LAMP2

The gene for LAMP2 has 9 coding exons and 2 alternate last exons, 9a and 9b.{{OMIM|309060|Lysosome-associated membrane protein 2}} 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.{{cite journal | vauthors = Konecki DS, Foetisch K, Zimmer KP, Schlotter M, Lichter-Konecki U | title = An alternatively spliced form of the human lysosome-associated membrane protein-2 gene is expressed in a tissue-specific manner | journal = Biochemical and Biophysical Research Communications | volume = 215 | issue = 2 | pages = 757–67 | date = October 1995 | doi = 10.1006/bbrc.1995.2528 | pmid = 7488019 }}

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.

LAMP2 has been specifically implicated in tumor cell metastasis.{{Cite web|url=https://www.uniprot.org/uniprot/P13473|title=LAMP2 - Lysosome-associated membrane glycoprotein 2 precursor - Homo sapiens (Human) - LAMP2 gene & protein|website=www.uniprot.org|access-date=2016-04-18}} 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.{{cite journal | vauthors = Sarafian V, Jadot M, Foidart JM, Letesson JJ, Van den Brûle F, Castronovo V, Wattiaux R, Coninck SW | title = Expression of Lamp-1 and Lamp-2 and their interactions with galectin-3 in human tumor cells | journal = International Journal of Cancer | volume = 75 | issue = 1 | pages = 105–11 | date = January 1998 | doi = 10.1002/(sici)1097-0215(19980105)75:1<105::aid-ijc16>3.0.co;2-f | pmid = 9426697 | doi-access = free }} 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{{cite journal | vauthors = Han Q, Chen S, Yang M, Zhang Z, Chen A, Hu C, Li S | title = [The effect of LAMP2A shRNA on the resistance of breast cancer cells to paclitaxel] | journal = Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology | volume = 30 | issue = 4 | pages = 351–4 | date = April 2014 | pmid = 24721399 }} and could inhibit cell proliferation in multiple myeloma cells.{{cite journal | vauthors = Li L, Li J | title = [Lentivirus-mediated shRNA silencing of LAMP2A inhibits the proliferation of multiple myeloma cells] | journal = Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology | volume = 31 | issue = 5 | pages = 605–8, 614 | date = May 2015 | pmid = 25940285 }}

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.{{cite journal | vauthors = Jennewein L, Ronellenfitsch MW, Antonietti P, Ilina EI, Jung J, Stadel D, Flohr LM, Zinke J, von Renesse J, Drott U, Baumgarten P, Braczynski AK, Penski C, Burger MC, Theurillat JP, Steinbach JP, Plate KH, Dikic I, Fulda S, Brandts C, Kögel D, Behrends C, Harter PN, Mittelbronn M | title = Diagnostic and clinical relevance of the autophago-lysosomal network in human gliomas | journal = Oncotarget | volume = 7 | issue = 15 | pages = 20016–32 | date = April 2016 | doi = 10.18632/oncotarget.7910 | pmid = 26956048 | pmc = 4991435 }}

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.{{cite journal | vauthors = Kazakova MH, Staykov DG, Koev IG, Kitov BD, Sarafian VS | title = A comparative study of LAMPs and YKL-40 tissue expression in glial tumors | journal = Folia Medica | volume = 56 | issue = 3 | pages = 194–8 | date = 2014-09-01 | doi = 10.2478/folmed-2014-0028 | pmid = 25507675 | doi-access = free }}

• CA77.1
• QX39{{cite journal | vauthors = Bourdenx M, Martín-Segura A, Scrivo A, Rodriguez-Navarro JA, Kaushik S, Tasset I, Diaz A, Storm NJ, Xin Q, Juste YR, Stevenson E, Luengo E, Clement CC, Choi SJ, Krogan NJ, Mosharov EV, Santambrogio L, Grueninger F, Collin L, Swaney DL, Sulzer D, Gavathiotis E, Cuervo AM | display-authors = 6 | title = Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome | journal = Cell | volume = 184| issue = 10| pages = 2696–2714.e25| date = April 2021 | pmid = 33891876 | doi = 10.1016/j.cell.2021.03.048 | pmc = 8152331 }}

