Sobp

Sine oculis-binding protein homolog (SOBP) also known as Jackson circler protein 1 (JXC1) is a is_associated_with::protein that in humans is encoded by the SOBP is_associated_with::gene. The first SOBP gene was identified in is_associated_with::Drosophila melanogaster in a yeast two-hybrid screen that used the SIX domain of the Sine oculis protein as bait. In most genomes, which harbor SOBP, the gene is present as a single copy.

Gene
In human, the SOBP gene is located at the long arm of is_associated_with::chromosome 6 at 6q21 and it spans a physical distance of slightly more than 171kbp. The is_associated_with::mRNA is transcribed from seven is_associated_with::exons, oriented from is_associated_with::centromere to is_associated_with::telomere, of which the first six exons build the open-reading-frame. The coding is_associated_with::mRNA counts 2,622 nucleotides that encode a protein of 873 amino acids.

In the mouse, Sopb is located at is_associated_with::chromosome 10 at cytogenetic band 10qB2 covering a physical region of 172kbp. As in humans, the mouse Sobp coding region spans six exons but its open-reading-frame is somewhat shorter, counting 2595 nucleotides that encode a protein of 864 amino acids. The protein features two is_associated_with::nuclear localization signals on each at its very amino- and carboxy-terminus, two proline-rich sequences in addition to two domains that are related to the FCS-type zinc finger domain. Furthermore, all SOBP proteins share two highly conserved motifs.

Expression
In the mouse, gene expression profiling by is_associated_with::RT-PCR showed a wide expression profile in adult and embryonic tissues with strongest expression being in the brain. By RNA in-situ hybridization, Sobp expression in neonatal tissue was demonstrated in is_associated_with::spiral ganglion, the sensory and supporting cells of the is_associated_with::maculae of saccule and is_associated_with::maculae of utricle, and cristae ampullaris. Sobp is also expressed in the is_associated_with::inner nuclear layer of the developing is_associated_with::retina at E15, the is_associated_with::olfactory epithelium, in neurons of the is_associated_with::trigeminal ganglion and in cells surrounding the is_associated_with::dermal papillae of is_associated_with::hair follicles.

Genetics
In human, an is_associated_with::autosomal recessive mutation causes severe is_associated_with::mental retardation with anterior maxillary protrusion and is_associated_with::strabismus, named MRAMS syndrome (OMIM #613671). Homozygosity-mapping linked MRAMS syndrome to a 9.8 Mbp region on 6q21. Evaluation of candidate genes within this interval identified a homozygous missense mutation in SOBP in patients with MARMS syndrome. The mutation truncates the SOBP protein near the carboxy-terminus (p.R661X).

In the mouse, two spontaneous recessive autosomal mutations occurred independently at is_associated_with::The Jackson Laboratory that were named is_associated_with::jackson circler (jc). The first mutation occurred in 1970 on the C57BL/6J background, named C57BL/6J-jc and the second occurred in a B6.129S6 background and was named jc2J. Genetic linkage analyses localized the mutations to chromosome 10. Molecular genetic studies aimed to identify the genetic defect in the jc locus demonstrated a small deletion of 10bp in exon 6 of the Sobp gene. The deletion comprises nucleotides c.1346-1355 and leads to a frame-shift of the open reading frame introducing a stop codon at amino acid position 490 (S449fsX490). In the jc2J allele, the mutation is a nonsense is_associated_with::transversion of a guanine to a thymidine (c.1894G>T) changing a glycine to a stop codon (p.G632X).

Phenotypes
In the mouse, the truncating mutations jc and jc2J lead to profound is_associated_with::hearing loss and erratic circling behavior. Specifically, the is_associated_with::cochlear duct is shortened, the is_associated_with::organ of Corti exhibits supernumerary is_associated_with::outer hair cells, mirror image duplications of tunnel of Corti and is_associated_with::inner hair cells, as well as ectopic expression of patches of vestibular-like hair cells in Kolliker's organ. The vestibular end organs have a smaller surface area and are thicker.