One of a family of fibrous structural proteins
Not to be confused with Carotene or Creatine.
Keratin (/ˈkɛrətɪn/) 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, horns, claws, hooves, and the outer layer of skin among vertebrates. Keratin also 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. Excessive keratinization participate in fortification of certain tissues such as in horns of cattle and rhinos, and armadillos\' osteoderm. The only other biological matter known to approximate the toughness of keratinized tissue is chitin.
Keratin comes in two types, the primitive, softer forms found in all vertebrates and harder, derived forms found only among sauropsids (reptiles and birds).
Spider silk is classified as keratin, although production of the protein may have evolved independently of the process in vertebrates.
Alpha-keratins (α-keratins) are found in all vertebrates. They form the hair (including wool), the outer layer of skin, horns, nails, claws and hooves of mammals, and the slime threads of hagfish. The baleen plates of filter-feeding whales are also made of keratin. Keratin filaments are abundant in keratinocytes in the hornified layer of the epidermis; these are proteins which have undergone keratinization. They are also present in epithelial cells in general. For example, mouse thymic epithelial cells react with antibodies for keratin 5, keratin 8, and keratin 14. These antibodies are used as fluorescent markers to distinguish subsets of mouse thymic epithelial cells in genetic studies of the thymus.
The harder beta-keratins (β-keratins) are found only in the sauropsids, that is all living reptiles and birds. They are found in the nails, scales, and claws of reptiles, in some reptile shells (testudines, such as tortoise, turtle, terrapin), and in the feathers, beaks, and claws of birds. These keratins are formed primarily in beta sheets. However, beta sheets are also found in α-keratins.
Recent scholarship has shown that sauropsid β-keratins are fundamentally different from α-keratins at a genetic and structural level. The new term corneous beta protein (CBP) has been proposed to avoid confusion with α-keratins.
Keratins (also described as cytokeratins) are polymers of type I and type II intermediate filaments that have been found only in chordates (vertebrates, amphioxus, urochordates). Nematodes and many other non-chordate animals seem to have only type VI intermediate filaments, fibers that structure the nucleus.
Genes
This section may require cleanup to meet Wikipedia\'s quality standards. The specific problem is: Not particularly helpful to dump a big list of KRT genes here. Using the source a bit more to explain what each gene and each zone of genes mean will be helpful, as we currently have no particular examples of a hair keratin. Please help improve this section if you can. (October 2022) (Learn how and when to remove this template message)
The human genome encodes 54 functional keratin genes, located in two clusters on chromosomes 12 and 17. This suggests that they 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.
KRT1
complement activation, lectin pathway
KRT1
retina homeostasis
KRT1
response to oxidative stress
KRT1
peptide cross-linking
KRT1
keratinization
KRT1
fibrinolysis
KRT1
intermediate filament organization
KRT1
regulation of angiogenesis
KRT1
negative regulation of inflammatory response
KRT1
protein heterotetramerization
KRT1
establishment of skin barrier
KRT10
morphogenesis of an epithelium
KRT10
epidermis development
KRT10
peptide cross-linking
KRT10
keratinocyte differentiation
KRT10
epithelial cell differentiation
KRT10
positive regulation of epidermis development
KRT10
protein heterotetramerization
KRT12
morphogenesis of an epithelium
KRT12
visual perception
KRT12
epidermis development
KRT12
epithelial cell differentiation
KRT12
cornea development in camera-type eye
KRT13
cytoskeleton organization
KRT13
epithelial cell differentiation
KRT13
regulation of translation in response to stress
KRT13
intermediate filament organization
KRT14
aging
KRT14
epidermis development
KRT14
keratinocyte differentiation
KRT14
epithelial cell differentiation
KRT14
hair cycle
KRT14
intermediate filament organization
KRT14
intermediate filament bundle assembly
KRT14
stem cell differentiation
KRT15
epidermis development
KRT15
epithelial cell differentiation
KRT15
intermediate filament organization
KRT16
morphogenesis of an epithelium
KRT16
inflammatory response
KRT16
cytoskeleton organization
KRT16
aging
KRT16
keratinocyte differentiation
KRT16
negative regulation of cell migration
KRT16
epithelial cell differentiation
KRT16
keratinization
KRT16
hair cycle
KRT16
innate immune response
KRT16
intermediate filament cytoskeleton organization
KRT16
intermediate filament organization
KRT16
keratinocyte migration
KRT16
establishment of skin barrier
KRT17
morphogenesis of an epithelium
