CDH2

Cadherin 2, type 1, N-cadherin (neuronal)
PDB rendering based on 1ncg.
Available structures PDB 1ncg, 1nch, 1nci, 1ncj
Identifiers
Symbols	CDH2; CD325; CDHN; CDw325; NCAD
External IDs	OMIM: 114020 MGI: 88355 HomoloGene: 20424 GeneCards: CDH2 Gene
Gene Ontology Molecular function • calcium ion binding • protein binding • beta-catenin binding • protein kinase binding • protein complex binding • RPTP-like protein binding • alpha-catenin binding • gamma-catenin binding Cellular component • plasma membrane • plasma membrane • cell-cell junction • cell-cell adherens junction • fascia adherens • integral to membrane • catenin complex • lamellipodium • synapse Biological process • cell adhesion • homophilic cell adhesion • heterophilic cell-cell adhesion • synapse assembly • calcium-dependent cell-cell adhesion • cell migration • regulation of myelination • regulation of protein localization • cell junction assembly • adherens junction organization • regulation of Rho protein signal transduction • muscle cell differentiation • positive regulation of MAPKKK cascade • cell-cell junction organization • blood vessel morphogenesis • regulation of axonogenesis • striated muscle cell differentiation • positive regulation of muscle cell differentiation • protein heterooligomerization • negative regulation of canonical Wnt receptor signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1000	12558
Ensembl	ENSG00000170558	ENSMUSG00000024304
UniProt	P19022	Q3UIC2
RefSeq (mRNA)	NM_001792.3	NM_007664.4
RefSeq (protein)	NP_001783.2	NP_031690.3
Location (UCSC)	Chr 18: 25.53 – 25.76 Mb	Chr 18: 16.75 – 16.97 Mb
PubMed search	[1]	[2]

Cadherin-2 (CDH2), also known as neural cadherin (NCAD) is a protein that in humans is encoded by the CDH2 gene.^[1][2] CDH2 has also been designated as CD325 (cluster of differentiation 325).

Function

Cadherin 2 a classical cadherin from the cadherin superfamily. Cadherin 2 is a calcium dependent cell-cell adhesion glycoprotein comprising five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. The protein functions during gastrulation and is required for establishment of left-right asymmetry. At certain central nervous system synapses, presynaptic to postsynaptic adhesion is mediated at least in part by this gene product.^[3]

Role in cancer metastasis

N-Cadherin 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 src kinase pathway, which phosphorylates beta-catenins attached to both N-cadherin (this protein) and E-cadherins. This causes the intercellular connection between two adjacent endothelial cells to fail and allows the cancer cell to slip through.^[4]

Interactions

CDH2 has been shown to interact with Beta-catenin,^[5][6] Plakoglobin,^[5][7] Catenin (cadherin-associated protein), alpha 1,^[5][6] CTNND1,^[5][6] LRRC7^[8], CDH11^[5], and type IIb RPTPs including PTPRM^[9][10].

References

1. ^ 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". J. Neurochem. 55 (3): 805–12. doi:10.1111/j.1471-4159.1990.tb04563.x. PMID 2384753. 
2. ^ Reid RA, Hemperly JJ (October 1990). "Human N-cadherin: nucleotide and deduced amino acid sequence". Nucleic Acids Res. 18 (19): 5896–5896. doi:10.1093/nar/18.19.5896. PMC 332345. PMID 2216790. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=332345. 
3. ^ "Entrez Gene: CDH2 cadherin 2, type 1, N-cadherin (neuronal)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1000. 
4. ^ Ramis-Conde I, Chaplain MA, Anderson AR, Drasdo D (2009). "Multi-scale modelling of cancer cell intravasation: the role of cadherins in metastasis". Phys Biol 6 (1): 016008. doi:10.1088/1478-3975/6/1/016008. PMID 19321920. 
5. ^ ^{a b c d e} Straub, Beate K; Boda Judit, Kuhn Caecilia, Schnoelzer Martina, Korf Ulrike, Kempf Tore, Spring Herbert, Hatzfeld Mechthild, Franke Werner W (Dec. 2003). "A novel cell-cell junction system: the cortex adhaerens mosaic of lens fiber cells". J. Cell. Sci. (England) 116 (Pt 24): 4985–95. doi:10.1242/jcs.00815. ISSN 0021-9533. PMID 14625392. 
6. ^ ^{a b c} Wahl, James K; Kim Young J, Cullen Janet M, Johnson Keith R, Wheelock Margaret J (May. 2003). "N-cadherin-catenin complexes form prior to cleavage of the proregion and transport to the plasma membrane". J. Biol. Chem. (United States) 278 (19): 17269–76. doi:10.1074/jbc.M211452200. ISSN 0021-9258. PMID 12604612. 
7. ^ Sacco, P A; McGranahan T M, Wheelock M J, Johnson K R (Aug. 1995). "Identification of plakoglobin domains required for association with N-cadherin and alpha-catenin". J. Biol. Chem. (UNITED STATES) 270 (34): 20201–6. doi:10.1074/jbc.270.34.20201. ISSN 0021-9258. PMID 7650039. 
8. ^ Izawa, Ichiro; Nishizawa Miwako, Ohtakara Kazuhiro, Inagaki Masaki (Feb. 2002). "Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses". J. Biol. Chem. (United States) 277 (7): 5345–50. doi:10.1074/jbc.M110052200. ISSN 0021-9258. PMID 11729199. 
9. ^ Brady-Kalnay SM, Rimm DL, Tonks NK (1995). "Receptor protein tyrosine phosphatase PTPmu associates with cadherins and catenins in vivo.". J Cell Biol 130 (4): 977-86. PMC PMC2199947. PMID 7642713. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC2199947. 
10. ^ Brady-Kalnay SM, Mourton T, Nixon JP, Pietz GE, Kinch M, Chen H et al. (1998). "Dynamic interaction of PTPmu with multiple cadherins in vivo.". J Cell Biol 141 (1): 287-96. PMC PMC2132733. PMID 9531566. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC2132733. 

