HGNC Approved Gene Symbol: NCAM2
Cytogenetic location: 21q21.1 Genomic coordinates (GRCh38): 21:20,998,409-21,543,329 (from NCBI)
In order to identify genes on human chromosome 21, Paoloni-Giacobino et al. (1997) performed exon trapping from chromosome 21-specific cosmids. They identified a novel trapped exon that showed homology to NCAM1 (116930). They cloned the corresponding cDNA from a human fetal brain cDNA library and reported that it encodes an 837-amino acid polypeptide containing 5 immunoglobulin-like domains, 2 fibronectin type III domains, and 1 predicted transmembrane domain. The overall size and structure of the predicted protein are similar to the shorter isoform of NCAM1. The authors were unable to identify any longer cDNAs. Paoloni-Giacobino et al. (1997) showed by Northern blot analysis that the NCAM2 gene is expressed as mRNAs of 9.5 and 4.4 kb in fetal and adult brain; they observed these and other transcript sizes at lower levels in several other tissues.
Nelson et al. (2006) reported that the NCAM2 gene contains 18 exons. They identified a STAT5 (601511)-binding site in intron 1.
Paoloni-Giacobino et al. (1997) screened somatic cell hybrid panels to map the NCAM2 gene to human chromosome 21q21. They stated that this gene may be involved in some Down syndrome phenotypes.
By searching human chromosomes 21 and 22 for clusters of STAT5-binding sites within regions of interspecies homology, Nelson et al. (2006) identified 4 regions, including 1 within intron 1 of NCAM2. The NCAM2 site resides approximately 200 kb from the first coding exon of NCAM2. The authors demonstrated that the NCAM2 site conferred STAT5-dependent transcriptional activity. Neither STAT1 (600555) nor STAT3 (102582) bound to this region. However, activation of STAT4 (600558) and STAT5 resulted in accumulation of both STATs at the NCAM2 regulatory region. Nelson et al. (2006) concluded that NCAM2 is a STAT4- and STAT5-regulated gene and that its expression is regulated by cytokines essential for natural killer cell survival and differentiation.
Nelson, E. A., Walker, S. R., Li, W., Liu, X. S., Frank, D. A. Identification of human STAT5-dependent gene regulatory elements based on interspecies homology. J. Biol. Chem. 281: 26216-26224, 2006. [PubMed: 16840779] [Full Text: https://doi.org/10.1074/jbc.M605001200]
Paoloni-Giacobino, A., Chen, H., Antonarakis, S. E. Cloning of a novel human neural cell adhesion molecule gene (NCAM2) that maps to chromosome region 21q21 and is potentially involved in Down syndrome. Genomics 43: 43-51, 1997. [PubMed: 9226371] [Full Text: https://doi.org/10.1006/geno.1997.4782]