Type II Keratin

Predicted MW (human): 53.7 kDa
Observed MW (SDS-PAGE, human): 52.5 kDa
Isoelectric point (human): 6.1 (R. Moll et al., Cell 1982)

Distribution: K8 and its preferred partner K18 are expressed in most simple epithelial tissues (e.g., liver, pancreas, kidney, gut epithelial lining, etc.).

Gene cloning and nucleotide sequence

Human:     R. Leube et al., Differentiation 1986 (cDNA)
                GenBank Accession Number NM_002273

Mouse:     T. Ouellet et al., Gene 1988
                A. Semat et al., Differentiation 1988
                GenBank Accession Numbers M22831 and X12789

Predicted amino acid sequence

Null mutation phenotype

K8 was the first intermediate filament gene to be inactivated in mouse. In the C57Bl/6x129Sv mixed background, the null mutation causes midgestational lethality (Baribault et al., Genes Dev. 7: 1191-202 (1993). In the FVB/N strain background, however, the K8 null mice are born and develop to adulthood. They develop severe colorectal hyperplasia, reportedly without major alterations in other epithelial tissues such as the liver, pancreas, and kidney. K8 null FVB/N females are infertile. Obviously, the function of K8 is subject to modulation by modifier genes. See Baribault et al., Genes Dev. 8: 2964-73 (1994) for details.

Involvement in human disease

No mutation reported thus far. Hyperphosphorylated K8 is a major
component of Mallory bodies, which are protein inclusions that form in
hepatocytes the context of chronic alcohol liver disease.