Characterization of the Human Hair Keratin–Associated Protein 2 (KRTAP2) Gene Family

Abstract

Hair keratin-associated proteins (KRTAPs) are one of the major structural components of the hair shaft. Approximately 100 KRTAP genes have been identified in humans to date, with each of the genes classified into a number of families based on their sequence homology and the nature of the repeat structures. The biophysical features of KRTAPs, however, have remained largely unknown. In this study, we investigated the characteristics of the human KRTAP2 family members at the DNA, RNA, and protein levels. We initially found that these genes had various size polymorphisms that were mainly due to differences in the length of the 3'-noncoding sequences. Reverse transcriptase-PCR experiments further detected the presence of KRTAP2 transcripts in plucked human hairs. Using indirect immunofluorescence with an anti-KRTAP2 antibody, we found that there was a predominant expression of the KRTAP2 proteins in the keratinizing zone of the human hair shaft cortex. In addition, we showed that the KRTAP2 proteins interacted with each other and preferentially bound to hair keratins, but not to epithelial keratins. Finally, we determined that the head domain of the hair keratins was essential for the affinity to KRTAP2 proteins. Our results further enhance the crucial roles of KRTAPs in hair shaft keratinization in humans.

Human hair shaft proteomic profiling: individual differences, site specificity and cuticle analysis

“…A previous study also pointed to differences in KAPs among subjects of African, Jamaican and African–American origin (Porter et al, 2009). These findings, and the frequent length polymorphisms they display (Fujikawa et al, 2012), often reflecting amino acid repeats in the coding region, may impel further focus on KAPs for this purpose.…”

Characterization of the Human Hair Shaft Cuticle–Specific Keratin-Associated Protein 10 Family

“…In this study, we described the biological features of the hair shaft cuticle-specific KRTAP10 proteins, which displayed characteristics similar to the hair shaft cortex-specific KRTAP2 proteins investigated previously (Fujikawa et al, 2012). It has been established in previous studies that KRTAP10 proteins are abundantly expressed in the exocuticle of the keratinized cells, as well as in the keratinizing cells of the hair shaft cuticle (Jones et al, 2010).…”

“…Co-IP assays showed that KRTAP10-1 protein bound to both K82 and K32 (Figure 2c), but not to K10 (Figure 2d). We have recently reported that KRTAP2-1 protein specifically bound to the head domain of hair keratins (Fujikawa et al, 2012). Here, we attempted to determine the domain of cuticle-specific hair keratins responsible for their interaction with KRTAP10-1.…”

“…KRTAPs are encoded by a large number of multigene families and are classified into three groups based on their amino acid composition: high sulfur (o30 mol% cysteine content), ultrahigh sulfur (430 mol% cysteine content), and high glycine/tyrosine (Powell and Rogers, 1997). We recently characterized the human hair shaft cortex-specific KRTAP2 family members at the DNA, RNA, and protein levels (Fujikawa et al, 2012). Specifically, we showed that the KRTAP2 proteins interacted with each other and preferentially bound to hair keratins but not to epithelial keratins.…”

<i>In vitro</i> Assembly Properties of Human Type I and II Hair Keratins

“…The molecular mechanism inducing the formation of these three types of MFs has not yet been clarified (Fraser et al, 2003;McKinnon, 2006;McKinnon and Harland, 2011). Differences in both the composition and content of KAPs in the three types of MFs suggest that they play an important role in determining the precise mode of MF packing (Fujikawa et al, 2011;Matsunaga et al, 2013;Plowman et al, 2007;Rogers et al, 2006). In addition, an unknown characteristic surface structure of hair keratin IFs, probably constructed by the head or tail domain, may also contribute to the IF-IF and IF-KAP interactions and the development of the three types of MFs.…”