LAMP2

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
LAMP2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesLAMP2, CD107b, LAMP-2, LAMPB, LGP110, lysosomal associated membrane protein 2, LGP-96, DND
External IDsOMIM: 309060 MGI: 96748 HomoloGene: 7809 GeneCards: LAMP2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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 MbChr X: 37.49 – 37.55 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.

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.[5] 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[edit]

The gene for LAMP2 has 9 coding exons and 2 alternate last exons, 9a and 9b.[6] 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.[7]

Function[edit]

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.[6]

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.[6] The biological functions of these glycoproteins are disputed.[8] 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.[6]

Role in cancer[edit]

LAMP2 has been specifically implicated in tumor cell metastasis.[9] 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.[8] 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[10] and could inhibit cell proliferation in multiple myeloma cells.[11]

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.[12]

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.[13]

Inducers[edit]

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000005893 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000016534 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: LAMP2 lysosomal-associated membrane protein 2".
  6. ^ a b c d Online Mendelian Inheritance in Man (OMIM): Lysosome-associated membrane protein 2 - 309060
  7. ^ 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.
  8. ^ a b Sarafian V, Jadot M, Foidart JM, Letesson JJ, Van den Brûle F, Castronovo V, Wattiaux R, Coninck SW (January 1998). "Expression of Lamp-1 and Lamp-2 and their interactions with galectin-3 in human tumor cells". International Journal of Cancer. 75 (1): 105–11. doi:10.1002/(sici)1097-0215(19980105)75:1<105::aid-ijc16>3.0.co;2-f. PMID 9426697.
  9. ^ "LAMP2 - Lysosome-associated membrane glycoprotein 2 precursor - Homo sapiens (Human) - LAMP2 gene & protein". www.uniprot.org. Retrieved 2016-04-18.
  10. ^ Han Q, Chen S, Yang M, Zhang Z, Chen A, Hu C, Li S (April 2014). "[The effect of LAMP2A shRNA on the resistance of breast cancer cells to paclitaxel]". Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology. 30 (4): 351–4. PMID 24721399.
  11. ^ Li L, Li J (May 2015). "[Lentivirus-mediated shRNA silencing of LAMP2A inhibits the proliferation of multiple myeloma cells]". Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology. 31 (5): 605–8, 614. PMID 25940285.
  12. ^ 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 (April 2016). "Diagnostic and clinical relevance of the autophago-lysosomal network in human gliomas". Oncotarget. 7 (15): 20016–32. doi:10.18632/oncotarget.7910. PMC 4991435. PMID 26956048.
  13. ^ Kazakova MH, Staykov DG, Koev IG, Kitov BD, Sarafian VS (2014-09-01). "A comparative study of LAMPs and YKL-40 tissue expression in glial tumors". Folia Medica. 56 (3): 194–8. doi:10.2478/folmed-2014-0028. PMID 25507675.
  14. ^ Bourdenx M, Martín-Segura A, Scrivo A, Rodriguez-Navarro JA, Kaushik S, Tasset I, et al. (April 2021). "Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome". Cell. 184 (10): 2696–2714.e25. doi:10.1016/j.cell.2021.03.048. PMC 8152331. PMID 33891876.

Further reading[edit]

External links[edit]


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