Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPVG40S)

• DOT Name: Roundabout homolog 3 (ROBO3)
• Synonyms: Roundabout-like protein 3
• Gene Name: ROBO3
• Related Disease:
  Acute myelogenous leukaemia
  Gaze palsy, familial horizontal, with progressive scoliosis 1
  Adult glioblastoma
  Advanced cancer
  Autism
  Autoimmune disease
  Breast neoplasm
  Chronic hepatitis B virus infection
  Chronic obstructive pulmonary disease
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Dermatomyositis
  Epithelial ovarian cancer
  Glioblastoma multiforme
  Graft-versus-host disease
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Herpes simplex infection
  Hutchinson-Gilford progeria syndrome
  Keratoconus
  Measles
  Neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Psoriasis
  Singleton-Merten dysplasia
  Systemic lupus erythematosus
  Zika virus infection
  Head-neck squamous cell carcinoma
  Influenza
  Respiratory syncytial virus infection
  Squamous cell carcinoma
  Melanoma
  Breast cancer
  Breast carcinoma
  Dengue
  Ebola virus infection
  Gastric cancer
  Nasopharyngeal carcinoma
  Pancreatic cancer
  Premature aging syndrome
  Rheumatoid arthritis
  Stomach cancer
• UniProt ID: ROBO3_HUMAN
• PDB ID: 6POG; 6POK; 6POL
• Pfam ID: PF00041 ; PF07679 ; PF13927
• Sequence:
  MLRYLLKTLLQMNLFADSLAGDISNSSELLLGFNSSLAALNHTLLPPGDPSLNGSRVGPE
  DAMPRIVEQPPDLLVSRGEPATLPCRAEGRPRPNIEWYKNGARVATVREDPRAHRLLLPS
  GALFFPRIVHGRRARPDEGVYTCVARNYLGAAASRNASLEVAVLRDDFRQSPGNVVVAVG
  EPAVLECVPPRGHPEPSVSWRKDGARLKEEEGRITIRGGKLMMSHTLKSDAGMYVCVASN
  MAGERESAAAEVMVLERPSFLRRPVNQVVLADAPVTFLCEVKGDPPPRLRWRKEDGELPT
  GRYEIRSDHSLWIGHVSAEDEGTYTCVAENSVGRAEASGSLSVHVPPQLVTQPQDQMAAP
  GESVAFQCETKGNPPPAIFWQKEGSQVLLFPSQSLQPTGRFSVSPRGQLNITAVQRGDAG
  YYVCQAVSVAGSILAKALLEIKGASLDGLPPVILQGPANQTLVLGSSVWLPCRVTGNPQP
  SVRWKKDGQWLQGDDLQFKTMANGTLYIANVQEMDMGFYSCVAKSSTGEATWSGWLKMRE
  DWGVSPDPPTEPSSPPGAPSQPVVTEITKNSITLTWKPNPQTGAAVTSYVIEAFSPAAGN
  TWRTVADGVQLETHTVSGLQPNTIYLFLVRAVGAWGLSEPSPVSEPVRTQDSSPSRPVED
  PWRGQQGLAEVAVRLQEPIVLGPRTLQVSWTVDGPVQLVQGFRVSWRVAGPEGGSWTMLD
  LQSPSQQSTVLRGLPPGTQIQIKVQAQGQEGLGAESLSVTRSIPEEAPSGPPQGVAVALG
  GDGNSSITVSWEPPLPSQQNGVITEYQIWCLGNESRFHLNRSAAGWARSAMLRGLVPGLL
  YRTLVAAATSAGVGVPSAPVLVQLPSPPDLEPGLEVGAGLAVRLARVLREPAFLAGSGAA
  CGALLLGLCAALYWRRKQRKELSHYTASFAYTPAVSFPHSEGLSGASSRPPMGLGPAPYS
  WLADSWPHPSRSPSAQEPRGSCCPSNPDPDDRYYNEAGISLYLAQTARGTAAPGEGPVYS
  TIDPAGEELQTFHGGFPQHPSGDLGPWSQYAPPEWSQGDSGAKGGKVKLLGKPVQMPSLN
  WPEALPPPPPSCELSCLEGPEEELEGSSEPEEWCPPMPERSHLTEPSSSGGCLVTPSRRE
  TPSPTPSYGQQSTATLTPSPPDPPQPPTDMPHLHQMPRRVPLGPSSPLSVSQPMLGIREA
  RPAGLGAGPAASPHLSPSPAPSTASSAPGRTWQGNGEMTPPLQGPRARFRKKPKALPYRR
  ENSPGDLPPPPLPPPEEEASWALELRAAGSMSSLERERSGERKAVQAVPLAAQRVLHPDE
  EAWLPYSRPSFLSRGQGTSTCSTAGSNSSRGSSSSRGSRGPGRSRSRSQSRSQSQRPGQK
  RREEPR
• Function: Receptor involved in axon guidance during development. Acts as a multifunctional regulator of pathfinding that simultaneously mediates NELL2 repulsion, inhibits SLIT repulsion, and facilitates Netrin-1/NTN1 attraction. In spinal cord development plays a role in guiding commissural axons probably by preventing premature sensitivity to Slit proteins thus inhibiting Slit signaling through ROBO1/ROBO2. Binding OF NELL2 to the receptor ROBO3 promotes oligomerization of ROBO3, resulting in the repulsion of commissural axons in the midline. ROBO3 also indirectly boosts axon attraction to NTN1 without interacting with NTN1 itself.
