Editing Keratin

{{Short description|Structural fibrous protein}}
{{Distinguish|Carotene|Creatine}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
[[File:KeratinF9.png|thumb|300px|Microscopy of keratin filaments inside cells]]

'''Keratin''' ({{IPAc-en|ˈ|k|ɛr|ə|t|ɪ|n}}<ref>''[[OED]]'' 2nd edition, 1989 as {{IPA|/ˈkɛrətɪn/}}</ref><ref>[http://www.merriam-webster.com/dictionary/keratin Entry "keratin"] {{Webarchive|url=https://web.archive.org/web/20130509074726/http://www.merriam-webster.com/dictionary/keratin |date=2013-05-09 }} in ''[http://www.merriam-webster.com/ Merriam-Webster Online Dictionary] {{Webarchive|url=https://web.archive.org/web/20170922151722/https://www.merriam-webster.com/ |date=2017-09-22 }}''.</ref>) is one of a family of structural [[fibrous protein]]s also known as ''scleroproteins''. It is the key structural material making up [[Scale (anatomy)|scales]], [[hair]], [[Nail (anatomy)|nails]], [[feather]]s, [[horn (anatomy)|horns]], [[claw]]s, [[Hoof|hooves]], and the outer layer of [[skin]] in vertebrates. Keratin also protects [[epithelial]] cells from damage or stress. Keratin is extremely insoluble in water and organic solvents. Keratin [[monomer]]s assemble into bundles to form [[intermediate filament]]s, which are tough and form strong [[mineralization (biology)|unmineralized]] epidermal appendages found in [[reptile]]s, [[bird]]s, [[amphibian]]s, and [[mammal]]s.<ref>{{Cite book | vauthors = Fraser R | title = Keratins: Their composition, structure and biosynthesis | location = Bannerstone House | pages = 3–6 | year = 1972 | publisher = Charles C Thomas | isbn = 978-0-398-02283-9 }}</ref><ref name="Wang 2016">{{cite journal | vauthors = Wang B, Yang W, McKittrick J, Meyers MA | title = Keratin: Structure, mechanical properties, occurrence in biological organisms, and efforts at bioinspiration | journal = Progress in Materials Science | volume = 76 | pages = 229–318 | date = March 2016 | doi = 10.1016/j.pmatsci.2015.06.001 }}</ref>  Excessive keratinization participate in fortification of certain tissues such as in horns of [[cattle]] and [[rhino]]s, and [[armadillo]]s' [[osteoderm]].<ref>{{Cite journal | vauthors = Nasoori A | title = Formation, structure, and function of extra-skeletal bones in mammals | journal = Biological Reviews of the Cambridge Philosophical Society | volume = 95 | issue = 4 | pages = 986–1019 | date = 2020 | pmid = 32338826 | doi = 10.1111/brv.12597 | url = https://archive.org/details/formation-structure-and-function-of-extra-skeletal-bones-in-mammals }}</ref> The only other [[biology|biological]] matter known to approximate the [[toughness]] of keratinized tissue is [[chitin]].<ref>{{cite web | title = Keratin | date = 22 May 2023 | work = Webster's Online Dictionary | url = https://www.merriam-webster.com/dictionary/keratin | access-date = 9 August 2018 | archive-date = 1 May 2021 | archive-url = https://web.archive.org/web/20210501121957/https://www.merriam-webster.com/dictionary/keratin | url-status = live }}</ref><ref>{{cite journal | vauthors = Vincent JF, Wegst UG | title = Design and mechanical properties of insect cuticle | journal = Arthropod Structure & Development | volume = 33 | issue = 3 | pages = 187–199 | date = July 2004 | pmid = 18089034 | doi = 10.1016/j.asd.2004.05.006 | bibcode = 2004ArtSD..33..187V }}</ref><ref>{{cite journal | vauthors = Tombolato L, Novitskaya EE, Chen PY, Sheppard FA, McKittrick J | title = Microstructure, elastic properties and deformation mechanisms of horn keratin | journal = Acta Biomaterialia | volume = 6 | issue = 2 | pages = 319–330 | date = February 2010 | pmid = 19577667 | doi = 10.1016/j.actbio.2009.06.033 }}</ref>
Keratin comes in two types: the primitive, softer forms found in all vertebrates and the harder, derived forms found only among [[Sauropsida|sauropsids]] (reptiles and birds).

