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 (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Keratins

Keratins Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, horn ...

are the

intermediate filament Intermediate filaments (IFs) are 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''. Intermedia ...

proteins that form a dense meshwork of filaments throughout the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

cells. Keratins form hetero

polymers A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic an ...

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 alters 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 multicellular ...

-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 f ...

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 digit, such as fingernail * Nail (beak), a plate of hard horny tissue at the tip ...

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 (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...

-containing

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

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 83 million base pairs (the building material of DNA) and represents between 2.5 and 3% of the total D ...

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 to ...

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

Keratin 6A

Keratin 6A (protein name K6A; gene name ''KRT6A''), is a type II cyto

keratin Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, ho ...

, one of a number of

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...

s of

keratin 6 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 o ...

encoded by separate genes located within the type II keratin gene cluster on human

q. 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 follicles. Mutations in t ...

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 en ...

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

filiform papillae Lingual papillae (singular 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 c ...

of the

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

, 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 is ...

and

esophagus The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the ...

, 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 between h ...

s. This keratin 6 isoform is thought to be the most abundant of the K6 isoforms. 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 ...

separated by 8

introns 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., gene. ...

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., gene. ...

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 sequen ...

organization to ''KRT6A'' and are more than 99% identical in their DNA coding sequences. 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 hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water rele ...

of the palms and soles, and oral

epithelia Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

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 dimerizes with keratin 14 and forms the intermediate filaments (IF) that make up the cytoskeleton of basal epithelial cells. This protein i ...

, 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