Sine oculis-binding protein homolog (SOBP) also known as Jackson circler protein 1 (JXC1) is a protein that in humans is encoded by the SOBPgene.[1][2][3] The first SOBP gene was identified in Drosophila melanogaster in a yeast two-hybrid screen that used the SIX domain of the Sine oculis protein as bait.[4] In most genomes, which harbor SOBP, the gene is present as a single copy.
In human, the SOBP gene is located at the long arm of chromosome 6 at 6q21 and it spans a physical distance of slightly more than 171kbp. The mRNA is transcribed from seven exons, oriented from centromere to telomere, of which the first six exons build the open-reading-frame. The coding mRNA counts 2,622 nucleotides that encode a protein of 873 amino acids.
In the mouse, Sopb is located at 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 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.[3]
In human, an autosomal recessive mutation causes severe mental retardation with anterior maxillary protrusion and 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 The Jackson Laboratory that were named 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 jclocus 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 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 hearing loss and erratic circling behavior. Specifically, the cochlear duct is shortened, the organ of Corti exhibits supernumerary outer hair cells, mirror image duplications of tunnel of Corti and 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.
↑Kenyon KL, Li DJ, Clouser C, Tran S, Pignoni F (November 2005). "Fly SIX-type homeodomain proteins Sine oculis and Optix partner with different cofactors during eye development". Dev. Dyn. 234 (3): 497–504. doi:10.1002/dvdy.20442. PMID15937930.
Further reading
Bonaldo MF, Lennon G, Soares MB (1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID8889548.
Stelzl U, Worm U, Lalowski M, et al. (2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID16169070.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.