[[Spider silk]] is classified as keratin,<ref>{{Cite web | title = Keratin | url = https://www.vedantu.com/biology/keratin,%20https://www.vedantu.com/biology/keratin,%20https://www.vedantu.com/biology/keratin,%20https://www.vedantu.com/biology/keratin | access-date = 2022-01-07 | website = VEDANTU }}{{Dead link|date=May 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> although production of the protein may have evolved independently of the process in vertebrates.

== Examples of occurrence ==
[[File:Male impala profile.jpg|thumb|The [[Horn (anatomy)|horns]] of the [[impala]] are made of keratin covering a core of [[bone]].]]
[[Alpha-keratin]]s (α-keratins) are found in all vertebrates. They form the [[hair]] (including [[wool]]), the [[stratum corneum|outer layer of skin]], [[horn (anatomy)|horns]], [[nail (anatomy)|nails]], [[claws]] and [[Hoof|hooves]] of mammals, and the slime threads of [[hagfish]].<ref name="Wang 2016"/> The [[baleen]] plates of filter-feeding [[whale]]s are also made of keratin. '''Keratin filaments''' are abundant in [[keratinocyte]]s in the hornified 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 react with [[Antibody|antibodies]] for keratin 5, keratin 8, and keratin 14. These antibodies are used as [[Fluorescent tag|fluorescent markers]] to distinguish subsets of mouse [[Thymus|thymic]] epithelial cells in genetic studies of the [[thymus]].

The harder [[beta-keratin]]s (β-keratins) are found only in the [[sauropsid]]s, i.e., all living [[reptile]]s and [[bird]]s. They are found in the nails, [[scale (zoology)|scales]], and claws of reptiles, in some reptile [[Exoskeleton|shells]] ([[Testudines]]), and in the [[feather]]s, [[beak]]s, and claws of birds.<ref>{{Cite book | vauthors = Hickman CP, Roberts LS, Larson AL | title = Integrated principles of zoology | location = Dubuque, IA | pages = [https://archive.org/details/isbn_9780072930283/page/538 538] | year = 2003 | publisher = McGraw-Hill | isbn = 978-0-07-243940-3 | url-access = registration | url = https://archive.org/details/isbn_9780072930283/page/538 }}</ref> These keratins are formed primarily in [[beta sheet]]s. However, beta sheets are also found in α-keratins.<ref>{{cite journal | vauthors = Kreplak L, Doucet J, Dumas P, Briki F | title = New Aspects of the α-Helix to β-Sheet Transition in Stretched Hard α-Keratin Fibers | journal = Biophysical Journal | volume = 87 | issue = 1 | pages = 640–647 | date = July 2004 | pmid = 15240497 | pmc = 1304386 | doi = 10.1529/biophysj.103.036749 | bibcode = 2004BpJ....87..640K }}<!--|access-date=15 April 2016--></ref><!-- 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.<ref>{{cite journal | vauthors = Alibardi L | title = Sauropsids Cornification is Based on Corneous Beta-Proteins, a Special Type of Keratin-Associated Corneous Proteins of the Epidermis | journal = Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution | volume = 326 | issue = 6 | pages = 338–351 | date = September 2016 | pmid = 27506161 | doi = 10.1002/jez.b.22689 | bibcode = 2016JEZB..326..338A }}</ref>

Keratins (also described as [[cytokeratins]]) are [[polymer]]s of type I and type II [[intermediate filaments]] that have been found only in [[chordate]]s ([[vertebrate]]s, [[Lancelet|amphioxi]], [[Tunicate|urochordates]]). [[Nematode]]s and many other non-chordate animals seem to have only type VI [[intermediate filaments]], [[lamins|fibers that structure the nucleus]].

