LAMP2 is a heavily N- and O-glycosylated single-pass type I membrane protein that is one of the most abundant components of the lysosomal limiting membrane. Its large luminal domain, built from two LAMP domains, forms part of the glycocalyx lining the lysosome, and its short cytoplasmic tail carries a tyrosine-based lysosomal sorting signal. Alternative splicing of the last exon yields LAMP-2A, -2B and -2C with distinct transmembrane and cytoplasmic regions. LAMP-2A is the receptor and rate-limiting component of chaperone-mediated autophagy, binding HSC70-delivered KFERQ-motif substrates and multimerizing into a translocation complex that imports them into the lysosome for degradation. LAMP1 and LAMP2 also directly inhibit the lysosomal cation channel TMEM175 to promote lysosomal acidification, and LAMP2 is required for efficient autophagosome-lysosome fusion. The protein resides mainly in lysosomes and late endosomes, shuttling through the plasma membrane, and appears at the cell surface (as CD107b) when lysosome-related granules of platelets and leukocytes undergo exocytosis. LAMP2 deficiency causes Danon disease.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000421 autophagosome membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: LAMP2 is found on autolysosomes/phagolysosomes formed by fusion with lysosomes. Reason: LAMP2 is delivered to autophagosome- and phagosome-derived compartments by fusion with lysosomes and is used as a marker for them; this reflects its lysosomal residence. Supporting Evidence: PMID:2912382 Transport of the proteins between organelles was evidenced by their marked accumulation in the membranes of phagolysosomes. |
| GO:0000421 autophagosome membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: LAMP2 is found on autolysosomes/phagolysosomes formed by fusion with lysosomes. Reason: LAMP2 is delivered to autophagosome- and phagosome-derived compartments by fusion with lysosomes and is used as a marker for them; this reflects its lysosomal residence. Supporting Evidence: PMID:2912382 Transport of the proteins between organelles was evidenced by their marked accumulation in the membranes of phagolysosomes. |
| GO:0005515 protein binding | IPI PMID:21194361 The lysosomal polypeptide transporter TAPL: more than a hous... | REMOVE | Summary: Interaction with a lysosomal membrane protein or CMA substrate (TAPL, PUMA, CT55, ABHD8). Reason: Bare protein binding is uninformative under the protein-binding policy; the relevant functional consequences (CMA substrate uptake, TAPL stabilization) are captured by other terms. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:26212789 Chaperone-mediated autophagy prevents apoptosis by degrading... | REMOVE | Summary: Interaction with a lysosomal membrane protein or CMA substrate (TAPL, PUMA, CT55, ABHD8). Reason: Bare protein binding is uninformative under the protein-binding policy; the relevant functional consequences (CMA substrate uptake, TAPL stabilization) are captured by other terms. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36481789 Deficiency of cancer/testis antigen gene CT55 causes male in... | REMOVE | Summary: Interaction with a lysosomal membrane protein or CMA substrate (TAPL, PUMA, CT55, ABHD8). Reason: Bare protein binding is uninformative under the protein-binding policy; the relevant functional consequences (CMA substrate uptake, TAPL stabilization) are captured by other terms. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:37390818 Lysosomal LAMP proteins regulate lysosomal pH by direct inhi... | MODIFY | Summary: LAMP2 binds the lysosomal channel TMEM175. Reason: Following the protein-binding policy, replace with the informative activity shown in the same paper, direct inhibition of TMEM175. Proposed replacements: ion channel inhibitor activity Supporting Evidence: PMID:37390818 We show that LAMP-1 and LAMP-2 directly interact with and inhibit the activity of the lysosomal cation channel TMEM175, a key player in lysosomal pH homeostasis implicated in Parkinson's disease. |
| GO:0005515 protein binding | IPI PMID:39225180 ABHD8 antagonizes inflammation by facilitating chaperone-med... | REMOVE | Summary: Interaction with a lysosomal membrane protein or CMA substrate (TAPL, PUMA, CT55, ABHD8). Reason: Bare protein binding is uninformative under the protein-binding policy; the relevant functional consequences (CMA substrate uptake, TAPL stabilization) are captured by other terms. Removal does not mean the interactions are false. |
| GO:0005576 extracellular region | IDA PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins... | KEEP AS NON CORE | Summary: Detected in secretions of human neutrophils. Reason: LAMP2 is a membrane protein but can be released with granule or vesicle material on degranulation; not a soluble extracellular protein. Supporting Evidence: PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum. |
| GO:0005764 lysosome | IDA PMID:12536145 Identification of a novel domain in two mammalian inositol-p... | MODIFY | Summary: LAMP2 localizes to lysosomes as an integral membrane protein. Reason: The location is right in essence, but LAMP2 is specifically an integral protein of the lysosomal membrane (its luminal domain faces the lumen but the protein is not a soluble luminal protein); the lysosomal membrane term, already accepted, is the appropriate specific location. Proposed replacements: lysosomal membrane Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures |
| GO:0005764 lysosome | IDA PMID:15229288 Over-expression of Rififylin, a new RING finger and FYVE-lik... | MODIFY | Summary: LAMP2 localizes to lysosomes as an integral membrane protein. Reason: The location is right in essence, but LAMP2 is specifically an integral protein of the lysosomal membrane (its luminal domain faces the lumen but the protein is not a soluble luminal protein); the lysosomal membrane term, already accepted, is the appropriate specific location. Proposed replacements: lysosomal membrane Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures |
