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Gene Review

KRT5  -  keratin 5, type II

Homo sapiens

Synonyms: 58 kDa cytokeratin, CK-5, CK5, Cytokeratin-5, DDD, ...
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Disease relevance of KRT5

  • Primers for exon-specific amplification of the KRT5 gene: identification of novel and recurrent mutations in epidermolysis bullosa simplex patients [1].
  • Factor IX in plasma of mice grafted with vectors containing the HPV-16 and hK5 elements was two- to three-fold higher than with vectors containing the CMV promoter alone [2].
  • In complex hyperplasia, p63 expression was also increased, whereas CK5/6 was positive in areas with squamous differentiation only [3].
  • Loss of p63 and cytokeratin 5/6 expression is associated with more aggressive tumors in endometrial carcinoma patients [3].
  • A specific increase in the proportion of K5 among the keratin subunits was suggestive of the nature of melanoma cells [4].

Psychiatry related information on KRT5

  • Although changes in PWA during physical activities are known to occur in DDD/R pacing, there is little information on the P wave stability in single pass lead VDD/R pacemakers using floating P wave sensing [5].
  • RESULTS: A fracture risk reduction was seen in women aged>or=50 years using >or=0.3 DDD/day [6].
  • A questionnaire with regard to cardiovascular symptoms, sleep disturbances, cognitive functioning, physical ability, social interaction, emotional functioning, and self-perceived health was completed after 2 months of atrial synchronous (DDD) and rate modulated ventricular pacing (VVI,R), respectively [7].
  • Pacing in the DDD mode temporarily assists the critical period preceding the onset of cerebral autoregulation that plays a key role in preventing the deleterious effects of vasodepression [8].
  • Significant improvement in the mean total quality-of-life score (20.5 +/- 14.9 vs 34.8 +/- 17.4) as well as in dyspnea on effort, dizzy spells, palpitation, sweating, fatigue, lethargy, emotional functioning, and self-perceived health was observed during DDD compared to VVIR pacing [9].

High impact information on KRT5

  • Epidermolysis bullosa simplex (EBS) is a group of epidermal blistering diseases almost invariably transmitted as a dominant trait, which has recently been shown to arise from mutations in keratins 14 and 5 (K14 and K5) [10].
  • DDT is reductively dechlorinated to DDD and dehydrochlorinated to DDE; it has been thought that DDE is not degraded further in the environment [11].
  • The relative risk reduction in time to syncope with DDD pacing was 30% (95% CI, -33% to 63%; 1-sided P =.14) [12].
  • Two DDT derivatives, Ethylan and DDD, were additionally associated with pancreatic cancer (RR = 5.0 and 4.3, respectively); exposures to these two chemicals were correlated, and it was not possible to determine whether each acted independently of the other [13].
  • Smoking was identified as an independent risk factor, but controlling for smoking (and other potential confounders) in the analyses did not appreciably alter the risks seen for DDT, DDD, or Ethylan [13].

Chemical compound and disease context of KRT5


Biological context of KRT5


Anatomical context of KRT5


Associations of KRT5 with chemical compounds

  • We describe a novel K5 mutation (V186L) that produces a conservative amino acid change (valine to leucine) at position 18 of the 1A helix [24].
  • Direct sequencing of polymerase chain reaction products revealed a T to C transition within codon 323 of K5 in affected individuals, resulting in a valine to alanine substitution of the seventh residue within the L12 linker domain [25].
  • Only keratins K5, K14, and K15, which are synthesized by epidermal basal cells, were solubilized in 2 M urea [26].
  • Our studies revealed that the epidermal keratins, K5, K6, K14, and K16, their mRNAs, and their transcripts were diminished relative to actin as a consequence of retinoic acid (RA) treatment [27].
  • Repression was also observed when 5' upstream sequences of K14 or K5 genes were used to drive expression of a chloramphenicol acetyltransferase reporter gene in SCC-13 keratinocytes [27].