== Genes ==
{{Cleanup section|reason=Not particularly helpful to dump a big list of KRT genes here. Using the source a bit more to explain what each gene and each zone of genes mean will be helpful, as we currently have no particular examples of a hair keratin.|date=October 2022}}
[[File:Chromosome 12.svg|thumb|The neutral&ndash;basic keratins are encoded on chromosome 12 (12q13.13).|left| 200x200px]]
[[File:Chromosome 17.svg|thumb|The acidic keratins are encoded on chromosome 17 (17q21.2).|right|200x200px]]
The [[human genome]] encodes 54 functional keratin [[gene]]s, located in two clusters on [[chromosome]]s 12 and 17. This suggests that they originated from a series of gene duplications on these chromosomes.<ref>{{cite journal | vauthors = Moll R, Divo M, Langbein L | title = The human keratins: biology and pathology | journal = Histochemistry and Cell Biology | volume = 129 | issue = 6 | pages = 705–733 | date = June 2008 | pmid = 18461349 | pmc = 2386534 | doi = 10.1007/s00418-008-0435-6 }}</ref>

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.<ref name="Schweizer_2006">{{cite journal | vauthors = Schweizer J, Bowden PE, Coulombe PA, Langbein L, Lane EB, Magin TM, Maltais L, Omary MB, Parry DA, Rogers MA, Wright MW | title = New consensus nomenclature for mammalian keratins | journal = The Journal of Cell Biology | volume = 174 | issue = 2 | pages = 169–174 | date = July 2006 | pmid = 16831889 | pmc = 2064177 | doi = 10.1083/jcb.200603161 }}</ref>
{| class="wikitable mw-collapsible mw-collapsed"
|+Table of keratin genes and biological processes ([[GeneCards]])<ref>{{Cite web | title = GeneCards - Human Genes {{!}} Gene Database|url=https://genecards.org/|access-date=2023-05-08|archive-date=2023-05-13|archive-url=https://web.archive.org/web/20230513220853/https://www.genecards.org/|url-status=live}}</ref>
!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 [https://www.ebi.ac.uk/Tools/msa/clustalo/ Clustal Omega].|centre|659x659px]]

== Protein structure ==
The first sequences of keratins were determined by [[Israel Hanukoglu]] and [[Elaine Fuchs]] (1982, 1983).<ref name="Hanukoglu_1982">{{cite journal | vauthors = Hanukoglu I, Fuchs E | title = The cDNA sequence of a human epidermal keratin: Divergence of sequence but conservation of structure among intermediate filament proteins | journal = Cell | volume = 31 | issue = 1 | pages = 243–252 | date = November 1982 | pmid = 6186381 | doi = 10.1016/0092-8674(82)90424-x }}</ref><ref name="Hanukoglu_1983">{{cite journal | vauthors = Hanukoglu I, Fuchs E | title = The cDNA sequence of a type II cytoskeletal keratin reveals constant and variable structural domains among keratins | journal = Cell | volume = 33 | issue = 3 | pages = 915–924 | date = July 1983 | pmid = 6191871 | doi = 10.1016/0092-8674(83)90034-x }}</ref> These sequences revealed that there are two distinct but homologous keratin families, which were named type I and type II keratins.<ref name="Hanukoglu_1983" /> 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.<ref name="Hanukoglu_1983" /> This model has been confirmed by the determination of the crystal structure of a helical domain of keratins.<ref name="Lee_2012">{{cite journal | vauthors = Lee CH, Kim MS, Chung BM, Leahy DJ, Coulombe PA | title = Structural basis for heteromeric assembly and perinuclear organization of keratin filaments | journal = Nature Structural & Molecular Biology | volume = 19 | issue = 7 | pages = 707–715 | date = July 2012 | pmid = 22705788 | pmc = 3864793 | doi = 10.1038/nsmb.2330 }}</ref>