| GO:0005764 lysosome | IDA PMID:19535332 Printor, a novel torsinA-interacting protein implicated in d... | MODIFY | Summary: LAMP2 localizes to lysosomes as an integral membrane protein. Reason: The location is right in essence, but LAMP2 is specifically an integral protein of the lysosomal membrane (its luminal domain faces the lumen but the protein is not a soluble luminal protein); the lysosomal membrane term, already accepted, is the appropriate specific location. Proposed replacements: lysosomal membrane Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures |
| GO:0005764 lysosome | IDA PMID:28743268 The lysosomal protein cathepsin L is a progranulin protease. | MODIFY | Summary: LAMP2 localizes to lysosomes as an integral membrane protein. Reason: The location is right in essence, but LAMP2 is specifically an integral protein of the lysosomal membrane (its luminal domain faces the lumen but the protein is not a soluble luminal protein); the lysosomal membrane term, already accepted, is the appropriate specific location. Proposed replacements: lysosomal membrane Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures |
| GO:0005764 lysosome | IEA GO_REF:0000107 | MODIFY | Summary: LAMP2 localizes to lysosomes as an integral membrane protein. Reason: The location is right in essence, but LAMP2 is specifically an integral protein of the lysosomal membrane (its luminal domain faces the lumen but the protein is not a soluble luminal protein); the lysosomal membrane term, already accepted, is the appropriate specific location. Proposed replacements: lysosomal membrane Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures |
| GO:0005765 lysosomal membrane | EXP PMID:18644871 The chaperone-mediated autophagy receptor organizes in dynam... | ACCEPT | Summary: LAMP2 is a type I integral membrane glycoprotein of the lysosomal limiting membrane. Reason: Purification, immuno-EM and lysosomal membrane proteomics place LAMP2 as a major lysosomal membrane protein, with a luminal glycosylated domain and a short cytoplasmic tail; this is its principal location. Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. |
| GO:0005765 lysosomal membrane | EXP PMID:2912382 Purification and characterization of human lysosomal membran... | ACCEPT | Summary: LAMP2 is a type I integral membrane glycoprotein of the lysosomal limiting membrane. Reason: Purification, immuno-EM and lysosomal membrane proteomics place LAMP2 as a major lysosomal membrane protein, with a luminal glycosylated domain and a short cytoplasmic tail; this is its principal location. Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. |
| GO:0005765 lysosomal membrane | HDA PMID:17897319 Integral and associated lysosomal membrane proteins. | ACCEPT | Summary: LAMP2 is a type I integral membrane glycoprotein of the lysosomal limiting membrane. Reason: Purification, immuno-EM and lysosomal membrane proteomics place LAMP2 as a major lysosomal membrane protein, with a luminal glycosylated domain and a short cytoplasmic tail; this is its principal location. Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. |
| GO:0005765 lysosomal membrane | IBA GO_REF:0000033 | ACCEPT | Summary: LAMP2 is a type I integral membrane glycoprotein of the lysosomal limiting membrane. Reason: Purification, immuno-EM and lysosomal membrane proteomics place LAMP2 as a major lysosomal membrane protein, with a luminal glycosylated domain and a short cytoplasmic tail; this is its principal location. Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. |
| GO:0005765 lysosomal membrane | IDA PMID:11082038 Unique properties of lamp2a compared to other lamp2 isoforms... | ACCEPT | Summary: LAMP2 is a type I integral membrane glycoprotein of the lysosomal limiting membrane. Reason: Purification, immuno-EM and lysosomal membrane proteomics place LAMP2 as a major lysosomal membrane protein, with a luminal glycosylated domain and a short cytoplasmic tail; this is its principal location. Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. |
| GO:0005765 lysosomal membrane | IDA PMID:15297306 The nucleotide transporter MRP4 (ABCC4) is highly expressed ... | ACCEPT | Summary: LAMP2 is a type I integral membrane glycoprotein of the lysosomal limiting membrane. Reason: Purification, immuno-EM and lysosomal membrane proteomics place LAMP2 as a major lysosomal membrane protein, with a luminal glycosylated domain and a short cytoplasmic tail; this is its principal location. Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. |
| GO:0005765 lysosomal membrane | IDA PMID:21896273 Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lys... | ACCEPT | Summary: LAMP2 is a type I integral membrane glycoprotein of the lysosomal limiting membrane. Reason: Purification, immuno-EM and lysosomal membrane proteomics place LAMP2 as a major lysosomal membrane protein, with a luminal glycosylated domain and a short cytoplasmic tail; this is its principal location. Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000120 | ACCEPT | Summary: LAMP2 is a type I integral membrane glycoprotein of the lysosomal limiting membrane. Reason: Purification, immuno-EM and lysosomal membrane proteomics place LAMP2 as a major lysosomal membrane protein, with a luminal glycosylated domain and a short cytoplasmic tail; this is its principal location. Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. |
| GO:0005770 late endosome | IDA PMID:15229288 Over-expression of Rififylin, a new RING finger and FYVE-lik... | MODIFY | Summary: LAMP2 is in endosomal membranes, chiefly late endosomes. Reason: Correct but less specific than warranted; LAMP2 is an integral membrane protein of late endosomes, a term already carried by the gene. Proposed replacements: late endosome membrane Supporting Evidence: file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. |
