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Keratin
Keratin
(/ˈkɛrətɪn/[1][2]) 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. Keratin
Keratin
is also the protein that protects epithelial cells from damage or stress. Keratin
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]

Contents

1 Etymology 2 Examples of occurrence 3 Genes 4 Protein
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[edit] Keratin
Keratin
derives from Greek κερατίνη from Greek keras (κέρας) (genitive keratos, κέρατος) meaning "horn" originating from the Proto-Indo-European
Proto-Indo-European
*ḱer- 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[edit]

Horns such as those of the impala are made up of keratin covering a core of live bone.

Keratin
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.[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, some reptile shells (Testudines, such as tortoise, turtle, terrapin), and in the feathers, beaks, and claws of birds.[11] (These keratins are formed primarily in beta sheets. However, beta sheets are also found in α-keratins.)[12]

Additionally, 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[edit]

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 chromosomes.[13] 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
KRT85
and KRT86
KRT86
have been used to describe keratins past 20.[14]

Protein
Protein
sequence alignment of human Keratin
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.

Protein
Protein
structure[edit] 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 α-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]

Keratin
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.[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
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.[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[edit] 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
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[edit] 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.[14] Keratin
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[edit]

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[edit] 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 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
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. Silk[edit] 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
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
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.[22] A somewhat analogous situation occurs with synthetic polymers such as nylon, developed as a silk substitute. Silk
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[edit] 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.[citation needed] 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]

Keratin
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.[25] Keratin
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[edit]

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

References[edit]

^ OED
OED
2nd edition, 1989 as /ˈkɛrətɪn/ ^ Entry "keratin" in Merriam-Webster Online Dictionary. ^ Fraser, R.D.B. (1972). Keratins: Their composition, structure and biosynthesis. Bannerstone House: Charles C Thomas. pp. 3–6. ISBN 0-398-02283-6.  ^ a b Wang, Bin (2016). "Keratin: Structure, mechanical properties, occurrence in biological organisms, and efforts at bioinspiration". Progress in Materials Science. 76: 229–318. doi:10.1016/j.pmatsci.2015.06.001.  ^ "Keratin". Webster's Online Dictionary. [permanent dead link] ^ 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.  ^ 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. PMID 19577667.  ^ "Keratin". Online Etymology Dictionary.  "Horn". Online Etymology Dictionary.  ^ "kerato-". Online Etymology Dictionary.  "Horn". Online Etymology Dictionary.  ^ "-in/-ine chemical suffix". Online Etymology Dictionary.  ^ 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.  ^ 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
Keratin
Fibers". Biophysical Journal. 87 (1): 640–647. doi:10.1529/biophysj.103.036749. PMC 1304386 . PMID 15240497.  ^ Moll, Roland; Divo, Markus; Langbein, Lutz (2008-05-07). "The human keratins: biology and pathology". Histochemistry and Cell Biology. 129 (6): 705–733. doi:10.1007/s00418-008-0435-6. ISSN 0948-6143.  ^ a b Schweizer J, Bowden PE, Coulombe PA, et al. (July 2006). "New consensus nomenclature for mammalian keratins". J. Cell Biol. 174 (2): 169–74. doi:10.1083/jcb.200603161. PMC 2064177 . PMID 16831889.  ^ 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): 243–52. doi:10.1016/0092-8674(82)90424-X. PMID 6186381.  ^ a b c Hanukoglu, I.; Fuchs, E. (Jul 1983). "The cDNA sequence of a Type II cytoskeletal keratin reveals constant and variable structural domains among keratins". Cell. 33 (3): 915–24. doi:10.1016/0092-8674(83)90034-X. PMID 6191871.  ^ Lee, CH.; Kim, MS.; Chung, BM.; Leahy, DJ.; Coulombe, PA. (Jul 2012). "Structural basis for heteromeric assembly and perinuclear organization of keratin filaments". Nat Struct Mol Biol. 19 (7): 707–15. doi:10.1038/nsmb.2330. PMC 3864793 . PMID 22705788.  ^ Voet, Donald; Voet, Judith; Pratt, Charlotte. "Proteins: Three-Dimensional Structure" (PDF). Fundamentals of Biochemistry. 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  ^ 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. PMID 24265184.  ^ "Secondary Protein". Elmhurst.edu. Archived from the original on 2010-09-22. Retrieved 2010-09-23.  ^ "What is Keratin?". WiseGEEK. Retrieved 11 May 2014.  ^ Australia. "Spiders – Silk
Silk
structure". Amonline.net.au. Archived from the original on 2009-05-08. Retrieved 2010-09-23.  ^ 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): 146–53. doi:10.1038/modpathol.3880506. PMID 11850543.  ^ 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): 854–61. doi:10.1038/modpathol.3880401. PMID 11557780.  ^ Omary MB, Ku NO, Strnad P, Hanada S (July 2009). "Toward unraveling the complexity of simple epithelial keratins in human disease". J. Clin. Invest. 119 (7): 1794–805. doi:10.1172/JCI37762. PMC 2701867 . PMID 19587454. 

External links[edit]

Wikisource
Wikisource
has the text of the 1920 Encyclopedia Americana
Encyclopedia Americana
article Keratin.

