LAMP2

Last updated
LAMP2
LAMP2.png
Available structures
PDB Ortholog search: PDBe RCSB
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
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 Mb Chr X: 37.49 – 37.55 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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.

Contents

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

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

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

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

See also

Related Research Articles

<span class="mw-page-title-main">Dystroglycan</span> Protein

Dystroglycan is a protein that in humans is encoded by the DAG1 gene.

<span class="mw-page-title-main">Galectin</span> Protein family binding to β-galactoside sugars

Galectins are a class of proteins that bind specifically to β-galactoside sugars, such as N-acetyllactosamine, which can be bound to proteins by either N-linked or O-linked glycosylation. They are also termed S-type lectins due to their dependency on disulphide bonds for stability and carbohydrate binding. There have been about 15 galectins discovered in mammals, encoded by the LGALS genes, which are numbered in a consecutive manner. Only galectin-1, -2, -3, -4, -7, -7B, -8, -9, -9B, 9C, -10, -12, -13, -14, and -16 have been identified in humans. Galectin-5 and -6 are found in rodents, whereas galectin-11 and -15 are uniquely found in sheep and goats. Members of the galectin family have also been discovered in other mammals, birds, amphibians, fish, nematodes, sponges, and some fungi. Unlike the majority of lectins they are not membrane bound, but soluble proteins with both intra- and extracellular functions. They have distinct but overlapping distributions but found primarily in the cytosol, nucleus, extracellular matrix or in circulation. Although many galectins must be secreted, they do not have a typical signal peptide required for classical secretion. The mechanism and reason for this non-classical secretion pathway is unknown.

<span class="mw-page-title-main">CD68</span> Mammalian protein found in Homo sapiens

CD68 is a protein highly expressed by cells in the monocyte lineage, by circulating macrophages, and by tissue macrophages.

The epididymal secretory protein E1, also known as NPC2( Niemann-Pick intracellular cholesterol transporter 2), is one of two main lysosomal transport proteins that assist in the regulation of cellular cholesterol by exportation of LDL-derived cholesterol from lysosomes. Lysosomes have digestive enzymes that allow it to break down LDL particles to LDL-derived cholesterol once the LDL particle is engulfed into the cell via receptor mediated endocytosis.

<span class="mw-page-title-main">CD9</span> Human protein-encoding gene

CD9 is a gene encoding a protein that is a member of the transmembrane 4 superfamily also known as the tetraspanin family. It is a cell surface glycoprotein that consists of four transmembrane regions and has two extracellular loops that contain disulfide bonds which are conserved throughout the tetraspanin family. Also containing distinct palmitoylation sites that allows CD9 to interact with lipids and other proteins.

<span class="mw-page-title-main">CD63</span> Mammalian protein found in Homo sapiens

CD63 antigen is a protein that, in humans, is encoded by the CD63 gene. CD63 is mainly associated with membranes of intracellular vesicles, although cell surface expression may be induced.

<span class="mw-page-title-main">UCP3</span> Protein-coding gene in the species Homo sapiens

Mitochondrial uncoupling protein 3 is a protein that in humans is encoded by the UCP3 gene. The gene is located in chromosome (11q13.4) with an exon count of 7 and is expressed on the inner mitochondrial membrane. Uncoupling proteins transfer anions from the inner mitochondrial membrane to the outer mitochondrial membrane, thereby separating oxidative phosphorylation from synthesis of ATP, and dissipating energy stored in the mitochondrial membrane potential as heat. Uncoupling proteins also reduce generation of reactive oxygen species.

<span class="mw-page-title-main">RAB7A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-7a is a protein that in humans is encoded by the RAB7A gene.

<span class="mw-page-title-main">HLA-DMB</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DM beta chain is a protein that in humans is encoded by the HLA-DMB gene.