| GO:0005770 late endosome | IEA GO_REF:0000107 | MODIFY | Summary: LAMP2 is in endosomal membranes, chiefly late endosomes. Reason: Correct but less specific than warranted; LAMP2 is an integral membrane protein of late endosomes, a term already carried by the gene. Proposed replacements: late endosome membrane Supporting Evidence: file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. |
| GO:0005886 plasma membrane | EXP PMID:17897319 Integral and associated lysosomal membrane proteins. | KEEP AS NON CORE | Summary: A minor pool of LAMP2 reaches the plasma membrane, with its luminal domain exposed extracellularly. Reason: LAMP2 shuttles via the plasma membrane and a fraction is detected on the surface of some cell types, and it appears at the surface after lysosome-related granule exocytosis (platelet and neutrophil degranulation). The surface pool is transient and minor compared with the lysosomal pool. Supporting Evidence: PMID:2912382 A fraction of each glycoprotein was also detected on the plasma membrane of U937 and HL-60 cells but not on a variety of other tissue culture cells. file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. |
| GO:0005886 plasma membrane | EXP PMID:2912382 Purification and characterization of human lysosomal membran... | KEEP AS NON CORE | Summary: A minor pool of LAMP2 reaches the plasma membrane, with its luminal domain exposed extracellularly. Reason: LAMP2 shuttles via the plasma membrane and a fraction is detected on the surface of some cell types, and it appears at the surface after lysosome-related granule exocytosis (platelet and neutrophil degranulation). The surface pool is transient and minor compared with the lysosomal pool. Supporting Evidence: PMID:2912382 A fraction of each glycoprotein was also detected on the plasma membrane of U937 and HL-60 cells but not on a variety of other tissue culture cells. file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: A minor pool of LAMP2 reaches the plasma membrane, with its luminal domain exposed extracellularly. Reason: LAMP2 shuttles via the plasma membrane and a fraction is detected on the surface of some cell types, and it appears at the surface after lysosome-related granule exocytosis (platelet and neutrophil degranulation). The surface pool is transient and minor compared with the lysosomal pool. Supporting Evidence: PMID:2912382 A fraction of each glycoprotein was also detected on the plasma membrane of U937 and HL-60 cells but not on a variety of other tissue culture cells. file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: A minor pool of LAMP2 reaches the plasma membrane, with its luminal domain exposed extracellularly. Reason: LAMP2 shuttles via the plasma membrane and a fraction is detected on the surface of some cell types, and it appears at the surface after lysosome-related granule exocytosis (platelet and neutrophil degranulation). The surface pool is transient and minor compared with the lysosomal pool. Supporting Evidence: PMID:2912382 A fraction of each glycoprotein was also detected on the plasma membrane of U937 and HL-60 cells but not on a variety of other tissue culture cells. file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A minor pool of LAMP2 reaches the plasma membrane, with its luminal domain exposed extracellularly. Reason: LAMP2 shuttles via the plasma membrane and a fraction is detected on the surface of some cell types, and it appears at the surface after lysosome-related granule exocytosis (platelet and neutrophil degranulation). The surface pool is transient and minor compared with the lysosomal pool. Supporting Evidence: PMID:2912382 A fraction of each glycoprotein was also detected on the plasma membrane of U937 and HL-60 cells but not on a variety of other tissue culture cells. file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-481010 | KEEP AS NON CORE | Summary: A minor pool of LAMP2 reaches the plasma membrane, with its luminal domain exposed extracellularly. Reason: LAMP2 shuttles via the plasma membrane and a fraction is detected on the surface of some cell types, and it appears at the surface after lysosome-related granule exocytosis (platelet and neutrophil degranulation). The surface pool is transient and minor compared with the lysosomal pool. Supporting Evidence: PMID:2912382 A fraction of each glycoprotein was also detected on the plasma membrane of U937 and HL-60 cells but not on a variety of other tissue culture cells. file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798739 | KEEP AS NON CORE | Summary: A minor pool of LAMP2 reaches the plasma membrane, with its luminal domain exposed extracellularly. Reason: LAMP2 shuttles via the plasma membrane and a fraction is detected on the surface of some cell types, and it appears at the surface after lysosome-related granule exocytosis (platelet and neutrophil degranulation). The surface pool is transient and minor compared with the lysosomal pool. Supporting Evidence: PMID:2912382 A fraction of each glycoprotein was also detected on the plasma membrane of U937 and HL-60 cells but not on a variety of other tissue culture cells. file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6800426 | KEEP AS NON CORE | Summary: A minor pool of LAMP2 reaches the plasma membrane, with its luminal domain exposed extracellularly. Reason: LAMP2 shuttles via the plasma membrane and a fraction is detected on the surface of some cell types, and it appears at the surface after lysosome-related granule exocytosis (platelet and neutrophil degranulation). The surface pool is transient and minor compared with the lysosomal pool. Supporting Evidence: PMID:2912382 A fraction of each glycoprotein was also detected on the plasma membrane of U937 and HL-60 cells but not on a variety of other tissue culture cells. file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. |
| GO:0006605 protein targeting | IEA GO_REF:0000107 | MODIFY | Summary: LAMP-2A targets/imports cytosolic proteins into lysosomes. Reason: True but general; the protein targeting and import LAMP2 performs is the lysosomal targeting and translocation step of chaperone-mediated autophagy, already annotated. Proposed replacements: protein targeting to lysosome involved in chaperone-mediated autophagy Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. PMID:18644871 Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. |
