thumb|300px|Microscopy of keratin filaments inside cells

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 tetrapod 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 the harder, derived forms found only among sauropsids (reptiles and birds).

Examples of occurrence

thumb|The [[Horn (anatomy)|horns of the impala are made of keratin covering a core of bone.]]

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. These keratins are formed primarily in beta sheets. However, beta sheets are also found in α-keratins.<!-- what exactly does this reference refer to? Not the distribution of a- and b-keratins it seems -->

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, amphioxi, urochordates). Nematodes and many other non-chordate animals seem to have only type V intermediate filaments, fibers that structure the nucleus.

Genes

thumb|The neutral&ndash;basic keratins are encoded on chromosome 12 (12q13.13).|left| 200x200px

thumb|The acidic keratins are encoded on chromosome 17 (17q21.2).|right|200x200px

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.

{| class="wikitable mw-collapsible mw-collapsed"

|+Table of keratin genes and biological processes (GeneCards)

!Symbol

!Biological process

|-

|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

|}

[[File:Human Keratins 1-8 Protein Alignment Rod Domain.tif|thumb|Protein sequence alignment of human keratin 1, 2A, 3,4, 5, 6A, 7, and 8 (KRT1 – KRT8). Only the first rod domain is shown above. Alignment was created using Clustal Omega.|centre|659x659px]]

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.

Type I and II keratins

The human genome has 54 functional annotated keratin genes, of which 28 are type I keratins and 26 are type II keratins.

thumb|Keratin (high molecular weight) in [[bile duct cell and oval cells of horse liver.]]

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 keratin's 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. 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.

thumb|A human [[Nail (anatomy)|toenail that fell off after a small trauma.]]

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 therefore exhibit 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.

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.

See also

  • Keratin-associated proteins (KRTAPs)
  • List of cutaneous conditions caused by mutations in keratins
  • List of keratins expressed in the human integumentary system
  • List of keratins
  • Keratinase

References

  • Hair-Science.com's entry on the microscopic elements of hair
  • Proteopedia page on keratins