=== Type I and II keratins ===
The human genome has 54 functional annotated keratin genes, of which 28 are [[type I keratin]]s and 26 are [[type II keratin]]s.<ref>{{cite book | vauthors = Bernot KM, Coulombe PA, Zaher H | chapter = Cytoskeleton &#124; Intermediate Filaments | title = Encyclopedia of Biological Chemistry III | pages = 193–199 | date = 2021 | doi = 10.1016/B978-0-12-819460-7.00037-2 | quote = Type I and type II IFs are part of the keratin (or cytokeratin) family of proteins found in all epithelia. The human genome features 54 functional keratin genes, with 28 type I and 26 type II keratin genes (see Table 1). Type I keratins tend to be smaller and acidic compared to the larger, neutral–basic type II keratins. | isbn = 978-0-12-822040-5 }}</ref> 
[[File:Keratin.jpg|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 [[superhelix|superhelical]] motif to multimerise, forming filaments consisting of multiple copies of the keratin [[monomer]].<ref name="Voet_1998">{{Cite book | vauthors = Voet D, Voet JG, Pratt CW | chapter = Proteins: Three-Dimensional Structure | title = Fundamentals of Biochemistry | pages = 158 | date = 1998 | quote = Fibrous proteins are characterized by a single type of secondary structure: a keratin is a left-handed coil of two a helices | chapter-url = http://biochem118.stanford.edu/Papers/Protein%20Papers/Voet%26Voet%20chapter6.pdf | archive-url = https://web.archive.org/web/20060917080333/http://biochem118.stanford.edu/Papers/Protein%20Papers/Voet%26Voet%20chapter6.pdf | archive-date = 2006-09-17 | url-status = live | publisher = Wiley | isbn = 978-0-471-58650-0 }}</ref>

The major force that keeps the coiled-coil structure is [[Hydrophobicity|hydrophobic interactions]] between [[apolar]] residues along the keratin's helical segments.<ref name="Hanukoglu_2014">{{cite journal | vauthors = Hanukoglu I, Ezra L | title = Proteopedia entry: Coiled-coil structure of keratins: Multimedia in Biochemistry and Molecular Biology Education | journal = Biochemistry and Molecular Biology Education : a Bimonthly Publication of the International Union of Biochemistry and Molecular Biology | volume = 42 | issue = 1 | pages = 93–94 | date = January 2014 | pmid = 24265184 | doi = 10.1002/bmb.20746 | doi-access = free }}</ref>