| GO:0006605 protein targeting | ISS GO_REF:0000024 | MODIFY | Summary: LAMP-2A targets/imports cytosolic proteins into lysosomes. Reason: True but general; the protein targeting and import LAMP2 performs is the lysosomal targeting and translocation step of chaperone-mediated autophagy, already annotated. Proposed replacements: protein targeting to lysosome involved in chaperone-mediated autophagy Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. PMID:18644871 Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. |
| GO:0006914 autophagy | IEA GO_REF:0000107 | MODIFY | Summary: LAMP2 acts in autophagy. Reason: Correct but general; LAMP-2A executes chaperone-mediated autophagy, already accepted (macroautophagy involvement via autophagosome maturation is retained separately as non-core). Proposed replacements: chaperone-mediated autophagy Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. |
| GO:0007042 lysosomal lumen acidification | IDA PMID:37390818 Lysosomal LAMP proteins regulate lysosomal pH by direct inhi... | ACCEPT | Summary: LAMP1/LAMP2 directly inhibit the lysosomal cation channel TMEM175, promoting lysosomal acidification. Reason: Cryo-EM, electrophysiology and in vivo imaging show direct LAMP-TMEM175 interaction and inhibition of TMEM175 proton conduction, lowering lysosomal pH. Supporting Evidence: PMID:37390818 We show that LAMP-1 and LAMP-2 directly interact with and inhibit the activity of the lysosomal cation channel TMEM175, a key player in lysosomal pH homeostasis implicated in Parkinson's disease. |
| GO:0007042 lysosomal lumen acidification | IEA GO_REF:0000117 | ACCEPT | Summary: LAMP1/LAMP2 directly inhibit the lysosomal cation channel TMEM175, promoting lysosomal acidification. Reason: Cryo-EM, electrophysiology and in vivo imaging show direct LAMP-TMEM175 interaction and inhibition of TMEM175 proton conduction, lowering lysosomal pH. Supporting Evidence: PMID:37390818 We show that LAMP-1 and LAMP-2 directly interact with and inhibit the activity of the lysosomal cation channel TMEM175, a key player in lysosomal pH homeostasis implicated in Parkinson's disease. |
| GO:0008200 ion channel inhibitor activity | IDA PMID:37390818 Lysosomal LAMP proteins regulate lysosomal pH by direct inhi... | ACCEPT | Summary: LAMP1/LAMP2 directly inhibit the lysosomal cation channel TMEM175, promoting lysosomal acidification. Reason: Cryo-EM, electrophysiology and in vivo imaging show direct LAMP-TMEM175 interaction and inhibition of TMEM175 proton conduction, lowering lysosomal pH. Supporting Evidence: PMID:37390818 We show that LAMP-1 and LAMP-2 directly interact with and inhibit the activity of the lysosomal cation channel TMEM175, a key player in lysosomal pH homeostasis implicated in Parkinson's disease. |
| GO:0008200 ion channel inhibitor activity | IEA GO_REF:0000117 | ACCEPT | Summary: LAMP1/LAMP2 directly inhibit the lysosomal cation channel TMEM175, promoting lysosomal acidification. Reason: Cryo-EM, electrophysiology and in vivo imaging show direct LAMP-TMEM175 interaction and inhibition of TMEM175 proton conduction, lowering lysosomal pH. Supporting Evidence: PMID:37390818 We show that LAMP-1 and LAMP-2 directly interact with and inhibit the activity of the lysosomal cation channel TMEM175, a key player in lysosomal pH homeostasis implicated in Parkinson's disease. |
| GO:0009267 cellular response to starvation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: CMA is induced by starvation, with increased lysosomal LAMP-2A. Reason: LAMP-2A levels and redistribution change with serum or nutrient withdrawal, and CMA activators include starvation; a contextual response. Supporting Evidence: PMID:11082038 Lamp2a also distributes to an unique subpopulation of perinuclear lysosomes in cultured fibroblasts in response to serum withdrawal |
| GO:0009267 cellular response to starvation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CMA is induced by starvation, with increased lysosomal LAMP-2A. Reason: LAMP-2A levels and redistribution change with serum or nutrient withdrawal, and CMA activators include starvation; a contextual response. Supporting Evidence: PMID:11082038 Lamp2a also distributes to an unique subpopulation of perinuclear lysosomes in cultured fibroblasts in response to serum withdrawal |
| GO:0009267 cellular response to starvation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CMA is induced by starvation, with increased lysosomal LAMP-2A. Reason: LAMP-2A levels and redistribution change with serum or nutrient withdrawal, and CMA activators include starvation; a contextual response. Supporting Evidence: PMID:11082038 Lamp2a also distributes to an unique subpopulation of perinuclear lysosomes in cultured fibroblasts in response to serum withdrawal |
| GO:0010008 endosome membrane | EXP PMID:17897319 Integral and associated lysosomal membrane proteins. | MODIFY | Summary: LAMP2 is in endosomal membranes, chiefly late endosomes. Reason: Correct but less specific than warranted; LAMP2 is an integral membrane protein of late endosomes, a term already carried by the gene. Proposed replacements: late endosome membrane Supporting Evidence: file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | MODIFY | Summary: LAMP2 is in endosomal membranes, chiefly late endosomes. Reason: Correct but less specific than warranted; LAMP2 is an integral membrane protein of late endosomes, a term already carried by the gene. Proposed replacements: late endosome membrane Supporting Evidence: file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. |
