Keratin 6A is one of the 27 different type II keratins expressed in humans. Keratin 6A was the first type II keratin sequence determined. Analysis of the sequence of this keratin together with that of the first type I keratin led to the discovery of the four helical domains in the central rod of keratins. In humans Keratin 6A is encoded by the ''KRT6A''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Keratin family

Keratins Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. It is the key structural material making up scales, hair, nails, feathers, horns, claws, hooves, and the outer layer of skin in vertebrates. Kera ...

are the

intermediate filament Intermediate filaments (IFs) are cytoskeleton, cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate ''Branchiostoma' ...

proteins that form a dense meshwork of filaments throughout the

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

cells. Keratins form hetero

polymers A polymer () is a substance or material that consists of very large molecules, or macromolecules, that are constituted by many repeating subunits derived from one or more species of monomers. Due to their broad spectrum of properties, b ...

consisting of a type I and a type II keratin. Keratins are generally expressed in particular pairs of type I and type II keratin proteins in a tissue-specific and

cellular differentiation Cellular differentiation is the process in which a stem cell changes from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellula ...

-specific manner. The keratin proteins of epithelial tissues are commonly known as "keratins" or are sometimes referred to as "epithelial keratins" or "cytokeratins". The specialized keratins of

hair Hair is a protein filament that grows from follicles found in the dermis. Hair is one of the defining characteristics of mammals. The human body, apart from areas of glabrous skin, is covered in follicles which produce thick terminal and ...

and

nail Nail or Nails may refer to: In biology * Nail (anatomy), toughened protective protein-keratin (known as alpha-keratin, also found in hair) at the end of an animal or human digit, such as fingernail * Nail (beak), a plate of hard horny tissue a ...

are known as "hard keratins" or " trichocyte keratins". Trichocytes are the specialized epithelial cells from which hair and nail are composed. Trichocyte keratins are similar in their gene and protein structure to keratins except that they are especially rich in the

sulfur Sulfur ( American spelling and the preferred IUPAC name) or sulphur ( Commonwealth spelling) is a chemical element; it has symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms ...

-containing

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

cysteine, which facilitates chemical cross-linking of the assembled hard keratins to form a more structurally resilient material. Both epithelial keratins and hard keratins can be further subdivided into type I (acidic) keratins and type II (neutral-basic) keratins. The genes for the type I keratins are located in a gene cluster on human

chromosome 17 Chromosome 17 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 17 spans more than 84 million base pairs (the building material of DNA) and represents between 2.5 and 3% of the total DN ...

q, whereas the genes for type II keratins are located in a cluster on human

chromosome 12 Chromosome 12 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 12 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tot ...

q (the exception being K18, a type I keratin located in the type II gene cluster).

Gene

The ''KRT6A'' gene consists of 9

exons An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence i ...

separated by 8

introns An intron is any Nucleic acid sequence, nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of ...

and is located in the type II keratin gene cluster on human ''chromosome'' 12q.

Keratin 6B Keratin 6B is a type II cytokeratin, one of a number of isoforms of keratin 6. It is found with keratin 16 and/or keratin 17 in the hair follicles, the filiform papillae of the tongue and the epithelial lining of oral mucosa and esophagus. This ker ...

and

keratin 6C Keratin 6C (protein name K6C; gene name ''KRT6C''), is a type II cytokeratin, one of a number of isoforms of keratin 6 encoded by separate genes located within the type II keratin gene cluster on human chromosome 12q. This gene was uncovered recent ...

are encoded by the neighbouring genes, which are identical in

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

organization to ''KRT6A'' and are more than 99% identical in their

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

coding sequences.

Tissue distribution

It is found with

keratin 16 Keratin 16 is a protein that in humans is encoded by the ''KRT16'' gene. Keratin 16 is a type I cytokeratin. It is paired with keratin 6 in a number of epithelial tissues, including nail bed, esophagus, tongue, and hair follicle The hair foll ...

and/or

keratin 17 Keratin, type I cytoskeletal 17 is a protein that in humans is encoded by the ''KRT17'' gene. Keratin 17 is a type I cytokeratin. It is found in nail beds, hair follicles, sebaceous glands, and other epidermal appendages. Mutations in the gene e ...

in the palm and sole epidermis, the epithelial cells of the nail bed, the

filiform papillae Lingual papillae (: papilla, ) are small structures on the upper surface of the tongue that give it its characteristic rough texture. The four types of papillae on the human tongue have different structures and are accordingly classified as circum ...

of the

tongue The tongue is a Muscle, muscular organ (anatomy), organ in the mouth of a typical tetrapod. It manipulates food for chewing and swallowing as part of the digestive system, digestive process, and is the primary organ of taste. The tongue's upper s ...

, the

lining of oral

mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...

and

esophagus The esophagus (American English), oesophagus (British English), or œsophagus (Œ, archaic spelling) (American and British English spelling differences#ae and oe, see spelling difference) all ; : ((o)e)(œ)sophagi or ((o)e)(œ)sophaguses), c ...

, as well as the

hair follicle The hair follicle is an organ found in mammalian skin. It resides in the dermal layer of the skin and is made up of 20 different cell types, each with distinct functions. The hair follicle regulates hair growth via a complex interaction betwee ...

Clinical significance

Antimicrobial

Keratin 6A has been shown to have antimicrobial properties, and is the main antimicrobial factor in the eye.

Genetic disorders

Mutations in the genes expressing this protein is associated with the PC-K6A subtype of

pachyonychia congenita Pachyonychia congenita (often abbreviated as "PC") is a rare group of autosomal dominant skin disorders that are caused by a mutation in one of five different keratin genes. Pachyonychia congenita is often associated with thickened toenails, plant ...

, an inherited disorder of the

tissues in which keratin 6A is expressed, particularly leading to structural abnormalities of the nails, the

epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the ...

of the palms and soles, and oral

epithelia Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of many ...

Immunohistochemistry

The expression of keratin 6A is often tested together with

keratin 5 Keratin 5, also known as KRT5, K5, or CK5, is a protein that is encoded in humans by the ''KRT5'' gene. It protein dimer, dimerizes with keratin 14 and forms the intermediate filaments (IF) that make up the cytoskeleton of Stratum basale, basal ...

, using CK5/6 antibodies, which target both keratin forms. Topic Completed: 3 June 2019. Revised: 8 December 2019

External links

GeneReviews/NCBI/NIH/UW entry on Pachyonychia Congenita

References

{{Cytoskeletal proteins Keratins