Cadherin-2
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| Location (UCSC) | Chr 18: 27.93 – 28.18 Mb | Chr 18: 16.72 – 16.94 Mb | |||||||
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Cadherin-2 also known as Neural cadherin (N-cadherin), is a protein that in humans is encoded by the CDH2 gene.[5][6][7] CDH2 has also been designated as CD325 (cluster of differentiation 325). Cadherin-2 is a
cardiomyocytes. Alterations in expression and integrity of Cadherin-2 has been observed in various forms of disease, including human dilated cardiomyopathy. Variants in CDH2 have also been identified to cause a syndromic neurodevelopmental disorder.[8]
Structure
Cadherin-2 is a
interact with Cadherin-2 on an adjacent cell in an anti-parallel conformation, thus creating a linear, adhesive "zipper" between cells.[10]
Function
Cadherin-2, originally named Neural cadherin for its role in
neural tissue, plays a role in neurons and later was found to also play a role in cardiac muscle and in cancer metastasis. Cadherin-2 is a transmembrane, homophilic glycoprotein belonging to the calcium-dependent cell adhesion molecule family. These proteins have extracellular domains that mediate homophilic interactions between adjacent cells, and C-terminal, cytoplasmic tails that mediate binding to catenins
, which in turn interact with
the actin cytoskeleton.[11][12][13]
Role in development
Cadherin-2 plays a role in development as a calcium dependent cell–cell adhesion
left-right asymmetry.[14]
Cadherin-2 is widely expressed in the
Role in cardiac muscle
In
cardiomyocytes, and neighboring cardiomyocytes lost cell–cell contact and gap junction plaques as well.[26]
Mouse models employing transgenesis have highlighted the function of N-cadherin in
Role in neurons
In neural cells, at certain central nervous system
Cadherin-catenin complex in learning and memory). Loss of N-cadherin is also associated with attention-deficit hyperactivity disorder in humans, and impaired synaptic functioning. [31]
Role in cancer metastasis
Cadherin-2 is commonly found in cancer cells and provides a mechanism for transendothelial migration. When a cancer cell adheres to the endothelial cells of a blood vessel it up-regulates the
E-cadherins. This causes the intercellular connection between two adjacent endothelial cells to fail and allows the cancer cell to slip through.[32]
Clinical significance
Variants in CDH2 have been identified to cause a syndromic neurodevelopmental disorder characterized by Corpus callosum, axon, cardiac, ocular, and genital differences.[8]
One study investigating genetic underpinnings of
obsessive-compulsive disorder and Tourette disorder found that while CDH2 variants are likely not disease-causing as single entities, they may confer risk when examined as part of a panel of related cell–cell adhesion genes.[33]
Further studies in larger cohorts will be required to unequivocally determine this.
In human
heart disease may be a component of remodeling.[34]
Interactions
Cadherin-2 has been shown to interact with:
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000170558 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024304 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "UniProt". www.uniprot.org. Retrieved 26 August 2022.
- S2CID 29840435.
- PMID 2216790.
- ^ PMID 31585109.
- ^ "Protein sequence of human CDH2 (Uniprot ID: P19022)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 24 September 2015. Retrieved 20 July 2015.
- S2CID 4314442.
- PMID 1623205.
- PMID 2197976.
- PMID 2788574.
- PMID 10807574.
- PMID 8978327.
- PMID 9015265.
- PMID 11356020.
- PMID 9187080.
- PMID 9466883.
- PMID 8044940.
- PMID 3904080.
- PMID 24766605.
- PMID 10756112.
- PMID 25332002.
- PMID 1576958.
- PMID 8834785.
- PMID 11950881.
- PMID 15662031.
- PMID 21507952.
- ^ "Entrez Gene: CDH2 cadherin 2, type 1, N-cadherin (neuronal)".
- PMID 34702855.
- S2CID 206096620.
- PMID 23321619.
- PMID 20591580.
- ^ PMID 14625392.
- ^ PMID 12604612.
- PMID 11729199.
- PMID 7642713.
- PMID 9531566.
- S2CID 23343123.
- PMID 7650039.
- S2CID 23393425.
- PMID 17485520.
Further reading
- Doherty P, Smith P, Walsh FS (1997). "Shared cell adhesion molecule (CAM) homology domains point to CAMs signalling via FGF receptors". Perspectives on Developmental Neurobiology. 4 (2–3): 157–68. PMID 9168198.
