Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGCFN4M)

• DOT Name: Enhancer of filamentation 1 (NEDD9)
• Synonyms: hEF1; CRK-associated substrate-related protein; CAS-L; CasL; Cas scaffolding protein family member 2; CASS2; Neural precursor cell expressed developmentally down-regulated protein 9; NEDD-9; Renal carcinoma antigen NY-REN-12; p105
• Gene Name: NEDD9
• UniProt ID: CASL_HUMAN
• PDB ID: 2L81; 5X3S
• Pfam ID: PF12026 ; PF08824 ; PF14604
• Sequence:
  MKYKNLMARALYDNVPECAEELAFRKGDILTVIEQNTGGLEGWWLCSLHGRQGIVPGNRV
  KLLIGPMQETASSHEQPASGLMQQTFGQQKLYQVPNPQAAPRDTIYQVPPSYQNQGIYQV
  PTGHGTQEQEVYQVPPSVQRSIGGTSGPHVGKKVITPVRTGHGYVYEYPSRYQKDVYDIP
  PSHTTQGVYDIPPSSAKGPVFSVPVGEIKPQGVYDIPPTKGVYAIPPSACRDEAGLREKD
  YDFPPPMRQAGRPDLRPEGVYDIPPTCTKPAGKDLHVKYNCDIPGAAEPVARRHQSLSPN
  HPPPQLGQSVGSQNDAYDVPRGVQFLEPPAETSEKANPQERDGVYDVPLHNPPDAKGSRD
  LVDGINRLSFSSTGSTRSNMSTSSTSSKESSLSASPAQDKRLFLDPDTAIERLQRLQQAL
  EMGVSSLMALVTTDWRCYGYMERHINEIRTAVDKVELFLKEYLHFVKGAVANAACLPELI
  LHNKMKRELQRVEDSHQILSQTSHDLNECSWSLNILAINKPQNKCDDLDRFVMVAKTVPD
  DAKQLTTTINTNAEALFRPGPGSLHLKNGPESIMNSTEYPHGGSQGQLLHPGDHKAQAHN
  KALPPGLSKEQAPDCSSSDGSERSWMDDYDYVHLQGKEEFERQQKELLEKENIMKQNKMQ
  LEHHQLSQFQLLEQEITKPVENDISKWKPSQSLPTTNSGVSAQDRQLLCFYYDQCETHFI
  SLLNAIDALFSCVSSAQPPRIFVAHSKFVILSAHKLVFIGDTLTRQVTAQDIRNKVMNSS
  NQLCEQLKTIVMATKMAALHYPSTTALQEMVHQVTDLSRNAQLFKRSLLEMATF
• Function: Scaffolding protein which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion. As a focal adhesion protein, plays a role in embryonic fibroblast migration. May play an important role in integrin beta-1 or B cell antigen receptor (BCR) mediated signaling in B- and T-cells. Integrin beta-1 stimulation leads to recruitment of various proteins including CRKL and SHPTP2 to the tyrosine phosphorylated form. Promotes adhesion and migration of lymphocytes; as a result required for the correct migration of lymphocytes to the spleen and other secondary lymphoid organs. Plays a role in the organization of T-cell F-actin cortical cytoskeleton and the centralization of T-cell receptor microclusters at the immunological synapse. Negatively regulates cilia outgrowth in polarized cysts. Modulates cilia disassembly via activation of AURKA-mediated phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin. Positively regulates RANKL-induced osteoclastogenesis. Required for the maintenance of hippocampal dendritic spines in the dentate gyrus and CA1 regions, thereby involved in spatial learning and memory.
• Tissue Specificity: Expressed in B-cells (at protein level) . Expressed in the respiratory epithelium of the main bronchi to the bronchioles in the lungs (at protein level) . High levels detected in kidney, lung, and placenta . Expressed in lymphocytes .

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Enhancer of filamentation 1 (NEDD9) affects the response to substance of Etoposide.	[26]
Mitomycin	DMH0ZJE	Approved	Enhancer of filamentation 1 (NEDD9) affects the response to substance of Mitomycin.	[26]

35 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 Enhancer of filamentation 1 (NEDD9).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Enhancer of filamentation 1 (NEDD9).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Enhancer of filamentation 1 (NEDD9).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Enhancer of filamentation 1 (NEDD9).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Enhancer of filamentation 1 (NEDD9).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Enhancer of filamentation 1 (NEDD9).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Enhancer of filamentation 1 (NEDD9).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Enhancer of filamentation 1 (NEDD9).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Enhancer of filamentation 1 (NEDD9).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Enhancer of filamentation 1 (NEDD9).	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Enhancer of filamentation 1 (NEDD9).	[3]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Enhancer of filamentation 1 (NEDD9).	[6]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Enhancer of filamentation 1 (NEDD9).	[11]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Enhancer of filamentation 1 (NEDD9).	[12]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Enhancer of filamentation 1 (NEDD9).	[6]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Enhancer of filamentation 1 (NEDD9).	[13]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Enhancer of filamentation 1 (NEDD9).	[6]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Enhancer of filamentation 1 (NEDD9).	[6]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Enhancer of filamentation 1 (NEDD9).	[6]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Enhancer of filamentation 1 (NEDD9).	[3]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of Enhancer of filamentation 1 (NEDD9).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Enhancer of filamentation 1 (NEDD9).	[14]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Enhancer of filamentation 1 (NEDD9).	[15]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Enhancer of filamentation 1 (NEDD9).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Enhancer of filamentation 1 (NEDD9).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Enhancer of filamentation 1 (NEDD9).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Enhancer of filamentation 1 (NEDD9).	[18]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Enhancer of filamentation 1 (NEDD9).	[20]
Tacedinaline	DM1Z74X	Discontinued in Phase 2	Tacedinaline increases the expression of Enhancer of filamentation 1 (NEDD9).	[21]
Oxamflatin	DM1TG3C	Terminated	Oxamflatin increases the expression of Enhancer of filamentation 1 (NEDD9).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Enhancer of filamentation 1 (NEDD9).	[23]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Enhancer of filamentation 1 (NEDD9).	[24]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Enhancer of filamentation 1 (NEDD9).	[25]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Enhancer of filamentation 1 (NEDD9).	[3]
Apicidin	DM83WVF	Investigative	Apicidin increases the expression of Enhancer of filamentation 1 (NEDD9).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Enhancer of filamentation 1 (NEDD9).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Enhancer of filamentation 1 (NEDD9).	[22]

References

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