• Cluster of differentiation

{{reflist|33em}}

{{refbegin|33em}}

• {{cite journal | vauthors = Chang MH, Karageorgos LE, Meikle PJ | title = CD107a (LAMP-1) and CD107b (LAMP-2) | journal = Journal of Biological Regulators and Homeostatic Agents | volume = 16 | issue = 2 | pages = 147–51 | year = 2003 | pmid = 12144129 }}
• {{cite journal | vauthors = Schleutker J, Haataja L, Renlund M, Puhakka L, Viitala J, Peltonen L, Aula P | title = Confirmation of the chromosomal localization of human lamp genes and their exclusion as candidate genes for Salla disease | journal = Human Genetics | volume = 88 | issue = 1 | pages = 95–7 | date = November 1991 | pmid = 1959930 | doi = 10.1007/BF00204936 | s2cid = 31520394 }}
• {{cite journal | vauthors = Manoni M, Tribioli C, Lazzari B, DeBellis G, Patrosso C, Pergolizzi R, Pellegrini M, Maestrini E, Rivella S, Vezzoni P | title = 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 | journal = Genomics | volume = 9 | issue = 3 | pages = 551–4 | date = March 1991 | pmid = 2032724 | doi = 10.1016/0888-7543(91)90424-D }}
• {{cite journal | vauthors = Carlsson SR, Fukuda M | title = The polylactosaminoglycans of human lysosomal membrane glycoproteins lamp-1 and lamp-2. Localization on the peptide backbones | journal = The Journal of Biological Chemistry | volume = 265 | issue = 33 | pages = 20488–95 | date = November 1990 | doi = 10.1016/S0021-9258(17)30530-6 | pmid = 2243102 | doi-access = free }}
• {{cite journal | vauthors = Mattei MG, Matterson J, Chen JW, Williams MA, Fukuda M | title = 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 | journal = The Journal of Biological Chemistry | volume = 265 | issue = 13 | pages = 7548–51 | date = May 1990 | doi = 10.1016/S0021-9258(19)39148-3 | pmid = 2332441 | doi-access = free }}
• {{cite journal | vauthors = Mane SM, Marzella L, Bainton DF, Holt VK, Cha Y, Hildreth JE, August JT | title = Purification and characterization of human lysosomal membrane glycoproteins | journal = Archives of Biochemistry and Biophysics | volume = 268 | issue = 1 | pages = 360–78 | date = January 1989 | pmid = 2912382 | doi = 10.1016/0003-9861(89)90597-3 }}
• {{cite journal | vauthors = Fukuda M, Viitala J, Matteson J, Carlsson SR | title = Cloning of cDNAs encoding human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2. Comparison of their deduced amino acid sequences | journal = The Journal of Biological Chemistry | volume = 263 | issue = 35 | pages = 18920–8 | date = December 1988 | doi = 10.1016/S0021-9258(18)37370-8 | pmid = 3198605 | doi-access = free }}
• {{cite journal | vauthors = Dahlgren C, Carlsson SR, Karlsson A, Lundqvist H, Sjölin C | title = The lysosomal membrane glycoproteins Lamp-1 and Lamp-2 are present in mobilizable organelles, but are absent from the azurophil granules of human neutrophils | journal = The Biochemical Journal | volume = 311 | issue = 2 | pages = 667–74 | date = October 1995 | pmid = 7487911 | pmc = 1136051 | doi = 10.1042/bj3110667}}
• {{cite journal | vauthors = Konecki DS, Foetisch K, Zimmer KP, Schlotter M, Lichter-Konecki U | title = An alternatively spliced form of the human lysosome-associated membrane protein-2 gene is expressed in a tissue-specific manner | journal = Biochemical and Biophysical Research Communications | volume = 215 | issue = 2 | pages = 757–67 | date = October 1995 | pmid = 7488019 | doi = 10.1006/bbrc.1995.2528 }}
• {{cite journal | vauthors = Konecki DS, Foetisch K, Schlotter M, Lichter-Konecki U | title = Complete cDNA sequence of human lysosome-associated membrane protein-2 | journal = Biochemical and Biophysical Research Communications | volume = 205 | issue = 1 | pages = 1–5 | date = November 1994 | pmid = 7999007 | doi = 10.1006/bbrc.1994.2620 }}
