Keratin, type II cytoskeletal 6A (KRT6A)
The protein contains 564 amino acids for an estimated molecular weight of 60045 Da.
Epidermis-specific type I keratin involved in wound healing. Involved in the activation of follicular keratinocytes after wounding, while it does not play a major role in keratinocyte proliferation or migration. Participates in the regulation of epithelial migration by inhibiting the activity of SRC during wound repair. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- 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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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
Antimicrobial humoral immune response mediated by antimicrobial peptide
Cell differentiation
Cornification
Cytolysis by host of symbiont cells
Cytolysis in other organism involved in symbiotic interaction
Defense response to Gram-positive bacterium
Keratinization
Morphogenesis of an epithelium
Negative regulation of cytolysis by symbiont of host cells
Negative regulation of entry of bacterium into host cell
Positive regulation of cell population proliferation
Wound healing
The reference OMIM entry for this protein is 148041
Keratin 6a; krt6a
Keratin, epidermal type ii, k6a; k6a
K6c
K6d
CLONING
Keratin 6A (K6A) is the dominant K6 isoform. Takahashi et al. (1995) screened human genomic and skin cDNA libraries with probes derived from the K6B gene (148042), and isolated clones containing the full-length gene and cDNA predicted to encode K6a. As many as 6 different human K6 protein isoforms that are highly related at the gene structure, nucleotide sequence, and predicted amino acid sequence levels were identified. Takahashi et al. (1995) proposed an evolutionary model in which the multiplicity of human K6 genes is explained by successive gene duplication events. They confirmed that K6A is clearly the dominant K6 isoform in skin tissue samples and cultured epithelial cell lines and that the various isoforms are differentially regulated within and between epithelial tissue types.GENE STRUCTURE
Tyner et al. (1985) provided information on the structure of a type II keratin gene. A recent duplication in the basic keratin gene family gave rise to 2 copies of the human K6 gene. One of the copies is expressed at very low levels and may be at a still unextinguished step on the way to becoming a traditional pseudogene. Takahashi et al. (1995) determined that the KRT6A gene contains 9 exons.MAPPING
Rosenberg et al. (1991) assigned the KRT6A gene to chromosome 12 by use of Southern blot analysis of somatic cell hybrids. By in situ hybridization of metaphase chromosomes, they demonstrated that the KRT6A gene is located in region 12q12-q14.MOLECULAR GENETICS
In affected members of a Slovenian family segregating pachyonychia congenita described as the Jadassohn-Lewandowsky type (PC3; 615726), Bowden et al. (1995) identified heterozygosity for a mutation in the KRT6A gene (148041.0001). Terrinoni et al. (2001) identified 3 novel mutations (148041.0002-148041.0004) and 2 previously identified mutations (see, e.g., 148041.0001) in the KRT6A gene in patients with pachyonychia congenita. Smith et al. (2005) identified keratin mutations in 30 probands from the International Pachyonychia Congenita Research Registry, 17 of whom had mutations in the KRT6A gene (see, e.g., 148041.0001 and 148041.0005-148041.0008). In a 32-year-old Chinese woman with pachyonychia congenita, Du et al. (2012) identified heterozygosity for a splice site mutation in the KRT6A gene (148041.0009). Her 7-year-old daughter, who had only focal plantar hyperkeratosis with no nail or hand involvement, was also heterozygous for the mutation.ANIMAL MODEL
Wong et al. (2000) found that K6-null mice have changes in the oral mucosa resembling those of pachyonychia congenita. They speculated on why the mice lacked obvious alterations in nail morphology, the conspicuous feature in pachyonychia congenita. Wojcik et al. (2001) generated mice deficient in both K6a and K6b. The majority of K6a/K6b double-null mice died of starvation within the first 2 weeks of life. The starvation was due to a localized disintegration of the dorsal tongue epithelium, which resulted in the buildup of a plaque of cell debris that severely impaired feeding. However, about 25% of K6a/K6b double-null mice survived to adulthood and had normal hair and nails. Wojcik et al. (2001) identified a third K6 gene expressed in hair follicles, K6hf (609025), and suggested that its presence offers an explanation for the absence of hair and nail defects in K6a/K6b double-null mice. ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for KRT6A
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 148041 was added.
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed