Biology:Keratin 19
 Generic protein structure example |
Keratin, type I cytoskeletal 19 also known as cytokeratin-19 (CK-19) or keratin-19 (K19) is a 40 kDa protein that in humans is encoded by the KRT19 gene.[1][2] Keratin 19 is a type I keratin.
Function
Keratin 19 is a member of the keratin family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins.
Keratin 19 is a type I keratin. The type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains. Unlike its related family members, this smallest known acidic cytokeratin is not paired with a basic cytokeratin in epithelial cells. It is specifically found in the periderm, the transiently superficial layer that envelops the developing epidermis. The type I cytokeratins are clustered in a region of chromosome 17q12-q21.[2]
Use as biomarker
KRT19 is also known as Cyfra 21-1.[3]
Due to its high sensitivity, KRT19 is the most used marker for the RT-PCR-mediated detection of tumor cells disseminated in lymph nodes, peripheral blood, and bone marrow of breast cancer patients. Depending on the assays, KRT19 has been shown to be both a specific and a non-specific marker. False positivity in such KRT19 RT-PCR studies include: illegitimate transcription (expression of small amounts of KRT19 mRNA by tissues in which it has no real physiological role), haematological disorders (KRT19 induction in peripheral blood cells by cytokines and growth factors, which circulate at higher concentrations in inflammatory conditions and neutropenia), the presence of pseudogenes (two KRT19 pseudogenes, KRT19a and KRT19b, have been identified, which have significant sequence homology to KRT19 mRNA. Subsequently, attempts to detect the expression of the authentic KRT19 may result in the detection of either or both of these pseudogenes), sample contamination (introduction of contaminating epithelial cells during peripheral blood sampling for subsequent RT-PCR analysis).[4] Moreover, Ck-19 is widely applied as post-operative diagnostic marker of papillary thyroid carcinoma.[5]
Keratin 19 is often used together with keratin 8 and keratin 18 to differentiate cells of epithelial origin from hematopoietic cells in tests that enumerate circulating tumor cells in blood.[6]
Interactions
Keratin 19 has been shown to interact with Pinin.[7]
References
- ↑ "New consensus nomenclature for mammalian keratins". The Journal of Cell Biology 174 (2): 169–74. July 2006. doi:10.1083/jcb.200603161. PMID 16831889.
- ↑ 2.0 2.1 "Entrez Gene: KRT19 keratin 19". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3880.
- ↑ "Serum CYFRA 21-1 (cytokeratin-19 fragments) is a useful tumour marker for detecting disease relapse and assessing treatment efficacy in breast cancer". Br J Cancer 91 (5): 873–8. 2004. doi:10.1038/sj.bjc.6602074. PMID 15280913.
- ↑ "Significance, detection and markers of disseminated breast cancer cells". Endocrine-Related Cancer 13 (4): 1033–67. December 2006. doi:10.1677/ERC-06-0001. PMID 17158753. https://erc.bioscientifica.com/downloadpdf/journals/erc/13/4/0131033.pdf.
- ↑ "Differential protein expression profiles of cyst fluid from papillary thyroid carcinoma and benign thyroid lesions". PLOS ONE 10 (5): e0126472. May 2015. doi:10.1371/journal.pone.0126472. PMID 25978681. Bibcode: 2015PLoSO..1026472D.
- ↑ "Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases". Clinical Cancer Research 10 (20): 6897–904. October 2004. doi:10.1158/1078-0432.CCR-04-0378. PMID 15501967. https://aacr.figshare.com/articles/journal_contribution/Supplementary_Data_from_Tumor_Cells_Circulate_in_the_Peripheral_Blood_of_All_Major_Carcinomas_but_not_in_Healthy_Subjects_or_Patients_With_Nonmalignant_Diseases/22440541/1/files/39891403.pdf.
- ↑ "Dissection of protein linkage between keratins and pinin, a protein with dual location at desmosome-intermediate filament complex and in the nucleus". The Journal of Biological Chemistry 275 (20): 14910–5. May 2000. doi:10.1074/jbc.275.20.14910. PMID 10809736.
