Keratin
Keratin (/ˈkɛrətɪn/[1][2]) is one of a family of fibrous
structural proteins known as scleroproteins. α-Keratin is a
type of keratin found in vertebrates. It is the key
structural material making up hair, nails, feathers, horns,
claws, hooves, calluses, 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.[3][4] The only other biological matter known
to approximate the toughness of keratinized tissue is
chitin.[5][6][7] Keratin comes in two types, the primitive,
softer forms found in all vertebrates and harder, derived
forms found only among sauropsids (reptiles and birds).
Keratin resists digestion, which is why cats regurgitate
Microscopy of keratin filaments inside cells.
hairballs.
Spider silk is classified as keratin, although production of
the protein may have evolved independently of the process in vertebrates.
Contents
Examples of occurrence
Genes
Protein structure
Disulfide bridges
Filament formation
Pairing
Cornification
Silk
Clinical significance
See also
References
External links
Examples of occurrence
Horns such as those of the impala are made of keratin covering a core of bone.
Keratin filaments are abundant in keratinocytes in the cornified 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 to 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 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.[4]
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, in some reptile shells
(Testudines, such as tortoise, turtle, terrapin), and in the
feathers, beaks, and claws of birds.[8] (These keratins are
formed primarily in beta sheets. However, beta sheets are
also found in α-keratins.)[9]
The baleen plates of filter-feeding whales are made of keratin. The horns of the impala are made of
keratin covering a core of bone
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
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.[10]
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
The neutral– been used to describe keratins past 20.[11] The acidic keratins
basic keratins are encoded on
are encoded on chromosome 17
chromosome 12 (17q21.2).
(12q13.13).
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
(https://www.ebi.ac.uk/Tools/msa/clustalo/).
Protein structure
The first sequences of keratins were determined by Israel Hanukoglu and Elaine Fuchs.[12][13] These
sequences revealed that there are two distinct but homologous keratin families, which were named type I and
type II keratins.[13] 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.[13] This model has been confirmed by the
determination of the crystal structure of a helical domain of keratins.[14]
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.[15]
The major force that keeps the coiled-coil structure is hydrophobic
interactions between apolar residues along the keratins helical segments.[16]
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 (high molecular
weight) in bile duct cell and
keratin, can have these two as 75–80% of the total, with 10–15% serine,
oval cells of horse liver.
with the rest having bulky side groups. The chains are antiparallel, with an
alternating C → N orientation.[17] 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[18]—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.
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.[11]
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
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, 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
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.[19] 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.
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[20][21]
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.[22]
Keratin is highly resistant to digestive acids if ingested, as occurs in the human disorder trichophagia. Thus,
cats (which groom themselves with their tongues) regularly ingest hair, leading to the gradual formation of a
hairball that may be vomited. Rapunzel syndrome, an extremely rare but potentially fatal intestinal condition in
humans, is caused by trichophagia.
See also
List of cutaneous conditions caused by mutations in keratins
List of keratins expressed in the human integumentary system
List of keratins
References
1. OED 2nd edition, 1989 as /ˈkɛrətɪn/
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. 3–6. ISBN 978-0-398-02283-9.
4. Wang, Bin (2016). "Keratin: Structure, mechanical properties, occurrence in biological
organisms, and efforts at bioinspiration" (https://escholarship.org/uc/item/5sb7q6jp). Progress in
Materials Science. 76: 229–318. doi:10.1016/j.pmatsci.2015.06.001 (https://doi.org/10.1016%2
Fj.pmatsci.2015.06.001).
5. "Keratin" (https://www.merriam-webster.com/dictionary/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): 187–199. doi:10.1016/j.asd.2004.05.006
(https://doi.org/10.1016%2Fj.asd.2004.05.006). PMID 18089034 (https://pubmed.ncbi.nlm.nih.g
ov/18089034).
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): 319–330. doi:10.1016/j.actbio.2009.06.033 (https://doi.o
rg/10.1016%2Fj.actbio.2009.06.033). PMID 19577667 (https://pubmed.ncbi.nlm.nih.gov/19577
667).
8. Hickman, Cleveland Pendleton; Roberts, Larry S.; Larson, Allan L. (2003). Integrated principles
of zoology (https://archive.org/details/isbn_9780072930283/page/538). Dubuque, IA: McGraw-
Hill. p. 538 (https://archive.org/details/isbn_9780072930283/page/538). ISBN 978-0-07-
243940-3.
9. Kreplak, L.; Doucet, J.; Dumas, P.; Briki, F. (July 2004). "New Aspects of the α-Helix to β-Sheet
Transition in Stretched Hard α-Keratin Fibers" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1
304386). Biophysical Journal. 87 (1): 640–647. doi:10.1529/biophysj.103.036749 (https://doi.or
g/10.1529%2Fbiophysj.103.036749). PMC 1304386 (https://www.ncbi.nlm.nih.gov/pmc/article
s/PMC1304386). PMID 15240497 (https://pubmed.ncbi.nlm.nih.gov/15240497).
10. Moll, Roland; Divo, Markus; Langbein, Lutz (2008-05-07). "The human keratins: biology and
pathology" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386534). Histochemistry and Cell
Biology. 129 (6): 705–733. doi:10.1007/s00418-008-0435-6 (https://doi.org/10.1007%2Fs00418
-008-0435-6). ISSN 0948-6143 (https://www.worldcat.org/issn/0948-6143). PMC 2386534 (http
s://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386534). PMID 18461349 (https://pubmed.ncbi.nl
m.nih.gov/18461349).