KRT17
positive regulation of cell growth
KRT17
epithelial cell differentiation
KRT17
hair follicle morphogenesis
KRT17
keratinization
KRT17
intermediate filament organization
KRT17
positive regulation of translation
KRT17
positive regulation of hair follicle development
KRT18
cell cycle
KRT18
anatomical structure morphogenesis
KRT18
tumor necrosis factor-mediated signaling pathway
KRT18
obsolete Golgi to plasma membrane CFTR protein transport
KRT18
Golgi to plasma membrane protein transport
KRT18
negative regulation of apoptotic process
KRT18
intermediate filament cytoskeleton organization
KRT18
extrinsic apoptotic signaling pathway
KRT18
hepatocyte apoptotic process
KRT18
cell-cell adhesion
KRT19
Notch signaling pathway
KRT19
epithelial cell differentiation
KRT19
response to estrogen
KRT19
intermediate filament organization
KRT19
sarcomere organization
KRT19
cell differentiation involved in embryonic placenta development
KRT2
keratinocyte development
KRT2
epidermis development
KRT2
peptide cross-linking
KRT2
keratinization
KRT2
keratinocyte activation
KRT2
keratinocyte proliferation
KRT2
intermediate filament organization
KRT2
positive regulation of epidermis development
KRT2
keratinocyte migration
KRT20
apoptotic process
KRT20
cellular response to starvation
KRT20
epithelial cell differentiation
KRT20
intermediate filament organization
KRT20
regulation of protein secretion
KRT23
epithelial cell differentiation
KRT23
intermediate filament organization
KRT24
biological_process
KRT25
cytoskeleton organization
KRT25
aging
KRT25
hair follicle morphogenesis
KRT25
hair cycle
KRT25
intermediate filament organization
KRT26
KRT27
biological_process
KRT27
hair follicle morphogenesis
KRT27
intermediate filament organization
KRT28
biological_process
KRT3
epithelial cell differentiation
KRT3
keratinization
KRT3
intermediate filament cytoskeleton organization
KRT3
intermediate filament organization
KRT31
epidermis development
KRT31
epithelial cell differentiation
KRT31
intermediate filament organization
KRT32
epidermis development
KRT32
epithelial cell differentiation
KRT32
intermediate filament organization
KRT33A
epithelial cell differentiation
KRT33A
intermediate filament organization
KRT33B
aging
KRT33B
epithelial cell differentiation
KRT33B
hair cycle
KRT33B
intermediate filament organization
KRT34
epidermis development
KRT34
epithelial cell differentiation
KRT34
intermediate filament organization
KRT35
anatomical structure morphogenesis
KRT35
epithelial cell differentiation
KRT35
intermediate filament organization
KRT36
biological_process
KRT36
epithelial cell differentiation
KRT36
intermediate filament organization
KRT36
regulation of keratinocyte differentiation
KRT37
epithelial cell differentiation
KRT37
intermediate filament organization
KRT38
epithelial cell differentiation
KRT38
intermediate filament organization
KRT39
epithelial cell differentiation
KRT39
intermediate filament organization
KRT4
cytoskeleton organization
KRT4
epithelial cell differentiation
KRT4
keratinization
KRT4
intermediate filament organization
KRT4
negative regulation of epithelial cell proliferation
KRT40
epithelial cell differentiation
KRT40
intermediate filament organization
KRT5
epidermis development
KRT5
response to mechanical stimulus
KRT5
regulation of cell migration
KRT5
keratinization
KRT5
regulation of protein localization
KRT5
intermediate filament polymerization
KRT5
intermediate filament organization
KRT6A
obsolete negative regulation of cytolysis by symbiont of host cells
KRT6A
morphogenesis of an epithelium
KRT6A
positive regulation of cell population proliferation
KRT6A
cell differentiation
KRT6A
keratinization
KRT6A
wound healing
KRT6A
intermediate filament organization
KRT6A
defense response to Gram-positive bacterium
KRT6A
cytolysis by host of symbiont cells
KRT6A
antimicrobial humoral immune response mediated by antimicrobial peptide
KRT6A
negative regulation of entry of bacterium into host cell
KRT6B
ectoderm development
KRT6B
keratinization
KRT6B
intermediate filament organization
KRT6C
keratinization
KRT6C
intermediate filament cytoskeleton organization
KRT6C
intermediate filament organization
KRT7
keratinization
KRT7
intermediate filament organization
KRT71
hair follicle morphogenesis
KRT71
keratinization
KRT71
intermediate filament organization
KRT72
biological_process
KRT72
keratinization
KRT72
intermediate filament organization
KRT73
biological_process
KRT73
keratinization
KRT73
intermediate filament organization
KRT74
keratinization
KRT74
intermediate filament cytoskeleton organization
KRT74
intermediate filament organization
KRT75
hematopoietic progenitor cell differentiation
KRT75
keratinization
KRT75
intermediate filament organization
KRT76
cytoskeleton organization
KRT76
epidermis development
KRT76
keratinization
KRT76
pigmentation
KRT76
intermediate filament organization
KRT76
