Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0I2B4J)

• DOT Name: EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2)
• Synonyms: Fibulin-4; FIBL-4; Protein UPH1
• Gene Name: EFEMP2
• Related Disease:
  Cutis laxa, autosomal recessive, type 1B
  Endometrial cancer
  Endometrial carcinoma
  Mycoses
  Advanced cancer
  Aortic aneurysm
  Arterial disorder
  Arterial tortuosity syndrome
  Autoimmune disease
  Cervical cancer
  Cervical carcinoma
  Cervical Intraepithelial neoplasia
  Colonic neoplasm
  Dilated cardiomyopathy 1A
  Duchenne muscular dystrophy
  Isolated congenital microcephaly
  Muscular dystrophy
  Neoplasm
  Osteoarthritis
  Osteogenesis imperfecta
  Ovarian neoplasm
  Pachyonychia congenita 3
  Prostate carcinoma
  Rheumatoid arthritis
  Systemic sclerosis
  Vascular disease
  Vibrio cholerae infection
  Cutis laxa, autosomal recessive, type 1A
  Familial thoracic aortic aneurysm and aortic dissection
  Pulmonary emphysema
  Autosomal recessive cutis laxa type 1
  Lethal arteriopathy syndrome due to fibulin-4 deficiency
  Asthma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Non-small-cell lung cancer
  Basal cell carcinoma
  Basal cell neoplasm
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Epithelioid mesothelioma
  Mesothelioma
  Osteosarcoma
  Prostate cancer
  Prostate neoplasm
• UniProt ID: FBLN4_HUMAN
• PDB ID: 2KL7
• Pfam ID: PF12662 ; PF07645 ; PF12661
• Sequence:
  MLPCASCLPGSLLLWALLLLLLGSASPQDSEEPDSYTECTDGYEWDPDSQHCRDVNECLT
  IPEACKGEMKCINHYGGYLCLPRSAAVINDLHGEGPPPPVPPAQHPNPCPPGYEPDDQDS
  CVDVDECAQALHDCRPSQDCHNLPGSYQCTCPDGYRKIGPECVDIDECRYRYCQHRCVNL
  PGSFRCQCEPGFQLGPNNRSCVDVNECDMGAPCEQRCFNSYGTFLCRCHQGYELHRDGFS
  CSDIDECSYSSYLCQYRCINEPGRFSCHCPQGYQLLATRLCQDIDECESGAHQCSEAQTC
  VNFHGGYRCVDTNRCVEPYIQVSENRCLCPASNPLCREQPSSIVHRYMTITSERSVPADV
  FQIQATSVYPGAYNAFQIRAGNSQGDFYIRQINNVSAMLVLARPVTGPREYVLDLEMVTM
  NSLMSYRASSVLRLTVFVGAYTF
• Function: Plays a crucial role in elastic fiber formation in tissue, and in the formation of ultrastructural connections between elastic laminae and smooth muscle cells in the aorta, therefore participates in terminal differentiation and maturation of smooth muscle cell (SMC) and in the mechanical properties and wall integrity maintenance of the aorta. In addition, is involved in the control of collagen fibril assembly in tissue throught proteolytic activation of LOX leading to cross- linking of collagen and elastin. Also promotes ELN coacervation and participates in the deposition of ELN coacervates on to microfibrils but also regulates ELN cross- linking through LOX interaction. Moreover adheres to the cells through heparin binding in a calcium-dependent manner and regulates vascularlar smooth muscle cells proliferation through angiotensin signaling.
• Reactome Pathway: Molecules associated with elastic fibres (R-HSA-2129379)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cutis laxa, autosomal recessive, type 1B	DISRVQS9	Definitive	Autosomal recessive	[1]
Endometrial cancer	DISW0LMR	Definitive	Biomarker	[2]
Endometrial carcinoma	DISXR5CY	Definitive	Biomarker	[2]
Mycoses	DIS9K7PB	Definitive	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Aortic aneurysm	DISQ5KRA	Strong	Genetic Variation	[5]
Arterial disorder	DISLG4XS	Strong	Genetic Variation	[6]
Arterial tortuosity syndrome	DISWG36B	Strong	Genetic Variation	[7]
Autoimmune disease	DISORMTM	Strong	Biomarker	[8]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[9]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[9]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Altered Expression	[9]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[10]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Altered Expression	[11]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[12]
Isolated congenital microcephaly	DISUXHZ6	Strong	Genetic Variation	[13]
Muscular dystrophy	DISJD6P7	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[14]
Osteogenesis imperfecta	DIS7XQSD	Strong	Genetic Variation	[7]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[15]
Pachyonychia congenita 3	DISZLC6C	Strong	Altered Expression	[16]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[16]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[8]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[8]
Vascular disease	DISVS67S	Strong	Biomarker	[6]
Vibrio cholerae infection	DISW7E3U	Strong	Biomarker	[17]
Cutis laxa, autosomal recessive, type 1A	DISKDUOX	moderate	GermlineCausalMutation	[13]
Familial thoracic aortic aneurysm and aortic dissection	DIS069FB	Moderate	Autosomal recessive	[18]
Pulmonary emphysema	DIS5M7HZ	moderate	Biomarker	[19]
Autosomal recessive cutis laxa type 1	DIS27S03	Supportive	Autosomal recessive	[20]
Lethal arteriopathy syndrome due to fibulin-4 deficiency	DISL1U86	Supportive	Autosomal recessive	[21]
Asthma	DISW9QNS	Disputed	Biomarker	[22]
Lung cancer	DISCM4YA	Disputed	Altered Expression	[23]
Lung carcinoma	DISTR26C	Disputed	Altered Expression	[23]
Lung neoplasm	DISVARNB	Disputed	Biomarker	[23]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Biomarker	[23]
Basal cell carcinoma	DIS7PYN3	Limited	Genetic Variation	[24]
Basal cell neoplasm	DIS37IXW	Limited	Genetic Variation	[24]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[25]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[4]
Epithelioid mesothelioma	DIS17SNY	Limited	Altered Expression	[26]
Mesothelioma	DISKWK9M	Limited	Biomarker	[26]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[25]
Prostate cancer	DISF190Y	Limited	Biomarker	[27]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[27]

3 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 EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[44]

18 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 EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[31]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[32]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[33]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[34]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[35]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[32]
Selenium	DM25CGV	Approved	Selenium increases the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[36]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[37]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[38]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[39]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[40]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[41]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[36]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[45]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2).	[46]

References

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