11. Schweizer J, Bowden PE, Coulombe PA, et al. (July 2006). "New consensus nomenclature for
mammalian keratins" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064177). J. Cell Biol.
174 (2): 169–74. doi:10.1083/jcb.200603161 (https://doi.org/10.1083%2Fjcb.200603161).
PMC 2064177 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064177). PMID 16831889 (http
s://pubmed.ncbi.nlm.nih.gov/16831889).
12. 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" (htt
ps://zenodo.org/record/890743). Cell. 31 (1): 243–52. doi:10.1016/0092-8674(82)90424-X (http
s://doi.org/10.1016%2F0092-8674%2882%2990424-X). PMID 6186381 (https://pubmed.ncbi.nl
m.nih.gov/6186381).
13. Hanukoglu, I.; Fuchs, E. (Jul 1983). "The cDNA sequence of a Type II cytoskeletal keratin
reveals constant and variable structural domains among keratins" (https://zenodo.org/record/89
0739). Cell. 33 (3): 915–24. doi:10.1016/0092-8674(83)90034-X (https://doi.org/10.1016%2F00
92-8674%2883%2990034-X). PMID 6191871 (https://pubmed.ncbi.nlm.nih.gov/6191871).
14. 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/PMC3864793). Nat Struct Mol Biol. 19 (7): 707–15.
doi:10.1038/nsmb.2330 (https://doi.org/10.1038%2Fnsmb.2330). PMC 3864793 (https://www.n
cbi.nlm.nih.gov/pmc/articles/PMC3864793). PMID 22705788 (https://pubmed.ncbi.nlm.nih.gov/
22705788).
15. Voet, Donald; Voet, Judith; Pratt, Charlotte. "Proteins: Three-Dimensional Structure" (http://bioc
hem118.stanford.edu/Papers/Protein%20Papers/Voet%26Voet%20chapter6.pdf) (PDF).
Fundamentals of Biochemistry (https://www.amazon.com/exec/obidos/ASIN/0471586501/whati
comascienli#reader_0471586501). p. 158. Retrieved 2010-10-01. "Fibrous proteins are
characterized by a single type of secondary structure: a keratin is a left-handed coil of two a
helices"
16. Hanukoglu I, Ezra L (Jan 2014). "Proteopedia: Coiled-coil structure of keratins". Biochem Mol
Biol Educ. 42 (1): 93–94. doi:10.1002/bmb.20746 (https://doi.org/10.1002%2Fbmb.20746).
PMID 24265184 (https://pubmed.ncbi.nlm.nih.gov/24265184).
17. "Secondary Protein" (https://web.archive.org/web/20100922111144/http://elmhurst.edu/~chm/v
chembook/566secprotein.html). Elmhurst.edu. Archived from the original (http://elmhurst.edu/~c
hm/vchembook/566secprotein.html) on 2010-09-22. Retrieved 2010-09-23.
18. "What is Keratin?" (http://www.wisegeek.org/what-is-keratin.htm). WiseGEEK. Retrieved
11 May 2014.
19. Australia. "Spiders – Silk structure" (https://web.archive.org/web/20090508161836/http://www.a
monline.net.au/spiders/toolkit/silk/structure.htm). Amonline.net.au. Archived from the original (ht
tp://www.amonline.net.au/spiders/toolkit/silk/structure.htm) on 2009-05-08. Retrieved
2010-09-23.
20. 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" (https://doi.org/10.1038/modpathol.3880506). Mod. Pathol. 15 (2):
146–53. doi:10.1038/modpathol.3880506 (https://doi.org/10.1038%2Fmodpathol.3880506).
PMID 11850543 (https://pubmed.ncbi.nlm.nih.gov/11850543).
21. 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" (https://doi.org/10.1038/modpathol.388
0401). Mod. Pathol. 14 (9): 854–61. doi:10.1038/modpathol.3880401 (https://doi.org/10.1038%
2Fmodpathol.3880401). PMID 11557780 (https://pubmed.ncbi.nlm.nih.gov/11557780).
22. Omary MB, Ku NO, Strnad P, Hanada S (July 2009). "Toward unraveling the complexity of
simple epithelial keratins in human disease" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC27
01867). J. Clin. Invest. 119 (7): 1794–805. doi:10.1172/JCI37762 (https://doi.org/10.1172%2FJ
CI37762). PMC 2701867 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701867).
PMID 19587454 (https://pubmed.ncbi.nlm.nih.gov/19587454).
External links
Composition and β-sheet structure of silk (https://web.archive.org/web/20060220123505/http://
www.elmhurst.edu/~chm/vchembook/566secprotein.html)
Hair-Science.com's entry on the microscopic elements of hair (https://web.archive.org/web/200
60113171639/http://www.hair-science.com/_int/_en/topic/topic_sousrub.aspx?tc=ROOT-HAIR-
SCIENCE^PORTRAIT-OF-AN-UNKNOWN-ELEMENT^SUPERB-CHEMISTRY&cur=SUPER
B-CHEMISTRY)
Proteopedia page on keratins (http://www.proteopedia.org/w/Keratins)
Retrieved from "https://en.wikipedia.org/w/index.php?title=Keratin&oldid=971500057"
This page was last edited on 6 August 2020, at 14:35 (UTC).
Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By using this
site, you agree to the Terms of Use and Privacy Policy. Wikipedia® is a registered trademark of the Wikimedia
Foundation, Inc., a non-profit organization.
