Biology:Keratin 19

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Keratin, type I cytoskeletal 19 (Keratin-19)) also known as cytokeratin-19 (CK-19) 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 embryonic periderm, the transiently superficial layer that envelops the developing epidermis. The type I cytokeratins are clustered in a region of chromosome 17 (q12-q21).[2]

Use as biomarker

CYFRA 21-1, a soluble fragment of KRT19, is a tumor marker of various types of cancer, including lung, breast, stomach, pancreas, ovary. KRT19 is commonly expressed in carcinomas of these organs and CYFRA 21-1 is produced when KRT19 is cleaved during cell apoptosis.[3][4]

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 CYFRA 21-1 / 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).[5]
  • trauma and stress (such as shear stress, heat shock, toxins, infection, aging and oxidative stress such as from smoking), which increase KRT19 expression and cell apoptosis[3]
  • weight loss and muscle wasting/apoptosis (KRT19 is expressed in muscle)[3]

Moreover, Ck-19 is widely applied as post-operative diagnostic marker of papillary thyroid carcinoma.[6]

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.[7]

Interactions

Keratin-19 has been shown to interact with Pinin.[8]

References

  1. ↑ "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. ↑ 2.0 2.1 "Entrez Gene: KRT19 keratin 19". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=3880. 
  3. ↑ 3.0 3.1 3.2 "Variability of serum CYFRA 21 − 1 and its susceptibility to clinical characteristics in individuals without cancer: a 4-year retrospective analysis". BMC Pulm Med 23 (1): 344. 2023. doi:10.1186/s12890-023-02650-x. PMID 37705035. 
  4. ↑ "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. 
  5. ↑ "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. 
  6. ↑ "Differential protein expression profiles of cyst fluid from papillary thyroid carcinoma and benign thyroid lesions". PLOS ONE 10 (5). May 2015. doi:10.1371/journal.pone.0126472. PMID 25978681. Bibcode: 2015PLoSO..1026472D. 
  7. ↑ "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. 
  8. ↑ "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



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