- Makrigiannakis A, Coukos G, Blaschuk O, Coutifaris C (2000). "Follicular atresia and luteolysis. Evidence of a role for N-cadherin". Annals of the New York Academy of Sciences. 900 (1): 46–55. S2CID 30583247.
- Hazan RB, Qiao R, Keren R, Badano I, Suyama K (April 2004). "Cadherin switch in tumor progression". Annals of the New York Academy of Sciences. 1014 (1): 155–63. S2CID 37486403.
- Cavallaro U (December 2004). "N-cadherin as an invasion promoter: a novel target for antitumor therapy?". Current Opinion in Investigational Drugs. 5 (12): 1274–8. PMID 15648948.
- Salomon D, Ayalon O, Patel-King R, Hynes RO, Geiger B (May 1992). "Extrajunctional distribution of N-cadherin in cultured human endothelial cells". Journal of Cell Science. 102 ( Pt 1) (1): 7–17. PMID 1500442.
- Knudsen KA, Wheelock MJ (August 1992). "Plakoglobin, or an 83-kD homologue distinct from beta-catenin, interacts with E-cadherin and N-cadherin". The Journal of Cell Biology. 118 (3): 671–9. PMID 1639850.
- Reid RA, Hemperly JJ (October 1990). "Human N-cadherin: nucleotide and deduced amino acid sequence". Nucleic Acids Research. 18 (19): 5896. PMID 2216790.
- Walsh FS, Barton CH, Putt W, Moore SE, Kelsell D, Spurr N, Goodfellow PN (September 1990). "N-cadherin gene maps to human chromosome 18 and is not linked to the E-cadherin gene". Journal of Neurochemistry. 55 (3): 805–12. S2CID 29840435.
- Selig S, Bruno S, Scharf JM, Wang CH, Vitale E, Gilliam TC, Kunkel LM (April 1995). "Expressed cadherin pseudogenes are localized to the critical region of the spinal muscular atrophy gene". Proceedings of the National Academy of Sciences of the United States of America. 92 (9): 3702–6. PMID 7731968.
- Wallis J, Fox MF, Walsh FS (July 1994). "Structure of the human N-cadherin gene: YAC analysis and fine chromosomal mapping to 18q11.2". Genomics. 22 (1): 172–9. PMID 7959764.
- Andersson AM, Edvardsen K, Skakkebaek NE (August 1994). "Expression and localization of N- and E-cadherin in the human testis and epididymis". International Journal of Andrology. 17 (4): 174–80. PMID 7995652.
- Matsuyoshi N, Imamura S (June 1997). "Multiple cadherins are expressed in human fibroblasts". Biochemical and Biophysical Research Communications. 235 (2): 355–8. PMID 9199196.
- Navarro P, Ruco L, Dejana E (March 1998). "Differential localization of VE- and N-cadherins in human endothelial cells: VE-cadherin competes with N-cadherin for junctional localization". The Journal of Cell Biology. 140 (6): 1475–84. PMID 9508779.
- Gaidar YA, Lepekhin EA, Sheichetova GA, Witt M (February 1998). "Distribution of N-cadherin and NCAM in neurons and endocrine cells of the human embryonic and fetal gastroenteropancreatic system". Acta Histochemica. 100 (1): 83–97. PMID 9542583.
- Kremmidiotis G, Baker E, Crawford J, Eyre HJ, Nahmias J, Callen DF (May 1998). "Localization of human cadherin genes to chromosome regions exhibiting cancer-related loss of heterozygosity". Genomics. 49 (3): 467–71. PMID 9615235.
- Lu Q, Paredes M, Medina M, Zhou J, Cavallo R, PMID 9971746.
- Shan WS, Tanaka H, Phillips GR, Arndt K, Yoshida M, Colman DR, Shapiro L (February 2000). "Functional cis-heterodimers of N- and R-cadherins". The Journal of Cell Biology. 148 (3): 579–90. PMID 10662782.
- Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG (July 2000). "Proteomic analysis of NMDA receptor-adhesion protein signaling complexes". Nature Neuroscience. 3 (7): 661–9. S2CID 14392630.
External links
- CDH2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- CDH2 human gene location in the UCSC Genome Browser.
- CDH2 human gene details in the UCSC Genome Browser.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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