| GO:0016020 membrane | IDA PMID:15297306 The nucleotide transporter MRP4 (ABCC4) is highly expressed ... | MODIFY | Summary: LAMP2 localizes to lysosomes as an integral membrane protein. Reason: The location is right in essence, but LAMP2 is specifically an integral protein of the lysosomal membrane (its luminal domain faces the lumen but the protein is not a soluble luminal protein); the lysosomal membrane term, already accepted, is the appropriate specific location. Proposed replacements: lysosomal membrane Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures |
| GO:0016020 membrane | IDA PMID:23093945 Regulation of ATG4B stability by RNF5 limits basal levels of... | MODIFY | Summary: LAMP2 localizes to lysosomes as an integral membrane protein. Reason: The location is right in essence, but LAMP2 is specifically an integral protein of the lysosomal membrane (its luminal domain faces the lumen but the protein is not a soluble luminal protein); the lysosomal membrane term, already accepted, is the appropriate specific location. Proposed replacements: lysosomal membrane Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: LAMP2 localizes to lysosomes as an integral membrane protein. Reason: The location is right in essence, but LAMP2 is specifically an integral protein of the lysosomal membrane (its luminal domain faces the lumen but the protein is not a soluble luminal protein); the lysosomal membrane term, already accepted, is the appropriate specific location. Proposed replacements: lysosomal membrane Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures |
| GO:0017038 protein import | TAS PMID:20176123 Chaperone-mediated autophagy: molecular mechanisms and physi... | MODIFY | Summary: LAMP-2A targets/imports cytosolic proteins into lysosomes. Reason: True but general; the protein targeting and import LAMP2 performs is the lysosomal targeting and translocation step of chaperone-mediated autophagy, already annotated. Proposed replacements: protein targeting to lysosome involved in chaperone-mediated autophagy Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. PMID:18644871 Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. |
| GO:0019899 enzyme binding | IPI PMID:22641697 The lysosomal polypeptide transporter TAPL is stabilized by ... | KEEP AS NON CORE | Summary: LAMP2 binds and stabilizes lysosomal membrane proteins (e.g. TAPL) or controls stability of CMA substrates. Reason: LAMPs retain TAPL on the limiting membrane and prevent its degradation, and CMA through LAMP-2A controls levels of substrates such as PUMA; these are real but secondary consequences. Supporting Evidence: PMID:22641697 However, in LAMP-deficient cells, the half-life of TAPL is decreased by a factor of five |
| GO:0019904 protein domain specific binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: LAMP2 binds and stabilizes lysosomal membrane proteins (e.g. TAPL) or controls stability of CMA substrates. Reason: LAMPs retain TAPL on the limiting membrane and prevent its degradation, and CMA through LAMP-2A controls levels of substrates such as PUMA; these are real but secondary consequences. Supporting Evidence: PMID:22641697 However, in LAMP-deficient cells, the half-life of TAPL is decreased by a factor of five |
| GO:0030670 phagocytic vesicle membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: LAMP2 is found on autolysosomes/phagolysosomes formed by fusion with lysosomes. Reason: LAMP2 is delivered to autophagosome- and phagosome-derived compartments by fusion with lysosomes and is used as a marker for them; this reflects its lysosomal residence. Supporting Evidence: PMID:2912382 Transport of the proteins between organelles was evidenced by their marked accumulation in the membranes of phagolysosomes. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:40281343 PSAT1 impairs ferroptosis and reduces immunotherapy efficacy... | KEEP AS NON CORE | Summary: LAMP-2A as an adaptor linking substrates to lysosomal degradation. Reason: LAMP-2A brings HSC70-bound substrates to the lysosomal membrane, which is compatible with an adaptor description, but its activity is better described as the CMA receptor and translocation component. Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. |
| GO:0030674 protein-macromolecule adaptor activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: LAMP-2A as an adaptor linking substrates to lysosomal degradation. Reason: LAMP-2A brings HSC70-bound substrates to the lysosomal membrane, which is compatible with an adaptor description, but its activity is better described as the CMA receptor and translocation component. Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. |
| GO:0031088 platelet dense granule membrane | IDA PMID:15297306 The nucleotide transporter MRP4 (ABCC4) is highly expressed ... | KEEP AS NON CORE | Summary: LAMP2 is a membrane component of lysosome-related secretory granules in platelets and neutrophils. Reason: Lysosome-related granules (platelet dense granules, neutrophil granules) contain LAMP2 in their limiting membrane; these are cell-type-specific versions of its lysosomal location. Supporting Evidence: PMID:15297306 Immunofluorescence microscopy using 2 MRP4-specific antibodies revealed staining mainly in intracellular structures, which largely colocalized with the accumulation of mepacrine as marker for delta-granules |
| GO:0031088 platelet dense granule membrane | TAS Reactome:R-HSA-481010 | KEEP AS NON CORE | Summary: LAMP2 is a membrane component of lysosome-related secretory granules in platelets and neutrophils. Reason: Lysosome-related granules (platelet dense granules, neutrophil granules) contain LAMP2 in their limiting membrane; these are cell-type-specific versions of its lysosomal location. Supporting Evidence: PMID:15297306 Immunofluorescence microscopy using 2 MRP4-specific antibodies revealed staining mainly in intracellular structures, which largely colocalized with the accumulation of mepacrine as marker for delta-granules |
