Molecule Information

General Information of the Molecule (ID: Mol00466)

• Name: Lysosome-associated membrane glycoprotein 2 (LAMP2) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: LAMP2
• Gene ID: 3920
• Location: chrX:120426148-120469365[-]
• Sequence:
  MVCFRLFPVPGSGLVLVCLVLGAVRSYALELNLTDSENATCLYAKWQMNFTVRYETTNKT
  YKTVTISDHGTVTYNGSICGDDQNGPKIAVQFGPGFSWIANFTKAASTYSIDSVSFSYNT
  GDNTTFPDAEDKGILTVDELLAIRIPLNDLFRCNSLSTLEKNDVVQHYWDVLVQAFVQNG
  TVSTNEFLCDKDKTSTVAPTIHTTVPSPTTTPTPKEKPEAGTYSVNNGNDTCLLATMGLQ
  LNITQDKVASVININPNTTHSTGSCRSHTALLRLNSSTIKYLDFVFAVKNENRFYLKEVN
  ISMYLVNGSVFSIANNNLSYWDAPLGSSYMCNKEQTVSVSGAFQINTFDLRVQPFNVTQG
  KYSTAQDCSADDDNFLVPIAVGAALAGVLILVLLAYFIGLKHHHAGYEQF
• Function: 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 and MLLT11, and targeting them for lysosomal degradation. 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 MHCII-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 MHCII subunits. Is not required for efficient MHCII-mediated presentation of endogenous antigens.
• Uniprot ID: LAMP2_HUMAN
• Ensembl ID: ENSG00000005893
• HGNC ID: HGNC:6501

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Azacitidine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Myelodysplastic syndrome [1]

• Resistant Disease: Myelodysplastic syndrome [ICD-11: 2A37.0]
• Resistant Drug: Azacitidine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: We show that treatment of MDS/AML cell lines and bone marrow samples from MDS/AML patients with Aza triggers loss of LAMP2 expression leading to CMA defects. LAMP2 deficiency is responsible for CMA defects, Aza resistance and hypersensitivity to lysosome and autophagy inhibitors. Low levels of LAMP2 expression in CD34+ blasts from MDS/AML patients correlate with an absence of response to Aza and are associated to a pejorative overall survival. We propose that CD34+/LAMP2Low patients at diagnosis or who become CD34+/LAMP2Low during the course of treatment with Aza could receive an autophagy inhibitor available in the clinic.

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Lung cancer [2]

• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-487b-5p regulates temozolomide resistance of lung cancer cells through lamp2-medicated autophagy.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

MyeloDysplastic syndromes [ICD-11: 2A37]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Bone marrow
• The Specified Disease: Myelodysplastic syndromes
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.42E-05; Fold-change: 4.33E-01; Z-score: 1.00E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.45E-01; Fold-change: 7.43E-01; Z-score: 6.10E-01

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.92E-04; Fold-change: 1.36E-01; Z-score: 3.99E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.10E-10; Fold-change: 3.01E-01; Z-score: 8.91E-01

References

• Ref 1: Azacitidine resistance caused by LAMP2 deficiency: a therapeutic window for the use of autophagy inhibitors in MDS/AML patients .Autophagy. 2019 May;15(5):927-929. doi: 10.1080/15548627.2019.1586259. Epub 2019 Mar 1. 10.1080/15548627.2019.1586259
• Ref 2: miR-487b-5p Regulates Temozolomide Resistance of Lung Cancer Cells Through LAMP2-Medicated Autophagy. DNA Cell Biol. 2016 Aug;35(8):385-92. doi: 10.1089/dna.2016.3259. Epub 2016 Apr 20.