• KEGG Pathway: Axon guidance (hsa04360)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Gaze palsy, familial horizontal, with progressive scoliosis 1	DIS4KXBA	Definitive	Autosomal recessive	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Autism	DISV4V1Z	Strong	Genetic Variation	[5]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Chronic hepatitis B virus infection	DISHL4NT	Strong	Altered Expression	[8]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Altered Expression	[9]
Colon cancer	DISVC52G	Strong	Biomarker	[10]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[11]
Dermatomyositis	DIS50C5O	Strong	Biomarker	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[13]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Graft-versus-host disease	DIS0QADF	Strong	Biomarker	[14]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[15]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[17]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[18]
Hutchinson-Gilford progeria syndrome	DISY55BU	Strong	Biomarker	[19]
Keratoconus	DISOONXH	Strong	Genetic Variation	[20]
Measles	DISXSUID	Strong	Altered Expression	[21]
Neoplasm	DISZKGEW	Strong	Biomarker	[22]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[23]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[13]
Psoriasis	DIS59VMN	Strong	Biomarker	[24]
Singleton-Merten dysplasia	DISYNAVB	Strong	Genetic Variation	[25]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[26]
Zika virus infection	DISQUCTY	Strong	Biomarker	[27]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[28]
Influenza	DIS3PNU3	moderate	Biomarker	[29]
Respiratory syncytial virus infection	DIS7FWHY	moderate	Biomarker	[30]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[31]
Melanoma	DIS1RRCY	Disputed	Biomarker	[32]
Breast cancer	DIS7DPX1	Limited	Biomarker	[7]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[7]
Dengue	DISKH221	Limited	Biomarker	[33]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[34]
Gastric cancer	DISXGOUK	Limited	Biomarker	[35]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[36]
Pancreatic cancer	DISJC981	Limited	Biomarker	[37]
Premature aging syndrome	DIS51AGT	Limited	Biomarker	[38]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[39]
Stomach cancer	DISKIJSX	Limited	Biomarker	[35]

7 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 Roundabout homolog 3 (ROBO3).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Roundabout homolog 3 (ROBO3).	[41]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Roundabout homolog 3 (ROBO3).	[42]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Roundabout homolog 3 (ROBO3).	[44]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Roundabout homolog 3 (ROBO3).	[45]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Roundabout homolog 3 (ROBO3).	[46]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Roundabout homolog 3 (ROBO3).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Roundabout homolog 3 (ROBO3).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Roundabout homolog 3 (ROBO3).	[48]

References

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