Enzymatic interactions of KRT5


Co-localisations of KRT5

  • Aggregation is purely a function of the K5-1649delG tail domain; in contrast, the cloned 109 residue-long tail domain from wild type K5 is distributed throughout the cytoplasm and colocalizes partly with keratin IFs [28].
  • Immunohistochemical analysis showed that TSC-22 protein expression in NP is restricted to the basal cells and colocalizes with the basal cell marker cytokeratin 5 [29].

Regulatory relationships of KRT5

  • K5 was expressed in all organotypic epithelia but K14 was absent in SVpgC2a [30].
  • Furthermore, pretreatment with neutralizing anti-EGF receptor antibody also suppressed UVB-induced keratin 5 and keratin 14 expression by SVHK, NHK and HaCaT cells [31].
  • In addition, RXR-specific ligands suppress cytokeratin K5 mRNA levels slightly, compared to RAR-specific ligands that strongly suppress K5 mRNA levels [32].

Other interactions of KRT5

  • In immortalized cells, which are preneoplastic or partially transformed, the levels of K5 mRNA and protein are lower than in normal cells, whereas the amount of K18 is increased [22].
  • All but six cases (91%) showed the typical immunoprofile of basal-like tumours (ER- and HER2-, EGFR+ and/or CK5/6+) [33].
  • Biochemically, using 2-DE and immunoblotting, stratified epithelial keratins K5/K14 and large amounts of K17 were present in all cases [34].
  • In the epidermis overlying tumour tissue, there was positive immunoreactivity with anti-CK 1-8, CK 5/6/18, CK 10 and CK 14 antibodies in all biopsy specimens [35].
  • A reduced expression of K18+ cells, without modification in K14 expression, was evident in high grade PCa in which we observed also an increment in K5 expression representing an intermediate basal/differentiating epithelial cell marker [36].