| GO:0031647 regulation of protein stability | IMP PMID:26212789 Chaperone-mediated autophagy prevents apoptosis by degrading... | KEEP AS NON CORE | Summary: LAMP2 binds and stabilizes lysosomal membrane proteins (e.g. TAPL) or controls stability of CMA substrates. Reason: LAMPs retain TAPL on the limiting membrane and prevent its degradation, and CMA through LAMP-2A controls levels of substrates such as PUMA; these are real but secondary consequences. Supporting Evidence: PMID:22641697 However, in LAMP-deficient cells, the half-life of TAPL is decreased by a factor of five |
| GO:0031902 late endosome membrane | IBA GO_REF:0000033 | ACCEPT | Summary: LAMP2 is present in late endosome membranes. Reason: LAMP2 traffics through and resides in late endosomes/lysosomes; late endosome membrane localization is well documented. Supporting Evidence: file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. PMID:21896273 Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes |
| GO:0031902 late endosome membrane | IDA PMID:21896273 Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lys... | ACCEPT | Summary: LAMP2 is present in late endosome membranes. Reason: LAMP2 traffics through and resides in late endosomes/lysosomes; late endosome membrane localization is well documented. Supporting Evidence: file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. PMID:21896273 Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes |
| GO:0031902 late endosome membrane | IEA GO_REF:0000107 | ACCEPT | Summary: LAMP2 is present in late endosome membranes. Reason: LAMP2 traffics through and resides in late endosomes/lysosomes; late endosome membrane localization is well documented. Supporting Evidence: file:human/LAMP2/LAMP2-uniprot.txt This protein shuttles between lysosomes, endosomes, and the plasma membrane. PMID:21896273 Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes |
| GO:0035577 azurophil granule membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: LAMP2 is a membrane component of lysosome-related secretory granules in platelets and neutrophils. Reason: Lysosome-related granules (platelet dense granules, neutrophil granules) contain LAMP2 in their limiting membrane; these are cell-type-specific versions of its lysosomal location. Supporting Evidence: PMID:15297306 Immunofluorescence microscopy using 2 MRP4-specific antibodies revealed staining mainly in intracellular structures, which largely colocalized with the accumulation of mepacrine as marker for delta-granules |
| GO:0035577 azurophil granule membrane | TAS Reactome:R-HSA-6798739 | KEEP AS NON CORE | Summary: LAMP2 is a membrane component of lysosome-related secretory granules in platelets and neutrophils. Reason: Lysosome-related granules (platelet dense granules, neutrophil granules) contain LAMP2 in their limiting membrane; these are cell-type-specific versions of its lysosomal location. Supporting Evidence: PMID:15297306 Immunofluorescence microscopy using 2 MRP4-specific antibodies revealed staining mainly in intracellular structures, which largely colocalized with the accumulation of mepacrine as marker for delta-granules |
| GO:0043202 lysosomal lumen | TAS PMID:20176123 Chaperone-mediated autophagy: molecular mechanisms and physi... | MODIFY | Summary: LAMP2 localizes to lysosomes as an integral membrane protein. Reason: The location is right in essence, but LAMP2 is specifically an integral protein of the lysosomal membrane (its luminal domain faces the lumen but the protein is not a soluble luminal protein); the lysosomal membrane term, already accepted, is the appropriate specific location. Proposed replacements: lysosomal membrane Supporting Evidence: PMID:2912382 Electron microscopic studies of human blood monocytes, HL-60, and U937 cells demonstrated that the principal location of these glycoproteins was intracellular, in vacuoles and lysosomal structures |
| GO:0044754 autolysosome | IDA PMID:25327288 Selective VPS34 inhibitor blocks autophagy and uncovers a ro... | KEEP AS NON CORE | Summary: LAMP2 is found on autolysosomes/phagolysosomes formed by fusion with lysosomes. Reason: LAMP2 is delivered to autophagosome- and phagosome-derived compartments by fusion with lysosomes and is used as a marker for them; this reflects its lysosomal residence. Supporting Evidence: PMID:2912382 Transport of the proteins between organelles was evidenced by their marked accumulation in the membranes of phagolysosomes. |
| GO:0050821 protein stabilization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: LAMP2 binds and stabilizes lysosomal membrane proteins (e.g. TAPL) or controls stability of CMA substrates. Reason: LAMPs retain TAPL on the limiting membrane and prevent its degradation, and CMA through LAMP-2A controls levels of substrates such as PUMA; these are real but secondary consequences. Supporting Evidence: PMID:22641697 However, in LAMP-deficient cells, the half-life of TAPL is decreased by a factor of five |
| GO:0050821 protein stabilization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: LAMP2 binds and stabilizes lysosomal membrane proteins (e.g. TAPL) or controls stability of CMA substrates. Reason: LAMPs retain TAPL on the limiting membrane and prevent its degradation, and CMA through LAMP-2A controls levels of substrates such as PUMA; these are real but secondary consequences. Supporting Evidence: PMID:22641697 However, in LAMP-deficient cells, the half-life of TAPL is decreased by a factor of five |
| GO:0061684 chaperone-mediated autophagy | IDA PMID:36586411 Palmitoylation prevents sustained inflammation by limiting N... | ACCEPT | Summary: LAMP-2A is the lysosomal receptor and translocation component for chaperone-mediated autophagy. Reason: Substrates bind the LAMP-2A cytosolic tail and are translocated through a LAMP-2A multimeric complex; LAMP-2A levels are rate limiting for CMA, and knockdown stabilizes CMA substrates such as AF1Q. Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. PMID:18644871 Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. PMID:24880125 Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. |
| GO:0061684 chaperone-mediated autophagy | IDA PMID:40281343 PSAT1 impairs ferroptosis and reduces immunotherapy efficacy... | ACCEPT | Summary: LAMP-2A is the lysosomal receptor and translocation component for chaperone-mediated autophagy. Reason: Substrates bind the LAMP-2A cytosolic tail and are translocated through a LAMP-2A multimeric complex; LAMP-2A levels are rate limiting for CMA, and knockdown stabilizes CMA substrates such as AF1Q. Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. PMID:18644871 Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. PMID:24880125 Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. |
| GO:0061684 chaperone-mediated autophagy | IEA GO_REF:0000107 | ACCEPT | Summary: LAMP-2A is the lysosomal receptor and translocation component for chaperone-mediated autophagy. Reason: Substrates bind the LAMP-2A cytosolic tail and are translocated through a LAMP-2A multimeric complex; LAMP-2A levels are rate limiting for CMA, and knockdown stabilizes CMA substrates such as AF1Q. Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. PMID:18644871 Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. PMID:24880125 Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. |
| GO:0061684 chaperone-mediated autophagy | IMP PMID:24880125 Degradation of AF1Q by chaperone-mediated autophagy. | ACCEPT | Summary: LAMP-2A is the lysosomal receptor and translocation component for chaperone-mediated autophagy. Reason: Substrates bind the LAMP-2A cytosolic tail and are translocated through a LAMP-2A multimeric complex; LAMP-2A levels are rate limiting for CMA, and knockdown stabilizes CMA substrates such as AF1Q. Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. PMID:18644871 Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. PMID:24880125 Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. |
| GO:0061684 chaperone-mediated autophagy | IMP PMID:27628032 LAMP-2 is required for incorporating syntaxin-17 into autoph... | ACCEPT | Summary: LAMP-2A is the lysosomal receptor and translocation component for chaperone-mediated autophagy. Reason: Substrates bind the LAMP-2A cytosolic tail and are translocated through a LAMP-2A multimeric complex; LAMP-2A levels are rate limiting for CMA, and knockdown stabilizes CMA substrates such as AF1Q. Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. PMID:18644871 Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. PMID:24880125 Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. |
| GO:0061684 chaperone-mediated autophagy | ISS GO_REF:0000024 | ACCEPT | Summary: LAMP-2A is the lysosomal receptor and translocation component for chaperone-mediated autophagy. Reason: Substrates bind the LAMP-2A cytosolic tail and are translocated through a LAMP-2A multimeric complex; LAMP-2A levels are rate limiting for CMA, and knockdown stabilizes CMA substrates such as AF1Q. Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. PMID:18644871 Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. PMID:24880125 Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. |
| GO:0061740 protein targeting to lysosome involved in chaperone-mediated autophagy | IBA GO_REF:0000033 | ACCEPT | Summary: LAMP-2A is the lysosomal receptor and translocation component for chaperone-mediated autophagy. Reason: Substrates bind the LAMP-2A cytosolic tail and are translocated through a LAMP-2A multimeric complex; LAMP-2A levels are rate limiting for CMA, and knockdown stabilizes CMA substrates such as AF1Q. Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. PMID:18644871 Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. PMID:24880125 Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. |
| GO:0061740 protein targeting to lysosome involved in chaperone-mediated autophagy | IEA GO_REF:0000107 | ACCEPT | Summary: LAMP-2A is the lysosomal receptor and translocation component for chaperone-mediated autophagy. Reason: Substrates bind the LAMP-2A cytosolic tail and are translocated through a LAMP-2A multimeric complex; LAMP-2A levels are rate limiting for CMA, and knockdown stabilizes CMA substrates such as AF1Q. Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. PMID:18644871 Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. PMID:24880125 Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. |
| GO:0061740 protein targeting to lysosome involved in chaperone-mediated autophagy | IMP PMID:27628032 LAMP-2 is required for incorporating syntaxin-17 into autoph... | ACCEPT | Summary: LAMP-2A is the lysosomal receptor and translocation component for chaperone-mediated autophagy. Reason: Substrates bind the LAMP-2A cytosolic tail and are translocated through a LAMP-2A multimeric complex; LAMP-2A levels are rate limiting for CMA, and knockdown stabilizes CMA substrates such as AF1Q. Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. PMID:18644871 Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. PMID:24880125 Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. |
| GO:0061740 protein targeting to lysosome involved in chaperone-mediated autophagy | ISS GO_REF:0000024 | ACCEPT | Summary: LAMP-2A is the lysosomal receptor and translocation component for chaperone-mediated autophagy. Reason: Substrates bind the LAMP-2A cytosolic tail and are translocated through a LAMP-2A multimeric complex; LAMP-2A levels are rate limiting for CMA, and knockdown stabilizes CMA substrates such as AF1Q. Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. PMID:18644871 Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. PMID:24880125 Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: LAMP2 is detected in exosome proteomes. Reason: Endosome-derived vesicles carry LAMP2; a secondary location consistent with its endolysosomal residence. Supporting Evidence: PMID:15908444 Exosomal-like vesicles are present in human blood plasma. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: LAMP2 is detected in exosome proteomes. Reason: Endosome-derived vesicles carry LAMP2; a secondary location consistent with its endolysosomal residence. Supporting Evidence: PMID:15908444 Exosomal-like vesicles are present in human blood plasma. |
