Keratin, type I cytoskeletal 17 (KRT17)
The protein contains 432 amino acids for an estimated molecular weight of 48106 Da.
Type I keratin involved in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair (By similarity). Required for the correct growth of hair follicles, in particular for the persistence of the anagen (growth) state (By similarity). Modulates the function of TNF-alpha in the specific context of hair cycling. Regulates protein synthesis and epithelial cell growth through binding to the adapter protein SFN and by stimulating Akt/mTOR pathway (By similarity). Involved in tissue repair. May be a marker of basal cell differentiation in complex epithelia and therefore indicative of a certain type of epithelial 'stem cells'. Acts as a promoter of epithelial proliferation by acting a regulator of immune response in skin: promotes Th1/Th17-dominated immune environment contributing to the development of basaloid skin tumors (By similarity). May act as an autoantigen in the immunopathogenesis of psoriasis, with certain peptide regions being a major target for autoreactive T-cells and hence causing their proliferation. (updated: Oct. 16, 2019)
Protein identification was indicated in the following studies:
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
Biological Process
Cornification
Epidermis development
Hair follicle morphogenesis
Intermediate filament organization
Keratinization
Positive regulation of cell growth
Positive regulation of hair follicle development
Positive regulation of translation
Signal transduction
The reference OMIM entry for this protein is 148069
Keratin 17, type i; krt17
K17
Ka17
Cytokeratin 17; ck17
CLONING
Among the members of the cytokeratin subfamily of intermediate filament (IF) proteins, cytokeratin-17 is remarkable since it is normally expressed in the basal cells of complex epithelia but not in stratified or simple epithelia. Troyanovsky et al. (1992) isolated a cDNA clone encoding KRT17 from a HeLa cDNA library. The KRT17 gene encodes a polypeptide of 432 amino acids with a calculated molecular mass of 48,000 Da. Synthesis of cytokeratin-17 seems to be a marker of basal cell differentiation in complex epithelia and therefore indicative of a certain type of epithelial 'stem cell.'MAPPING
Troyanovsky et al. (1992) isolated a number of lambda-phage clones on chromosome 17 that covered 3 distinct, noncontiguous gene regions. Only one of these contained the functional KRT17 gene, which is located about 5 kb 5-prime upstream of the KRT16 gene (148067), whereas the other 2 contain unprocessed KRT17 pseudogenes. Each of these genes is part of the large keratin type I gene cluster on chromosome 17. The functional KRT17 gene differs from the pseudogenes by the extent of methylation of certain DNA sequences in the 5-prime upstream region. Using S1-nuclease protection assays and RNAs from several cell lines, Troyanovsky et al. (1992) identified a single transcriptional start point 26 nucleotides downstream from a TATA box element.GENE STRUCTURE
Troyanovsky et al. (1992) determined that the KRT17 gene is 5 kb long with 8 exons.GENE FUNCTION
Kim et al. (2006) showed that keratin-17, an intermediate filament protein rapidly induced in wounded stratified epithelia, regulates cell growth through binding to the adaptor protein 14-3-3-sigma (601290). Mouse skin keratinocytes lacking keratin-17 show depressed protein translation and are of smaller size, correlating with decreased Akt/mTOR (164730/601231) signaling activity. Other signaling kinases have normal activity, pointing to the specificity of this defect. Two amino acid residues located in the N-terminal head domain of keratin-17 are required for the serum-dependent relocalization of 14-3-3-sigma from the nucleus to the cytoplasm, and for the concomitant stimulation of mTOR activity and cell growth. Kim et al. (2006) concluded that their findings revealed a new and unexpected role for the intermediate filament cytoskeleton in influencing cell growth and size by regulating protein synthesis. In mice, Takeo et al. (2013) showed that nail stem cells (NSCs) reside in the proximal nail matrix and are defined by high expression of keratin-14 (148066), keratin-17, and KI67 (MKI67; 176741). The mechanisms governing NSC differentiation are coupled directly to their ability to orchestrate digit regeneration. Early nail progenitors undergo Wnt (see 164820)-dependent differentiation into the nail. After amputation, this Wnt activation is required for nail regeneration and also for attracting nerves that promote mesenchymal blastema growth, leading to the regeneration of the digit. Amputations proximal to the Wnt-active nail progenitors result in failure to regenerate the nail or digit. Nevertheless, beta-catenin (116806) stabilization in the NSC region induced their regeneration. Takeo et al. (2013) concluded that their results established a link between nail stem cell differentiation and digit regeneration, and suggested that NSCs may have the potential to contribute to the development of novel treatments for amputees.MOLECULAR GENETICS
Mc ... More on the omim web site
Oct. 27, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 148069 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).