sebaceous gland development
KRT77
biological_process
KRT77
keratinization
KRT77
intermediate filament organization
KRT78
keratinization
KRT78
intermediate filament organization
KRT79
keratinization
KRT79
intermediate filament organization
KRT8
keratinization
KRT8
tumor necrosis factor-mediated signaling pathway
KRT8
intermediate filament organization
KRT8
sarcomere organization
KRT8
response to hydrostatic pressure
KRT8
response to other organism
KRT8
cell differentiation involved in embryonic placenta development
KRT8
extrinsic apoptotic signaling pathway
KRT8
hepatocyte apoptotic process
KRT80
keratinization
KRT80
intermediate filament organization
KRT81
keratinization
KRT81
intermediate filament organization
KRT82
biological_process
KRT82
keratinization
KRT82
intermediate filament organization
KRT83
aging
KRT83
epidermis development
KRT83
keratinization
KRT83
hair cycle
KRT83
intermediate filament organization
KRT84
hair follicle development
KRT84
keratinization
KRT84
nail development
KRT84
intermediate filament organization
KRT84
regulation of keratinocyte differentiation
KRT85
epidermis development
KRT85
keratinization
KRT85
intermediate filament organization
KRT86
keratinization
KRT86
intermediate filament organization
KRT9
spermatogenesis
KRT9
epidermis development
KRT9
epithelial cell differentiation
KRT9
skin development
KRT9
intermediate filament organization
Protein structure
The first sequences of keratins were determined by Israel Hanukoglu and Elaine Fuchs (1982, 1983). These sequences revealed that there are two distinct but homologous keratin families, which were named type I and type II keratins. By analysis of the primary structures of these keratins and other intermediate filament proteins, Hanukoglu and Fuchs suggested a model in which 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.
Type 1 and 2 Keratins
The human genome has 54 functional annotated Keratin genes, 28 are in the Keratin type 1 family, and 26 are in the Keratin type 2 family.
Fibrous keratin molecules supercoil to form a very stable, left-handed superhelical motif to multimerise, forming filaments consisting of multiple copies of the keratin monomer.
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 of structural proteins, for which H-bonded close packing is more important than chemical specificity.
Disulfide bridges
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.
Thiolated polymers (=thiomers) can form disulfide bridges with cysteine substructures of keratins getting covalently attached to these proteins. Thiomers exhibit therefore high binding properties to keratins found in hair, on skin and on the surface of many cell types.
Filament formation
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.
Pairing
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
Cornification is the process of forming an epidermal barrier in
stratified squamous epithelial tissue. At the cellular level,
cornification is characterised by:
production of keratin
production of small proline-rich (SPRR) proteins and transglutaminase which eventually form a cornified cell envelope beneath the plasma membrane
terminal differentiation
loss of nuclei and organelles, in the final stages of cornification
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 are 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 molt 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
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The silk fibroins produced by insects and spiders are often classified as keratins, though it is unclear whether they are phylogenetically related to vertebrate 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 micrometers (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.
Glue
Glues made from partially-hydrolysed keratin include hoof glue and horn glue.
Clinical significance
Abnormal growth of keratin can occur in a variety of conditions including keratosis, hyperkeratosis and keratoderma.
Mutations in keratin gene expression can lead to, among others:
Alopecia Areata
Epidermolysis bullosa simplex
Ichthyosis bullosa of Siemens
Epidermolytic hyperkeratosis
Steatocystoma multiplex
Keratosis pharyngis
Rhabdoid cell formation in Large cell lung carcinoma with rhabdoid phenotype
Several diseases, such as athlete\'s foot and ringworm, are caused by infectious fungi that feed on keratin.
Keratin is highly resistant to digestive acids if ingested. Cats regularly ingest hair as part of their grooming behavior, leading to the gradual formation of hairballs that may be expelled orally or excreted. In humans, trichophagia may lead to Rapunzel syndrome, an extremely rare but potentially fatal intestinal condition.
Diagnostic use
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 CK8 and CK18, and cholangiocarcinomas express CK7, CK8 and CK18, while metastases of colorectal carcinomas express CK20, but not CK7.
