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Keratin
From Wikipedia, the free encyclopedia

Keratin (/krtn/[1][2]) is one of a family of fibrous

structural proteins. Keratin is the protein that protects
epithelial cells from damage or stress. Keratin is extremely
insoluble in water and organic solvents. It is the key structural
material making up the outer layer of human skin. 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.[3][4] The only other biological matter known to
approximate the toughness of keratinized tissue is
chitin.[5][6][7]

Contents
1 Etymology
2 Examples of occurrence Microscopy of keratin filaments inside cells.
3 Genes
4 Protein structure
4.1 Disulfide bridges
4.2 Filament formation
4.3 Pairing
5 Cornification
6 Silk
7 Clinical significance
8 See also
9 References
10 External links

Etymology
Keratin derives from Greek from Greek keras () (genitive keratos, ) meaning "horn"
originating from the Proto-Indo-European *er- of the same meaning.[8] It is composed of "horn like", i.e.,
kerato,[9] to which the chemical suffix -in is appended.[10] The Greek keras (or keros) is used in many animal
names, e.g. Rhinoceros, meaning "nose with a horn".

Examples of occurrence
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 -keratins in the hair (including wool), stratum corneum, horns, nails, claws and hooves of mammals and
the hagfish slime threads.[4]
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the harder -keratins found in nails and in the scales and claws of
reptiles, their shells (Testudines, such as tortoise, turtle, terrapin), and
in the feathers, beaks, claws of birds and quills of porcupines.[11]
(These keratins are formed primarily in beta sheets. However, beta
sheets are also found in -keratins.)[12]

The baleen plates of filter-feeding whales are made of keratin.

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).

Genes
The human genome encodes 54 functional keratin
genes which are located in two clusters on
chromosomes 12 and 17. This suggests that they have
Horns such as those of the impala are
originated from a series of gene duplications on these made up of keratin covering a core of
chromosomes.[13] live bone

The neutral-basic The keratins include the following proteins of which

keratins are KRT23, KRT24, KRT25, KRT26, KRT27, KRT28, KRT31, KRT32,
found on KRT33A, KRT33B, KRT34, KRT35, KRT36, KRT37, KRT38, KRT39,
chromosome 12 KRT40, KRT71, KRT72, KRT73, KRT74, KRT75, KRT76, KRT77,
(12q13.13). KRT78, KRT79, KRT8, KRT80, KRT81, KRT82, KRT83, KRT84,
KRT85 and KRT86 have been used to describe keratins past 20.[14]

While the acidic

keratins are
found on
chromosome 17
(17q21.2).

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 (tool available online).

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Protein structure
The first sequences of keratins were determined by Hanukoglu and Fuchs.[15][16] These sequences revealed that
there are two distinct but homologous keratin families which were named as Type I keratin and Type II keratins.[16]
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 -helical conformation that are separated by three short linker segments predicted to be in
beta-turn conformation.[16] This model has been confirmed by the determination of the crystal structure of a helical
domain of keratins.[17]

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.[18]

The major force that keeps the coiled-coil structure is hydrophobic interactions
between apolar residues along the keratins helical segments.[19]

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 -keratin, can Keratin (high molecular weight)
in bile duct cell and oval cells of
have these two as 7580% of the total, with 1015% serine, with the rest having
horse liver
bulky side groups. The chains are antiparallel, with an alternating C N
orientation.[20] 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.

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[21]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 -keratins consist of -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 -
keratins of reptiles and birds have -pleated sheets twisted together, then stabilized and hardened by disulfide
bridges.

Filament formation

It was theorized that keratins are combined into 'hard' and 'soft,' 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.[14]

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
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into long filaments.

Pairing

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
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 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 -keratins in feathers, and this is probably characteristic of all keratins.

Silk
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.

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Silk found in insect pupae, and in spider webs and egg casings, also has twisted -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 (m) thick, compared with about 60 m 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.[22] 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 m 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.

Clinical significance
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
Epidermolytic hyperkeratosis
Steatocystoma multiplex
Keratosis pharyngis
Rhabdoid cell formation in Large cell lung carcinoma with rhabdoid phenotype[23][24]

Furthermore, 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 expresse K8 and K18, and cholangiocarcinomas
express K7, K8 and K18, while metastases of colorectal carcinomas express K20, but not K7.[25]

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 Tricophagia.