• {{cite journal | vauthors = Carlsson SR, Lycksell PO, Fukuda M | title = Assignment of O-glycan attachment sites to the hinge-like regions of human lysosomal membrane glycoproteins lamp-1 and lamp-2 | journal = Archives of Biochemistry and Biophysics | volume = 304 | issue = 1 | pages = 65–73 | date = July 1993 | pmid = 8323299 | doi = 10.1006/abbi.1993.1322 }}
• {{cite journal | vauthors = Sawada R, Jardine KA, Fukuda M | title = 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 | journal = The Journal of Biological Chemistry | volume = 268 | issue = 12 | pages = 9014–22 | date = April 1993 | doi = 10.1016/S0021-9258(18)52972-0 | pmid = 8517882 | doi-access = free }}
• {{cite journal | vauthors = Kannan K, Stewart RM, Bounds W, Carlsson SR, Fukuda M, Betzing KW, Holcombe RF | title = 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 | journal = Cellular Immunology | volume = 171 | issue = 1 | pages = 10–9 | date = July 1996 | pmid = 8660832 | doi = 10.1006/cimm.1996.0167 }}
• {{cite journal | vauthors = Israels SJ, McMillan EM, Robertson C, Singhory S, McNicol A | title = The lysosomal granule membrane protein, LAMP-2, is also present in platelet dense granule membranes | journal = Thrombosis and Haemostasis | volume = 75 | issue = 4 | pages = 623–9 | date = April 1996 | doi = 10.1055/s-0038-1650333 | pmid = 8743190 | s2cid = 25093464 }}
• {{cite journal | vauthors = Aumüller G, Renneberg H, Hasilik A | title = Distribution and subcellular localization of a lysosome-associated protein in human genital organs | journal = Cell and Tissue Research | volume = 287 | issue = 2 | pages = 335–42 | date = February 1997 | pmid = 8995204 | doi = 10.1007/s004410050758 | s2cid = 6940687 }}
• {{cite journal | vauthors = Akasaki K, Michihara A, Fujiwara Y, Mibuka K, Tsuji H | title = 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 = Journal of Biochemistry | volume = 120 | issue = 6 | pages = 1088–94 | date = December 1996 | pmid = 9010755 | doi = 10.1093/oxfordjournals.jbchem.a021526 }}
• {{cite journal | vauthors = Karlsson K, Carlsson SR | title = 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 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 30 | pages = 18966–73 | date = July 1998 | pmid = 9668075 | doi = 10.1074/jbc.273.30.18966 | doi-access = free }}
• {{cite journal | vauthors = Ayala P, Lin L, Hopper S, Fukuda M, So M | title = Infection of epithelial cells by pathogenic neisseriae reduces the levels of multiple lysosomal constituents | journal = Infection and Immunity | volume = 66 | issue = 10 | pages = 5001–7 | date = October 1998 | doi = 10.1128/IAI.66.10.5001-5007.1998 | pmid = 9746610 | pmc = 108621 }}
• {{cite journal | vauthors = Furuta K, Yang XL, Chen JS, Hamilton SR, August JT | title = Differential expression of the lysosome-associated membrane proteins in normal human tissues | journal = Archives of Biochemistry and Biophysics | volume = 365 | issue = 1 | pages = 75–82 | date = May 1999 | pmid = 10222041 | doi = 10.1006/abbi.1999.1147 | doi-access = free }}
• {{cite journal | vauthors = 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 | title = Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease) | journal = Nature | volume = 406 | issue = 6798 | pages = 906–10 | date = August 2000 | pmid = 10972294 | doi = 10.1038/35022604 | bibcode = 2000Natur.406..906N | s2cid = 4332055 }}

{{refend}}

• {{MeshName|LAMP2+protein,+human}}
• [https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/P13473 PDBe-KB] provides an overview of all the structure information available in the PDB for Human Lysosome-associated membrane glycoprotein 2

{{NLM content}}

{{Clusters of differentiation}}

{{Peroxisomal proteins}}

Category:Clusters of differentiation