Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPJ17M8)

• DOT Name: Breast cancer anti-estrogen resistance protein 3 (BCAR3)
• Synonyms: Novel SH2-containing protein 2; SH2 domain-containing protein 3B
• Gene Name: BCAR3
• Related Disease:
  Breast neoplasm
  Alphavirus infectious disease
  Drug dependence
  Estrogen resistance syndrome
  Gastroenteritis
  Major depressive disorder
  Schizophrenia
  Substance abuse
  Substance dependence
  Hypertension, pregnancy-induced
  Plasma cell myeloma
  Polycystic ovarian syndrome
  Severe acute respiratory syndrome (SARS)
• UniProt ID: BCAR3_HUMAN
• PDB ID: 3T6A
• Pfam ID: PF00617 ; PF00017
• Sequence:
  MAAGKFASLPRNMPVNHQFPLASSMDLLSSRSPLAEHRPDAYQDVSIHGTLPRKKKGPPP
  IRSCDDFSHMGTLPHSKSPRQNSPVTQDGIQESPWQDRHGETFTFRDPHLLDPTVEYVKF
  SKERHIMDRTPEKLKKELEEELLLSSEDLRSHAWYHGRIPRQVSENLVQRDGDFLVRDSL
  SSPGNFVLTCQWKNLAQHFKINRTVLRLSEAYSRVQYQFEMESFDSIPGLVRCYVGNRRP
  ISQQSGAIIFQPINRTVPLRCLEEHYGTSPGQAREGSLTKGRPDVAKRLSLTMGGVQARE
  QNLPRGNLLRNKEKSGSQPACLDHMQDRRALSLKAHQSESYLPIGCKLPPQSSGVDTSPC
  PNSPVFRTGSEPALSPAVVRRVSSDARAGEALRGSDSQLCPKPPPKPCKVPFLKVPSSPS
  AWLNSEANYCELNPAFATGCGRGAKLPSCAQGSHTELLTAKQNEAPGPRNSGVNYLILDD
  DDRERPWEPAAAQMEKGQWDKGEFVTPLLETVSSFRPNEFESKFLPPENKPLETAMLKRA
  KELFTNNDPKVIAQHVLSMDCRVARILGVSEEMRRNMGVSSGLELITLPHGHQLRLDIIE
  RHNTMAIGIAVDILGCTGTLEDRAATLSKIIQVAVELKDSMGDLYSFSALMKALEMPQIT
  RLEKTWTALRHQYTQTAILYEKQLKPFSKLLHEGRESTCVPPNNVSVPLLMPLVTLMERQ
  AVTFEGTDMWEKNDQSCEIMLNHLATARFMAEAADSYRMNAERILAGFQPDEEMNEICKT
  EFQMRLLWGSKGAQVNQTERYEKFNQILTALSRKLEPPPVKQAEL
• Function: Acts as an adapter protein downstream of several growth factor receptors to promote cell proliferation, migration, and redistribution of actin fibers. Specifically involved in INS/insulin signaling pathway by mediating MAPK1/ERK2-MAPK3/ERK1 activation and DNA synthesis. Promotes insulin-mediated membrane ruffling. In response to vasoconstrictor peptide EDN1, involved in the activation of RAP1 downstream of PTK2B via interaction with phosphorylated BCAR1. Inhibits cell migration and invasion via regulation of TGFB-mediated matrix digestion, actin filament rearrangement, and inhibition of invadopodia activity. May inhibit TGFB-SMAD signaling, via facilitating BCAR1 and SMAD2 and/or SMAD3 interaction. Regulates EGF-induced DNA synthesis. Required for the maintenance of ocular lens morphology and structural integrity, potentially via regulation of focal adhesion complex signaling. Acts upstream of PTPRA to regulate the localization of BCAR1 and PTPRA to focal adhesions, via regulation of SRC-mediated phosphorylation of PTPRA. Positively regulates integrin-induced tyrosine phosphorylation of BCAR1. Acts as a guanine nucleotide exchange factor (GEF) for small GTPases RALA, RAP1A and RRAS. However, in a contrasting study, lacks GEF activity towards RAP1.
• Tissue Specificity: Ubiquitously expressed. Found in several cancer cell lines, but not in nonmalignant breast tissue.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Definitive	Biomarker	[1]
Alphavirus infectious disease	DISZGSCJ	Strong	Genetic Variation	[2]
Drug dependence	DIS9IXRC	Strong	Biomarker	[3]
Estrogen resistance syndrome	DIS2SYXC	Strong	Biomarker	[4]
Gastroenteritis	DISXQCG5	Strong	Biomarker	[5]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[6]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[7]
Substance abuse	DIS327VW	Strong	Biomarker	[3]
Substance dependence	DISDRAAR	Strong	Biomarker	[3]
Hypertension, pregnancy-induced	DISHNU25	moderate	Genetic Variation	[8]
Plasma cell myeloma	DIS0DFZ0	moderate	Altered Expression	[9]
Polycystic ovarian syndrome	DISZ2BNG	moderate	Biomarker	[10]
Severe acute respiratory syndrome (SARS)	DISYW14W	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Breast cancer anti-estrogen resistance protein 3 (BCAR3) affects the response to substance of Fulvestrant.	[38]
Afimoxifene	DMFORDT	Phase 2	Breast cancer anti-estrogen resistance protein 3 (BCAR3) decreases the response to substance of Afimoxifene.	[39]

25 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 Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[18]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[19]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[20]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[21]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[15]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[22]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[23]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[24]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[25]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[26]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[27]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[28]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[34]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[35]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[36]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[37]

3 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 Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[30]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Breast cancer anti-estrogen resistance protein 3 (BCAR3).	[33]

References

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