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Gene Review

KRT3  -  keratin 3, type II

Homo sapiens

Synonyms: 65 kDa cytokeratin, CK-3, CK3, Cytokeratin-3, K3, ...
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Disease relevance of KRT3


High impact information on KRT3

  • Heterozygous missense mutations in K3 (E509K) and in K12 (V143L; R135T) completely co-segregated with MCD in the families and were not found in 100 normal unrelated chromosomes [6].
  • The intermediate filament cytoskeleton of corneal epithelial cells is composed of cornea-specific keratins K3 and K12 (refs 1,2) [6].
  • We now show that modification of K3-associated class I by lysine-63-linked polyubiquitin chains is necessary for their efficient endocytosis and endolysosomal degradation and present three lines of evidence that monoubiquitination of class I molecules provides an inefficient internalisation signal [7].
  • The Kaposi's sarcoma-associated herpes virus gene product K3 (KK3) subverts the MHC class I antigen presentation pathway by downregulating MHC class I from the plasma membrane [8].
  • Remarkably, these actions of K3 are functionally and genetically separable; the N-terminal zinc finger motif and the central sorting motif are involved in triggering internalization of MHC class I molecules and redirecting them to the TGN [3].

Chemical compound and disease context of KRT3

  • In vitro analysis of KSHV-infected primary effusion lymphoma cell lines in the presence of 12-O-tetradecanoylphorbol-13-acetate and phosphonoformic acid suggests that one latent transcript is coterminal with the previously annotated K3 gene encoding an ubiquitin-ligase known to downregulate major histocompatibility complex class I expression [9].
  • The mutated K3 TYQ[K3HPg/C297S/K311D]DS (r-K3mut) was expressed in Escherichia coli, isolated on an Ni2(+)-nitrilotriacetic acid-agarose column, refolded and purified on a lysine Bio-Gel column [10].

Biological context of KRT3


Anatomical context of KRT3

  • Epithelial cell outgrowth on iAM expressed more p63 but less K3 and K12 than did that on dAM [14].
  • Real-time PCR analysis showed that the transcription level of K3 and K12 in cultured cells was lower than in freshly isolated limbal cells or cells from central cornea (P <0.01) [15].
  • Meesmann's corneal dystrophy (MCD) is an autosomal dominant disorder causing fragility of the anterior corneal epithelium, where K3 and K12 are specifically expressed [6].
  • Immunohistochemical study demonstrated that K3, but not K12, was expressed in the transplanted cultivated oral mucosal epithelium that was similar to oral mucosal tissue [16].
  • In this report, we demonstrate that the internalization of MHC class I by the K3 protein is the result of multiple, consecutive trafficking pathways that accelerate the endocytosis of class I molecules, redirect them to the trans-Golgi network (TGN), and target MHC class I to the lysosomal compartment [3].

Associations of KRT3 with chemical compounds


Other interactions of KRT3

  • BACKGROUND: The molecular basis of Meesmann's epithelial corneal dystrophy (MECD) has recently been attributed to mutations in the cornea specific keratin genes KRT3 and KRT12 [21].
  • Novel mutations in the helix termination motif of keratin 3 and keratin 12 in 2 Taiwanese families with Meesmann corneal dystrophy [11].
  • Immunocytochemistry of resulting cultures for keratin 3 and p63 revealed a similar phenotype to those established under current best-practice conditions (i3T3, foetal bovine serum, EGF and insulin) [22].
  • The gels were sectioned and immunostained for keratin 3 (AE5) and keratin 19 [23].
  • Expression of corneal lineage specific differentiation marker keratin 3 (K3) was correlated with p63 expression [24].

Analytical, diagnostic and therapeutic context of KRT3

  • Imaging by UV transillumination of protein gels containing nuclear extracts from K3-treated cells revealed a prominent 17-kDa band shown to be histone H3 by immunoblotting and mass spectrometry (MS) [17].
  • Independent of MAPK signaling was the progressive appearance of K3-induced cellular fluorescence, principally nuclear in origin and suggested by in vitro fluorimetry to have been caused by K3 thiol arylation [17].
  • We used fluorescence in situ hybridization to localize the human gene for cytokeratin 3 (KRT3), a member of the type II subfamily of cytokeratins, within the human genome [12].
  • The differentiation ability of each subclone was determined by Western blot with antibodies against the differentiation-linked keratin pair K3/K12 and by measuring LDH activity and LDH isozymes in cytosolic extracts [25].
  • Using a sensitive immunoprecipitation procedure we show that the IEF 31 antibody crossreacts with three human acidic epidermal keratins, termed K1, K2, and K3, having molecular weights of 44,000, 47,500, and 54,000, respectively [26].


