Keratin (/ˈkɛrətɪn/) is one of a family of fibrous
structural proteins. It is the key structural material making up hair,
horns, claws, hooves, and the outer layer of human skin.
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.
2 Examples of occurrence
4.1 Disulfide bridges
4.2 Filament formation
7 Clinical significance
8 See also
10 External links
Keratin derives from Greek κερατίνη keratíni from κέρας
keras (genitive κέρατος keratos) meaning "horn" originating
Proto-Indo-European *ḱer- of the same meaning. It is
composed of "horn like", i.e., kerato, to which the chemical suffix
-in is appended. The Greek keras (or keros) is used in many animal
names, e.g. Rhinoceros, meaning "nose with a horn".
Examples of occurrence
Horns such as those of the impala are made up of keratin covering a
core of live bone.
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.
the α-keratins are found in all vertebrates. They form the hair
(including wool), stratum corneum, horns, nails, claws and hooves of
mammals and the hagfish slime threads.
the harder 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, 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.)
Additionally, the baleen plates of filter-feeding whales are made of
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 neutral-basic keratins are found on chromosome 12 (12q13.13).
While the acidic keratins are found on chromosome 17 (17q21.2).
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
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,
KRT86 have been used to describe keratins past
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.
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.
Keratin (high molecular weight) in bile duct cell and oval cells of
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
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
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
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 was theorized that keratins are combined into 'hard' and 'soft,' or
'cytokeratins' and 'other keratins'[clarification needed]. 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.
keratin 1, keratin 2
keratin 9, keratin 10
stratum corneum, keratinocytes
keratin 14, keratin 15
keratin 16, keratin 17
keratin 18, keratin 20
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
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 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.
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 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.
Some infectious fungi, such as those that cause athlete's foot and
ringworm (i.e. the dermatophytes), or Batrachochytrium dendrobatidis
(Chytrid fungus), feed on keratin.
Diseases caused by mutations in the keratin genes include:
Epidermolysis bullosa simplex
Ichthyosis bullosa of Siemens
Rhabdoid cell formation in Large cell lung carcinoma with rhabdoid
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 it is 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 is an extremely rare but
potentially fatal intestinal condition in humans that is caused by
List of cutaneous conditions caused by mutations in keratins
List of keratins expressed in the human integumentary system
List of keratins
OED 2nd edition, 1989 as /ˈkɛrətɪn/
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"Horn". Online Etymology Dictionary.
^ "kerato-". Online Etymology Dictionary.
"Horn". Online Etymology Dictionary.
^ "-in/-ine chemical suffix". Online Etymology Dictionary.
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Wikisource has the text of the 1920
Encyclopedia Americana article
Composition and β-sheet structure of silk
Hair-Science.com's entry on the microscopic elements of hair
Proteopedia page on keratins
type II (COL2A1)
FACIT: type IX
type XII (COL12A1)
basement membrane: type IV
other: type VI
type VII (COL7A1)
type X (COL10A1)
Prolyl hydroxylase/Lysyl hydroxylase
Cartilage associated protein/Leprecan
Matrix gla protein
Cartilage oligomeric matrix protein
Proteins of the cytoskeleton
T 1 2 3
C 1 2
I 1 2 3
actin depolymerizing factors
Wiskott-Aldrich syndrome protein
type I/chromosome 17
type II/chromosome 12
type I/chromosome 17
type II/chromosome 12
Nuclear lamins: A/C
Plakoglobin (gamma catenin)
Major sperm proteins
See also: cytoskeletal defects