Type I Keratin

Predicted MW (human): 51.3 kDa
Observed MW (SDS-PAGE, human): 48 kDa
Isoelectric point (human): 5.1 (R. Moll et al., Cell 1982)

Related to K14 and K17 in sequence

Distribution: K16 is expressed along with K6 isoforms in a number of
complex epithelia - but there is as of yet no obvious relationship between its expression and a particular program of terminal differentiation or epithelial function. Of note K16 gene regulation feature a constitutive and an inducible components. In normal skin, it is found in a subset of epithelial cells within appendages (hair, nail. glands).It also occurs in several epithelia within the oral mucosa, in the esophagus and forestomach, and in other complex epithelia. K16 expression is strongly induced after acute challenges (e.g., injury), and in the context of diseases featuring aberrant epithelial differentiation (e.g., psoriasis).

Gene cloning and nucleotide sequence

Human:           Raychaudhury et al (Mol. Cell. Biol. 1986) (Gene)
                       See also Rosenberg et al. (Mol. Cell. Biol. 1988)
                       GenBank Accession Number AH002854

                      Paladini et al. (Biochem. Biophys. Res. Comm. 1995)
                      GenBank Accession Number S79867 - cDNA seq.

Mouse:           McGowan et al. (Unpublished) (Gene and cDNA)
                       GenBank Accession Number AF264006

                      Porter et al. (J. Biol. Chem. 1998) (cDNA)
                      GenBank Acc. Numbers NM_008470 and AF053235

Predicted amino acid sequence

' Note: Mouse K16 exists as two isoforms encoded by separate mRNAs that are produced by the same gene. The differential use of two contiguous splice acceptor sites at the intron 7-exon 8 boundary produced mRNAs that encode proteins that differ by the presence of an extra serine codon. This is  particular to the mouse sequence. See GenBank AF264006 for details.

Null mutation phenotype

Unknown.

Involvement in human disease

Inherited mutations in K16 can cause either one of two distinct disorders. One of them is type 1 pachyonychia congenita congenita (a.k.a. the Jadahsson- Lewandowsky variant of PC disease), a disorder characterized by severe nail dystrophy as well as alterations to other types of epithelial appendages. The other one is non-epidermolytic focal palmoplantar keratoderma (NEPPK), a disorder affecting palm and sole epidermis. The genetic and/or biochemical basis for this clinical heterogeneity is not understood.

Ectopic K16 expression is a hallmark of certain forms of skin cancers, notably squamous cell carcinoma, of psoriasis (one of the most frequent skin diseases in western countries) and other chronic hyperproliferative skin conditions. The significance of this phenomenon is not understood.