Keratin (/ˈkɛrətɪn/) is one of a family of fibrous structural proteins. It is the key structural material making up hair, nails, feathers, horns, claws, hooves, and the outer layer of skin. Keratin is also the protein that protects epithelial cells from damage or stress. Keratin is extremely insoluble in water and organic solvents. Keratin monomers assemble into bundles to form intermediate filaments, which are tough and form strong unmineralized epidermal appendages found in reptiles, birds, amphibians, and mammals. The only other biological matter known to approximate the toughness of keratinized tissue is chitin.
Keratin filaments are abundant in keratinocytes in the cornified layer of the epidermis; these are proteins which have undergone keratinization. In addition, keratin filaments are present in epithelial cells in general. For example, mouse thymic epithelial cells (TECs) are known to react with antibodies for keratin 5, keratin 8, and keratin 14. These antibodies are used as fluorescent markers to distinguish subsets of TECs in genetic studies of the thymus.
Keratins (also described as cytokeratins) are polymers of type I and type II intermediate filaments, which have only been found in the genomes of chordates (vertebrates, Amphioxus, urochordates). Nematodes and many other non-chordate animals seem to only have type VI intermediate filaments, lamins, which have a long rod domain (vs. a short rod domain for the keratins).
The human genome encodes 54 functional keratin genes which are located in two clusters on chromosomes 12 and 17. This suggests that they have originated from a series of gene duplications on these chromosomes.
The keratins include the following proteins of which KRT23, KRT24, KRT25, KRT26, KRT27, KRT28, KRT31, KRT32, KRT33A, KRT33B, KRT34, KRT35, KRT36, KRT37, KRT38, KRT39, KRT40, KRT71, KRT72, KRT73, KRT74, KRT75, KRT76, KRT77, KRT78, KRT79, KRT8, KRT80, KRT81, KRT82, KRT83, KRT84, KRT85 and KRT86 have been used to describe keratins past 20.
The first sequences of keratins were determined by Hanukoglu and Fuchs. These sequences revealed that there are two distinct but homologous keratin families which were named as Type I keratin and Type II keratins. By analysis of the primary structures of these keratins and other intermediate filament proteins, Hanukoglu and Fuchs suggested a model that keratins and intermediate filament proteins contain a central ~310 residue domain with four segments in α-helical conformation that are separated by three short linker segments predicted to be in beta-turn conformation. This model has been confirmed by the determination of the crystal structure of a helical domain of keratins.
The major force that keeps the coiled-coil structure is hydrophobic interactions between apolar residues along the keratins helical segments.
Limited interior space is the reason why the triple helix of the (unrelated) structural protein collagen, found in skin, cartilage and bone, likewise has a high percentage of glycine. The connective tissue protein elastin also has a high percentage of both glycine and alanine. Silk fibroin, considered a β-keratin, can have these two as 75–80% of the total, with 10–15% serine, with the rest having bulky side groups. The chains are antiparallel, with an alternating C → N orientation. A preponderance of amino acids with small, nonreactive side groups is characteristic for structural proteins, for which H-bonded close packing is more important than chemical specificity.
In addition to intra- and intermolecular hydrogen bonds, the distinguishing feature of keratins is the presence of large amounts of the sulfur-containing amino acid cysteine, required for the disulfide bridges that confer additional strength and rigidity by permanent, thermally stable crosslinking—in much the same way that non-protein sulfur bridges stabilize vulcanized rubber. Human hair is approximately 14% cysteine. The pungent smells of burning hair and skin are due to the volatile sulfur compounds formed. Extensive disulfide bonding contributes to the insolubility of keratins, except in a small number of solvents such as dissociating or reducing agents.
The more flexible and elastic keratins of hair have fewer interchain disulfide bridges than the keratins in mammalian fingernails, hooves and claws (homologous structures), which are harder and more like their analogs in other vertebrate classes. Hair and other α-keratins consist of α-helically coiled single protein strands (with regular intra-chain H-bonding), which are then further twisted into superhelical ropes that may be further coiled. The β-keratins of reptiles and birds have β-pleated sheets twisted together, then stabilized and hardened by disulfide bridges.
It has been proposed that keratins can be divided into 'hard' and 'soft' forms, or 'cytokeratins' and 'other keratins'. That model is now understood to be correct. A new nuclear addition in 2006 to describe keratins takes this into account.
