Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPVY3ZR)

• DOT Name: Brevican core protein (BCAN)
• Synonyms: Brain-enriched hyaluronan-binding protein; BEHAB; Chondroitin sulfate proteoglycan 7
• Gene Name: BCAN
• Related Disease:
  Neoplasm
  Advanced cancer
  Alzheimer disease
  Bladder cancer
  Malignant glioma
  Schizophrenia
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adult glioblastoma
  Glioblastoma multiforme
  Glioma
• UniProt ID: PGCB_HUMAN
• Pfam ID: PF00008 ; PF00059 ; PF00084 ; PF07686 ; PF00193
• Sequence:
  MAQLFLPLLAALVLAQAPAALADVLEGDSSEDRAFRVRIAGDAPLQGVLGGALTIPCHVH
  YLRPPPSRRAVLGSPRVKWTFLSRGREAEVLVARGVRVKVNEAYRFRVALPAYPASLTDV
  SLALSELRPNDSGIYRCEVQHGIDDSSDAVEVKVKGVVFLYREGSARYAFSFSGAQEACA
  RIGAHIATPEQLYAAYLGGYEQCDAGWLSDQTVRYPIQTPREACYGDMDGFPGVRNYGVV
  DPDDLYDVYCYAEDLNGELFLGDPPEKLTLEEARAYCQERGAEIATTGQLYAAWDGGLDH
  CSPGWLADGSVRYPIVTPSQRCGGGLPGVKTLFLFPNQTGFPNKHSRFNVYCFRDSAQPS
  AIPEASNPASNPASDGLEAIVTVTETLEELQLPQEATESESRGAIYSIPIMEDGGGGSST
  PEDPAEAPRTLLEFETQSMVPPTGFSEEEGKALEEEEKYEDEEEKEEEEEEEEVEDEALW
  AWPSELSSPGPEASLPTEPAAQEESLSQAPARAVLQPGASPLPDGESEASRPPRVHGPPT
  ETLPTPRERNLASPSPSTLVEAREVGEATGGPELSGVPRGESEETGSSEGAPSLLPATRA
  PEGTRELEAPSEDNSGRTAPAGTSVQAQPVLPTDSASRGGVAVVPASGDCVPSPCHNGGT
  CLEEEEGVRCLCLPGYGGDLCDVGLRFCNPGWDAFQGACYKHFSTRRSWEEAETQCRMYG
  AHLASISTPEEQDFINNRYREYQWIGLNDRTIEGDFLWSDGVPLLYENWNPGQPDSYFLS
  GENCVVMVWHDQGQWSDVPCNYHLSYTCKMGLVSCGPPPELPLAQVFGRPRLRYEVDTVL
  RYRCREGLAQRNLPLIRCQENGRWEAPQISCVPRRPARALHPEEDPEGRQGRLLGRWKAL
  LIPPSSPMPGP
• Function: May play a role in the terminally differentiating and the adult nervous system during postnatal development. Could stabilize interactions between hyaluronan (HA) and brain proteoglycans.
• Tissue Specificity: Expressed in the retina, specifically in the inner nuclear layer, inner plexiform layer and ganglion cell layer (at protein level) . Detected in cerebrospinal fluid (at protein level) . Detected in urine (at protein level) .
• Reactome Pathway:
  A tetrasaccharide linker sequence is required for GAG synthesis (R-HSA-1971475)
  Chondroitin sulfate biosynthesis (R-HSA-2022870)
  Dermatan sulfate biosynthesis (R-HSA-2022923)
  CS/DS degradation (R-HSA-2024101)
  ECM proteoglycans (R-HSA-3000178)
  Defective B4GALT7 causes EDS, progeroid type (R-HSA-3560783)
  Defective B3GAT3 causes JDSSDHD (R-HSA-3560801)
  Defective CHST3 causes SEDCJD (R-HSA-3595172)
  Defective CHST14 causes EDS, musculocontractural type (R-HSA-3595174)
  Defective CHSY1 causes TPBS (R-HSA-3595177)
  Defective B3GALT6 causes EDSP2 and SEMDJL1 (R-HSA-4420332)
  Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Malignant glioma	DISFXKOV	Strong	Biomarker	[5]
Schizophrenia	DISSRV2N	Strong	Biomarker	[6]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[7]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[8]
Glioma	DIS5RPEH	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Brevican core protein (BCAN).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Brevican core protein (BCAN).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Brevican core protein (BCAN).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Brevican core protein (BCAN).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Brevican core protein (BCAN).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Brevican core protein (BCAN).	[14]

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 decreases the methylation of Brevican core protein (BCAN).	[13]

References

• [1] Brevican knockdown reduces late-stage glioma tumor aggressiveness.J Neurooncol. 2014 Oct;120(1):63-72. doi: 10.1007/s11060-014-1541-z. Epub 2014 Jul 23.
• [2] Somatic chromosomal engineering identifies BCAN-NTRK1 as a potent glioma driver and therapeutic target.Nat Commun. 2017 Jul 11;8:15987. doi: 10.1038/ncomms15987.
• [3] Hippocampal administration of chondroitinase ABC increases plaque-adjacent synaptic marker and diminishes amyloid burden in aged APPswe/PS1dE9 mice.Acta Neuropathol Commun. 2015 Sep 4;3:54. doi: 10.1186/s40478-015-0233-z.
• [4] BCAN Think Tank session 2: Molecular detection of bladder cancer: the path to progress.Urol Oncol. 2010 May-Jun;28(3):334-7. doi: 10.1016/j.urolonc.2009.07.026.
• [5] Novel tumor-specific isoforms of BEHAB/brevican identified in human malignant gliomas.Cancer Res. 2005 Aug 1;65(15):6726-33. doi: 10.1158/0008-5472.CAN-05-0585.
• [6] Candidate gene analysis of the human natural killer-1 carbohydrate pathway and perineuronal nets in schizophrenia: B3GAT2 is associated with disease risk and cortical surface area.Biol Psychiatry. 2011 Jan 1;69(1):90-6. doi: 10.1016/j.biopsych.2010.07.035. Epub 2010 Oct 15.
• [7] Human glioblastomas overexpress ADAMTS-5 that degrades brevican.Acta Neuropathol. 2005 Sep;110(3):239-46. doi: 10.1007/s00401-005-1032-6. Epub 2005 Aug 30.
• [8] Matrix-degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas.Int J Cancer. 2006 Jan 1;118(1):55-61. doi: 10.1002/ijc.21258.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [11] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.