Alternative titles; symbols
HGNC Approved Gene Symbol: KRT19
Cytogenetic location: 17q21.2 Genomic coordinates (GRCh38): 17:41,523,617-41,528,308 (from NCBI)
Keratin proteins belong to 2 families: acidic (or type I) and basic (or type II). As a rule they are coordinately synthesized in pairs so that at least 1 member of each family is expressed in each epithelial cell. For example, keratins 1 (KRT1; 139350) and 10 (KRT10; 148080) are specific for the epidermis, keratins 3 (KRT3; 148043) and 12 (KRT12; 601687) for cornea, keratins 6 (KRT6; see 148041) and 16 (KRT16; 148067) for hyperproliferative conditions of the epidermis, etc. The most striking exception to the keratin-pair rule is the smallest known (40 kD) acidic keratin, KRT19. This keratin is found in the periderm, the transient superficial layer that envelopes the developing epidermis. It is expressed often in epithelial cells in culture and in some carcinomas. Although its alpha-helical central domain fully conforms to the canonical structure of all keratins, KRT19 is unique because it completely lacks a C-terminal nonhelical extension (summary by Savtchenko et al., 1988).
Bader et al. (1986) and Stasiak and Lane (1987) sequenced human cDNA for KRT19.
Eckert (1988) reported that the amino acid sequence of the human 40-kD keratin has 89% overall identity of amino acid sequence to the corresponding bovine keratin, suggesting that there is strong evolutionary pressure to conserve the structure of this keratin. This in turn suggests an important and universal role for this intermediate filament subunit in all species.
Langbein et al. (2005) examined the expression of several keratins in eccrine sweat gland and in plantar epidermis. In the sweat gland, KRT19 was expressed throughout the duct region and also in the deeper secretory portion of the gland. In plantar epidermis, KRT19 was expressed only in the stratum corneum through to the middle suprabasal layer.
In the early murine embryo, 2 keratin proteins, Krt8 (148060) and Krt18 (148070) are coordinately expressed as cytoskeletal components at the 4- to 8-cell stage. Comparable data for human embryos do not exist, although several processed pseudogenes corresponding to KRT8 and KRT18 have been discovered in the human genome. Processed pseudogenes arose from integration of reverse transcripts of RNA into the genome. They lack completely the intervening sequences found in functional genes. Only those genes that are expressed in germline and pre-germline cells to make functional mRNA can have processed pseudogenes. The mRNAs expressed only in differentiated cells do not produce processed pseudogenes. Therefore, the existence of a correctly initiated and processed pseudogene is ipso facto evidence for expression of the corresponding gene in early-embryo or germline cells. Savtchenko et al. (1988) found in the human genome a processed pseudogene corresponding to KRT19. This implies expression of KRT19 in addition to KRT8 and KRT18 in the early human embryo. Blumenberg (1988) proposed that keratin 19 evolved specifically to redress unbalanced production of various basic keratins, and the findings of Savtchenko et al. (1988) suggest that it may fulfill the same role during human embryogenesis.
By immunohistochemical analysis of fetal and neonatal human skin, Gkegkes et al. (2013) found that KRT19 expression was high during skin development from embryonic to late fetal period and that it was gradually restricted to basal layer during maturation. KRT19 expression persisted in scarce basal cell nests at term and postnatally. Gkegkes et al. (2013) concluded that KRT19 is a marker of germinative layers in fetal skin and possible nests of epidermal stem cells.
Eckert (1988) noted that KRT19 expression is increased by vitamin A treatment of cultured human keratinocytes.
By RT-PCR analysis, Tang et al. (2014) showed that expression of LINC00974 (620053), a long noncoding RNA (lncRNA) located upstream of the KRT19 gene, was upregulated in hepatocellular carcinoma (HCC; 114550). The methylation level of the LINC00974 promoter region was lower in HCC tumor tissue compared with adjacent nontumor tissue. LINC00974 expression correlated with KRT19 expression in HCC. Knockdown of LINC00974 in Huh7 cells resulted in inhibition of cell proliferation and invasion, along with activation of apoptosis and cell cycle arrest, and these findings were confirmed in vivo by xenotransplantation in nude mice. LINC00974 knockdown decreased expression of KRT19, suggesting that LINC00974 promoted cell proliferation and invasiveness by modulating KRT19 expression. LINC00974 regulation of KRT19 expression was not direct. Instead, LINC00974 competed with microRNA-642 (MIR642), a suppressor of KRT19, by acting as a sponge to absorb MIR642, thereby releasing MIR642 suppression of KRT19 and leading to upregulation of KRT19. Microarray analysis revealed that upregulation of KRT19 by LINC00974 promoted the NOTCH (see 190198) and TGFB (see 190180) signaling pathways in Huh7 cells.
Von Frowein et al. (2011) presented evidence suggesting that a mature microRNA, MIR492 (see 614384), can be processed from the coding sequence of the KRT19 gene. The miRNA precursor sequence is located within exons 1 and 2 of KRT19 and is 93% identical to the MIR492 precursor sequence located within the KRT19 pseudogene on chromosome 17. Both MIR492 precursors yield identical mature sequences. Von Frowein et al. (2011) identified several functional PLAG1 (603026)-binding sites within intron 1 and the 3-prime UTR of the KRT19 gene.
