Lysosome-associated membrane glycoprotein 2 (LAMP2)
The protein contains 410 amino acids for an estimated molecular weight of 44961 Da.
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). Functions by binding target proteins, such as GAPDH and MLLT11, and targeting them for lysosomal degradation (PubMed:8662539, PubMed:11082038, PubMed:18644871, PubMed:24880125). 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 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 (PubMed:20518820). Is not required for efficient MHCII-mediated presentation of endogenous antigens (PubMed:20518820).', 'Modulates chaperone-mediated autophagy. Decreases presentation of endogenous antigens by MHCII. Does not play a role in the presentation of exogenous and mem (updated: Dec. 11, 2019)
Protein identification was indicated in the following studies:
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| dbSNP:rs1043878 | |
| DAND |
No binding partner found
Biological Process
Autophagosome maturation
Cellular response to starvation
Chaperone-mediated autophagy
Establishment of protein localization to organelle
Lysosomal protein catabolic process
Muscle cell cellular homeostasis
Negative regulation of protein-containing complex assembly
Neutrophil degranulation
Platelet degranulation
Protein import
Protein stabilization
Protein targeting
Protein targeting to lysosome involved in chaperone-mediated autophagy
Regulation of protein stability
Cellular Component
Autolysosome
Azurophil granule membrane
Chaperone-mediated autophagy translocation complex
Extracellular exosome
Extracellular space
Ficolin-1-rich granule membrane
Integral component of autophagosome membrane
Late endosome
Late endosome membrane
Lysosomal lumen
Lysosomal matrix
Lysosomal membrane
Lysosome
Membrane
Membrane raft
Obsolete cell
Perinuclear region of cytoplasm
Phagocytic vesicle membrane
Plasma membrane
Platelet dense granule membrane
Trans-Golgi network
The reference OMIM entry for this protein is 300257
Danon disease
Vacuolar cardiomyopathy and myopathy, x-linked
Pseudoglycogenosis ii
Antopol disease
Lysosomal glycogen storage disease without acid maltase deficiency, formerly
Glycogen storage disease iib; gsd2b, formerly
Gsd iib, formerl
A number sign (#) is used with this entry because of evidence that Danon disease, also known as X-linked vacuolar cardiomyopathy and myopathy, is caused by mutation in the gene encoding lysosome-associated membrane protein-2 (LAMP2; 309060).
DESCRIPTION
Danon disease is an X-linked dominant disorder predominantly affecting cardiac muscle. Skeletal muscle involvement and mental retardation are variable features. The accumulation of glycogen in muscle and lysosomes originally led to the classification of Danon disease as a variant of glycogen storage disease II (Pompe disease; 232300) with 'normal acid maltase' or alpha-glucosidase (GAA; 606800) (Danon et al., 1981). However, Nishino et al. (2000) stated that Danon disease is not a glycogen storage disease because glycogen is not always increased. Sugie et al. (2005) classified Danon disease as a form of autophagic vacuolar myopathy, characterized by intracytoplasmic autophagic vacuoles with sarcolemmal features. The characteristic vacuole is believed to be an autolysosome surrounded by secondarily-generated membranes containing sarcolemmal proteins, basal lamina, and acetylcholinesterase activity. X-linked myopathy with excessive autophagy (XMEA; 310440) is a distinct disorder with similar pathologic features.CLINICAL FEATURES
Antopol et al. (1940) described 2 brothers who died in the second decade of life with heart failure. Autopsy of 1 patient showed glycogen storage disease limited to the myocardium. Mehrizi and Oppenheimer (1960) reported 2 related patients with heart failure associated with unusual deposition of glycogen in the myocardium. Danon et al. (1981) reported 2 unrelated males with mental retardation, hypertrophic cardiomyopathy, and proximal muscle weakness. One patient had hepatomegaly. Examination of skeletal muscle biopsies showed features suggestive of a lysosomal glycogen storage disease. However, acid alpha-glucosidase activity was normal, excluding a diagnosis of Pompe disease, or glycogen storage disease type II (GSD II). Both patients died at the age of 17 years. Riggs et al. (1983) described lysosomal storage disease with normal acid maltase activity in 2 brothers. One of the brothers showed muscle weakness at age 3 years. Both patients had Wolff-Parkinson-White electrocardiographic findings. Bergia et al. (1986) reported a kindred in which 2 sisters gave birth to a total of 3 sons with mental retardation, scapuloperoneal muscular weakness, and hypertrophic cardiomyopathy. Intellectual deterioration began at about age 5 years. Hypertrophic cardiomyopathy manifesting itself in the teens led to death at ages 17 and 21 years in 2 of the patients. On evaluation in their teens, the affected males showed wasting of distal muscle groups, positive Gowers maneuver, and predominant humeroperoneal distribution of muscle weakness. Creatine kinase was elevated as was also lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase. A marked myopia was also present. The mother of 2 of the patients, a presumed carrier of the mutant gene, had evidence of cardiomyopathy without elevated serum muscle enzymes. Tripathy et al. (1988) described an 18-year-old black male who developed manifestations of complete atrioventricular nodal block; endomyocardial biopsy showed membrane-bound glycogen resembling the findings of GSD II. The glycogenosis appeared to be limited to the myocardium because the rest of the physical examination, the histolog ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 300257 was added.
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).