Composition and β-sheet structure of silk Hair-Science.com's entry on the microscopic elements of hair Proteopedia page on keratins

v t e

Protein: scleroproteins

Extracellular matrix

Collagen

Fibril forming

type I

COL1A1 COL1A2

type II (COL2A1) type III type V

COL5A1 COL5A2 COL5A3

COL24A1 COL26A1

Other

FACIT: type IX

COL9A1 COL9A2 COL9A3

type XII (COL12A1) COL14A1 COL16A1 COL19A1 COL20A1 COL21A1 COL22A1

basement membrane: type IV

COL4A1 COL4A2 COL4A3 COL4A4 COL4A5 COL4A6

multiplexin: COL15A1 type XVIII

COL18A1 Endostatin

transmembrane: COL13A1 COL17A1 COL23A1 COL25A1

other: type VI

COL6A1 COL6A2 COL6A3 COL6A5

type VII (COL7A1) type VIII

COL8A1 COL8A2

type X (COL10A1) type XI

COL11A1 COL11A2

COL27A1 COL28A1

Enzymes

Prolyl hydroxylase/Lysyl hydroxylase Cartilage
Cartilage
associated protein/Leprecan ADAMTS2 Procollagen peptidase Lysyl oxidase

Laminin

alpha

LAMA1 LAMA2 LAMA3 LAMA4 LAMA5

beta

LAMB1 LAMB2 LAMB3 LAMB4

gamma

LAMC1 LAMC2 LAMC3

Other

ALCAM Elastin

Tropoelastin

Vitronectin FRAS1 FREM2 Decorin FAM20C ECM1 Matrix gla protein Tectorin

TECTA TECTB

Other

Keratin/Cytokeratin Gelatin Reticulin Cartilage
Cartilage
oligomeric matrix protein

v t e

Proteins of the cytoskeleton

Human

Microfilaments and ABPs

Myofilament

Actins

A1 A2 B C1 G1 G2

Myosins

I

MYO1A MYO1B MYO1C MYO1D MYO1E MYO1F MYO1G MYO1H)

II

MYH1 MYH2 MYH3 MYH4 MYH6 MYH7 MYH7B MYH8 MYH9 MYH10 MYH11 MYH13 MYH14 MYH15 MYH16

III

MYO3A MYO3B

V

MYO5A MYO5B MYO5C

VI

MYO6

VII

MYO7A MYO7B

IX

MYO9A MYO9B

X

MYO10

XV

MYO15A

XVIII

MYO18A MYO18B

LC

MYL1 MYL2 MYL3 MYL4 MYL5 MYL6 MYL6B MYL7 MYL9 MYLIP MYLK MYLK2 MYLL1

Other

Tropomodulin

1 2 3 4

Troponin

T 1 2 3 C 1 2 I 1 2 3

Tropomyosin

1 2 3 4

Actinin

1 2 3 4

Arp2/3 complex actin depolymerizing factors

Cofilin

1 2

Destrin

Gelsolin Profilin

1 2

Titin

Other

Wiskott-Aldrich syndrome protein Fibrillin Filamin

FLNA FLNB FLNC

Espin TRIOBP

Intermediate filaments

Type 1/2 (Keratin, Cytokeratin)

Epithelial
Epithelial
keratins (soft alpha-keratins)

type I/chromosome 17

10 12 13 14 15 16 17 19 20

chromosome 12

18

none

21

type II/chromosome 12

1 2A 3 4 5 6A 6B 7 8 9

Hair
Hair
keratins (hard alpha-keratins)

type I/chromosome 17

31 32 33A 33B 34 35 36 37 38

type II/chromosome 12

81 82 83 84 85 86

Ungrouped alpha

chromosome 17

23 24 25 26 27 28 39 40

chromosome 12

71 72 73 74 75 76 77 78 79 80

Not alpha

Beta-keratin

Type 3

Desmin GFAP Peripherin Vimentin

Type 4

Internexin Nestin Neurofilament

NEFL NEFM NEFH

Synemin Syncoilin

Type 5

Nuclear lamins: A/C B1 B2

Microtubules and MAPs

Kinesins

KIF1A KIF1B KIF2A KIF2C KIF3B KIF3C KIF4A KIF4B KIF5A KIF5B KIF5C KIF6 KIF7 KIF9 KIF11 KIF12 KIF13A KIF13B KIF14 KIF15 KIF16B KIF17 KIF18A KIF18B KIF19 KIF20A KIF20B KIF21A KIF21B KIF22 KIF23 KIF24 KIF25 KIF26A KIF26B KIF27 KIFC1 KIFC2 KIFC3

Dyneins

axonemal: DNAH1 DNAH2 DNAH3 DNAH5 DNAH6 DNAH7 DNAH8 DNAH9 DNAH10 DNAH11 DNAH12 DNAH13 DNAH14 DNAH17 DNAI1 DNAI2 DNALI1 DNAL1 DNAL4

cytoplasmic: DYNC1H1 DYNC2H1 DYNC1I1 DYNC1I2 DYNC1LI1 DYNC1LI2 DYNC2LI1 DYNLL1 DYNLL2 DYNLRB1 DYNLRB2 DYNLT1 DYNLT3

Other

Tau protein Dynactin

DCTN1

Tubulins

TUBA1A TUBA1B TUBA1C TUBA3C TUBA3D TUBA3E TUBA4A TUBA8

Stathmin Tektin

TEKT1 TEKT2 TEKT3 TEKT4 TEKT5

Dynamin

DNM1 DNM2 DNM3

Catenins

Alpha catenin Beta catenin

APC

Plakoglobin
Plakoglobin
(gamma catenin) Delta catenin GAN

Membrane

Dystrophin

Dystroglycan

Utrophin Ankyrin

ANK1 ANK2 ANK3

Spectrin

SPTA1 SPTAN1 SPTB SPTBN1 SPTBN2 SPTBN4 SPTBN5

Other

Plakins

Corneodesmosin Desmoplakin Dystonin Envoplakin MACF1 Periplakin Plectin

Talin

TLN1

Vinculin Plakophilin

PKP1 PKP2

Nonhuman

Major sperm proteins Prokaryotic cytoskeleton

Crescentin FtsZ MreB

See also: cytoskeletal defects

Authority control

N