Keratin 19

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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

  1. Schweizer J, Bowden PE, Coulombe PA, Langbein L, Lane EB, Magin TM, Maltais L, Omary MB, Parry DA, Rogers MA, Wright MW (July 2006). "New consensus nomenclature for mammalian keratins". The Journal of Cell Biology. 174 (2): 169–74. doi:10.1083/jcb.200603161. PMC 2064177. PMID 16831889.
  2. 2.0 2.1 "Entrez Gene: KRT19 keratin 19".
  3. Nakata B, Takashima T, Ogawa Y, Ishikawa T, Hirakawa K. "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. doi:10.1038/sj.bjc.6602074. PMC 2409884. PMID 15280913.
  4. Lacroix M (December 2006). "Significance, detection and markers of disseminated breast cancer cells". Endocrine-Related Cancer. 13 (4): 1033–67. doi:10.1677/ERC-06-0001. PMID 17158753.
  5. Dinets A, Pernemalm M, Kjellin H, Sviatoha V, Sofiadis A, Juhlin CC, Zedenius J, Larsson C, Lehtiö J, Höög A (May 2015). "Differential protein expression profiles of cyst fluid from papillary thyroid carcinoma and benign thyroid lesions". PLOS ONE. 10 (5): e0126472. doi:10.1371/journal.pone.0126472. PMC 4433121. PMID 25978681.
  6. Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AG, Uhr JW, Terstappen LW (October 2004). "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. doi:10.1158/1078-0432.CCR-04-0378. PMID 15501967.
  7. Shi J, Sugrue SP (May 2000). "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. doi:10.1074/jbc.275.20.14910. PMID 10809736.

Further reading


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