Keratin 19

Keratin 19
Identifiers
Symbols	KRT19; CK19; K19; K1CS; MGC15366
External IDs	OMIM: 148020 MGI: 96693 HomoloGene: 105650 GeneCards: KRT19 Gene
Gene Ontology Molecular function • structural constituent of cytoskeleton • protein binding • structural constituent of muscle Cellular component • intermediate filament • Z disc • sarcolemma • costamere • cell periphery Biological process • response to estrogen stimulus • interspecies interaction between organisms • sarcomere organization • cell differentiation involved in embryonic placenta development Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3880	16669
Ensembl	ENSG00000171345	ENSMUSG00000020911
UniProt	P08727	P19001
RefSeq (mRNA)	NM_002276.4	NM_008471
RefSeq (protein)	NP_002267.2	NP_032497
Location (UCSC)	Chr 17: 39.68 – 39.68 Mb	Chr 11: 99.96 – 99.96 Mb
PubMed search	[1]	[2]

Keratin, type I cytoskeletal 19 also known as cytokeratin-19 (CK-19) or keratin-19 (K19) is a 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

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).^[3]

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.^[4]

Interactions

Keratin 19 has been shown to interact with Pinin.^[5]

References

1. ^ Schweizer J, Bowden PE, Coulombe PA, Langbein L, Lane EB, Magin TM, Maltais L, Omary MB, Parry DA, Rogers MA, Wright MW (Jul 2006). "New consensus nomenclature for mammalian keratins". J Cell Biol 174 (2): 169–74. doi:10.1083/jcb.200603161. PMC 2064177. PMID 16831889. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2064177. 
2. ^ ^{a b} "Entrez Gene: KRT19 keratin 19". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3880. 
3. ^ Lacroix, M (2006). "Significance, detection and markers of disseminated breast cancer cells". Endocrine-Related Cancer 13 (4): 1033–1067. doi:10.1677/ERC-06-0001. PMID 17158753. 
4. ^ W. Jeffrey Allard, Jeri Matera, M. Craig Miller, et al. (October 2004). "Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases". Clin. Cancer Research 10 (20): 6897–6904. doi:10.1158/1078-0432.CCR-04-0378. PMID 15501967. 
5. ^ Shi, J; Sugrue S P (May. 2000). "Dissection of protein linkage between keratins and pinin, a protein with dual location at desmosome-intermediate filament complex and in the nucleus". J. Biol. Chem. (UNITED STATES) 275 (20): 14910–5. doi:10.1074/jbc.275.20.14910. ISSN 0021-9258. PMID 10809736. 

Further reading

• Otsuka Y, Ichikawa Y, Kunisaki C, et al. (2007). "Correlating purity by microdissection with gene expression in gastric cancer tissue". Scand. J. Clin. Lab. Invest. 67 (4): 367–79. doi:10.1080/00365510601046334. PMID 17558891. 
• Rasmussen HH, van Damme J, Puype M, et al. (1993). "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. 
• Bader BL, Magin TM, Hatzfeld M, Franke WW (1986). "Amino acid sequence and gene organization of cytokeratin no. 19, an exceptional tail-less intermediate filament protein". EMBO J. 5 (8): 1865–75. PMC 1167052. PMID 2428612. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1167052. 
• Stasiak PC, Lane EB (1988). "Sequence of cDNA coding for human keratin 19". Nucleic Acids Res. 15 (23): 10058. doi:10.1093/nar/15.23.10058. PMC 306562. PMID 2447559. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=306562. 
• Eckert RL (1988). "Sequence of the human 40-kDa keratin reveals an unusual structure with very high sequence identity to the corresponding bovine keratin". Proc. Natl. Acad. Sci. U.S.A. 85 (4): 1114–8. doi:10.1073/pnas.85.4.1114. PMC 279716. PMID 2448790. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=279716. 
• Blumenberg M (1988). "Concerted gene duplications in the two keratin gene families". J. Mol. Evol. 27 (3): 203–11. doi:10.1007/BF02100075. PMID 2458477. 
• Bader BL, Jahn L, Franke WW (1989). "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". Eur. J. Cell Biol. 47 (2): 300–19. PMID 2468493. 
• Stasiak PC, Purkis PE, Leigh IM, Lane EB (1989). "Keratin 19: predicted amino acid sequence and broad tissue distribution suggest it evolved from keratinocyte keratins". J. Invest. Dermatol. 92 (5): 707–16. doi:10.1111/1523-1747.ep12721500. PMID 2469734. 
• Shezen E, Okon E, Ben-Hur H, Abramsky O (1995). "Cytokeratin expression in human thymus: immunohistochemical mapping". Cell Tissue Res. 279 (1): 221–31. doi:10.1007/BF00300707. PMID 7534649. 
• Milisavljevic V, Freedberg IM, Blumenberg M (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, et al. (1997). "Human type I cytokeratin genes are a compact cluster". Cytogenet. Cell Genet. 77 (3–4): 169–74. doi:10.1159/000134566. PMID 9284906. 
• Kucharzik T, Lügering N, Schmid KW, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1726964. 
• Yang GP, Ross DT, Kuang WW, et al. (1999). "Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes". Nucleic Acids Res. 27 (6): 1517–23. doi:10.1093/nar/27.6.1517. PMC 148347. PMID 10037815. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=148347. 
• Zhou X, Liao J, Hu L, et al. (1999). "Characterization of the major physiologic phosphorylation site of human keratin 19 and its role in filament organization". J. Biol. Chem. 274 (18): 12861–6. doi:10.1074/jbc.274.18.12861. PMID 10212274. 
• Salas PJ (1999). "Insoluble gamma-tubulin-containing structures are anchored to the apical network of intermediate filaments in polarized CACO-2 epithelial cells". J. Cell Biol. 146 (3): 645–58. doi:10.1083/jcb.146.3.645. PMC 2150552. PMID 10444072. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2150552. 
• Whittock NV, Eady RA, McGrath JA (2000). "Genomic organization and amplification of the human keratin 15 and keratin 19 genes". Biochem. Biophys. Res. Commun. 267 (1): 462–5. doi:10.1006/bbrc.1999.1966. PMID 10623642. 
• Shi J, Sugrue SP (2000). "Dissection of protein linkage between keratins and pinin, a protein with dual location at desmosome-intermediate filament complex and in the nucleus". J. Biol. Chem. 275 (20): 14910–5. doi:10.1074/jbc.275.20.14910. PMID 10809736. 
• Brembeck FH, Rustgi AK (2000). "The tissue-dependent keratin 19 gene transcription is regulated by GKLF/KLF4 and Sp1". J. Biol. Chem. 275 (36): 28230–9. doi:10.1074/jbc.M004013200. PMID 10859317. 
• Kagaya M, Kaneko S, Ohno H, et al. (2002). "Cloning and characterization of the 5'-flanking region of human cytokeratin 19 gene in human cholangiocarcinoma cell line". J. Hepatol. 35 (4): 504–11. doi:10.1016/S0168-8278(01)00167-2. PMID 11682035. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.