LAMP2

Lysosome-associated membrane protein 2 (LAMP2), also known as CD107b (Cluster of Differentiation 107b) and Mac-3, is a human gene. Its protein, LAMP2, is one of the lysosome-associated membrane glycoproteins.

LAMP2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2MOF, 2MOM
Identifiers
Aliases	LAMP2, CD107b, LAMP-2, LAMPB, LGP110, lysosomal associated membrane protein 2, LGP-96, DND
External IDs	OMIM: 309060; MGI: 96748; HomoloGene: 7809; GeneCards: LAMP2; OMA:LAMP2 - orthologs
Gene location (Human) Chr. X chromosome (human) Band Xq24 Start 120,426,148 bp End 120,469,365 bp
Gene location (Mouse) Chr. X chromosome (mouse) Band X A3.3|X 22.67 cM Start 37,490,234 bp End 37,545,331 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in corpus callosum external globus pallidus kidney tubule parotid gland gallbladder inferior ganglion of vagus nerve stromal cell of endometrium C1 segment gingival epithelium pars reticulata Top expressed in ciliary body iris Epithelium of choroid plexus conjunctival fornix vestibular sensory epithelium aortic valve right kidney hair follicle stroma of bone marrow molar More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein domain specific binding protein binding enzyme binding Cellular component integral component of membrane membrane microdomain endosome late endosome phagocytic vesicle membrane chaperone-mediated autophagy translocation complex membrane late endosome membrane plasma membrane lysosomal membrane lysosomal lumen platelet dense granule membrane lysosome endosome membrane extracellular exosome autophagosome membrane extracellular space trans-Golgi network cytoplasmic vesicle azurophil granule membrane autolysosome perinuclear region of cytoplasm integral component of autophagosome membrane ficolin-1-rich granule membrane membrane raft lysosomal matrix Biological process regulation of protein stability muscle cell cellular homeostasis protein stabilization platelet degranulation protein import protein targeting autophagy cellular response to starvation negative regulation of protein homooligomerization neutrophil degranulation chaperone-mediated autophagy protein targeting to lysosome involved in chaperone-mediated autophagy autophagosome maturation lysosomal protein catabolic process establishment of protein localization to organelle Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3920 16784 Ensembl ENSG00000005893 ENSMUSG00000016534 UniProt P13473 P17047 RefSeq (mRNA) NM_013995 NM_001122606 NM_002294 NM_001017959 NM_001290485 NM_010685 RefSeq (protein) NP_001116078 NP_002285 NP_054701 NP_001017959 NP_001277414 NP_034815 Location (UCSC) Chr X: 120.43 – 120.47 Mb Chr X: 37.49 – 37.55 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

The protein encoded by this gene is a member of a family of membrane glycoproteins. This glycoprotein provides selectins with carbohydrate ligands. It may play a role in tumor cell metastasis. It may also function in the protection, maintenance, and adhesion of the lysosome. Alternative splicing of the gene produces three variants - LAMP-2A, LAMP-2B and LAMP-2C. LAMP-2A is the receptor for chaperone-mediated autophagy. Recently it has been determined that antibodies against LAMP-2 account for a fraction of patients who get a serious kidney disease termed focal necrotizing glomerulonephritis.

LAMP-2B is associated with Danon disease.

Structure and tissue distribution

The gene for LAMP2 has 9 coding exons and 2 alternate last exons, 9a and 9b. When the last exon is spliced with the alternative exon, it is a variant called LAMP2b, which varies in the last 11 amino acids of its C-terminal sequence: in the luminal domain, the transmembrane domain, and the cytoplasmic tail. The original (LAMP2a) is highly expressed in the placenta, lung, and liver, while LAMP2b is highly expressed in skeletal muscle.

Function

Lysosomes are cell organelles found in most animal cells. Their main functions center around breaking down materials and debris in the cell. Some of this is done via acid hydrolases that degrade foreign materials and have specialized autolytic functions. These hydrolyses are stored in the lysosomal membrane, which also house lysosomal membrane glycoproteins.

LAMP1 and LAMP2 make up about 50% of lysosomal membrane glycoproteins. (See LAMP1 for more information on both LAMP1 and LAMP2.) Both of these consist of polypeptides of about 40 kD, with the core polypeptide surrounded by 16 to 20 attached N-linked saccharides. The biological functions of these glycoproteins are disputed. They are believed to be significantly involved in operations of the lysosomes, including maintaining integrity, pH and catabolism. Further, some of the functions of LAMP2 are believed to be protecting the lysosomal membrane from proteolytic enzymes that are within the lysosome itself (as in autodigestion), acting as a receptor into the lysosome for proteins, adhesion (when expressed on the outside surface of the plasma membrane) and signal transduction, both inter- and intra-. It also provides protection for the cell from methylating mutagens.

