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 KRT19gene.[5][6] Keratin 19 is a type I keratin.
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.[6]
Use as biomarkeredit
KRT19 is also known as Cyfra 21-1.[7] 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).[8] Moreover, Ck-19 is widely applied as post-operative diagnostic marker of papillary thyroid carcinoma.[9]
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.[10]
^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. PMC2409884. PMID 15280913.
^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.
^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. PMC4433121. PMID 25978681.
^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.
^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 readingedit
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. PMC1167052. 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. PMC306562. 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. PMC279716. 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. PMC1726964. 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. PMC148347. 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. PMC2150552. 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.
March 16, 2024
keratin, keratin, type, cytoskeletal, also, known, cytokeratin, keratin, protein, that, humans, encoded, krt19, gene, type, keratin, krt19identifiersaliaseskrt19, ck19, k1cs, keratin, 19external, idsomim, 148020, 96693, homologene, 1713, genecards, krt19gene, . 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 5 6 Keratin 19 is a type I keratin KRT19IdentifiersAliasesKRT19 CK19 K19 K1CS keratin 19External IDsOMIM 148020 MGI 96693 HomoloGene 1713 GeneCards KRT19Gene location Human Chr Chromosome 17 human 1 Band17q21 2Start41 523 617 bp 1 End41 528 308 bp 1 Gene location Mouse Chr Chromosome 11 mouse 2 Band11 D 11 63 42 cMStart100 031 636 bp 2 End100 039 491 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inpalpebral conjunctivaamniotic fluidgallbladderbronchial epithelial celltracheagerminal epitheliumrectumright uterine tubeurethramucosa of urinary bladderTop expressed inepithelium of stomachcrypt of lieberkuhn of small intestinemucous cell of stomachpyloric antrumleft colonduodenumconjunctival fornixileumcervixPaneth cellMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionprotein containing complex binding structural constituent of muscle structural constituent of cytoskeleton protein binding structural molecule activityCellular componentterminal web plasma membrane sarcolemma costamere dystrophin associated glycoprotein complex Z disc extracellular exosome intermediate filament cell periphery cytosol apicolateral plasma membraneBiological processNotch signaling pathway viral process sarcomere organization cell differentiation involved in embryonic placenta development response to estrogen keratinization cornificationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez388016669EnsemblENSG00000171345ENSMUSG00000020911UniProtP08727P19001RefSeq mRNA NM 002276NM 008471NM 001313963RefSeq protein NP 002267NP 001300892NP 032497Location UCSC Chr 17 41 52 41 53 MbChr 11 100 03 100 04 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Use as biomarker 3 Interactions 4 References 5 Further readingFunction editKeratin 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 6 Use as biomarker editKRT19 is also known as Cyfra 21 1 7 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 8 Moreover Ck 19 is widely applied as post operative diagnostic marker of papillary thyroid carcinoma 9 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 10 Interactions editKeratin 19 has been shown to interact with Pinin 11 References edit a b c GRCh38 Ensembl release 89 ENSG00000171345 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000020911 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine 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 a b Entrez Gene KRT19 keratin 19 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 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 Dinets A Pernemalm M Kjellin H Sviatoha V Sofiadis A Juhlin CC Zedenius J Larsson C Lehtio J Hoog 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 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 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 editOtsuka 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 Lugering 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 Retrieved from https en wikipedia org w index php title 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