HGNC Approved Gene Symbol: CBLN2
Cytogenetic location: 18q22.3 Genomic coordinates (GRCh38): 18:72,536,681-72,638,521 (from NCBI)
The cerebellum-specific hexadecapeptide, cerebellin, is derived from a larger precursor, precerebellin (CBLN1; 600432), that has sequence homology to the complement component C1QB (120570). Kavety et al. (1994) cloned mouse Cbln1 and a closely related gene, Cbln2. The predicted amino acid sequence of Cbln2 is 88% identical to the C-terminal region of Cbln1.
Using qualitative PCR, Wei et al. (2012) found variable Cbln2 expression in all specific mouse brain regions examined, with highest expression in cerebral cortex and hypothalamus, followed by olfactory bulb and thalamus.
Iijima et al. (2007) showed that mouse Cbln1, Cbln2, and Cbln4 (615029) were secreted into the culture medium of transfected cells, whereas Cbln3 (612978) was retained within the endoplasmic reticulum or cis Golgi. Protein interaction assays showed that all Cbln proteins could form homomeric complexes. They also assembled into heteromeric complexes upon coexpression, but not when mixed following secretion.
Using in vitro binding and Western blot analysis, Wei et al. (2012) found that mouse Cbln1, Cbln2, and Cbln4 had unique binding partners and/or binding affinities, suggesting that they function in multiple signaling pathways. Cbln1 bound consistently to the glutamate receptors Grid1 (610659) and Grid2 (602368), whereas Cbln2 bound more weakly to Grid1 and Grid2. Both Cbln1 and Cbln2 bound to specific isoforms of the neurexins Nrxn1 (600565), Nrxn2 (600566), and Nrxn3 (600567). In contrast, Cbln4 bound robustly to the netrin receptor Dcc (120470) and competed with netrin (NTN1; 601614) for Dcc binding.
Germain et al. (2013) showed that CBLN2 mRNA is expressed in the whole lung, and at lower levels, in circulating cells such as lymphocytes. CBLN2 mRNA levels were significantly higher in lungs explanted from individuals with pulmonary arterial hypertension (PAH; see 178600) than in histologically normal lung tissue. CBLN2 protein was detected in endothelial, epithelial, and circulating cells from subjects with PAH and in control lung samples via immunohistochemistry, with markedly varied protein amounts among samples.
Kavety et al. (1994) mapped the mouse Cbln2 gene to the distal end of chromosome 18, 1.7 cM telomeric of Mbp (159430), predicting a chromosome 18q23 location for the human homolog.
Hartz (2013) mapped the CBLN2 gene to chromosome 18q22.3 based on an alignment of the CBLN2 sequence (GenBank AK125422) with the genomic sequence (GRCh37).
For a discussion of a possible association between variation in the CBLN2 gene and increased risk of pulmonary arterial hypertension (PAH), see 178600.
Germain, M., Eyries, M., Montani, D., Poirier, O., Girerd, B., Dorfmuller, P., Coulet, F., Nadaud, S., Maugenre, S., Guignabert, C., Carpentier, W., Vonk-Noordegraaf, A., and 21 others. Genome-wide association analysis identifies a susceptibility locus for pulmonary arterial hypertension. Nature Genet. 45: 518-521, 2013. [PubMed: 23502781] [Full Text: https://doi.org/10.1038/ng.2581]
Hartz, P. A. Personal Communication. Baltimore, Md. 1/16/2013.
Iijima, T., Miura, E., Matsuda, K., Kamekawa, Y., Watanabe, M., Yuzaki, M. Characterization of a transneuronal cytokine family Cbln: regulation of secretion by heteromeric assembly. Europ. J. Neurosci. 25: 1049-1057, 2007. [PubMed: 17331201] [Full Text: https://doi.org/10.1111/j.1460-9568.2007.05361.x]
Kavety, B., Jenkins, N. A., Fletcher, C. F., Copeland, N. G., Morgan, J. I. Genomic structure and mapping of precerebellin and a precerebellin-related gene. Brain Res. Molec. Brain Res. 27: 152-156, 1994. [PubMed: 7877445] [Full Text: https://doi.org/10.1016/0169-328x(94)90196-1]
Wei, P., Pattarini, R., Rong, Y., Guo, H., Bansal, P. K., Kusnoor, S. V., Deutch, A. Y., Parris, J., Morgan, J. I. The Cbln family of proteins interact with multiple signaling pathways. J. Neurochem. 121: 717-729, 2012. [PubMed: 22220752] [Full Text: https://doi.org/10.1111/j.1471-4159.2012.07648.x]