Type I Keratin

Predicted MW (human): 48.1 kDa
Observed MW (SDS-PAGE, human): 48 kDa
Isoelectric point (human): 5.1 (Moll et al., 1982)

Related to K14 and K16 in sequence

Distribution: K17 exhibits an intriguing expression pattern in complex
epithelia, and is also found in some simple epithelial settings. In complex
epithelia, it can be expressed in mitotically-active as well as differentiating
cells. It can be co-regulated with several type II keratin genes, including K6
isoforms, K5, and K8. A distinct location where K17 is expressed is in the
myoepithelial compartment of relevant glandular epithelia. As is the case for
K6 and K16, however, there is no apparent relationship between its expression
and a particular program of terminal differentiation or epithelial function, and
the K17 gene is regulated in a constitutive and an inducible fashion. Induction
occurs after acute challenges to complex epithelia (e.g., injury, inflammation,
viral infections).

Gene cloning and nucleotide sequence

Human: Troyanovsky et al. (Eur. J. Cell. Biol. 1992)
GenBank Accession Number NM_000422

Mouse: McGowan and Coulombe (J. Cell Biol. 1998)
GenBank Accession Number AB013608

Predicted amino acid sequence

Null mutation phenotype

A null mutant strain has been produced in the context of a collaboration
between ours and Charles Babinet's laboratory at the Pasteur Institute. K17
null mice show an interesting skin phenotype which is dampened by a
compensatory induction of the related K16. A full report is forthcoming in
2001.

Involvement in human disease

Inherited mutations in keratin can cause either one of two distinct ectodermal
dysplasias. One of them is type 2 pachyonychia congenita (a.k.a. the Jackson-
Lawler variant of PC disease), a disorder characterized by severe nail
dystrophy as well as alterations to other types of epithelial appendages.
Another one is steatocystoma multiplex, a proliferative glandular disorder
characterized by large subcutaneous cysts. The genetic and/or biochemical
basis for this clinical heterogenetiy is not understood.

Ectopic K17 expression is a hallmark of certain forms of skin cancers, notably
basal cell carcinoma, of psoriasis (one of the most frequent skin diseases in
western countries), vial infections, and inflammatory disorders. The
significance of this phenomenon is not understood.