Bader et al. (1988) mapped KRT19 to chromosome 17.
Ceratto et al. (1997) concluded that the KRT13 (148065), KRT14 (148066), KRT15 (148030), and KRT16 genes and the linked type I genes KRT17 (148069) and KRT19 are contained in less than 150 kb of genomic DNA in the region 17q21-q22.
Gross (2022) mapped the KRT19 gene to chromosome 17q21.2 based on an alignment of the KRT19 sequence (GenBank BC010409) with the genomic sequence (GRCh38).
Lussier et al. (1990) found close homology between the mouse gene and the human and bovine KRT19 genes. Furthermore, they demonstrated that the gene is located on mouse chromosome 11 with the other type-I keratin-encoding genes.
Bader, B. L., Jahn, L., Franke, W. W. Low level expression of cytokeratins 8, 18 and 19 in vascular smooth muscle cells of human umbilical cord and in cultured cells derived therefrom, with an analysis of the chromosomal locus containing the cytokeratin 19 gene. Europ. J. Cell Biol. 47: 300-319, 1988. [PubMed: 2468493]
Bader, B. L., Magin, T. M., Hatzfield, M., Franke, W. W. Amino acid sequence and gene organization of cytokeratin no. 19, an exceptional tail-less intermediate filament protein. EMBO J. 5: 1865-1875, 1986. [PubMed: 2428612] [Full Text: https://doi.org/10.1002/j.1460-2075.1986.tb04438.x]
Blumenberg, M. Concerted gene duplications in the two keratin gene families. J. Molec. Evol. 27: 203-211, 1988. [PubMed: 2458477] [Full Text: https://doi.org/10.1007/BF02100075]
Ceratto, N., Dobkin, C., Carter, M., Jenkins, E., Yao, X.-L., Cassiman, J.-J., Aly, M. S., Bosco, P., Leube, R., Langbein, L., Feo, S., Romano, V. Human type I cytokeratin genes are a compact cluster. Cytogenet. Cell Genet. 77: 169-174, 1997. [PubMed: 9284906] [Full Text: https://doi.org/10.1159/000134566]
Eckert, R. L. Sequence of the human 40-kDa keratin reveals an unusual structure with very high sequence identity to the corresponding bovine keratin. Proc. Nat. Acad. Sci. 85: 1114-1118, 1988. [PubMed: 2448790] [Full Text: https://doi.org/10.1073/pnas.85.4.1114]
Gkegkes, I. D., Aroni, K., Agrogiannis, G., Patsouris, E. S., Konstantinidou, A. E. Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development. Arch. Derm. Res. 305: 379-387, 2013. [PubMed: 23377137] [Full Text: https://doi.org/10.1007/s00403-013-1319-8]
Gross, M. B. Personal Communication. Baltimore, Md. 9/22/2022.
Langbein, L., Rogers, M. A., Praetzel, S., Cribier, B., Peltre, B., Gassler, N., Schweizer, J. Characterization of a novel human type II epithelial keratin K1b, specifically expressed in eccrine sweat glands. J. Invest. Derm. 125: 428-444, 2005. [PubMed: 16117782] [Full Text: https://doi.org/10.1111/j.0022-202X.2005.23860.x]
Lussier, M., Filion, M., Compton, J. G., Nadeau, J. H., Lapointe, L., Royal, A. The mouse keratin 19-encoding gene: sequence, structure and chromosomal assignment. Gene 95: 203-213, 1990. [PubMed: 1701153] [Full Text: https://doi.org/10.1016/0378-1119(90)90363-v]
Savtchenko, E. S., Schiff, T. A., Jiang, C.-K., Freedberg, I. M., Blumenberg, M. Embryonic expression of the human 40-kD keratin: evidence from a processed pseudogene sequence. Am. J. Hum. Genet. 43: 630-637, 1988. [PubMed: 2461075]
Stasiak, P. C., Lane, E. B. Sequence of cDNA coding for human keratin #19. Nucleic Acids Res. 15: 10058 only, 1987. [PubMed: 2447559] [Full Text: https://doi.org/10.1093/nar/15.23.10058]
Tang, J., Zhuo, H., Zhang, X., Jiang, R., Ji, J., Deng, L., Qian, X., Zhang, F., Sun, B. A novel biomarker Linc00974 interacting with KRT19 promotes proliferation and metastasis in hepatocellular carcinoma. Cell Death Dis. 5: e1549, 2014. [PubMed: 25476897] [Full Text: https://doi.org/10.1038/cddis.2014.518]
von Frowein, J., Pagel, P., Kappler, R., von Schweinitz, D., Roscher, A., Schmid, I. MicroRNA-492 is processed from the keratin 19 gene and up-regulated in metastatic hepatoblastoma. Hepatology 53: 833-842, 2011. [PubMed: 21319197] [Full Text: https://doi.org/10.1002/hep.24125]