Role in cancer

LAMP2 has been specifically implicated in tumor cell metastasis. Both LAMP1 and LAMP2 have been found expressed on the surface of cancerous tumors, specifically in cells of highly metastatic cancer such as colon cancer and melanoma. They are rarely found on the plasma membranes of normal cells, and are found more on highly metastatic tumors than on poorly metastatic ones. LAMP2, along with LAMP1, interact with E-selectin and galectins to mediate the adhesion of some cancer cells to the ECM. The two LAMP molecules act as ligands for the cell-adhesion molecules.

It has also been shown that the down-regulation of LAMP2 could both reduce the resistance of breast cancer cells to the paclitaxel and could inhibit cell proliferation in multiple myeloma cells.

Along with other genes such as LC3B, p62 and CTSB, a strong up regulation of LAMP2 was detected in perinecrotic areas of glioblastomas. This suggests autophagy induction in gliomas could be caused by micro-environmental changes.

In a study of glial tumors, the cell membranes of glial and endothelial cells were found to contain LAMP1 and LAMP2, while YKL-40 (a different glycoprotein) was found in the cytoplasm. This suggests that the three glycoproteins are involved in tumor development, specifically in the processes of angiogenesis and tissue remodeling.

Inducers

• CA77.1
• QX39

See also

• Cluster of differentiation

Further reading

• Chang MH, Karageorgos LE, Meikle PJ (2003). "CD107a (LAMP-1) and CD107b (LAMP-2)". Journal of Biological Regulators and Homeostatic Agents. 16 (2): 147–51. PMID 12144129.
• Schleutker J, Haataja L, Renlund M, Puhakka L, Viitala J, Peltonen L, Aula P (November 1991). "Confirmation of the chromosomal localization of human lamp genes and their exclusion as candidate genes for Salla disease". Human Genetics. 88 (1): 95–7. doi:10.1007/BF00204936. PMID 1959930. S2CID 31520394.
• Manoni M, Tribioli C, Lazzari B, DeBellis G, Patrosso C, Pergolizzi R, Pellegrini M, Maestrini E, Rivella S, Vezzoni P (March 1991). "The nucleotide sequence of a CpG island demonstrates the presence of the first exon of the gene encoding the human lysosomal membrane protein lamp2 and assigns the gene to Xq24". Genomics. 9 (3): 551–4. doi:10.1016/0888-7543(91)90424-D. PMID 2032724.
• Carlsson SR, Fukuda M (November 1990). "The polylactosaminoglycans of human lysosomal membrane glycoproteins lamp-1 and lamp-2. Localization on the peptide backbones". The Journal of Biological Chemistry. 265 (33): 20488–95. doi:10.1016/S0021-9258(17)30530-6. PMID 2243102.
• Mattei MG, Matterson J, Chen JW, Williams MA, Fukuda M (May 1990). "Two human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2, are encoded by genes localized to chromosome 13q34 and chromosome Xq24-25, respectively". The Journal of Biological Chemistry. 265 (13): 7548–51. doi:10.1016/S0021-9258(19)39148-3. PMID 2332441.
• Mane SM, Marzella L, Bainton DF, Holt VK, Cha Y, Hildreth JE, August JT (January 1989). "Purification and characterization of human lysosomal membrane glycoproteins". Archives of Biochemistry and Biophysics. 268 (1): 360–78. doi:10.1016/0003-9861(89)90597-3. PMID 2912382.
• Fukuda M, Viitala J, Matteson J, Carlsson SR (December 1988). "Cloning of cDNAs encoding human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2. Comparison of their deduced amino acid sequences". The Journal of Biological Chemistry. 263 (35): 18920–8. doi:10.1016/S0021-9258(18)37370-8. PMID 3198605.
• Dahlgren C, Carlsson SR, Karlsson A, Lundqvist H, Sjölin C (October 1995). "The lysosomal membrane glycoproteins Lamp-1 and Lamp-2 are present in mobilizable organelles, but are absent from the azurophil granules of human neutrophils". The Biochemical Journal. 311 (2): 667–74. doi:10.1042/bj3110667. PMC 1136051. PMID 7487911.