Keratin filaments are intermediate filaments. Like all intermediate filaments, keratin proteins form filamentous polymers in a series of assembly steps beginning with dimerization; dimers assemble into tetramers and octamers and eventually, if the current hypothesis holds, into unit-length-filaments (ULF) capable of annealing end-to-end into long filaments.
|A (neutral-basic)||B (acidic)||Occurrence|
|keratin 1, keratin 2||keratin 9, keratin 10||stratum corneum, keratinocytes|
|keratin 3||keratin 12||cornea|
|keratin 4||keratin 13||stratified epithelium|
|keratin 5||keratin 14, keratin 15||stratified epithelium|
|keratin 6||keratin 16, keratin 17||squamous epithelium|
|keratin 7||keratin 19||ductal epithelia|
|keratin 8||keratin 18, keratin 20||simple epithelium|
Cornification is the process of forming an epidermal barrier in stratified squamous epithelial tissue. At the cellular level, cornification is characterised by:
Metabolism ceases, and the cells are almost completely filled by keratin. During the process of epithelial differentiation, cells become cornified as keratin protein is incorporated into longer keratin intermediate filaments. Eventually the nucleus and cytoplasmic organelles disappear, metabolism ceases and cells undergo a programmed death as they become fully keratinized. In many other cell types, such as cells of the dermis, keratin filaments and other intermediate filaments function as part of the cytoskeleton to mechanically stabilize the cell against physical stress. It does this through connections to desmosomes, cell-cell junctional plaques, and hemidesmosomes, cell-basement membrane adhesive structures.
Cells in the epidermis contain a structural matrix of keratin, which makes this outermost layer of the skin almost waterproof, and along with collagen and elastin, gives skin its strength. Rubbing and pressure cause thickening of the outer, cornified layer of the epidermis and form protective calluses, which is useful for athletes and on the fingertips of musicians who play stringed instruments. Keratinized epidermal cells are constantly shed and replaced.
These hard, integumentary structures are formed by intercellular cementing of fibers formed from the dead, cornified cells generated by specialized beds deep within the skin. Hair grows continuously and feathers moult and regenerate. The constituent proteins may be phylogenetically homologous but differ somewhat in chemical structure and supermolecular organization. The evolutionary relationships are complex and only partially known. Multiple genes have been identified for the β-keratins in feathers, and this is probably characteristic of all keratins.
Silk found in insect pupae, and in spider webs and egg casings, also has twisted β-pleated sheets incorporated into fibers wound into larger supermolecular aggregates. The structure of the spinnerets on spiders’ tails, and the contributions of their interior glands, provide remarkable control of fast extrusion. Spider silk is typically about 1 to 2 micrometres (µm) thick, compared with about 60 µm for human hair, and more for some mammals. The biologically and commercially useful properties of silk fibers depend on the organization of multiple adjacent protein chains into hard, crystalline regions of varying size, alternating with flexible, amorphous regions where the chains are randomly coiled. A somewhat analogous situation occurs with synthetic polymers such as nylon, developed as a silk substitute. Silk from the hornet cocoon contains doublets about 10 µm across, with cores and coating, and may be arranged in up to 10 layers, also in plaques of variable shape. Adult hornets also use silk as a glue, as do spiders.
Diseases caused by mutations in the keratin genes include:
Keratin expression is helpful in determining epithelial origin in anaplastic cancers. Tumors that express keratin include carcinomas, thymomas, sarcomas and trophoblastic neoplasms. Furthermore, the precise expression-pattern of keratin subtypes allows prediction of the origin of the primary tumor when assessing metastases. For example, hepatocellular carcinomas typically express K8 and K18, and cholangiocarcinomas express K7, K8 and K18, while metastases of colorectal carcinomas express K20, but not K7.
Keratin is highly resistant to digestive acids if ingested (trichophagia). Because of this, cats (which groom themselves with their tongues) regularly ingest hair which will eventually result in the gradual formation of a hairball that is occasionally vomited when it becomes too big. Rapunzel syndrome, an extremely rare but potentially fatal intestinal condition in humans, is caused by trichophagia.
Fibrous proteins are characterized by a single type of secondary structure: a keratin is a left-handed coil of two a helices
Cytokeratins are keratin proteins found in the intracytoplasmic cytoskeleton of epithelial tissue. They are an important component of intermediate filaments, which help cells resist mechanical stress. Expression of these cytokeratins within epithelial cells is largely specific to particular organs or tissues. Thus they are used clinically to identify the cell of origin of various human tumors.Hair keratin
Hair keratin is a type of keratin found in hair and nails. There are two types of hair keratin:
the acidic type I hair keratin
type I hair keratin 1, KRT31
type I hair keratin 2, KRT32
type I hair keratin 3A, KRT33A
type I hair keratin 3B, KRT33B
type I hair keratin 4, KRT34
type I hair keratin 5, KRT35
type I hair keratin 6, KRT36
type I hair keratin 7, KRT37
type I hair keratin 8, KRT38
the basic type II hair keratin.
type II hair keratin 1, KRT81
type II hair keratin 2, KRT82
type II hair keratin 3, KRT83
type II hair keratin 4, KRT84
type II hair keratin 5, KRT85
type II hair keratin 6, KRT86Horn (anatomy)
A horn - a permanent pointed projection on the head of various animals - consists of a covering of keratin and other proteins surrounding a core of live bone. Horns are distinct from antlers, which are not permanent. In mammals, true horns are found mainly among the ruminant artiodactyls, in the families Antilocapridae (pronghorn) and Bovidae (cattle, goats, antelope etc.).
One pair of horns is usual; however, two or more pairs occur in a few wild species and in some domesticated breeds of sheep. Polycerate (multi-horned) sheep breeds include the Hebridean, Icelandic, Jacob, Manx Loaghtan, and the Navajo-Churro.
