Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT29944Y)

• DOT Name: Integrin-binding sialoprotein (IBSP)
• Synonyms: Bone sialoprotein 2; Bone sialoprotein II; BSP II; Cell-binding sialoprotein
• Gene Name: IBSP
• Related Disease:
  Bladder cancer
  Breast adenocarcinoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Cleidocranial dysplasia 1
  Colorectal carcinoma
  Ductal carcinoma
  Epileptic encephalopathy
  Esophageal squamous cell carcinoma
  Gilbert syndrome
  Hepatocellular carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Periodontal disease
  Postmenopausal osteoporosis
  Progressive familial intrahepatic cholestasis
  Prostate neoplasm
  Squamous cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Vitamin D deficiency
  X-linked Opitz G/BBB syndrome
  Chronic hepatitis B virus infection
  Periodontitis
  Type-1/2 diabetes
• UniProt ID: SIAL_HUMAN
• Pfam ID: PF05432
• Sequence:
  MKTALILLSILGMACAFSMKNLHRRVKIEDSEENGVFKYRPRYYLYKHAYFYPHLKRFPV
  QGSSDSSEENGDDSSEEEEEEEETSNEGENNEESNEDEDSEAENTTLSATTLGYGEDATP
  GTGYTGLAAIQLPKKAGDITNKATKEKESDEEEEEEEEGNENEESEAEVDENEQGINGTS
  TNSTEAENGNGSSGGDNGEEGEEESVTGANAEDTTETGRQGKGTSKTTTSPNGGFEPTTP
  PQVYRTTSPPFGKTTTVEYEGEYEYTGANEYDNGYEIYESENGEPRGDNYRAYEDEYSYF
  KGQGYDGYDGQNYYHHQ
• Function: Binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction. Promotes adhesion and migration of various cells via the alpha-V/beta-3 integrin receptor (ITGAV:ITGB3).
• Tissue Specificity: Expressed in bone (at protein level) . Expressed in trophoblast cells of placenta (at protein level) . Expressed in brain .
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Human papillomavirus infection (hsa05165)
• Reactome Pathway:
  ECM proteoglycans (R-HSA-3000178)
  Integrin cell surface interactions (R-HSA-216083)

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Biomarker	[1]
Breast adenocarcinoma	DISMPHJ0	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	Strong	Altered Expression	[4]
Cleidocranial dysplasia 1	DIS2OHLA	Strong	Altered Expression	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Ductal carcinoma	DIS15EA5	Strong	Biomarker	[2]
Epileptic encephalopathy	DISZOCA3	Strong	Genetic Variation	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[8]
Gilbert syndrome	DISMUZF4	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Posttranslational Modification	[10]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[11]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Periodontal disease	DISJQHVN	Strong	Genetic Variation	[12]
Postmenopausal osteoporosis	DISS0RQZ	Strong	Genetic Variation	[13]
Progressive familial intrahepatic cholestasis	DIS3J8HT	Strong	Genetic Variation	[14]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[15]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[16]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[1]
Vitamin D deficiency	DISAWKYI	Strong	Altered Expression	[17]
X-linked Opitz G/BBB syndrome	DISQ14EC	Strong	Genetic Variation	[7]
Chronic hepatitis B virus infection	DISHL4NT	moderate	Genetic Variation	[18]
Periodontitis	DISI9JOI	Limited	Genetic Variation	[12]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	Integrin-binding sialoprotein (IBSP) decreases the response to substance of Camptothecin.	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Integrin-binding sialoprotein (IBSP).	[20]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Integrin-binding sialoprotein (IBSP).	[21]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Integrin-binding sialoprotein (IBSP).	[22]
Vitamin C	DMXJ7O8	Approved	Vitamin C increases the expression of Integrin-binding sialoprotein (IBSP).	[23]
Magnesium	DMU4ORS	Approved	Magnesium increases the expression of Integrin-binding sialoprotein (IBSP).	[24]
Calcidiol	DMN4CV5	Approved	Calcidiol increases the expression of Integrin-binding sialoprotein (IBSP).	[21]
GSK2816126	DMJDVW4	Phase 1	GSK2816126 increases the expression of Integrin-binding sialoprotein (IBSP).	[26]
Eugenol	DM7US1H	Patented	Eugenol decreases the expression of Integrin-binding sialoprotein (IBSP).	[27]
Alpha-ketoglutaric acid	DM5LFYN	Investigative	Alpha-ketoglutaric acid increases the expression of Integrin-binding sialoprotein (IBSP).	[28]
ODQ	DMSAJO8	Investigative	ODQ decreases the expression of Integrin-binding sialoprotein (IBSP).	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Integrin-binding sialoprotein (IBSP).	[25]