• Konecki DS, Foetisch K, Zimmer KP, Schlotter M, Lichter-Konecki U (October 1995). "An alternatively spliced form of the human lysosome-associated membrane protein-2 gene is expressed in a tissue-specific manner". Biochemical and Biophysical Research Communications. 215 (2): 757–67. doi:10.1006/bbrc.1995.2528. PMID 7488019.
• Konecki DS, Foetisch K, Schlotter M, Lichter-Konecki U (November 1994). "Complete cDNA sequence of human lysosome-associated membrane protein-2". Biochemical and Biophysical Research Communications. 205 (1): 1–5. doi:10.1006/bbrc.1994.2620. PMID 7999007.
• Carlsson SR, Lycksell PO, Fukuda M (July 1993). "Assignment of O-glycan attachment sites to the hinge-like regions of human lysosomal membrane glycoproteins lamp-1 and lamp-2". Archives of Biochemistry and Biophysics. 304 (1): 65–73. doi:10.1006/abbi.1993.1322. PMID 8323299.
• Sawada R, Jardine KA, Fukuda M (April 1993). "The genes of major lysosomal membrane glycoproteins, lamp-1 and lamp-2. 5'-flanking sequence of lamp-2 gene and comparison of exon organization in two genes". The Journal of Biological Chemistry. 268 (12): 9014–22. doi:10.1016/S0021-9258(18)52972-0. PMID 8517882.
• Kannan K, Stewart RM, Bounds W, Carlsson SR, Fukuda M, Betzing KW, Holcombe RF (July 1996). "Lysosome-associated membrane proteins h-LAMP1 (CD107a) and h-LAMP2 (CD107b) are activation-dependent cell surface glycoproteins in human peripheral blood mononuclear cells which mediate cell adhesion to vascular endothelium". Cellular Immunology. 171 (1): 10–9. doi:10.1006/cimm.1996.0167. PMID 8660832.
• Israels SJ, McMillan EM, Robertson C, Singhory S, McNicol A (April 1996). "The lysosomal granule membrane protein, LAMP-2, is also present in platelet dense granule membranes". Thrombosis and Haemostasis. 75 (4): 623–9. doi:10.1055/s-0038-1650333. PMID 8743190. S2CID 25093464.
• Aumüller G, Renneberg H, Hasilik A (February 1997). "Distribution and subcellular localization of a lysosome-associated protein in human genital organs". Cell and Tissue Research. 287 (2): 335–42. doi:10.1007/s004410050758. PMID 8995204. S2CID 6940687.
• Akasaki K, Michihara A, Fujiwara Y, Mibuka K, Tsuji H (December 1996). "Biosynthetic transport of a major lysosome-associated membrane glycoprotein 2, lamp-2: a significant fraction of newly synthesized lamp-2 is delivered to lysosomes by way of early endosomes". Journal of Biochemistry. 120 (6): 1088–94. doi:10.1093/oxfordjournals.jbchem.a021526. PMID 9010755.
• Karlsson K, Carlsson SR (July 1998). "Sorting of lysosomal membrane glycoproteins lamp-1 and lamp-2 into vesicles distinct from mannose 6-phosphate receptor/gamma-adaptin vesicles at the trans-Golgi network". The Journal of Biological Chemistry. 273 (30): 18966–73. doi:10.1074/jbc.273.30.18966. PMID 9668075.
• Ayala P, Lin L, Hopper S, Fukuda M, So M (October 1998). "Infection of epithelial cells by pathogenic neisseriae reduces the levels of multiple lysosomal constituents". Infection and Immunity. 66 (10): 5001–7. doi:10.1128/IAI.66.10.5001-5007.1998. PMC 108621. PMID 9746610.
• Furuta K, Yang XL, Chen JS, Hamilton SR, August JT (May 1999). "Differential expression of the lysosome-associated membrane proteins in normal human tissues". Archives of Biochemistry and Biophysics. 365 (1): 75–82. doi:10.1006/abbi.1999.1147. PMID 10222041.
• Nishino I, Fu J, Tanji K, Yamada T, Shimojo S, Koori T, Mora M, Riggs JE, Oh SJ, Koga Y, Sue CM, Yamamoto A, Murakami N, Shanske S, Byrne E, Bonilla E, Nonaka I, DiMauro S, Hirano M (August 2000). "Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease)". Nature. 406 (6798): 906–10. Bibcode:2000Natur.406..906N. doi:10.1038/35022604. PMID 10972294. S2CID 4332055.

External links

• LAMP2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• PDBe-KB provides an overview of all the structure information available in the PDB for Human Lysosome-associated membrane glycoprotein 2

This article incorporates text from the United States National Library of Medicine, which is in the public domain.