HGNC Approved Gene Symbol: RPTN
Cytogenetic location: 1q21.3 Genomic coordinates (GRCh38) : 1:152,153,595-152,159,228 (from NCBI)
The RPTN gene encodes repetin, an extracellular epidermal matrix protein that is expressed in the epidermis and at high levels in eccrine sweat glands, the inner sheaths of hair roots, and the filiform papilli of the tongue (summary by Green et al., 2010).
Using mouse Rptn to probe a human chromosome 1-specific cosmid library, followed by 5-prime RACE of human keratinocyte RNA, Huber et al. (2005) cloned full-length RPTN. The deduced 784-amino acid protein has a calculated molecular mass of 91 kD. RPTN contains 2 N-terminal EF hand motifs, a central domain containing 28 repeats of the consensus sequence QxDRQGQSSHYG, and a glutamine- and arginine-rich C-terminal domain. Northern blot analysis detected a 4-kb RPTN transcript in human thymus, epidermis, and foreskin and in keratinocyte suspension cultures. Very low expression was detected in adherent keratinocyte cultures, and none was detected in other tissues. Immunofluorescence analysis detected RPTN in the upper granular layer of human interfollicular epidermis, in acrosyringium, in the upper cell layers of foreskin epidermis, in a granular pattern in filiform papillae of tongue, in upper layer cells of lingual interpapillae, and in the inner root sheath of hair follicle. Immunoelectron microscopy showed strongest RPTN immunoreactivity in granular layers associated with keratohyalin granules, with more diffuse cytoplasmic expression in the transition zone between stratum granulosum and stratum corneum. RPTN was not expressed in upper cornified layers of skin. RPTN had an apparent molecular mass of 100 kD by SDS-PAGE.
Huber et al. (2005) showed that the recombinant N-terminal domain of RPTN bound calcium reversibly.
Huber et al. (2005) determined that the RPTN gene contains 3 exons and spans at least 5.6 kb. The first exon is noncoding.
By genomic sequence analysis and FISH, Huber et al. (2005) mapped the RPTN gene to chromosome 1q21, where it lies between the trichohyalin (TCHH; 190370) and profilaggrin (FLG; 135940) genes within the epidermal differentiation complex. They mapped the mouse Rptn gene to a region of chromosome 3F that shares homology of synteny with human chromosome 1q21.
Green et al. (2010) published a draft sequence of the Neandertal genome. Comparisons of the Neandertal genome to the genomes of 5 present-day humans from different parts of the world identified a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development. Green et al. (2010) found 78 nucleotide substitutions that change the protein coding capacity of genes where modern humans are fixed for a derived state and where Neandertals carry the ancestral (chimpanzee-like) state. Thus, relatively few amino acid changes have become fixed in the last few hundred thousand years of human evolution, an observation consistent with a complementary study (Burbano et al., 2010). There are only 5 genes with more than 1 fixed substitution changing the primary structure of the encoding proteins. One of these is RPTN, which encodes repetin, an extracellular epidermal matrix protein that is expressed in the epidermis and at high levels in eccrine sweat glands, the inner sheaths of hair roots, and the filiform papilli of the tongue. Green et al. (2010) also showed that Neandertals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neandertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other.
Burbano, H. A., Hodges, E., Green, R. E., Briggs, A. W., Krause, J., Meyer, M., Good, J. M., Maricic, T., Johnson, P. L. F., Xuan, Z., Rooks, M., Bhattacharjee, A., Brizuela, L., Albert, F. W., de la Rasilla, M., Fortea, J., Rosas, A., Lachmann, M., Hannon, G. J., Paabo, S. Targeted investigation of the Neandertal genome by array-based sequence capture. Science 328: 723-725, 2010. [PubMed: 20448179] [Full Text: https://doi.org/10.1126/science.1188046]
Green, R. E., Krause, J., Briggs, A. W., Maricic, T., Stenzel, U., Kircher, M., Patterson, N., Li, H., Zhai, W., Fritz, M. H.-Y., Hansen, N. F., Durand, E. Y., and 44 others. A draft sequence of the Neandertal genome. Science 328: 710-722, 2010. [PubMed: 20448178] [Full Text: https://doi.org/10.1126/science.1188021]
Huber, M., Siegenthaler, G., Mirancea, N., Marenholz, I., Nizetic, D., Breitkreutz, D., Mischke, D., Hohl, D. Isolation and characterization of human repetin, a member of the fused gene family of the epidermal differentiation complex. J. Invest. Derm. 124: 998-1007, 2005. [PubMed: 15854042] [Full Text: https://doi.org/10.1111/j.0022-202X.2005.23675.x]