Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPB54Y3)

• DOT Name: Ras-related protein Rab-8A (RAB8A)
• Synonyms: EC 3.6.5.2; Oncogene c-mel
• Gene Name: RAB8A
• Related Disease:
  Parkinson disease
  Acute erythroid leukemia
  Adenoma
  Advanced cancer
  Bardet biedl syndrome
  Breast carcinoma
  Ciliopathy
  Colitis
  Colorectal carcinoma
  Gastrointestinal mucositis
  Hepatocellular carcinoma
  Hereditary hemochromatosis
  Hyperlipidemia
  Insulinoma
  Intestinal disorder
  leukaemia
  Leukemia
  Melanoma
  Metastatic malignant neoplasm
  Metastatic melanoma
  Myopia 6
  Neoplasm
  Neuralgia
  Non-small-cell lung cancer
  Plasma cell myeloma
  Promyelocytic leukaemia
  Retinitis pigmentosa
  Rheumatoid arthritis
  Spinal muscular atrophy
  Uveal Melanoma
  Microvillus inclusion disease
  Squamous cell carcinoma
  Bone osteosarcoma
  Cutaneous melanoma
  Glioma
  Hyperglycemia
  Myeloid neoplasm
  Neuroblastoma
  Osteosarcoma
  Prostate adenocarcinoma
• UniProt ID: RAB8A_HUMAN
• PDB ID: 3QBT; 3TNF; 4LHV; 4LHW; 4LHX; 4LHY; 4LHZ; 4LI0; 5SZI; 6RIR; 6SQ2; 6STF; 6STG; 6WHE; 6YX5; 6ZSI; 6ZSJ; 7BWT; 7LWB
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MAKTYDYLFKLLLIGDSGVGKTCVLFRFSEDAFNSTFISTIGIDFKIRTIELDGKRIKLQ
  IWDTAGQERFRTITTAYYRGAMGIMLVYDITNEKSFDNIRNWIRNIEEHASADVEKMILG
  NKCDVNDKRQVSKERGEKLALDYGIKFMETSAKANINVENAFFTLARDIKAKMDKKLEGN
  SPQGSNQGVKITPDQQKRSSFFRCVLL
• Function: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in polarized vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Regulates the compacted morphology of the Golgi. Together with MYO5B and RAB11A participates in epithelial cell polarization. Also involved in membrane trafficking to the cilium and ciliogenesis. Together with MICALL2, may also regulate adherens junction assembly. May play a role in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore play a role in glucose homeostasis. Involved in autophagy. Participates in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-dependent endososomal export route.
• KEGG Pathway:
  Autophagy - animal (hsa04140)
  Endocytosis (hsa04144)
  AMPK sig.ling pathway (hsa04152)
  Tight junction (hsa04530)
  Pancreatic secretion (hsa04972)
  Amyotrophic lateral sclerosis (hsa05014)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway:
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  VxPx cargo-targeting to cilium (R-HSA-5620916)
  TBC/RABGAPs (R-HSA-8854214)
  RAB geranylgeranylation (R-HSA-8873719)
  RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Definitive	Biomarker	[1]
Acute erythroid leukemia	DISZFC1O	Strong	Genetic Variation	[2]
Adenoma	DIS78ZEV	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Bardet biedl syndrome	DISTBNZW	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Ciliopathy	DIS10G4I	Strong	Biomarker	[7]
Colitis	DISAF7DD	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[9]
Gastrointestinal mucositis	DIS140OB	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[11]
Hereditary hemochromatosis	DISVG5MT	Strong	Biomarker	[12]
Hyperlipidemia	DIS61J3S	Strong	Genetic Variation	[13]
Insulinoma	DISIU1JS	Strong	Biomarker	[14]
Intestinal disorder	DISGPMUQ	Strong	Biomarker	[15]
leukaemia	DISS7D1V	Strong	Biomarker	[16]
Leukemia	DISNAKFL	Strong	Biomarker	[16]
Melanoma	DIS1RRCY	Strong	Biomarker	[6]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[17]
Metastatic melanoma	DISSL43L	Strong	Biomarker	[18]
Myopia 6	DIS1ZT40	Strong	Genetic Variation	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Neuralgia	DISWO58J	Strong	Biomarker	[21]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[22]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[23]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[16]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[24]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[25]
Spinal muscular atrophy	DISTLKOB	Strong	Altered Expression	[26]
Uveal Melanoma	DISA7ZGL	Strong	Biomarker	[27]
Microvillus inclusion disease	DIS6L4RW	moderate	Biomarker	[28]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[29]
Bone osteosarcoma	DIST1004	Limited	Genetic Variation	[11]
Cutaneous melanoma	DIS3MMH9	Limited	Genetic Variation	[30]
Glioma	DIS5RPEH	Limited	Biomarker	[31]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[32]
Myeloid neoplasm	DIS2YOWO	Limited	Biomarker	[33]
Neuroblastoma	DISVZBI4	Limited	Genetic Variation	[11]
Osteosarcoma	DISLQ7E2	Limited	Genetic Variation	[11]
Prostate adenocarcinoma	DISBZYU8	Limited	Genetic Variation	[34]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Ras-related protein Rab-8A (RAB8A) decreases the response to substance of Cisplatin.	[51]

14 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 Ras-related protein Rab-8A (RAB8A).	[35]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ras-related protein Rab-8A (RAB8A).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rab-8A (RAB8A).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ras-related protein Rab-8A (RAB8A).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ras-related protein Rab-8A (RAB8A).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras-related protein Rab-8A (RAB8A).	[40]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ras-related protein Rab-8A (RAB8A).	[41]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Ras-related protein Rab-8A (RAB8A).	[42]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Ras-related protein Rab-8A (RAB8A).	[43]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Ras-related protein Rab-8A (RAB8A).	[44]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Ras-related protein Rab-8A (RAB8A).	[45]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ras-related protein Rab-8A (RAB8A).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ras-related protein Rab-8A (RAB8A).	[49]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Ras-related protein Rab-8A (RAB8A).	[50]

2 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 affects the methylation of Ras-related protein Rab-8A (RAB8A).	[46]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Ras-related protein Rab-8A (RAB8A).	[48]

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