Horns usually have a curved or spiral shape, often with ridges or fluting. In many species, only males have horns. Horns start to grow soon after birth and continue to grow throughout the life of the animal (except in pronghorns, which shed the outer layer annually, but retain the bony core). Partial or deformed horns in livestock are called scurs. Similar growths on other parts of the body are not usually called horns, but spurs, claws or hoofs - depending on the part of the body on which they occur.KRT73
KRT73 is a keratin gene. It is responsible for hair formation, along with other genes, and it encodes a protein present in the inner root sheath of hair follicles.Keratin 1
Keratin 1 is a member of the keratin family. It is specifically expressed in the spinous and granular layers of the epidermis with family member keratin 10. Mutations in this gene have been associated with the variants of bullous congenital ichthyosiform erythroderma in which the palms and soles of the feet are affected.Keratin 10
Keratin, type I cytoskeletal 10 also known as cytokeratin-10 (CK-10) or keratin-10 (K10) is a protein that in humans is encoded by the KRT10 gene. Keratin 10 is a type I keratin.Keratin 12
Keratin 12 is a protein that in humans is encoded by the KRT12 gene.Keratin 12 is keratin found expressed in corneal epithelia. Mutations in the gene encoding this protein lead to Meesmann corneal dystrophy.Keratin 13
Keratin 13 (or cytokeratin 13) is a protein that in humans is encoded by the KRT13 gene.Keratin 13 is a type I cytokeratin, it is paired with keratin 4 and found in the suprabasal layers of non-cornified stratified epithelia. Mutations in the gene encoding this protein and keratin 4 have been associated with the autosomal dominant disorder White Sponge Nevus.Keratin 14
Keratin 14 is a member of the type I keratin family of intermediate filament proteins. Keratin 14 was the first type I keratin sequence determined.
Keratin 14 is also known as cytokeratin-14 (CK-14) or keratin-14 (KRT14). In humans it is encoded by the KRT14 gene.Keratin 14 is usually found as a heterodimer with type II keratin 5 and form the cytoskeleton of epithelial cells.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 the gene encoding this protein are associated with the genetic skin disorders including pachyonychia congenita, non-epidermolytic palmoplantar keratoderma and unilateral palmoplantar verrucous nevus.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 encoding this protein lead to PC-K17 (previously known as Jackson-Lawler) type pachyonychia congenita and steatocystoma multiplex.Keratin 18
Keratin 18 is a type I cytokeratin. It is, together with its filament partner keratin 8, perhaps the most commonly found products of the intermediate filament gene family. They are expressed in single layer epithelial tissues of the body. Mutations in this gene have been linked to cryptogenic cirrhosis. Two transcript variants encoding the same protein have been found for this gene.Keratin 18 is often used together with keratin 8 and keratin 19 to differentiate cells of epithelial origin from hematopoietic cells in tests that enumerate circulating tumor cells in blood.Keratin 19
Keratin, type I cytoskeletal 19 also known as cytokeratin-19 (CK-19) or keratin-19 (K19) is a 40 kDa protein that in humans is encoded by the KRT19 gene. Keratin 19 is a type I keratin.Keratin 2A
Keratin 2A also known as keratin 2E or keratin 2 is a protein that in humans is encoded by the KRT2A gene.Keratin 2A is a type II cytokeratin. It is found largely in the upper spinous layer of epidermal keratinocytes and mutations in the gene encoding this protein have been associated with ichthyosis bullosa of Siemens.Keratin 3
Keratin 3 also known as cytokeratin 3 is a protein that in humans is encoded by the KRT3 gene. Keratin 3 is a type II cytokeratin. It is specifically found in the corneal epithelium together with keratin 12.
Mutations in the KRT3 encoding this protein have been associated with Meesmanns Corneal Dystrophy.Keratin 4
Keratin, type I cytoskeletal 4 also known as cytokeratin-4 (CK-4) or keratin-4 (K4) is a protein that in humans is encoded by the KRT4 gene.Keratin 4 is a type II cytokeratin. It is specifically found in differentiated layers of the mucosal and esophageal epithelia together with keratin 13. Mutations in the genes encoding this protein have been associated with White Sponge Nevus, characterized by oral, esophageal, and anal leukoplakia.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 keratin 6 isoform is thought be less abundant than the closely related keratin 6A protein. Mutations in the gene encoding this protein have been associated with pachyonychia congenita, an inherited disorder of the epithelial tissues in which this keratin is expressed, particularly leading to structural abnormalities of the nails, the epidermis of the palms and soles, and oral epithelia. Keratin 6B is associated with the PC-K6B subtype of pachyonychia congenita.Keratin 8
Keratin, type II cytoskeletal 8 also known as cytokeratin-8 (CK-8) or keratin-8 (K8) is a keratin protein that is encoded in humans by the KRT8 gene. It is often paired with keratin 18.Type II hair keratin
Type II hair keratin is one of the two types of hair keratin. It is a basic protein which heterodimerizes with type I hair keratins to form hair and nails.
See also: cytoskeletal defects