<span class="mw-page-title-main">Tripeptidyl peptidase I</span> Protein-coding gene in the species Homo sapiens

Tripeptidyl-peptidase 1, also known as Lysosomal pepstatin-insensitive protease, is an enzyme that in humans is encoded by the TPP1 gene. TPP1 should not be confused with the TPP1 shelterin protein which protects telomeres and is encoded by the ACD gene. Mutations in the TPP1 gene leads to late infantile neuronal ceroid lipofuscinosis.

<span class="mw-page-title-main">LAMP1</span> Protein-coding gene in the species Homo sapiens

Lysosomal-associated membrane protein 1 (LAMP-1) also known as lysosome-associated membrane glycoprotein 1 and CD107a, is a protein that in humans is encoded by the LAMP1 gene. The human LAMP1 gene is located on the long arm (q) of chromosome 13 at region 3, band 4 (13q34).

<span class="mw-page-title-main">CTNS (gene)</span> Protein-coding gene in the species Homo sapiens

CTNS may also refer to the Center for Theology and the Natural Sciences.

<span class="mw-page-title-main">HLA-DOA</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DO alpha chain is a protein that in humans is encoded by the HLA-DOA gene.

<span class="mw-page-title-main">HLA-DOB</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DO beta chain is a protein that in humans is encoded by the HLA-DOB gene.

<span class="mw-page-title-main">SCARB2</span> Protein-coding gene in the species Homo sapiens

Lysosomal integral membrane protein 2 (LIMP-2) is a protein that in humans is encoded by the SCARB2 gene. LIMP-2 is expressed in brain, heart, liver, lung and kidney, mainly in the membrane of lysosome organelles; however, in cardiac muscle, LIMP-2 is also expressed at intercalated discs. LIMP-2 in a membrane protein in lysosomes that functions to regulate lysosomal/endosomal transport. Mutations in LIMP-2 have been shown to cause Gaucher disease, myoclonic epilepsy, and action myoclonus–renal failure syndrome. Abnormal levels of LIMP-2 have also been found in patients with hypertrophic cardiomyopathy.

<span class="mw-page-title-main">Collagen, type XV, alpha 1</span> Protein found in humans

Collagen alpha-1(XV) chain is a protein that in humans is encoded by the COL15A1 gene.

<span class="mw-page-title-main">LAMP3</span> Protein-coding gene in the species Homo sapiens

Lysosome-associated membrane glycoprotein 3 is a protein that in humans is encoded by the LAMP3 gene. It is one of the lysosome-associated membrane glycoproteins.

Lysosome-associated membrane glycoproteins (LAMPs) are integral membrane proteins, specific to lysosomes, and whose exact biological function is not yet clear. Structurally, the lamp proteins consist of two internally homologous lysosome-luminal domains separated by a proline-rich hinge region; at the C-terminal extremity there is a transmembrane region (TM) followed by a very short cytoplasmic tail (C). In each of the duplicated domains, there are two conserved disulfide bonds. This structure is schematically represented in the figure below.

 +-----+ +-----+ +-----+ +-----+  | | | | | | | |  xCxxxxxCxxxxxxxxxxxxCxxxxxCxxxxxxxxxCxxxxxCxxxxxxxxxxxxCxxxxxCxxxxxxxx  +--------------------------++Hinge++--------------------------++TM++C+
<span class="mw-page-title-main">Chaperone-mediated autophagy</span>

Chaperone-mediated autophagy (CMA) refers to the chaperone-dependent selection of soluble cytosolic proteins that are then targeted to lysosomes and directly translocated across the lysosome membrane for degradation. The unique features of this type of autophagy are the selectivity on the proteins that are degraded by this pathway and the direct shuttling of these proteins across the lysosomal membrane without the requirement for the formation of additional vesicles.

<span class="mw-page-title-main">ADP/ATP translocase 2</span> Protein-coding gene in humans

ADP/ATP translocase 2 is a protein that in humans is encoded by the SLC25A5 gene on the X chromosome.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000005893 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 3 4 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. 1 2 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


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