Disease relevance of KRT86

• An aberrant truncated hHb1 hair keratin transcript, named hHb1-DeltaN, was previously identified in breast carcinomas [1].
• A preliminary study has suggested that hHb1 could be expressed in pilomatrixoma [2].
• Furthermore, neoplasms with follicular differentiation, including trichoblastoma, trichoepithelioma, pilomatricoma, pilar carcinoma and basal-cell carcinoma, were analysed for hHb1 gene expression [3].
• Toxicity of hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX) to earthworm was evaluated [4].

High impact information on KRT86

• In a three-generation French family with monilethrix of a milder and variable phenotype, we detected another heterozygous point mutation in the same glutamic acid codon of hHb6, which resulted in a conservative aspartic acid substitution (Glu 410 Asp) [5].
• Although cuticular differentiation proceeded without the expression of further type II hair keratins, cortex cells simultaneously expressed hHb1, hHb3, and hHb6 at an advanced stage of differentiation [6].
• We found that hHb1-DeltaN transcription is initiated at an unusual cryptic promoter within the fourth intron of the hHb1 gene and is dependent on two proximal Sp1 binding sites for its baseline activity [1].
• The hHa2 gene could be mapped to the long arm of chromosome 17, whereas the hHb1 gene was found on the long arm of chromosome 12 [7].
• The specific 3'-noncoding sequences of hHa2 and hHb1 were also used to isolate genomic fragments for both keratins from human genomic libraries which were than used for fluorescence in situ hybridization to human metaphase chromosomes [7].

Biological context of KRT86

• We investigated 21 affected individuals in two unrelated monilethrix families of Indian origin and identified point mutation (g.4624G>A) in the HTM motif (exon-7) of the KRTHB6 gene in all the affected members leading to E413K change in this basic keratin [8].
• Presence of E413K mutation in the HTM of KRTHB6 gene was not observed in the background of the allelic variant with three SNPs in KRTHB1 gene in homozygous condition in all the affected members of Family 1, affected with a localized but severe form of the disease [8].
• It has been suggested that mutation in hHb1 produces a less severe phenotype [9].
• Amino acid sequences comparisons of these keratins, including the previously characterized human K2.9 ortholog hHb1, show extreme conservation not only in the alpha-helices but also in the aminoterminal and proximal carboxyterminal domains [10].
• We have screened the basal promoter region, of KRTHB6 gene involving CAAT and TATA boxes in randomly selected 125 individuals of Indian origin by PCR-SSCP and DNA sequencing [11].

Anatomical context of KRT86

• Thus the underlying G-->A transition represents a spontaneous germ-line mutation in the hHb6 gene [12].
• Expression pattern of human hair keratin basic 1 (hHb1) in hair follicle and pilomatricoma [3].
• 2. In comparison with fishes from temperate waters, the blood of this teleost contains a reduced number of erythrocytes and concentration of hemoglobin; the erythrocytes contain two hemoglobins, Hb1 and Hb2, respectively accounting for approximately 90, and 5% of the total [13].
• The cDNA encoding a human ecto-apyrase (HB6), predicted to have seven N-linked glycosylation sites, was transiently expressed in mammalian COS cells and the resulting membrane preparations were treated with peptide N-glycosidase F (PNGase-F) [14].
• Here, we report that this CD71+ (HB4/HB6/CDw75/CDw76)+ cell is an erythroid precursor cell instead [15].

Associations of KRT86 with chemical compounds

• In addition two novel mutations within the helix initiation motif of hHb6 were found in Scottish and Portuguese cases, in whom the same highly conserved asparagine residue N114 was mutated to histidine (N114H) or aspartic acid (N114D) residues, respectively [9].
• Four new echinocystic acid 3,28-O-bisdesmosides, scaberosides Ha, Hb1, Hb2 and Hc1, were isolated as their methyl esters from the ground part of Aster scaber THUNB [16].
• Here we report a novel mutation in a French monilethrix family, which again consists of a lysine substitution of another highly conserved glutamic acid residue, Glu402 (Glu106 of the 2B subdomain), in the EIATYRRLLEGEE motif of hHb1 [17].
• A soil sample taken from an ammunition plant contained RDX (342 micromol kg(-1)), HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine; 3,057 micromol kg(-1)), MNX (hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine; 155 micromol kg(-1)), and traces of NDAB (3.8 micromol kg(-1)) [18].
• In one route, RDX was reduced to give the familiar nitroso derivatives hexahydro-1-nitroso-3,5-dinitro-1,3, 5-triazine (MNX) and hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine (DNX) [19].

Other interactions of KRT86

• We have cloned two complete type II hair-specific keratin genes (ghHb1 and ghHb6) [20].
• Monilethrix is an hereditary hair dystrophy recently shown to be due to mutations in the helix termination motif of two type II (basic) human hair keratin genes, hHb1 and hHb6 [9].

Analytical, diagnostic and therapeutic context of KRT86

• We have determined the complete amino acid sequence of P. bernacchii Hb1 and also the structure of its carbonmonoxy derivative by X-ray crystallography, to a resolution of 2.5 A [21].

References