gamma R-mediated phagocytosis (hsa04666)
  Regulation of actin cytoskeleton (hsa04810)
  Viral carcinogenesis (hsa05203)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[2]
Adenoma	DIS78ZEV	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
B-cell neoplasm	DISVY326	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Altered Expression	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[5]
Prostate cancer	DISF190Y	Strong	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[5]
Bladder cancer	DISUHNM0	moderate	Altered Expression	[7]
Gastric cancer	DISXGOUK	moderate	Biomarker	[8]
Lung cancer	DISCM4YA	moderate	Biomarker	[9]
Lung carcinoma	DISTR26C	moderate	Biomarker	[9]
Stomach cancer	DISKIJSX	moderate	Biomarker	[8]
Urinary bladder cancer	DISDV4T7	moderate	Altered Expression	[7]
Urinary bladder neoplasm	DIS7HACE	moderate	Altered Expression	[7]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[10]
Melanoma	DIS1RRCY	Limited	Biomarker	[11]

3 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 Scinderin (SCIN).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Scinderin (SCIN).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Scinderin (SCIN).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Scinderin (SCIN).	[13]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Scinderin (SCIN).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Scinderin (SCIN).	[17]

References

• [1] Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis.Blood. 2001 Oct 1;98(7):2210-9. doi: 10.1182/blood.v98.7.2210.
• [2] Decreased SCIN expression, associated with promoter methylation, is a valuable predictor for prognosis in acute myeloid leukemia.Mol Carcinog. 2018 Jun;57(6):735-744. doi: 10.1002/mc.22794. Epub 2018 Mar 6.
• [3] Tumor-specific usage of alternative transcription start sites in colorectal cancer identified by genome-wide exon array analysis.BMC Genomics. 2011 Oct 14;12:505. doi: 10.1186/1471-2164-12-505.
• [4] Scinderin-knockdown inhibits proliferation and promotes apoptosis in human breast carcinoma cells.Oncol Lett. 2018 Sep;16(3):3207-3214. doi: 10.3892/ol.2018.9009. Epub 2018 Jun 21.
• [5] Loss of scinderin decreased expression of epidermal growth factor receptor and promoted apoptosis of castration-resistant prostate cancer cells.FEBS Open Bio. 2018 Apr 10;8(5):743-750. doi: 10.1002/2211-5463.12412. eCollection 2018 May.
• [6] Aberrant Scinderin Expression Correlates With Liver Metastasis and Poor Prognosis in Colorectal Cancer.Front Pharmacol. 2019 Oct 31;10:1183. doi: 10.3389/fphar.2019.01183. eCollection 2019.
• [7] Adseverin modulates morphology and invasive function of MCF7 cells.Biochim Biophys Acta Mol Basis Dis. 2019 Oct 1;1865(10):2716-2725. doi: 10.1016/j.bbadis.2019.07.015. Epub 2019 Jul 29.
• [8] Scinderin promotes the invasion and metastasis of gastric cancer cells and predicts the outcome of patients.Cancer Lett. 2016 Jun 28;376(1):110-7. doi: 10.1016/j.canlet.2016.03.035. Epub 2016 Mar 24.
• [9] Lentivirus-mediated silencing of SCIN inhibits proliferation of human lung carcinoma cells.Gene. 2015 Jan 1;554(1):32-9. doi: 10.1016/j.gene.2014.10.013. Epub 2014 Oct 7.
• [10] Scinderin is a novel transcriptional target of BRMS1 involved in regulation of hepatocellular carcinoma cell apoptosis.Am J Cancer Res. 2018 Jun 1;8(6):1008-1018. eCollection 2018.
• [11] A comprehensive genome-wide analysis of melanoma Breslow thickness identifies interaction between CDC42 and SCIN genetic variants.Int J Cancer. 2016 Nov 1;139(9):2012-20. doi: 10.1002/ijc.30245. Epub 2016 Jul 23.
• [12] 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.
• [13] 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.
• [14] Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
• [15] 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.
• [16] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [17] 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.