Alternative titles; symbols
HGNC Approved Gene Symbol: NCAN
Cytogenetic location: 19p13.11 Genomic coordinates (GRCh38): 19:19,211,958-19,252,233 (from NCBI)
Neurocan is a chondroitin sulfate proteoglycan thought to be involved in the modulation of cell adhesion and migration.
Neurocan was first described in the early postnatal rat brain where it accounts for 20 to 30% of the total chondroitin sulfate proteoglycan. Rauch et al. (1992) cloned the rat cDNA using degenerate primers based on partial amino acid sequence of immunoaffinity-purified protein. The mouse neurocan cDNA encodes a deduced 1,257-amino acid protein with a predicted molecular mass of 136 kD. The large protein is processed into a smaller form in the adult brain. The predicted protein has a 22-amino acid signal peptide followed by an immunoglobin-like domain and repeating motifs characteristic of the hyaluronic acid-binding region of aggregating proteoglycans. The C terminus shows approximately 60% identity to the fibroblast and cartilage proteoglycans versican (118661) and aggrecan (155760). Northern blots detected a 7.5-kb transcript from 4-day and adult rat brains.
Prange et al. (1998) cloned human neurocan cDNAs from infant and adult brain cDNA libraries. The deduced 1,321-amino acid protein shares 63% sequence identity with both mouse and rat neurocan proteins. Like other known proteoglycans, its N terminus contains an immunoglobulin domain and a series of hyaluronic acid-binding tandem repeats, and its C terminus contains an EGF-like domain, a lectin-like domain, and a complement regulatory-like domain. Northern blot analysis detected expression of a 7.5-kb transcript in fetal and adult tissues from all brain regions tested.
See also brevican (600347).
Rauch et al. (1995) determined the structure of the mouse neurocan gene and showed that it contains 15 exons spanning approximately 25 kb of genomic DNA. The gene structure resembles that of versican and aggrecan.
Prange et al. (1998) determined that the human CSPG3 gene contains 14 exons and spans at least 41 kb of genomic DNA.
Zhang et al. (2003) examined the retinal distribution of neurocan in RCS rats (see 604705). Neurocan accumulation in association with the retinal vasculature did not correlate with photoreceptor cell loss, because similar deposits were not observed in the retinas of rhodopsin mutant rats. In RCS rats, however, neurocan immunostaining was seen in association with retinal vessels from postnatal day 15 onward. The authors hypothesized that with time, the accumulated perivascular neurocan might, via interaction with other matrix molecules, modulate at least some of the vascular alterations observed in the RCS rat model.
Prange et al. (1998) identified the CSPG3 sequence within a mapped contig on chromosome 19p13.1-p12. Masternak et al. (1998) reported that, in the transcript map (EST map), CSPG3 resides on 19p12, in the order MEF2B (600661), RFXANK (603200), and CSPG3.
Rauch et al. (1995) used an SSCP to map the neurocan gene to the central region of mouse chromosome 8 between markers D8Mit29 and D8Mit78.
Human evolution is characterized by a dramatic increase in brain size and complexity. To probe its genetic basis, Dorus et al. (2004) examined the evolution of genes involved in diverse aspects of nervous system biology. These genes, including CSPG3, displayed significantly higher rates of protein evolution in primates than in rodents. This trend was most pronounced for the subset of genes implicated in nervous system development. Moreover, within primates, the acceleration of protein evolution was most prominent in the lineage leading from ancestral primates to humans. Dorus et al. (2004) concluded that the phenotypic evolution of the human nervous system has a salient molecular correlate, i.e., accelerated evolution of the underlying genes, particularly those linked to nervous system development.
Dorus, S., Vallender, E. J., Evans, P. D., Anderson, J. R., Gilbert, S. L., Mahowald, M., Wyckoff, G. J., Malcom, C. M., Lahn, B. T. Accelerated evolution of nervous system genes in the origin of Homo sapiens. Cell 119: 1027-1040, 2004. [PubMed: 15620360] [Full Text: https://doi.org/10.1016/j.cell.2004.11.040]
Masternak, K., Barras, E., Zufferey, M., Conrad, B., Corthals, G., Aebersold, R., Sanchez, J.-C., Hochstrasser, D. F., Mach, B., Reith, W. A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patients. Nature Genet. 20: 273-277, 1998. [PubMed: 9806546] [Full Text: https://doi.org/10.1038/3081]
Prange, C. K., Pennacchio, L. A., Lieuallen, K., Fan, W., Lennon, G. G. Characterization of the human neurocan gene, CSPG3. Gene 221: 199-205, 1998. [PubMed: 9795216] [Full Text: https://doi.org/10.1016/s0378-1119(98)00455-7]
Rauch, U., Grimpe, B., Kulbe, G., Arnold-Ammer, I., Beier, D. R., Fassler, R. Structure and chromosomal localization of the mouse neurocan gene. Genomics 28: 405-410, 1995. [PubMed: 7490074] [Full Text: https://doi.org/10.1006/geno.1995.1168]
Rauch, U., Karthikeyan, L., Maurel, P., Margolis, R. U., Margolis, R. K. Cloning and primary structure of neurocan, a developmentally regulated, aggregating chondroitin sulfate proteoglycan of brain. J. Biol. Chem. 267: 19536-19547, 1992. [PubMed: 1326557]
Zhang, Y., Rauch, U., Perez, M.-T. R. Accumulation of neurocan, a brain chondroitin sulfate proteoglycan, in association with the retinal vasculature in RCS rats. Invest. Ophthal. Vis. Sci. 44: 1252-1261, 2003. [PubMed: 12601056] [Full Text: https://doi.org/10.1167/iovs.02-0450]