Further reading
- "Correlating purity by microdissection with gene expression in gastric cancer tissue". Scandinavian Journal of Clinical and Laboratory Investigation 67 (4): 367–79. 2007. doi:10.1080/00365510601046334. PMID 17558891.
- "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes". Electrophoresis 13 (12): 960–9. December 1992. doi:10.1002/elps.11501301199. PMID 1286667.
- "Amino acid sequence and gene organization of cytokeratin no. 19, an exceptional tail-less intermediate filament protein". The EMBO Journal 5 (8): 1865–75. August 1986. doi:10.1002/j.1460-2075.1986.tb04438.x. PMID 2428612.
- "Sequence of cDNA coding for human keratin 19". Nucleic Acids Research 15 (23): 10058. December 1987. doi:10.1093/nar/15.23.10058. PMID 2447559.
- "Sequence of the human 40-kDa keratin reveals an unusual structure with very high sequence identity to the corresponding bovine keratin". Proceedings of the National Academy of Sciences of the United States of America 85 (4): 1114–8. February 1988. doi:10.1073/pnas.85.4.1114. PMID 2448790. Bibcode: 1988PNAS...85.1114E.
- "Concerted gene duplications in the two keratin gene families". Journal of Molecular Evolution 27 (3): 203–11. 1988. doi:10.1007/BF02100075. PMID 2458477. Bibcode: 1988JMolE..27..203B.
- "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". European Journal of Cell Biology 47 (2): 300–19. December 1988. PMID 2468493.
- "Keratin 19: predicted amino acid sequence and broad tissue distribution suggest it evolved from keratinocyte keratins". The Journal of Investigative Dermatology 92 (5): 707–16. May 1989. doi:10.1111/1523-1747.ep12721500. PMID 2469734.
- "Cytokeratin expression in human thymus: immunohistochemical mapping". Cell and Tissue Research 279 (1): 221–31. Jan 1995. doi:10.1007/BF00300707. PMID 7534649.
- "Close linkage of the two keratin gene clusters in the human genome". Genomics 34 (1): 134–8. May 1996. doi:10.1006/geno.1996.0252. PMID 8661035.
- "Human type I cytokeratin genes are a compact cluster". Cytogenetics and Cell Genetics 77 (3–4): 169–74. 1997. doi:10.1159/000134566. PMID 9284906.
- "Human intestinal M cells exhibit enterocyte-like intermediate filaments". Gut 42 (1): 54–62. Jan 1998. doi:10.1136/gut.42.1.54. PMID 9505886.
- "Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes". Nucleic Acids Research 27 (6): 1517–23. March 1999. doi:10.1093/nar/27.6.1517. PMID 10037815.
- "Characterization of the major physiologic phosphorylation site of human keratin 19 and its role in filament organization". The Journal of Biological Chemistry 274 (18): 12861–6. April 1999. doi:10.1074/jbc.274.18.12861. PMID 10212274.
- "Insoluble gamma-tubulin-containing structures are anchored to the apical network of intermediate filaments in polarized CACO-2 epithelial cells". The Journal of Cell Biology 146 (3): 645–58. August 1999. doi:10.1083/jcb.146.3.645. PMID 10444072.
- "Genomic organization and amplification of the human keratin 15 and keratin 19 genes". Biochemical and Biophysical Research Communications 267 (1): 462–5. Jan 2000. doi:10.1006/bbrc.1999.1966. PMID 10623642.
- "Dissection of protein linkage between keratins and pinin, a protein with dual location at desmosome-intermediate filament complex and in the nucleus". The Journal of Biological Chemistry 275 (20): 14910–5. May 2000. doi:10.1074/jbc.275.20.14910. PMID 10809736.
- "The tissue-dependent keratin 19 gene transcription is regulated by GKLF/KLF4 and Sp1". The Journal of Biological Chemistry 275 (36): 28230–9. September 2000. doi:10.1074/jbc.M004013200. PMID 10859317.
- "Cloning and characterization of the 5'-flanking region of human cytokeratin 19 gene in human cholangiocarcinoma cell line". Journal of Hepatology 35 (4): 504–11. October 2001. doi:10.1016/S0168-8278(01)00167-2. PMID 11682035. https://kanazawa-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=38821&item_no=1&attribute_id=26&file_no=1.
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