References

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• [8] Upregulation of IBSP Expression Predicts Poor Prognosis in Patients With Esophageal Squamous Cell Carcinoma.Front Oncol. 2019 Oct 25;9:1117. doi: 10.3389/fonc.2019.01117. eCollection 2019.
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• [12] Periodontal diagnosis in the context of the BSP implementation plan for the 2017 classification system of periodontal diseases and conditions: presentation of a patient with a history of periodontal treatment.Br Dent J. 2019 Feb;226(4):265-267. doi: 10.1038/s41415-019-0015-2.
• [13] Endochondral ossification pathway genes and postmenopausal osteoporosis: Association and specific allele related serum bone sialoprotein levels in Han Chinese.Sci Rep. 2015 Nov 16;5:16783. doi: 10.1038/srep16783.
• [14] A study of inheritance in progressive intrahepatic cholestasis: hepatic excretory function in unaffected family members.Pediatr Res. 1979 Sep;13(9):1002-5. doi: 10.1203/00006450-197909000-00010.
• [15] Differential expression of osteopontin and bone sialoprotein in bone metastasis of breast and prostate carcinoma.Clin Exp Metastasis. 2003;20(5):437-44. doi: 10.1023/a:1025419708343.
• [16] Detection of bone sialoprotein in human (pre)neoplastic lesions of the uterine cervix.Calcif Tissue Int. 2003 Jul;73(1):9-14. doi: 10.1007/s00223-002-2108-0.
• [17] Vitamin D and genomic stability.Mutat Res. 2001 Apr 18;475(1-2):69-87. doi: 10.1016/s0027-5107(01)00080-x.
• [18] Stimulation of human lymphocyte proliferation and CD40 antigen expression by phosphorothioate oligonucleotides complementary to hepatitis B virus genome.J Viral Hepat. 1996 Jul;3(4):167-72. doi: 10.1111/j.1365-2893.1996.tb00091.x.
• [19] Gene expression changes in cancellous bone of type 2 diabetics: a biomolecular basis for diabetic bone disease.Langenbecks Arch Surg. 2014 Jun;399(5):639-47. doi: 10.1007/s00423-014-1188-4. Epub 2014 Apr 10.
• [20] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [21] Effects of 25-hydroxyvitamin D(3) on proliferation and osteoblast differentiation of human marrow stromal cells require CYP27B1/1alpha-hydroxylase. J Bone Miner Res. 2011 May;26(5):1145-53.
• [22] Zoledronic acid up-regulates bone sialoprotein expression in osteoblastic cells through Rho GTPase inhibition. Biochem J. 2004 Dec 15;384(Pt 3):591-8. doi: 10.1042/BJ20040380.
• [23] Potential osteoinductive effects of calcitriol on the m-RNA of mesenchymal stem cells derived from human alveolar periosteum. Biomed Res Int. 2016;2016:3529561.
• [24] Effect of surface chemical modification of bioceramic on phenotype of human bone-derived cells. J Biomed Mater Res. 1999 Mar 15;44(4):389-96. doi: 10.1002/(sici)1097-4636(19990315)44:4<389::aid-jbm4>3.0.co;2-o.
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• [26] Epigenetic control of skeletal development by the histone methyltransferase Ezh2. J Biol Chem. 2015 Nov 13;290(46):27604-17.
• [27] Cytotoxic effect of eugenol on the expression of molecular markers related to the osteogenic differentiation of human dental pulp cells. Odontology. 2011 Jul;99(2):188-92. doi: 10.1007/s10266-011-0009-2. Epub 2011 Jun 26.
• [28] Alpha ketoglutarate exerts a pro-osteogenic effect in osteoblast cell lines through activation of JNK and mTOR/S6K1/S6 signaling pathways. Toxicol Appl Pharmacol. 2019 Jul 1;374:53-64.
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