Alternative titles; symbols
HGNC Approved Gene Symbol: NETO1
Cytogenetic location: 18q22.3 Genomic coordinates (GRCh38): 18:72,742,314-72,867,987 (from NCBI)
By screening a human retina cDNA library with sequence corresponding to an EST derived from retinal tissue, followed by 5-prime and 3-prime RACE and RT-PCR amplification, Stohr et al. (2002) cloned a novel retina- and brain-specific cDNA encoding a putative type I transmembrane protein. The protein contains an N-terminal signal sequence and 2 conserved extracellular CUB domains followed by a single copy of the low density lipoprotein class A (LDLa) module. Its cytoplasmic domain contains an FXNPXY-like motif. Because the CUB domains showed significant sequence homology with the CUB motifs of neuropilins (see 602069) and the Drosophila dorsal-ventral patterning protein tolloid (112264), Stohr et al. (2002) designated the gene NETO1 (neuropilin and tolloid like-1). NETO1 generates 3 isoforms. Isoform 1, produced by alternative usage of exon 5, encodes a 135-amino acid sequence with a classic signal peptide of 21 amino acids giving rise to a mature 114-amino acid protein with a calculated molecular mass of 15.4 kD. Isoforms 2 and 3, with start sites in exons 1a and 1b, respectively, encode distinct precursor proteins but result in a single mature protein of 511 identical amino acids with a calculated molecular mass of 57.8 kD. Isoform 1 encodes a putative soluble protein, called sNETO1, that has only 1 CUB domain and lacks the LDLa module. Northern blot analysis detected retina-specific expression of isoform 1 as a 2.0-kb mRNA species, which was confirmed by RT-PCR. RT-PCR detected expression of isoform 2 in retina only and expression of isoform 3 in retina as well as at lower levels in adult and fetal brain. Stohr et al. (2002) also cloned mouse Neto1 encoding a protein that shares 95% identity with the human protein.
Using the signal sequence trap method, Michishita et al. (2003) cloned mouse Neto1, which they called Btcl1. Northern blot analysis detected a single transcript specifically in brain. In situ hybridization analysis revealed high expression in the hippocampal CA3 region, olfactory bulb, and neocortex in the adult brain.
Stohr et al. (2002) determined that the NETO1 gene contains 13 exons spanning more than 120 kb.
By sequence analysis, Stohr et al. (2002) mapped the NETO gene to chromosome 18q22-q23.
Michishita, M., Ikeda, T., Nakashiba, T., Ogawa, M., Tashiro, K., Honjo, T., Doi, K., Itohara, S., Endo, S. A novel gene, Btcl1, encoding CUB and LDLa domains is expressed in restricted areas of mouse brain. Biochem. Biophys. Res. Commun. 306: 680-686, 2003. [PubMed: 12810072] [Full Text: https://doi.org/10.1016/s0006-291x(03)01035-0]
Stohr, H., Berger, C., Frohlich, S., Weber, B. H. F. A novel gene encoding a putative transmembrane protein with two extracellular CUB domains and a low-density lipoprotein class A module: isolation of alternatively spliced isoforms in retina and brain. Gene 286: 223-231, 2002. [PubMed: 11943477] [Full Text: https://doi.org/10.1016/s0378-1119(02)00438-9]