Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9SQRWY)

• DOT Name: Ras-related protein Rab-27A (RAB27A)
• Synonyms: Rab-27; EC 3.6.5.2; GTP-binding protein Ram
• Gene Name: RAB27A
• Related Disease:
  Griscelli syndrome type 2
  Acute myelogenous leukaemia
  Adult respiratory distress syndrome
  Advanced cancer
  Albinism
  Alzheimer disease
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Choroideremia
  Colorectal carcinoma
  Congenital alveolar dysplasia
  Cystic fibrosis
  Gastric cancer
  Glioma
  Griscelli syndrome
  Hepatocellular carcinoma
  Hypopigmentation of the skin
  Immunodeficiency
  Juvenile idiopathic arthritis
  Non-small-cell lung cancer
  Platelet storage pool deficiency
  Stomach cancer
  Triple negative breast cancer
  Tuberculosis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Hemophagocytic syndrome
  Hereditary hemophagocytic lymphohistiocytosis
  Hermansky-Pudlak syndrome 1
  leukaemia
  Leukemia
  Metastatic malignant neoplasm
  Melanoma
  Non-insulin dependent diabetes
  Asthma
  Clear cell renal carcinoma
  Immune system disorder
  Liver cirrhosis
  Microphthalmia
  Nervous system disease
  Pancreatic cancer
  Pancreatic ductal carcinoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: RB27A_HUMAN
• PDB ID: 6HUF; 7OPP; 7OPQ; 7OPR
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MSDGDYDYLIKFLALGDSGVGKTSVLYQYTDGKFNSKFITTVGIDFREKRVVYRASGPDG
  ATGRGQRIHLQLWDTAGQERFRSLTTAFFRDAMGFLLLFDLTNEQSFLNVRNWISQLQMH
  AYCENPDIVLCGNKSDLEDQRVVKEEEAIALAEKYGIPYFETSAANGTNISQAIEMLLDL
  IMKRMERCVDKSWIPEGVVRSNGHASTDQLSEEKEKGACGC
• Function: Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion. Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse.
• Tissue Specificity: Found in all the examined tissues except in brain. Low expression was found in thymus, kidney, muscle and placenta. Detected in melanocytes, and in most tumor cell lines examined. Expressed in cytotoxic T-lymphocytes (CTL) and mast cells.
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  RAB geranylgeranylation (R-HSA-8873719)
  RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)
  Insulin processing (R-HSA-264876)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Griscelli syndrome type 2	DISDQRBS	Definitive	Autosomal recessive	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Albinism	DIS5D82I	Strong	Genetic Variation	[5]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[6]
Bladder cancer	DISUHNM0	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[8]
Choroideremia	DISH4N9B	Strong	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[10]
Congenital alveolar dysplasia	DIS1IYUN	Strong	Genetic Variation	[3]
Cystic fibrosis	DIS2OK1Q	Strong	Altered Expression	[11]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[12]
Glioma	DIS5RPEH	Strong	Genetic Variation	[13]
Griscelli syndrome	DISTHCOQ	Strong	Genetic Variation	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
Hypopigmentation of the skin	DIS39YKC	Strong	Genetic Variation	[16]
Immunodeficiency	DIS093I0	Strong	Genetic Variation	[17]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Genetic Variation	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[19]
Platelet storage pool deficiency	DISHODOH	Strong	Biomarker	[20]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[12]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[21]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[22]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[7]
Hemophagocytic syndrome	DIS3TMN4	moderate	Genetic Variation	[23]
Hereditary hemophagocytic lymphohistiocytosis	DISQP21Z	moderate	Biomarker	[14]
Hermansky-Pudlak syndrome 1	DIS966LQ	moderate	Biomarker	[24]
leukaemia	DISS7D1V	moderate	Biomarker	[25]
Leukemia	DISNAKFL	moderate	Biomarker	[25]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[26]
Melanoma	DIS1RRCY	Disputed	Biomarker	[27]
Non-insulin dependent diabetes	DISK1O5Z	Disputed	Altered Expression	[28]
Asthma	DISW9QNS	Limited	Altered Expression	[29]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[30]
Immune system disorder	DISAEGPH	Limited	Genetic Variation	[31]
Liver cirrhosis	DIS4G1GX	Limited	Altered Expression	[15]
Microphthalmia	DISGEBES	Limited	Altered Expression	[32]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[33]
Pancreatic cancer	DISJC981	Limited	Biomarker	[34]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Altered Expression	[34]
Prostate cancer	DISF190Y	Limited	Altered Expression	[26]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Alitretinoin	DMME8LH	Approved	Ras-related protein Rab-27A (RAB27A) decreases the response to substance of Alitretinoin.	[51]

15 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ras-related protein Rab-27A (RAB27A).	[35]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ras-related protein Rab-27A (RAB27A).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rab-27A (RAB27A).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ras-related protein Rab-27A (RAB27A).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ras-related protein Rab-27A (RAB27A).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ras-related protein Rab-27A (RAB27A).	[40]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras-related protein Rab-27A (RAB27A).	[41]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Ras-related protein Rab-27A (RAB27A).	[43]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Ras-related protein Rab-27A (RAB27A).	[44]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Ras-related protein Rab-27A (RAB27A).	[45]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Ras-related protein Rab-27A (RAB27A).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ras-related protein Rab-27A (RAB27A).	[47]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras-related protein Rab-27A (RAB27A).	[48]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Ras-related protein Rab-27A (RAB27A).	[49]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ras-related protein Rab-27A (RAB27A).	[50]

1 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 Ras-related protein Rab-27A (RAB27A).	[42]

References

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