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". Ann. N. Y. Acad. Sci. 900: 46–55. doi:10.1111/j.1749-6632.2000.tb06215.x. PMID 10818391. 
• Hazan RB et al. (2004). "Cadherin switch in tumor progression". Ann. N. Y. Acad. Sci. 1014: 155–63. doi:10.1196/annals.1294.016. PMID 15153430. 
• Cavallaro U (2005). "N-cadherin as an invasion promoter: a novel target for antitumor therapy?". Current opinion in investigational drugs (London, England : 2000) 5 (12): 1274–8. PMID 15648948. 
• Salomon D et al. (1992). "Extrajunctional distribution of N-cadherin in cultured human endothelial cells". J. Cell. Sci. 102 ( Pt 1): 7–17. PMID 1500442. 
• Knudsen KA, Wheelock MJ (1992). "Plakoglobin, or an 83-kD homologue distinct from beta-catenin, interacts with E-cadherin and N-cadherin". J. Cell Biol. 118 (3): 671–9. doi:10.1083/jcb.118.3.671. PMC 2289540. PMID 1639850. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2289540. 
• Reid RA, Hemperly JJ (1990). "Human N-cadherin: nucleotide and deduced amino acid sequence". Nucleic Acids Res. 18 (19): 5896–5896. doi:10.1093/nar/18.19.5896. PMC 332345. PMID 2216790. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=332345. 
• Walsh FS et al. (1990). "N-cadherin gene maps to human chromosome 18 and is not linked to the E-cadherin gene". J. Neurochem. 55 (3): 805–12. doi:10.1111/j.1471-4159.1990.tb04563.x. PMID 2384753. 
• Selig S et al. (1995). "Expressed cadherin pseudogenes are localized to the critical region of the spinal muscular atrophy gene". Proc. Natl. Acad. Sci. U.S.A. 92 (9): 3702–6. doi:10.1073/pnas.92.9.3702. PMC 42029. PMID 7731968. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=42029. 
• Wallis J, Fox MF, Walsh FS (1994). "Structure of the human N-cadherin gene: YAC analysis and fine chromosomal mapping to 18q11.2". Genomics 22 (1): 172–9. doi:10.1006/geno.1994.1358. PMID 7959764. 
• Andersson AM, Edvardsen K, Skakkebaek NE (1995). "Expression and localization of N- and E-cadherin in the human testis and epididymis". Int. J. Androl. 17 (4): 174–80. doi:10.1111/j.1365-2605.1994.tb01239.x. PMID 7995652. 
• Matsuyoshi N, Imamura S (1997). "Multiple cadherins are expressed in human fibroblasts". Biochem. Biophys. Res. Commun. 235 (2): 355–8. doi:10.1006/bbrc.1997.6707. PMID 9199196. 
• Navarro P, Ruco L, Dejana E (1998). "Differential localization of VE- and N-cadherins in human endothelial cells: VE-cadherin competes with N-cadherin for junctional localization". J. Cell Biol. 140 (6): 1475–84. doi:10.1083/jcb.140.6.1475. PMC 2132661. PMID 9508779. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132661. 
• Gaidar YA, Lepekhin EA, Sheichetova GA, Witt M (1998). "Distribution of N-cadherin and NCAM in neurons and endocrine cells of the human embryonic and fetal gastroenteropancreatic system". Acta Histochem. 100 (1): 83–97. PMID 9542583. 
• Kremmidiotis G et al. (1998). "Localization of human cadherin genes to chromosome regions exhibiting cancer-related loss of heterozygosity". Genomics 49 (3): 467–71. doi:10.1006/geno.1998.5281. PMID 9615235. 
• Lu Q et al. (1999). "delta-catenin, an adhesive junction-associated protein that promotes cell scattering". J. Cell Biol. 144 (3): 519–32. doi:10.1083/jcb.144.3.519. PMC 2132907. PMID 9971746. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132907. 
• Shan WS et al. (2000). "Functional cis-heterodimers of N- and R-cadherins". J. Cell Biol. 148 (3): 579–90. doi:10.1083/jcb.148.3.579. PMC 2174798. PMID 10662782. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2174798. 
• Husi H et al. (2000). "Proteomic analysis of NMDA receptor-adhesion protein signaling complexes". Nat. Neurosci. 3 (7): 661–9. doi:10.1038/76615. PMID 10862698. 

External links

• MeSH CDH2+protein,+human

1nch: STRUCTURAL BASIS OF CELL-CELL ADHESION BY CADHERINS

1nci: STRUCTURAL BASIS OF CELL-CELL ADHESION BY CADHERINS

1ncj: N-CADHERIN, TWO-DOMAIN FRAGMENT