Keratins (previously also called cytokeratins) are filament-forming proteins of epithelial cells and are essential for normal tissue structure and function. Keratin genes account for most of the intermediate filament genes in the human genome, making up the two largest sequence homology groups, type I and II, of this large multigene family. They are highly differentiation-specific in their expression patterns, implying functional differences. Mutations in most of them are now associated with specific tissue-fragility disorders, and antibodies to keratins are important markers of tissue differentiation and, therefore, tools in diagnostic pathology. Since the first keratins were sequenced and identified as type I and II intermediate filament proteins, the increasing numbers of keratins has provided an ongoing challenge for their clear identification and logical classification across species.
The first attempt at providing a comprehensive keratin nomenclature dates back to 1982. Moll et al. (1982)
used 2D isoelectric focusing and SDS-PAGE to map the keratin profiles of a large number of normal human epithelia, tumors, and cultured cells. They grouped the basic-to-neutral type II keratins as K1–K8 and the acidic type I keratins as K9–K19 (Moll et al., 1982
). Although not open-ended for type II keratins, this system has so far proven manageable, as the incorporation of a few novel type II keratins could be accomplished by the addition of discriminatory suffix letters to keratins exhibiting similar gel-electrophoretic properties (Collin et al., 1992a
; Winter et al., 1998
). Moreover, the Moll nomenclature has not been further challenged by the “hard” α-keratins of hair and nail (hair keratins), as these keratins were named Ha (acidic, type I) or Hb (basic to neutral, type II) followed by a number, with H standing for hair (Heid and Franke, 1986
; Rogers et al., 1998
). Overall, however, the present naming of keratins has not been systematic, and a reorganized and durable scheme is long overdue.
Genome analyses have recently demonstrated that humans possess a total of 54 functional keratin genes, i.e., 28 type I and 26 type II keratins, forming two clusters of 27 genes each on chromosomes 17q21.2 and 12q13.13 (the gene for the type I keratin K18 being located in the type II keratin gene domain; Hesse et al., 2001
; Rogers et al., 2004
; ). Recognition of the extent of this large mammalian gene family led to a suggested revised nomenclature (Hesse et al., 2004
) based on an extended Moll system, K1–K8, and K9–K24 (Moll et al., 1982
, 1990; Chandler et al., 1991
; Zhang et al., 2001
; Sprecher et al., 2002
), and conceptually close to an earlier proposal (Rogers and Powell, 1993
). In this nomenclature, all human type I keratins were named Ka9 to KaX and all type II keratins were named Kb1 to KbY, thus, enabling type I and II keratins of other mammalian species to be added consecutively into this open-ended system. At the 2004 Gordon Conference on Intermediate Filaments in Oxford, an initiative to achieve international consensus led to the formation of a broad-based Keratin Nomenclature Committee that included active investigators in the keratin field and members of the Human Genome Nomenclature Committee (HGNC) and the Mouse Genome Nomenclature Committee. This committee evaluated several potential nomenclature schemes and, after extensive deliberation and consultation with other colleagues in the intermediate filament field, arrived at the consensus nomenclature system that is detailed in the following sections.
To structure the new nomenclature system, the 54 human keratins and their genes are divided into three categories: (1) epithelial keratins/genes, (2) hair keratins/genes, and (3) keratin pseudogenes. The nomenclature is also structured to allow for the inclusion of a fourth category of nonhuman epithelial and hair keratins of other mammalian species, whose genes are either absent or occur as pseudogenes in the human genome.
For both type I and II keratins, these four categories are numerically arranged in the following order (): (1) human epithelial keratins, (2) human hair keratins, (3) nonhuman epithelial/hair keratins, and (4) human keratin pseudogenes.
Numbering scheme of keratin categories