Keratin 19

KRT19
Identifiers
Aliases	KRT19 , CK19, K19, K1CS, keratin 19
External IDs	OMIM: 148020; MGI: 96693; HomoloGene: 1713; GeneCards: KRT19; OMA:KRT19 - orthologs
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17q21.2 Start 41,523,617 bp [1] End 41,528,308 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11 D|11 63.42 cM Start 100,031,636 bp [2] End 100,039,491 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in palpebral conjunctiva mucosa of transverse colon nasal epithelium mucosa of sigmoid colon olfactory zone of nasal mucosa amniotic fluid epithelium of nasopharynx epithelium of bronchus gallbladder bronchial epithelial cell Top expressed in epithelium of stomach crypt of lieberkuhn of small intestine mucous cell of stomach transitional epithelium of urinary bladder pyloric antrum left colon duodenum conjunctival fornix ileum lactiferous gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein-containing complex binding structural constituent of muscle structural constituent of cytoskeleton protein binding structural molecule activity Cellular component terminal web plasma membrane sarcolemma costamere dystrophin-associated glycoprotein complex Z discdkac extracellular exosome intermediate filament cell periphery cytosol apicolateral plasma membrane Biological process Notch signaling pathway viral process sarcomere organization cell differentiation involved in embryonic placenta development response to estrogen keratinization cornification Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3880 16669 Ensembl ENSG00000171345 ENSMUSG00000020911 UniProt P08727 P19001 RefSeq (mRNA) NM_002276 NM_008471 NM_001313963 RefSeq (protein) NP_002267 NP_001300892 NP_032497 Location (UCSC) Chr 17: 41.52 – 41.53 Mb Chr 11: 100.03 – 100.04 Mb PubMed search [3] [4]
Wikidata
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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. ^{[5] [6]} 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). ^[6]

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. ^{[7] [8]}

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). ^[9]
• 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 ^[7]
• weight loss and muscle wasting/apoptosis (KRT19 is expressed in muscle) ^[7]

Moreover, Ck-19 is widely applied as post-operative diagnostic marker of papillary thyroid carcinoma. ^[10]

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. ^[11]

Interactions

Keratin-19 has been shown to interact with Pinin. ^[12]

References

1. GRCh38: Ensembl release 89: ENSG00000171345 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020911 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "Entrez Gene: KRT19 keratin 19".
7. Minamibata A, Kono Y, Arimoto T, Marunaka Y, Takayama K (2023). "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. doi: 10.1186/s12890-023-02650-x . PMC   10500899 . PMID   37705035.
8. Nakata B, Takashima T, Ogawa Y, Ishikawa T, Hirakawa K (2004). "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.
9. Lacroix M (December 2006). "Significance, detection and markers of disseminated breast cancer cells" (PDF). Endocrine-Related Cancer. 13 (4): 1033–67. doi:10.1677/ERC-06-0001. PMID   17158753. S2CID   10708900.
10. 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. Bibcode:2015PLoSO..1026472D. doi: 10.1371/journal.pone.0126472 . PMC   4433121 . PMID   25978681.
11. 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" (PDF). Clinical Cancer Research. 10 (20): 6897–904. doi: 10.1158/1078-0432.CCR-04-0378 . PMID   15501967.
12. 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

• Otsuka Y, Ichikawa Y, Kunisaki C, Matsuda G, Akiyama H, Nomura M, Togo S, Hayashizaki Y, Shimada H (2007). "Correlating purity by microdissection with gene expression in gastric cancer tissue". Scandinavian Journal of Clinical and Laboratory Investigation. 67 (4): 367–79. doi:10.1080/00365510601046334. PMID   17558891. S2CID   36635804.
• Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J (December 1992). "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes". Electrophoresis. 13 (12): 960–9. doi:10.1002/elps.11501301199. PMID   1286667. S2CID   41855774.
• Bader BL, Magin TM, Hatzfeld M, Franke WW (August 1986). "Amino acid sequence and gene organization of cytokeratin no. 19, an exceptional tail-less intermediate filament protein". The EMBO Journal. 5 (8): 1865–75. doi:10.1002/j.1460-2075.1986.tb04438.x. PMC   1167052 . PMID   2428612.
• Stasiak PC, Lane EB (December 1987). "Sequence of cDNA coding for human keratin 19". Nucleic Acids Research. 15 (23): 10058. doi:10.1093/nar/15.23.10058. PMC   306562 . PMID   2447559.
• Eckert RL (February 1988). "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. Bibcode:1988PNAS...85.1114E. doi: 10.1073/pnas.85.4.1114 . PMC   279716 . PMID   2448790.
• Blumenberg M (1988). "Concerted gene duplications in the two keratin gene families". Journal of Molecular Evolution. 27 (3): 203–11. Bibcode:1988JMolE..27..203B. doi:10.1007/BF02100075. PMID   2458477. S2CID   5606956.
• Bader BL, Jahn L, Franke WW (December 1988). "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. PMID   2468493.
• Stasiak PC, Purkis PE, Leigh IM, Lane EB (May 1989). "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. doi:10.1111/1523-1747.ep12721500. PMID   2469734.
• Shezen E, Okon E, Ben-Hur H, Abramsky O (January 1995). "Cytokeratin expression in human thymus: immunohistochemical mapping". Cell and Tissue Research. 279 (1): 221–31. doi:10.1007/BF00300707. PMID   7534649. S2CID   23434233.
• Milisavljevic V, Freedberg IM, Blumenberg M (May 1996). "Close linkage of the two keratin gene clusters in the human genome". Genomics. 34 (1): 134–8. doi: 10.1006/geno.1996.0252 . PMID   8661035.
• Ceratto N, Dobkin C, Carter M, Jenkins E, Yao XL, Cassiman JJ, Aly MS, Bosco P, Leube R, Langbein L, Feo S, Romano V (1997). "Human type I cytokeratin genes are a compact cluster". Cytogenetics and Cell Genetics. 77 (3–4): 169–74. doi:10.1159/000134566. PMID   9284906.
• Kucharzik T, Lügering N, Schmid KW, Schmidt MA, Stoll R, Domschke W (January 1998). "Human intestinal M cells exhibit enterocyte-like intermediate filaments". Gut. 42 (1): 54–62. doi:10.1136/gut.42.1.54. PMC   1726964 . PMID   9505886.
• Yang GP, Ross DT, Kuang WW, Brown PO, Weigel RJ (March 1999). "Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes". Nucleic Acids Research. 27 (6): 1517–23. doi:10.1093/nar/27.6.1517. PMC   148347 . PMID   10037815.
• Zhou X, Liao J, Hu L, Feng L, Omary MB (April 1999). "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. doi: 10.1074/jbc.274.18.12861 . PMID   10212274.
• Salas PJ (August 1999). "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. doi:10.1083/jcb.146.3.645. PMC   2150552 . PMID   10444072.
• Whittock NV, Eady RA, McGrath JA (January 2000). "Genomic organization and amplification of the human keratin 15 and keratin 19 genes". Biochemical and Biophysical Research Communications. 267 (1): 462–5. doi:10.1006/bbrc.1999.1966. PMID   10623642.
• 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.
• Brembeck FH, Rustgi AK (September 2000). "The tissue-dependent keratin 19 gene transcription is regulated by GKLF/KLF4 and Sp1". The Journal of Biological Chemistry. 275 (36): 28230–9. doi: 10.1074/jbc.M004013200 . PMID   10859317.
• Kagaya M, Kaneko S, Ohno H, Inamura K, Kobayashi K (October 2001). "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. doi:10.1016/S0168-8278(01)00167-2. hdl: 2297/15681 . PMID   11682035.