| GO:0070062 extracellular exosome | IDA PMID:15908444 Exosomal-like vesicles are present in human blood plasma. | KEEP AS NON CORE | Summary: LAMP2 is detected in exosome proteomes. Reason: Endosome-derived vesicles carry LAMP2; a secondary location consistent with its endolysosomal residence. Supporting Evidence: PMID:15908444 Exosomal-like vesicles are present in human blood plasma. |
| GO:0097352 autophagosome maturation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: LAMP2 is required for autophagosome-lysosome fusion. Reason: LAMP-2-deficient cells fail to recruit STX17 to autophagosomes and accumulate unfused autophagosomes; LAMP2 supports maturation indirectly rather than being fusion machinery. Supporting Evidence: PMID:27628032 Thus, LAMP-2 is essential for STX17 expression by the autophagosomes and this absence is sufficient to explain their failure to fuse with lysosomes. |
| GO:0097352 autophagosome maturation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: LAMP2 is required for autophagosome-lysosome fusion. Reason: LAMP-2-deficient cells fail to recruit STX17 to autophagosomes and accumulate unfused autophagosomes; LAMP2 supports maturation indirectly rather than being fusion machinery. Supporting Evidence: PMID:27628032 Thus, LAMP-2 is essential for STX17 expression by the autophagosomes and this absence is sufficient to explain their failure to fuse with lysosomes. |
| GO:0097352 autophagosome maturation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: LAMP2 is required for autophagosome-lysosome fusion. Reason: LAMP-2-deficient cells fail to recruit STX17 to autophagosomes and accumulate unfused autophagosomes; LAMP2 supports maturation indirectly rather than being fusion machinery. Supporting Evidence: PMID:27628032 Thus, LAMP-2 is essential for STX17 expression by the autophagosomes and this absence is sufficient to explain their failure to fuse with lysosomes. |
| GO:0098857 membrane microdomain | TAS PMID:20176123 Chaperone-mediated autophagy: molecular mechanisms and physi... | KEEP AS NON CORE | Summary: LAMP-2A is enriched in lysosomal membrane lipid microdomains that regulate its turnover. Reason: The CMA review describes partitioning of LAMP-2A into lysosomal membrane microdomains as a regulatory step; a sub-location of the lysosomal membrane. Supporting Evidence: PMID:20176123 We have placed particular emphasis on the critical role that changes in the lipid composition of the lysosomal membrane play in the regulation of CMA |
| GO:0101003 ficolin-1-rich granule membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: LAMP2 is a membrane component of lysosome-related secretory granules in platelets and neutrophils. Reason: Lysosome-related granules (platelet dense granules, neutrophil granules) contain LAMP2 in their limiting membrane; these are cell-type-specific versions of its lysosomal location. Supporting Evidence: PMID:15297306 Immunofluorescence microscopy using 2 MRP4-specific antibodies revealed staining mainly in intracellular structures, which largely colocalized with the accumulation of mepacrine as marker for delta-granules |
| GO:0101003 ficolin-1-rich granule membrane | TAS Reactome:R-HSA-6800426 | KEEP AS NON CORE | Summary: LAMP2 is a membrane component of lysosome-related secretory granules in platelets and neutrophils. Reason: Lysosome-related granules (platelet dense granules, neutrophil granules) contain LAMP2 in their limiting membrane; these are cell-type-specific versions of its lysosomal location. Supporting Evidence: PMID:15297306 Immunofluorescence microscopy using 2 MRP4-specific antibodies revealed staining mainly in intracellular structures, which largely colocalized with the accumulation of mepacrine as marker for delta-granules |
| GO:0160020 positive regulation of ferroptosis | IDA PMID:40281343 PSAT1 impairs ferroptosis and reduces immunotherapy efficacy... | KEEP AS NON CORE | Summary: CMA-mediated degradation of GPX4 via LAMP-2A promotes ferroptosis. Reason: Effect on ferroptosis is a downstream consequence of LAMP-2A-dependent degradation of a CMA substrate. Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. |
| GO:0160020 positive regulation of ferroptosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CMA-mediated degradation of GPX4 via LAMP-2A promotes ferroptosis. Reason: Effect on ferroptosis is a downstream consequence of LAMP-2A-dependent degradation of a CMA substrate. Supporting Evidence: PMID:11082038 Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. |
| GO:1905146 lysosomal protein catabolic process | IMP PMID:24880125 Degradation of AF1Q by chaperone-mediated autophagy. | ACCEPT | Summary: LAMP-2A mediates lysosomal degradation of CMA substrates. Reason: LAMP-2A knockdown increases the levels of the CMA substrate AF1Q, consistent with its receptor role in lysosomal protein catabolism. Supporting Evidence: PMID:24880125 Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. |
| GO:0061742 chaperone-mediated autophagy translocation complex | IDA PMID:18644871 The chaperone-mediated autophagy receptor organizes in dynam... | NEW | Summary: LAMP-2A assembles at the lysosomal membrane into a high-molecular-weight complex required for substrate translocation. Reason: The translocation complex is a LAMP-2A multimer; the cited study shows its assembly is directly linked to CMA activity and required for substrate translocation. Supporting Evidence: PMID:18644871 Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. |
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Download this section (compressed HTML)Q: How does a single-pass LAMP-2A multimer translocate unfolded substrates across the lysosomal membrane, and is there a pore?
Q: Do LAMP-2B and LAMP-2C have isoform-specific functions beyond modulating CMA (e.g. in Danon disease cardiomyopathy)?
Experiment: Reconstitute purified LAMP-2A with HSC70 and lysosomal HSC70 in proteoliposomes to test whether LAMP-2A multimers are sufficient for substrate translocation.
Type: in vitro reconstitution
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