Analytical, diagnostic and therapeutic context of KRT5


  1. Primers for exon-specific amplification of the KRT5 gene: identification of novel and recurrent mutations in epidermolysis bullosa simplex patients. Stephens, K., Ehrlich, P., Weaver, M., Le, R., Spencer, A., Sybert, V.P. J. Invest. Dermatol. (1997) [Pubmed]
  2. Differentiation-specific enhancer activity in transduced keratinocytes: a model for epidermal gene therapy. Page, S.M., Brownlee, G.G. Gene Ther. (1998) [Pubmed]
  3. Loss of p63 and cytokeratin 5/6 expression is associated with more aggressive tumors in endometrial carcinoma patients. Stefansson, I.M., Salvesen, H.B., Akslen, L.A. Int. J. Cancer (2006) [Pubmed]
  4. Keratin expression and its significance in five cultured melanoma cell lines derived from primary, recurrent and metastasized melanomas. Katagata, Y., Kondo, S. FEBS Lett. (1997) [Pubmed]
  5. Comparative evaluation of bipolar atrial electrogram amplitude during everyday activities: atrial active fixation versus two types of single pass VDD/R leads. Chan, C.C., Lau, C.P., Leung, S.K., Tai, Y.T., Leung, W.H., Lee, I., Tang, M.O. Pacing and clinical electrophysiology : PACE. (1994) [Pubmed]
  6. Fracture reducing potential of hormone replacement therapy on a population level. Vestergaard, P., Rejnmark, L., Mosekilde, L. Maturitas. (2006) [Pubmed]
  7. Quality-of-life in patients treated with atrioventricular synchronous pacing compared to rate modulated ventricular pacing: a long-term, double-blind, crossover study. Linde-Edelstam, C., Nordlander, R., Undén, A.L., Orth-Gomér, K., Rydén, L. Pacing and clinical electrophysiology : PACE. (1992) [Pubmed]
  8. Cerebral hemodynamics during carotid massage in patients with carotid sinus syndrome. Leftheriotis, G., Rozak, P., Dupuis, J.M., Victor, J., Tadeï, A., Saumet, J.L. Pacing and clinical electrophysiology : PACE. (1998) [Pubmed]
  9. Quality-of-life during DDD and dual sensor VVIR pacing. Lukl, J., Doupal, V., Heinc, P. Pacing and clinical electrophysiology : PACE. (1994) [Pubmed]
  10. A missense mutation in the rod domain of keratin 14 associated with recessive epidermolysis bullosa simplex. Hovnanian, A., Pollack, E., Hilal, L., Rochat, A., Prost, C., Barrandon, Y., Goossens, M. Nat. Genet. (1993) [Pubmed]
  11. Reductive dechlorination of DDE to DDMU in marine sediment microcosms. Quensen, J.F., Mueller, S.A., Jain, M.K., Tiedje, J.M. Science (1998) [Pubmed]
  12. Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial. Connolly, S.J., Sheldon, R., Thorpe, K.E., Roberts, R.S., Ellenbogen, K.A., Wilkoff, B.L., Morillo, C., Gent, M. JAMA (2003) [Pubmed]
  13. DDT and related compounds and risk of pancreatic cancer. Garabrant, D.H., Held, J., Langholz, B., Peters, J.M., Mack, T.M. J. Natl. Cancer Inst. (1992) [Pubmed]
  14. Epidermolysis bullosa simplex: a keratin 5 mutation is a fully dominant allele in epidermal cytoskeleton function. Stephens, K., Zlotogorski, A., Smith, L., Ehrlich, P., Wijsman, E., Livingston, R.J., Sybert, V.P. Am. J. Hum. Genet. (1995) [Pubmed]
  15. Cytokeratins in primary cutaneous amyloidosis. Huilgol, S.C., Ramnarain, N., Carrington, P., Leigh, I.M., Black, M.M. Australas. J. Dermatol. (1998) [Pubmed]
  16. Expression of basal cell keratins in human prostate cancer metastases and cell lines. van Leenders, G.J., Aalders, T.W., Hulsbergen-van de Kaa, C.A., Ruiter, D.J., Schalken, J.A. J. Pathol. (2001) [Pubmed]
  17. Epidermolysis bullosa simplex (Weber-Cockayne) associated with a novel missense mutation of Asp328 to Val in Linker 12 domain of keratin 5. Matsuki, M., Hashimoto, K., Yoshikawa, K., Yasuno, H., Yamanishi, K. Hum. Mol. Genet. (1995) [Pubmed]
  18. Type II keratins are phosphorylated on a unique motif during stress and mitosis in tissues and cultured cells. Toivola, D.M., Zhou, Q., English, L.S., Omary, M.B. Mol. Biol. Cell (2002) [Pubmed]
  19. Epidermolysis bullosa simplex: recurrent and de novo mutations in the KRT5 and KRT14 genes, phenotype/genotype correlations, and implications for genetic counseling and prenatal diagnosis. Pfendner, E.G., Sadowski, S.G., Uitto, J. J. Invest. Dermatol. (2005) [Pubmed]
  20. The genetic basis of epidermolysis bullosa simplex with mottled pigmentation. Uttam, J., Hutton, E., Coulombe, P.A., Anton-Lamprecht, I., Yu, Q.C., Gedde-Dahl, T., Fine, J.D., Fuchs, E. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  21. Human keratin diseases: hereditary fragility of specific epithelial tissues. Corden, L.D., McLean, W.H. Exp. Dermatol. (1996) [Pubmed]
