Details of Drug Off-Target (DOT)

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

• DOT Name: Ragulator complex protein LAMTOR2 (LAMTOR2)
• Synonyms: Endosomal adaptor protein p14; Late endosomal/lysosomal Mp1-interacting protein; Late endosomal/lysosomal adaptor and MAPK and MTOR activator 2; Mitogen-activated protein-binding protein-interacting protein; MAPBP-interacting protein; Roadblock domain-containing protein 3
• Gene Name: LAMTOR2
• Related Disease:
  Adenocarcinoma
  Glioma
  Hepatocellular carcinoma
  Medulloblastoma
  Acute myelogenous leukaemia
  Acute myocardial infarction
  Advanced cancer
  Bladder cancer
  Breast neoplasm
  Clear cell renal carcinoma
  Cystic fibrosis
  Familial adenomatous polyposis
  Hepatitis B virus infection
  Hepatitis C virus infection
  Immunodeficiency
  Liver cirrhosis
  Lung cancer
  Lung carcinoma
  Lymphoma
  Neoplasm
  Pancreatic cancer
  Plasma cell myeloma
  Promyelocytic leukaemia
  Renal cell carcinoma
  Rheumatoid arthritis
  Schizophrenia
  Severe congenital neutropenia
  Sjogren syndrome
  Skin cancer
  Small lymphocytic lymphoma
  Small-cell lung cancer
  Squamous cell carcinoma
  Systemic lupus erythematosus
  Systemic sclerosis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Lung adenocarcinoma
  Pediatric lymphoma
  Stroke
  Primary immunodeficiency syndrome due to p14 deficiency
  Carcinoma
  Adult lymphoma
  Colorectal carcinoma
  Intellectual disability
  Melanoma
  Type-1/2 diabetes
• UniProt ID: LTOR2_HUMAN
• PDB ID: 5X6U; 5X6V; 5Y39; 5Y3A; 5YK3; 6B9X; 6EHP; 6EHR; 6NZD; 6U62; 6ULG; 6WJ2; 6WJ3; 7T3A; 7T3B; 7T3C; 7UX2; 7UXC; 7UXH; 8DHB
• Pfam ID: PF03259
• Sequence:
  MLRPKALTQVLSQANTGGVQSTLLLNNEGSLLAYSGYGDTDARVTAAIASNIWAAYDRNG
  NQAFNEDNLKFILMDCMEGRVAITRVANLLLCMYAKETVGFGMLKAKAQALVQYLEEPLT
  QVAAS
• Function: As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2.
• KEGG Pathway: mTOR sig.ling pathway (hsa04150)
• Reactome Pathway:
  MTOR signalling (R-HSA-165159)
  mTORC1-mediated signalling (R-HSA-166208)
  Energy dependent regulation of mTOR by LKB1-AMPK (R-HSA-380972)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  MAP2K and MAPK activation (R-HSA-5674135)
  Neutrophil degranulation (R-HSA-6798695)
  Regulation of PTEN gene transcription (R-HSA-8943724)
  Amino acids regulate mTORC1 (R-HSA-9639288)
  Macroautophagy (R-HSA-1632852)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Posttranslational Modification	[1]
Glioma	DIS5RPEH	Definitive	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Definitive	Genetic Variation	[3]
Medulloblastoma	DISZD2ZL	Definitive	Biomarker	[4]
Acute myelogenous leukaemia	DISCSPTN	Strong	Posttranslational Modification	[5]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[6]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[7]
Bladder cancer	DISUHNM0	Strong	Posttranslational Modification	[8]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[10]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[11]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[12]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[13]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[14]
Immunodeficiency	DIS093I0	Strong	Altered Expression	[15]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[16]
Lung cancer	DISCM4YA	Strong	Posttranslational Modification	[17]
Lung carcinoma	DISTR26C	Strong	Posttranslational Modification	[17]
Lymphoma	DISN6V4S	Strong	Altered Expression	[18]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[12]
Plasma cell myeloma	DIS0DFZ0	Strong	Posttranslational Modification	[19]
Promyelocytic leukaemia	DISYGG13	Strong	Posttranslational Modification	[5]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[10]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[11]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[20]
Severe congenital neutropenia	DISES99N	Strong	Genetic Variation	[21]
Sjogren syndrome	DISUBX7H	Strong	Altered Expression	[11]
Skin cancer	DISTM18U	Strong	Genetic Variation	[22]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[23]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[24]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[25]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[11]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[11]
Urinary bladder cancer	DISDV4T7	Strong	Posttranslational Modification	[8]
Urinary bladder neoplasm	DIS7HACE	Strong	Posttranslational Modification	[8]
Lung adenocarcinoma	DISD51WR	moderate	Altered Expression	[26]
Pediatric lymphoma	DIS51BK2	moderate	Altered Expression	[18]
Stroke	DISX6UHX	moderate	Genetic Variation	[27]
Primary immunodeficiency syndrome due to p14 deficiency	DISJNKN8	Supportive	Autosomal recessive	[28]
Carcinoma	DISH9F1N	Disputed	Biomarker	[29]
Adult lymphoma	DISK8IZR	Limited	Altered Expression	[18]
Colorectal carcinoma	DIS5PYL0	Limited	Posttranslational Modification	[30]
Intellectual disability	DISMBNXP	Limited	Biomarker	[31]
Melanoma	DIS1RRCY	Limited	Biomarker	[32]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[33]

12 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 Ragulator complex protein LAMTOR2 (LAMTOR2).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ragulator complex protein LAMTOR2 (LAMTOR2).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ragulator complex protein LAMTOR2 (LAMTOR2).	[37]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ragulator complex protein LAMTOR2 (LAMTOR2).	[38]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ragulator complex protein LAMTOR2 (LAMTOR2).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ragulator complex protein LAMTOR2 (LAMTOR2).	[40]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ragulator complex protein LAMTOR2 (LAMTOR2).	[41]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Ragulator complex protein LAMTOR2 (LAMTOR2).	[42]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Ragulator complex protein LAMTOR2 (LAMTOR2).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ragulator complex protein LAMTOR2 (LAMTOR2).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ragulator complex protein LAMTOR2 (LAMTOR2).	[45]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Ragulator complex protein LAMTOR2 (LAMTOR2).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Ragulator complex protein LAMTOR2 (LAMTOR2).	[35]

References

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