Sobp

SOBP
Identifiers
Aliases	SOBP , JXC1, MRAMS, Sobp, sine oculis binding protein homolog
External IDs	OMIM: 613667 MGI: 1924427 HomoloGene: 41216 GeneCards: SOBP
Gene location (Human) Chr. Chromosome 6 (human) [1] Band 6q21 Start 107,490,106 bp [1] End 107,661,306 bp [1]
Gene location (Mouse) Chr. Chromosome 10 (mouse) [2] Band 10 B2|10 22.89 cM Start 42,878,496 bp [2] End 43,050,526 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell middle temporal gyrus Brodmann area 23 tibia entorhinal cortex Brodmann area 46 cerebellar vermis orbitofrontal cortex postcentral gyrus inferior olivary nucleus Top expressed in superior frontal gyrus facial motor nucleus skeletal muscle tissue hippocampus proper cerebellar cortex olfactory bulb ganglionic eminence Region I of hippocampus proper prefrontal cortex external granular layer More reference expression data BioGPS n/a
Gene ontology Molecular function metal ion binding SUMO polymer binding Cellular component nucleus Biological process cochlea development sensory perception of sound inner ear morphogenesis cognition locomotory behavior Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 55084 109205 Ensembl ENSG00000112320 ENSMUSG00000038248 UniProt A7XYQ1 Q0P5V2 RefSeq (mRNA) NM_018013 NM_175407 RefSeq (protein) NP_060483 NP_780616 Location (UCSC) Chr 6: 107.49 – 107.66 Mb Chr 10: 42.88 – 43.05 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Sine oculis-binding protein homolog (SOBP) also known as Jackson circler protein 1 (JXC1) is a protein that in humans is encoded by the SOBP gene. ^{[5] [6] [7]} 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. ^[8] 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 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. ^[7]

Expression

In the mouse, gene expression profiling by 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 spiral ganglion, the sensory and supporting cells of the maculae of saccule and maculae of utricle, and cristae ampullaris. Sobp is also expressed in the inner nuclear layer of the developing retina at E15, the olfactory epithelium, in neurons of the trigeminal ganglion and in cells surrounding the dermal papillae of hair follicles.

Genetics

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 jc^2J. 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 jc^2J 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 jc^2J 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.

References

1. GRCh38: Ensembl release 89: ENSG00000112320 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000038248 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: sine oculis binding protein homolog (Drosophila)".
6. Birk, E.; Har-Zahav, A.; Manzini, C. M.; Pasmanik-Chor, M.; Kornreich, L.; Walsh, C. A.; Noben-Trauth, K.; Albin, A.; Simon, A. J.; Colleaux, L.; Morad, Y.; Rainshtein, L.; Tischfield, D. J.; Wang, P.; Magal, N.; Maya, I.; Shoshani, N.; Rechavi, G.; Gothelf, D.; Maydan, G.; Shohat, M.; Basel-Vanagaite, L. (2010). "SOBP is Mutated in Syndromic and Nonsyndromic Intellectual Disability and is Highly Expressed in the Brain Limbic System". The American Journal of Human Genetics. 87 (5): 694–700. doi:10.1016/j.ajhg.2010.10.005. PMC   2978971 . PMID   21035105.
7. Chen, Z.; Montcouquiol, M.; Calderon, R.; Jenkins, N. A.; Copeland, N. G.; Kelley, M. W.; Noben-Trauth, K. (2008). "Jxc1/Sobp, Encoding a Nuclear Zinc Finger Protein, is Critical for Cochlear Growth, Cell Fate, and Patterning of the Organ of Corti". Journal of Neuroscience. 28 (26): 6633–41. doi:10.1523/JNEUROSCI.1280-08.2008. PMC   2556235 . PMID   18579736.
8. 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. PMID   15937930. S2CID   11462221.

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 . PMID   8889548.
• 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. hdl: 11858/00-001M-0000-0010-8592-0 . PMID   16169070. S2CID   8235923.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Rose JE, Behm FM, Drgon T, et al. (2010). "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score". Mol. Med. 16 (7–8): 247–53. doi:10.2119/molmed.2009.00159. PMC   2896464 . PMID   20379614.
• Birk E, Har-Zahav A, Manzini CM, et al. (2010). "SOBP is mutated in syndromic and nonsyndromic intellectual disability and is highly expressed in the brain limbic system". Am. J. Hum. Genet. 87 (5): 694–700. doi:10.1016/j.ajhg.2010.10.005. PMC   2978971 . PMID   21035105.
• 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 . PMID   14702039.
• Calderon, A.; Derr, A.; Stagner, B.; Johnson, K.; Martin, G.; Nobentrauth, K. (2006). "Cochlear developmental defect and background-dependent hearing thresholds in the Jackson circler (jc) mutant mouse". Hearing Research. 221 (1–2): 44–58. doi:10.1016/j.heares.2006.07.008. PMID   16962269. S2CID   25996561.