See also
List of cutaneous conditions caused by mutations in keratins
List of keratins expressed in the human integumentary system

References
1. OED 2nd edition, 1989 as /krtn/
2. Entry "keratin" (http://www.merriam-webster.com/dictionary/keratin) in Merriam-Webster Online
Dictionary (http://www.merriam-webster.com/).
3. Fraser, R.D.B. (1972). Keratins: Their composition, structure and biosynthesis. Bannerstone House: Charles
C Thomas. pp. 36. ISBN 0-398-02283-6.
4. Wang, Bin (2016). "Keratin: Structure, mechanical properties, occurrence in biological organisms, and
efforts at bioinspiration". Progress in Materials Science. 76: 229318. doi:10.1016/j.pmatsci.2015.06.001 (ht
tps://doi.org/10.1016%2Fj.pmatsci.2015.06.001).
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5. "Keratin" (http://www.websters-online-dictionary.org/definitions/Keratin). Webster's Online Dictionary.

6. Vincent, Julian F.V; Wegst, Ulrike G.K (July 2004). "Design and mechanical properties of insect cuticle".
Arthropod Structure & Development. 33 (3): 187199. doi:10.1016/j.asd.2004.05.006 (https://doi.org/10.101
6%2Fj.asd.2004.05.006).
7. Tombolato, Luca; Novitskaya, Ekaterina E.; Chen, Po-Yu; Sheppard, Fred A.; McKittrick, Joanna (February
2010). "Microstructure, elastic properties and deformation mechanisms of horn keratin". Acta Biomaterialia.
6 (2): 319330. PMID 19577667 (https://www.ncbi.nlm.nih.gov/pubmed/19577667).
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8. "Keratin" (http://www.etymonline.com/index.php?term=keratin&allowed_are_frame=0). Online Etymology
Dictionary.
"Horn" (http://www.etymonline.com/index.php?term=kerato-&allowed_in_frame=0). Online Etymology
Dictionary.
9. "kerato-" (http://www.etymonline.com/index.php?term=keratin&allowed_in_frame=0). Online Etymology
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"Horn" (http://www.etymonline.com/index.php?term=horn&allowed_in_frame=0). Online Etymology
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10. "-in/-ine chemical suffix" (http://www.etymonline.com/index.php?term=-ine&allowed_in_frame=0). Online
Etymology Dictionary.
11. Hickman, Cleveland Pendleton; Roberts, Larry S.; Larson, Allan L. (2003). Integrated principles of zoology.
Dubuque, IA: McGraw-Hill. p. 538. ISBN 0-07-243940-8.
12. Kreplak, L.; Doucet, J.; Dumas, P.; Briki, F. (July 2004). "New Aspects of the -Helix to -Sheet Transition
in Stretched Hard -Keratin Fibers" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1304386). Biophysical
Journal. 87 (1): 640647. PMC 1304386 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1304386) .
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s://doi.org/10.1529%2Fbiophysj.103.036749).
13. Moll, Roland; Divo, Markus; Langbein, Lutz (2008-05-07). "The human keratins: biology and pathology" (h
ttps://link.springer.com/article/10.1007/s00418-008-0435-6). Histochemistry and Cell Biology. 129 (6): 705
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oi.org/10.1007%2Fs00418-008-0435-6).
14. Schweizer J, Bowden PE, Coulombe PA, et al. (July 2006). "New consensus nomenclature for mammalian
keratins" (http://www.jcb.org/cgi/pmidlookup?view=long&pmid=16831889). J. Cell Biol. 174 (2): 16974.
PMC 2064177 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064177) . PMID 16831889 (https://www.
ncbi.nlm.nih.gov/pubmed/16831889). doi:10.1083/jcb.200603161 (https://doi.org/10.1083%2Fjcb.20060316
1).
15. Hanukoglu, I.; Fuchs, E. (Nov 1982). "The cDNA sequence of a human epidermal keratin: divergence of
sequence but conservation of structure among intermediate filament proteins". Cell. 31 (1): 24352.
