Alternative titles; symbols
HGNC Approved Gene Symbol: NID2
Cytogenetic location: 14q22.1 Genomic coordinates (GRCh38): 14:52,004,809-52,069,059 (from NCBI)
Basement membranes, which are composed of type IV collagens (see 120130), laminins (see LAMC1; 150290), perlecan (HSPG2; 142461), and nidogen (see NID1; 131390), are thin pericellular protein matrices that control a large number of cellular activities, including adhesion, migration, differentiation, gene expression, and apoptosis.
By sequencing several overlapping cDNA clones in both directions, Kohfeldt et al. (1998) obtained a cDNA encoding NID2. Sequence analysis predicted that the 1,375-amino acid NID2 protein, which is 46% identical to NID1, contains a 30-residue signal peptide, 49 primarily central cys residues, 5 potential N-linked glycosylation sites, 2 tyr residues in a potential O-sulfation sequence, and a YGD rather than an RGD cell adhesion sequence. Electron microscopy confirmed the presence of 3 deduced globular domains connected by a link and a rod-like region. Additional predicted structures similar to those found in NID1 include 5 epidermal growth factor (EGF; 131530)-like modules, 2 of which have potential calcium-binding sequences; 2 thyroglobulin (188450) type I modules; and 5 low density lipoprotein (LDL) receptor (606945) modules. SDS-PAGE analysis showed that NID2 is expressed as a 200-kD protein, larger than the calculated mass of 148 kD, presumably due to oligosaccharide substitution as indicated by hexosamine analysis. Northern blot analysis revealed ubiquitous expression of a 5.5-kb NID2 transcript that was strongest in heart and placenta, moderate in pancreas, kidney, and skeletal muscle, and weakest in brain. Immunoblot analysis detected expression of NID2 in muscle, heart, placenta, kidney, skin, and testis, with weaker expression in liver and brain. Immunofluorescence analysis of mouse tissues showed staining of basement membranes usually in close colocalization with NID1.
Schymeinsky et al. (2002) cloned mouse Nid2. Northern blot analysis revealed expression of a 5.5-kb transcript in all tissues examined.
Binding analysis by Kohfeldt et al. (1998) determined that NID2 interacts with collagens I and IV and perlecan at levels comparable to NID1, but NID2 failed to bind to fibulins (see FBLN2; 135821). NID2 bound to laminin-1, but only moderately to the epitope on the LAMC1 chain, which promotes high-affinity binding of NID1. In culture, NID2 was at least as active in promoting cell adhesion as NID1.
Bercsenyi et al. (2014) showed that the presence of nidogens (also known as entactins) at the neuromuscular junction is the main determinant for tetanus neurotoxin (TeNT) binding. Inhibition of the TeNT-nidogen interaction by using small nidogen-derived peptides or genetic ablation of nidogens prevented the binding of TeNT to neurons and protected mice from TeNT-induced spastic paralysis. Bercsenyi et al. (2014) concluded that their findings demonstrated the direct involvement of an extracellular matrix protein as a receptor for tetanus neurotoxin at the neuromuscular junction.
Schymeinsky et al. (2002) determined that the mouse Nid2 gene contains 21 exons. The promoter region contains several putative SP1 (189906) and CAAT recognition sites, but lacks a TATA box.
By radiation hybrid analysis, Schymeinsky et al. (2002) mapped the mouse Nid2 gene to chromosome 14.
Schymeinsky et al. (2002) developed mice carrying a phenotypic null mutation in the Nid2 gene. Nid2-deficient mice showed no overt abnormalities, and their basement membranes appeared normal by ultrastructural analysis and immunostaining. Nid2 deficiency did not lead to hemorrhages, and Nid2 did not appear essential for basement membrane formation or maintenance.
Bercsenyi, K., Schmieg, N., Bryson, J. B., Wallace, M., Caccin, P., Golding, M., Zanotti, G., Greensmith, L., Nischt, R., Schiavo, G. Nidogens are therapeutic targets for the prevention of tetanus. Science 346: 1118-1123, 2014. [PubMed: 25430769] [Full Text: https://doi.org/10.1126/science.1258138]
Kohfeldt, E., Sasaki, T., Gohring, W., Timpl, R. Nidogen-2: a new basement membrane protein with diverse binding properties. J. Molec. Biol. 282: 99-109, 1998. [PubMed: 9733643] [Full Text: https://doi.org/10.1006/jmbi.1998.2004]
Schymeinsky, J., Nedbal, S., Miosge, N., Poschl, E., Rao, C., Beier, D. R., Skarnes, W. C., Timpl, R., Bader, B. L. Gene structure and functional analysis of the mouse nidogen-2 gene: nidogen-2 is not essential for basement membrane formation in mice. Molec. Cell. Biol. 22: 6820-6830, 2002. [PubMed: 12215539] [Full Text: https://doi.org/10.1128/MCB.22.19.6820-6830.2002]