LAMP2 : lysosomal associated membrane protein 2
Description
The LAMP2 (lysosomal associated membrane protein 2) is a protein-coding gene located on chromosome X.
The LAMP2 gene provides instructions for making a protein called lysosome-associated membrane glycoprotein 2 (LAMP-2). As its name suggests, this protein is found in the membrane of cellular structures called lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of materials. The LAMP-2 protein helps transport cellular materials or digestive enzymes into the lysosome. Slightly different versions (isoforms) of the LAMP-2 protein are produced: LAMP-2A, LAMP-2B, and LAMP-2C. These isoforms have slightly different functions and are found in different tissues throughout the body. The LAMP-2A isoform helps transport certain proteins into the lysosome to be broken down. The LAMP-2B isoform is needed to transport materials into lysosomes using a formation of cellular structures called autophagic vacuoles (or autophagosomes). Cellular material is first enclosed in an autophagic vacuole inside the cell. The autophagic vacuole attaches (fuses) to a lysosome to transfer the cellular material into the lysosome where it can be broken down. The LAMP-2B isoform is involved in the fusion between autophagic vacuoles and lysosomes. LAMP-2B is the main isoform found in the heart and the muscles used for movement (skeletal muscles). The LAMP-2C isoform helps transport building blocks of DNA and RNA (nucleotides) into the lysosome to be broken down.
Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:8662539, PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:36586411, PubMed:37390818). 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 (PubMed:37390818). 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 (PubMed:8662539, PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:36586411). Functions by binding target proteins, such as GAPDH, NLRP3 and MLLT11, and targeting them for lysosomal degradation (PubMed:8662539, PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:36586411). 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 (PubMed:36586411). Plays a role in lysosomal protein degradation in response to starvation (By similarity). Required for the fusion of autophagosomes with lysosomes during autophagy (PubMed:27628032). 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 (PubMed:27628032). Required for normal degradation of the contents of autophagosomes (PubMed:27628032). 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 (PubMed:20518820, PubMed:15894275). Is not required for efficient MHC class II-mediated presentation of endogenous antigens (PubMed:20518820). {ECO:0000250|UniProtKB:P17046, ECO:0000269|PubMed:11082038, ECO:0000269|PubMed:15894275, ECO:0000269|PubMed:18644871, ECO:0000269|PubMed:20518820, ECO:0000269|PubMed:24880125, ECO:0000269|PubMed:27628032, ECO:0000269|PubMed:36586411, ECO:0000269|PubMed:37390818, ECO:0000269|PubMed:8662539}
LAMP2 is also known as CD107b, DND, LAMP-2, LAMPB, LGP-96, LGP110.