PMID 6186381 (https://www.ncbi.nlm.nih.gov/pubmed/6186381). doi:10.1016/0092-8674(82)90424-X (http
s://doi.org/10.1016%2F0092-8674%2882%2990424-X).
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and variable structural domains among keratins". Cell. 33 (3): 91524. PMID 6191871 (https://www.ncbi.nl
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17. Lee, CH.; Kim, MS.; Chung, BM.; Leahy, DJ.; Coulombe, PA. (Jul 2012). "Structural basis for heteromeric
assembly and perinuclear organization of keratin filaments" (https://www.ncbi.nlm.nih.gov/pmc/articles/PM
C3864793). Nat Struct Mol Biol. 19 (7): 70715. PMC 3864793 (https://www.ncbi.nlm.nih.gov/pmc/articles/
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18. Voet, Donald; Voet, Judith; Pratt, Charlotte. "Proteins: Three-Dimensional Structure" (http://biochem118.stan
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ttps://www.amazon.com/exec/obidos/ASIN/0471586501/whaticomascienli#reader_0471586501). p. 158.
Retrieved 2010-10-01. "Fibrous proteins are characterized by a single type of secondary structure: a keratin
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19. Hanukoglu I, Ezra L (Jan 2014). "Proteopedia: Coiled-coil structure of keratins". Biochem Mol Biol Educ. 42
(1): 9394. PMID 24265184 (https://www.ncbi.nlm.nih.gov/pubmed/24265184). doi:10.1002/bmb.20746 (ht
tps://doi.org/10.1002%2Fbmb.20746).
20. "Secondary Protein" (https://web.archive.org/web/20100922111144/http://elmhurst.edu/~chm/vchembook/56
6secprotein.html). Elmhurst.edu. Archived from the original (http://elmhurst.edu/~chm/vchembook/566secpr
otein.html) on 2010-09-22. Retrieved 2010-09-23.
21. "What is Keratin?" (http://www.wisegeek.org/what-is-keratin.htm). WiseGEEK. Retrieved 11 May 2014.
22. Australia. "Spiders Silk structure" (https://web.archive.org/web/20090508161836/http://www.amonline.ne
t.au/spiders/toolkit/silk/structure.htm). Amonline.net.au. Archived from the original (http://www.amonline.n
et.au/spiders/toolkit/silk/structure.htm) on 2009-05-08. Retrieved 2010-09-23.
23. Shiratsuchi H, Saito T, Sakamoto A, et al. (February 2002). "Mutation analysis of human cytokeratin 8 gene
in malignant rhabdoid tumor: a possible association with intracytoplasmic inclusion body formation". Mod.
Pathol. 15 (2): 14653. PMID 11850543 (https://www.ncbi.nlm.nih.gov/pubmed/11850543).
doi:10.1038/modpathol.3880506 (https://doi.org/10.1038%2Fmodpathol.3880506).
24. Itakura E, Tamiya S, Morita K, et al. (September 2001). "Subcellular distribution of cytokeratin and vimentin
in malignant rhabdoid tumor: three-dimensional imaging with confocal laser scanning microscopy and
double immunofluorescence". Mod. Pathol. 14 (9): 85461. PMID 11557780 (https://www.ncbi.nlm.nih.gov/
pubmed/11557780). doi:10.1038/modpathol.3880401 (https://doi.org/10.1038%2Fmodpathol.3880401).
25. Omary MB, Ku NO, Strnad P, Hanada S (July 2009). "Toward unraveling the complexity of simple epithelial
keratins in human disease" (http://www.jci.org/articles/view/37762). J. Clin. Invest. 119 (7): 1794805.
PMC 2701867 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701867) . PMID 19587454 (https://www.
ncbi.nlm.nih.gov/pubmed/19587454). doi:10.1172/JCI37762 (https://doi.org/10.1172%2FJCI37762).

External links
Composition and -sheet structure of silk (http://www.elmhurst.edu/~chm/vchembook/566secprotein.html)
Hair-Science.com's entry on the microscopic elements of hair (http://www.hair-science.com/_int/_en/topic/to
pic_sousrub.aspx?tc=ROOT-HAIR-SCIENCE^PORTRAIT-OF-AN-UNKNOWN-ELEMENT^SUPERB-CH
EMISTRY&cur=SUPERB-CHEMISTRY)
Proteopedia page on keratins (http://www.proteopedia.org/w/Keratins)

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