Details of Drug Off-Target (DOT)

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

• DOT Name: Lysosome-associated membrane glycoprotein 2 (LAMP2)
• Synonyms: LAMP-2; Lysosome-associated membrane protein 2; CD107 antigen-like family member B; LGP-96; CD antigen CD107b
• Gene Name: LAMP2
• Related Disease: Danon disease
• UniProt ID: LAMP2_HUMAN
• PDB ID: 2MOF; 2MOM
• Pfam ID: PF01299 ; PF21222
• Sequence:
  MVCFRLFPVPGSGLVLVCLVLGAVRSYALELNLTDSENATCLYAKWQMNFTVRYETTNKT
  YKTVTISDHGTVTYNGSICGDDQNGPKIAVQFGPGFSWIANFTKAASTYSIDSVSFSYNT
  GDNTTFPDAEDKGILTVDELLAIRIPLNDLFRCNSLSTLEKNDVVQHYWDVLVQAFVQNG
  TVSTNEFLCDKDKTSTVAPTIHTTVPSPTTTPTPKEKPEAGTYSVNNGNDTCLLATMGLQ
  LNITQDKVASVININPNTTHSTGSCRSHTALLRLNSSTIKYLDFVFAVKNENRFYLKEVN
  ISMYLVNGSVFSIANNNLSYWDAPLGSSYMCNKEQTVSVSGAFQINTFDLRVQPFNVTQG
  KYSTAQDCSADDDNFLVPIAVGAALAGVLILVLLAYFIGLKHHHAGYEQF
• Function: Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy. Acts as an important regulator of lysosomal lumen pH regulation by acting as a direct inhibitor of the proton channel TMEM175, facilitating lysosomal acidification for optimal hydrolase activity. Plays an important role in chaperone-mediated autophagy, a process that mediates lysosomal degradation of proteins in response to various stresses and as part of the normal turnover of proteins with a long biological half-live. Functions by binding target proteins, such as GAPDH, NLRP3 and MLLT11, and targeting them for lysosomal degradation. In the chaperone-mediated autophagy, acts downstream of chaperones, such as HSPA8/HSC70, which recognize and bind substrate proteins and mediate their recruitment to lysosomes, where target proteins bind LAMP2. Plays a role in lysosomal protein degradation in response to starvation. Required for the fusion of autophagosomes with lysosomes during autophagy. Cells that lack LAMP2 express normal levels of VAMP8, but fail to accumulate STX17 on autophagosomes, which is the most likely explanation for the lack of fusion between autophagosomes and lysosomes. Required for normal degradation of the contents of autophagosomes. Required for efficient MHC class II-mediated presentation of exogenous antigens via its function in lysosomal protein degradation; antigenic peptides generated by proteases in the endosomal/lysosomal compartment are captured by nascent MHC II subunits. Is not required for efficient MHC class II-mediated presentation of endogenous antigens ; [Isoform LAMP-2C]: Modulates chaperone-mediated autophagy. Decreases presentation of endogenous antigens by MHCII. Does not play a role in the presentation of exogenous and membrane-derived antigens by MHCII; (Microbial infection) Supports the FURIN-mediated cleavage of mumps virus fusion protein F by interacting with both FURIN and the unprocessed form but not the processed form of the viral protein F.
• Tissue Specificity: Isoform LAMP-2A is highly expressed in placenta, lung and liver, less in kidney and pancreas, low in brain and skeletal muscle . Isoform LAMP-2B is detected in spleen, thymus, prostate, testis, small intestine, colon, skeletal muscle, brain, placenta, lung, kidney, ovary and pancreas and liver . Isoform LAMP-2C is detected in small intestine, colon, heart, brain, skeletal muscle, and at lower levels in kidney and placenta .
• KEGG Pathway:
  Autophagy - animal (hsa04140)
  Lysosome (hsa04142)
  Phagosome (hsa04145)
  Tuberculosis (hsa05152)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Chaperone Mediated Autophagy (R-HSA-9613829)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Danon disease	DIS45YLU	Definitive	X-linked	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Lysosome-associated membrane glycoprotein 2 (LAMP2) affects the response to substance of Paclitaxel.	[20]

17 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 Lysosome-associated membrane glycoprotein 2 (LAMP2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[7]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[8]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[7]
Rigosertib	DMOSTXF	Phase 3	Rigosertib affects the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[17]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[18]
Methylenedioxymethamphetamine	DMYVU47	Investigative	Methylenedioxymethamphetamine increases the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[19]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[12]

1 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 increases the methylation of Lysosome-associated membrane glycoprotein 2 (LAMP2).	[13]

References

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