  1. Characterization of corneal pannus removed from patients with total limbal stem cell deficiency. Espana, E.M., Di Pascuale, M.A., He, H., Kawakita, T., Raju, V.K., Liu, C.Y., Tseng, S.C. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  2. Proteome profiling of corneal epithelium and identification of marker proteins for keratoconus, a pilot study. Nielsen, K., Vorum, H., Fagerholm, P., Birkenkamp-Demtröder, K., Honoré, B., Ehlers, N., Orntoft, T.F. Exp. Eye Res. (2006) [Pubmed]
  3. Multiple endocytic trafficking pathways of MHC class I molecules induced by a Herpesvirus protein. Means, R.E., Ishido, S., Alvarez, X., Jung, J.U. EMBO J. (2002) [Pubmed]
  4. 3D structure of amyloid protofilaments of beta2-microglobulin fragment probed by solid-state NMR. Iwata, K., Fujiwara, T., Matsuki, Y., Akutsu, H., Takahashi, S., Naiki, H., Goto, Y. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. DNA sequence of the tail fiber genes 37, encoding the receptor recognizing part of the fiber, of bacteriophages T2 and K3. Riede, I., Drexler, K., Eschbach, M.L., Henning, U. J. Mol. Biol. (1986) [Pubmed]
  6. Mutations in cornea-specific keratin K3 or K12 genes cause Meesmann's corneal dystrophy. Irvine, A.D., Corden, L.D., Swensson, O., Swensson, B., Moore, J.E., Frazer, D.G., Smith, F.J., Knowlton, R.G., Christophers, E., Rochels, R., Uitto, J., McLean, W.H. Nat. Genet. (1997) [Pubmed]
  7. Lysine-63-linked ubiquitination is required for endolysosomal degradation of class I molecules. Duncan, L.M., Piper, S., Dodd, R.B., Saville, M.K., Sanderson, C.M., Luzio, J.P., Lehner, P.J. EMBO J. (2006) [Pubmed]
  8. Ubiquitylation of MHC class I by the K3 viral protein signals internalization and TSG101-dependent degradation. Hewitt, E.W., Duncan, L., Mufti, D., Baker, J., Stevenson, P.G., Lehner, P.J. EMBO J. (2002) [Pubmed]
  9. Transcriptional analysis of latent and inducible Kaposi's sarcoma-associated herpesvirus transcripts in the K4 to K7 region. Taylor, J.L., Bennett, H.N., Snyder, B.A., Moore, P.S., Chang, Y. J. Virol. (2005) [Pubmed]
  10. Expression, isolation and characterization of a mutated human plasminogen kringle 3 with a functional lysine binding site. Bürgin, J., Schaller, J. Cell. Mol. Life Sci. (1999) [Pubmed]
  11. Novel mutations in the helix termination motif of keratin 3 and keratin 12 in 2 Taiwanese families with Meesmann corneal dystrophy. Chen, Y.T., Tseng, S.H., Chao, S.C. Cornea (2005) [Pubmed]
  12. Assignment of the human cytokeratin 3 gene (KRT3) to 12q12-->q13 by FISH. Raimondi, E., Moralli, D., De Carli, L., Ceratto, N., Balzaretti, M., Leube, R., Collin, C., Romano, V. Cytogenet. Cell Genet. (1994) [Pubmed]
  13. Comprehensive analysis of keratin gene clusters in humans and rodents. Hesse, M., Zimek, A., Weber, K., Magin, T.M. Eur. J. Cell Biol. (2004) [Pubmed]
  14. Basement membrane dissolution and reassembly by limbal corneal epithelial cells expanded on amniotic membrane. Li, W., He, H., Kuo, C.L., Gao, Y., Kawakita, T., Tseng, S.C. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  15. Human limbal progenitor cell characteristics are maintained in tissue culture. Liu, S., Li, J., Wang, C., Tan, D., Beuerman, R. Ann. Acad. Med. Singap. (2006) [Pubmed]
  16. Ocular surface reconstruction with combination of cultivated autologous oral mucosal epithelial transplantation and penetrating keratoplasty. Inatomi, T., Nakamura, T., Kojyo, M., Koizumi, N., Sotozono, C., Kinoshita, S. Am. J. Ophthalmol. (2006) [Pubmed]
  17. Vitamin K3 (menadione)-induced oncosis associated with keratin 8 phosphorylation and histone H3 arylation. Scott, G.K., Atsriku, C., Kaminker, P., Held, J., Gibson, B., Baldwin, M.A., Benz, C.C. Mol. Pharmacol. (2005) [Pubmed]
  18. Investigation of a peptide responsible for amyloid fibril formation of beta 2-microglobulin by achromobacter protease I. Kozhukh, G.V., Hagihara, Y., Kawakami, T., Hasegawa, K., Naiki, H., Goto, Y. J. Biol. Chem. (2002) [Pubmed]
  19. Seeding-dependent propagation and maturation of amyloid fibril conformation. Yamaguchi, K., Takahashi, S., Kawai, T., Naiki, H., Goto, Y. J. Mol. Biol. (2005) [Pubmed]
  20. Dual roles of diadenosine polyphosphates in corneal epithelial cell migration. Mediero, A., Peral, A., Pintor, J. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  21. A novel mutation in KRT12 associated with Meesmann's epithelial corneal dystrophy. Irvine, A.D., Coleman, C.M., Moore, J.E., Swensson, O., Morgan, S.J., McCarthy, J.H., Smith, F.J., Black, G.C., McLean, W.H. The British journal of ophthalmology. (2002) [Pubmed]
  22. Vitronectin supports migratory responses of corneal epithelial cells to substrate bound IGF-I and HGF, and facilitates serum-free cultivation. Ainscough, S.L., Barnard, Z., Upton, Z., Harkin, D.G. Exp. Eye Res. (2006) [Pubmed]
  23. A fibrin-based bioengineered ocular surface with human corneal epithelial stem cells. Han, B., Schwab, I.R., Madsen, T.K., Isseroff, R.R. Cornea (2002) [Pubmed]
  24. Factors modulating p63 expression in cultured limbal epithelial cells. Salehi-Had, H., Alvarenga, L.S., Isseroff, R., Schwab, I.R. Cornea (2005) [Pubmed]
  25. RCE1 Corneal Epithelial Cell Line: Its Variability on Phenotype Expression and Differential Response to Growth Factors. Tamariz, E., Hernandez-Quintero, M., Sánchez-Guzman, E., Arguello, C., Castro-Muñozledo, F. Arch. Med. Res. (2007) [Pubmed]
  26. Differential immunological crossreactivity of HeLa keratin antibodies with human epidermal keratins. Fey, S.J., Larsen, P.M., Bravo, R., Celis, A., Celis, J.E. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
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