  22. Keratins as markers that distinguish normal and tumor-derived mammary epithelial cells. Trask, D.K., Band, V., Zajchowski, D.A., Yaswen, P., Suh, T., Sager, R. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  23. Dominant and recessive compound heterozygous mutations in epidermolysis bullosa simplex demonstrate the role of the stutter region in keratin intermediate filament assembly. Yasukawa, K., Sawamura, D., McMillan, J.R., Nakamura, H., Shimizu, H. J. Biol. Chem. (2002) [Pubmed]
  24. A novel keratin 5 mutation (K5V186L) in a family with EBS-K: a conservative substitution can lead to development of different disease phenotypes. Liovic, M., Stojan, J., Bowden, P.E., Gibbs, D., Vahlquist, A., Lane, E.B., Komel, R. J. Invest. Dermatol. (2001) [Pubmed]
  25. A novel mutation in the L12 domain of keratin 5 in the Köbner variant of epidermolysis bullosa simplex. Galligan, P., Listwan, P., Siller, G.M., Rothnagel, J.A. J. Invest. Dermatol. (1998) [Pubmed]
  26. Differential extraction of keratin subunits and filaments from normal human epidermis. Eichner, R., Kahn, M. J. Cell Biol. (1990) [Pubmed]
  27. Retinoid-mediated transcriptional regulation of keratin genes in human epidermal and squamous cell carcinoma cells. Stellmach, V., Leask, A., Fuchs, E. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  28. Defining the properties of the nonhelical tail domain in type II keratin 5: insight from a bullous disease-causing mutation. Gu, L.H., Coulombe, P.A. Mol. Biol. Cell (2005) [Pubmed]
  29. Differential expression of TGFbeta-stimulated clone 22 in normal prostate and prostate cancer. Rentsch, C.A., Cecchini, M.G., Schwaninger, R., Germann, M., Markwalder, R., Heller, M., van der Pluijm, G., Thalmann, G.N., Wetterwald, A. Int. J. Cancer (2006) [Pubmed]
  30. Expression of keratins in normal, immortalized and malignant oral epithelia in organotypic culture. Hansson, A., Bloor, B.K., Haig, Y., Morgan, P.R., Ekstrand, J., Grafström, R.C. Oral Oncol. (2001) [Pubmed]
  31. Ultraviolet B irradiation increases keratin 5 and keratin 14 expression through epidermal growth factor receptor of SV40-transformed human keratinocytes. Kinouchi, M., Takahashi, H., Itoh, Y., Ishida-Yamamoto, A., Iizuka, H. Arch. Dermatol. Res. (2002) [Pubmed]
  32. Differential regulation of human ectocervical epithelial cell line proliferation and differentiation by retinoid X receptor- and retinoic acid receptor-specific retinoids. Agarwal, C., Chandraratna, R.A., Teng, M., Nagpal, S., Rorke, E.A., Eckert, R.L. Cell Growth Differ. (1996) [Pubmed]
  33. Metaplastic breast carcinomas are basal-like tumours. Reis-Filho, J.S., Milanezi, F., Steele, D., Savage, K., Simpson, P.T., Nesland, J.M., Pereira, E.M., Lakhani, S.R., Schmitt, F.C. Histopathology (2006) [Pubmed]
  34. Biochemical and immunohistochemical analyses of keratin expression in basal cell carcinoma. Yoshikawa, K., Katagata, Y., Kondo, S. J. Dermatol. Sci. (1998) [Pubmed]
  35. Cytokeratin contents of basal cell carcinoma, epidermis overlying tumour, and associated stromal amyloidosis: an immunohistochemical study. Apaydin, R., Gürbüz, Y., Bayramgürler, D., Bilen, N. Amyloid (2005) [Pubmed]
  36. Epithelial and prostatic marker expression in short-term primary cultures of human prostate tissue samples. Festuccia, C., Angelucci, A., Gravina, G.L., Muzi, P., Miano, R., Vicentini, C., Bologna, M. Int. J. Oncol. (2005) [Pubmed]
  37. A mutation (N177S) in the structurally conserved helix initiation peptide motif of keratin 5 causes a mild EBS phenotype. Liovic, M., Bowden, P.E., Marks, R., Komel, R. Exp. Dermatol. (2004) [Pubmed]
  38. Sequence and expression of a type II keratin, K5, in human epidermal cells. Lersch, R., Fuchs, E. Mol. Cell. Biol. (1988) [Pubmed]
  39. Intermediate cells in human prostate epithelium are enriched in proliferative inflammatory atrophy. van Leenders, G.J., Gage, W.R., Hicks, J.L., van Balken, B., Aalders, T.W., Schalken, J.A., De Marzo, A.M. Am. J. Pathol. (2003) [Pubmed]
  40. Expression of luminal and basal cytokeratins in human breast carcinoma. Abd El-Rehim, D.M., Pinder, S.E., Paish, C.E., Bell, J., Blamey, R.W., Robertson, J.F., Nicholson, R.I., Ellis, I.O. J. Pathol. (2004) [Pubmed]
  41. Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. Kaufmann, O., Fietze, E., Mengs, J., Dietel, M. Am. J. Clin. Pathol. (2001) [Pubmed]
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