Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKT2C2N)

• DOT Name: Breast cancer anti-estrogen resistance protein 1 (BCAR1)
• Synonyms: CRK-associated substrate; Cas scaffolding protein family member 1; p130cas
• Gene Name: BCAR1
• Related Disease:
  Carcinoma
  Acute myelogenous leukaemia
  Adenocarcinoma
  Adult glioblastoma
  Alzheimer disease
  Breast neoplasm
  Childhood apraxia of speech
  Colon carcinoma
  Colorectal carcinoma
  Congestive heart failure
  Depression
  Ductal carcinoma
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  leukaemia
  Lung cancer
  Lung carcinoma
  Melanocytic nevus
  Metastatic malignant neoplasm
  Multi-drug resistant tuberculosis
  Non-small-cell lung cancer
  Oral cancer
  Pancreatic cancer
  Pancreatic tumour
  Prostate carcinoma
  Renal cell carcinoma
  Squamous cell carcinoma
  Triple negative breast cancer
  Type-1/2 diabetes
  Urinary bladder neoplasm
  Carotid stenosis
  Estrogen resistance syndrome
  Extrapulmonary tuberculosis
  Leukemia
  Neuroblastoma
  Coronary atherosclerosis
  Coronary heart disease
  Epithelial ovarian cancer
  Melanoma
  Non-insulin dependent diabetes
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate neoplasm
• UniProt ID: BCAR1_HUMAN
• PDB ID: 1WYX; 3T6G; 5O2M; 5O2P; 5O2Q
• Pfam ID: PF12026 ; PF08824 ; PF00018
• Sequence:
  MNHLNVLAKALYDNVAESPDELSFRKGDIMTVLEQDTQGLDGWWLCSLHGRQGIVPGNRL
  KILVGMYDKKPAGPGPGPPATPAQPQPGLHAPAPPASQYTPMLPNTYQPQPDSVYLVPTP
  SKAQQGLYQVPGPSPQFQSPPAKQTSTFSKQTPHHPFPSPATDLYQVPPGPGGPAQDIYQ
  VPPSAGMGHDIYQVPPSMDTRSWEGTKPPAKVVVPTRVGQGYVYEAAQPEQDEYDIPRHL
  LAPGPQDIYDVPPVRGLLPSQYGQEVYDTPPMAVKGPNGRDPLLEVYDVPPSVEKGLPPS
  NHHAVYDVPPSVSKDVPDGPLLREETYDVPPAFAKAKPFDPARTPLVLAAPPPDSPPAED
  VYDVPPPAPDLYDVPPGLRRPGPGTLYDVPRERVLPPEVADGGVVDSGVYAVPPPAEREA
  PAEGKRLSASSTGSTRSSQSASSLEVAGPGREPLELEVAVEALARLQQGVSATVAHLLDL
  AGSAGATGSWRSPSEPQEPLVQDLQAAVAAVQSAVHELLEFARSAVGNAAHTSDRALHAK
  LSRQLQKMEDVHQTLVAHGQALDAGRGGSGATLEDLDRLVACSRAVPEDAKQLASFLHGN
  ASLLFRRTKATAPGPEGGGTLHPNPTDKTSSIQSRPLPSPPKFTSQDSPDGQYENSEGGW
  MEDYDYVHLQGKEEFEKTQKELLEKGSITRQGKSQLELQQLKQFERLEQEVSRPIDHDLA
  NWTPAQPLAPGRTGGLGPSDRQLLLFYLEQCEANLTTLTNAVDAFFTAVATNQPPKIFVA
  HSKFVILSAHKLVFIGDTLSRQAKAADVRSQVTHYSNLLCDLLRGIVATTKAAALQYPSP
  SAAQDMVERVKELGHSTQQFRRVLGQLAAA
• Function: Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion. Implicated in induction of cell migration and cell branching. Involved in the BCAR3-mediated inhibition of TGFB signaling.
• Tissue Specificity: Expressed in B-cells (at protein level) . Widely expressed with an abundant expression in the testis . Low level of expression seen in the liver, thymus, and peripheral blood leukocytes .
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Chemokine sig.ling pathway (hsa04062)
  Efferocytosis (hsa04148)
  Focal adhesion (hsa04510)
  Leukocyte transendothelial migration (hsa04670)
  Regulation of actin cytoskeleton (hsa04810)
  Growth hormone synthesis, secretion and action (hsa04935)
  Bacterial invasion of epithelial cells (hsa05100)
  Shigellosis (hsa05131)
  Yersinia infection (hsa05135)
  Human cytomegalovirus infection (hsa05163)
• Reactome Pathway:
  p130Cas linkage to MAPK signaling for integrins (R-HSA-372708)
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases (R-HSA-8849471)
  Downstream signal transduction (R-HSA-186763)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[2]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Childhood apraxia of speech	DISIR974	Strong	Genetic Variation	[7]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[10]
Depression	DIS3XJ69	Strong	Altered Expression	[10]
Ductal carcinoma	DIS15EA5	Strong	Biomarker	[11]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[12]
Glioma	DIS5RPEH	Strong	Posttranslational Modification	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
leukaemia	DISS7D1V	Strong	Biomarker	[15]
Lung cancer	DISCM4YA	Strong	Biomarker	[16]
Lung carcinoma	DISTR26C	Strong	Biomarker	[16]
Melanocytic nevus	DISYS32D	Strong	Biomarker	[17]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[18]
Multi-drug resistant tuberculosis	DIS1A2CS	Strong	Biomarker	[19]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[20]
Oral cancer	DISLD42D	Strong	Biomarker	[21]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[22]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[23]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[24]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[20]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[26]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[27]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[28]
Carotid stenosis	DISZA8D0	moderate	Biomarker	[29]
Estrogen resistance syndrome	DIS2SYXC	moderate	Biomarker	[30]
Extrapulmonary tuberculosis	DIS6KM28	moderate	Genetic Variation	[31]
Leukemia	DISNAKFL	moderate	Altered Expression	[32]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[33]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[34]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[34]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[35]
Melanoma	DIS1RRCY	Limited	Biomarker	[36]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[37]
Obesity	DIS47Y1K	Limited	Genetic Variation	[38]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[35]
Ovarian neoplasm	DISEAFTY	Limited	Altered Expression	[35]
Prostate cancer	DISF190Y	Limited	Biomarker	[24]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Breast cancer anti-estrogen resistance protein 1 (BCAR1) increases the response to substance of Cisplatin.	[21]
Afimoxifene	DMFORDT	Phase 2	Breast cancer anti-estrogen resistance protein 1 (BCAR1) decreases the response to substance of Afimoxifene.	[58]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[40]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[45]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[53]
Caffeic acid phenethyl ester	DMRJKIV	Investigative	Caffeic acid phenethyl ester decreases the phosphorylation of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[55]
[3H]oxotremorine-M	DM5L7D3	Investigative	[3H]oxotremorine-M increases the phosphorylation of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[56]

14 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 Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[42]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[43]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[44]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[46]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[47]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[48]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[44]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[49]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[50]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[50]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[51]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[52]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Breast cancer anti-estrogen resistance protein 1 (BCAR1).	[54]

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