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, 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.<ref>{{cite web | title = Secondary Protein | url = http://elmhurst.edu/~chm/vchembook/566secprotein.html | publisher = Elmhurst.edu | access-date = 2010-09-23 | url-status = dead | archive-url = https://web.archive.org/web/20100922111144/http://elmhurst.edu/~chm/vchembook/566secprotein.html | archive-date = 2010-09-22 }}</ref> A preponderance of [[amino acid]]s with small, [[chemical reaction|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 bond]]s, the distinguishing feature of keratins is the presence of large amounts of the [[sulfur]]-containing amino acid [[cysteine]], required for the [[disulfide bond|disulfide bridges]] that confer additional strength and rigidity by permanent, thermally stable [[cross-link|crosslinking]]<ref>{{cite web | title = What is Keratin? | url = http://www.wisegeek.org/what-is-keratin.htm | publisher = WiseGEEK | access-date = 11 May 2014 | archive-date = 13 May 2014 | archive-url = https://web.archive.org/web/20140513010609/http://www.wisegeek.org/what-is-keratin.htm | url-status = live }}</ref>—in much the same way that non-protein sulfur bridges stabilize [[vulcanization|vulcanized]] [[rubber]]. Human hair is approximately 14% cysteine. The [[pungency|pungent]] smells of burning hair and skin are due to the volatile sulfur compounds formed. Extensive disulfide bonding contributes to the [[soluble|insolubility]] of keratins, except in a small number of solvents such as [[dissociation (chemistry)|dissociating]] or [[redox|reducing]] agents.
[[File:Toe nail.jpg|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]] [[fingernail]]s, hooves and claws (homologous structures), which are harder and more like their analogs in other vertebrate classes.<ref>{{cite journal | vauthors = H Bragulla H, G Homberger D | title = Structure and functions of keratin proteins in simple, stratified, keratinized and cornified epithelia | journal = Journal of Anatomy | volume = 214 | issue = 4 | pages = 516–559 | date = Apr 2009 | pmid = 19422428 | pmc = 2736122 | doi = 10.1111/j.1469-7580.2009.01066.x }}</ref> Hair and other α-keratins consist of [[alpha helix|α-helically]] coiled single protein strands (with regular intra-chain [[hydrogen bond|H-bonding]]), which are then further twisted into superhelical [[rope]]s 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.<ref>{{cite journal | vauthors = Leichner C, Jelkmann M, Bernkop-Schnürch A | title = Thiolated polymers: Bioinspired polymers utilizing one of the most important bridging structures in nature | journal = Advanced Drug Delivery Reviews | volume = 151-152 | pages = 191–221 | date = 2019 | pmid = 31028759 | doi = 10.1016/j.addr.2019.04.007 }}</ref> Thiomers therefore exhibit high binding properties to keratins found in hair,<ref>{{cite patent | title = Cosmetic compositions containing thiomers for hair color retention | number = 20110229430A1 | inventor = Hawkins G, Afriat IR, Xavier JH, Popescu LC | country = US | pubdate = 22 September 2011 }}</ref> on skin<ref>{{cite journal | vauthors = Grießinger J, Bonengel S, Partenhauser A, Ijaz M, Bernkop-Schnürch A | title = Thiolated polymers: Evaluation of their potential as dermoadhesive excipients | journal = Drug Development and Industrial Pharmacy | volume = 43 | issue = 2 | pages = 204–212 | date = 2017 | pmid = 27585266 | doi = 10.1080/03639045.2016.1231809 }}</ref><ref>{{cite journal | vauthors = Partenhauser A, Zupančič O, Rohrer J, Bonengel S, Bernkop-Schnürch A | title = Thiolated silicone oils as adhesive skin protectants for improved barrier function | journal = International Journal of Cosmetic Science | volume = 38 | issue = 3 | pages = 257–265 | date = 2015 | pmid = 26444859 | doi = 10.1111/ics.12284 }}</ref> and on the surface of many cell types.<ref>{{cite journal | vauthors = Le-Vinh B, Steinbring C, Nguyen Le N, Matuszczak B, Bernkop-Schnürch A | title = S-Protected thiolated chitosan versus thiolated chitosan as cell adhesive biomaterials for tissue engineering. | journal = ACS Applied Materials & Interfaces | volume = 15 | issue = 34 | pages = 40304–40316 | date = 2023 | pmid = 37594415 | pmc = 10472333 | doi = 10.1021/acsami.3c09337 }}</ref>

===Filament formation===
It has been proposed that keratins can be divided into 'hard' and 'soft' forms, or '[[cytokeratin]]s' and 'other keratins'.{{Clarify|date=May 2010}}{{dubious|reason=Not supported by source. Every keratin is cytokeratin until it gets squeezed out by cell death, which happens a bit more often for hair/nail (hard) stuff. The ref does not recommend the cyto- name at all.|date=October 2022}} That model is now understood to be correct. A new nuclear addition in 2006 to describe keratins takes this into account.<ref name="Schweizer_2006" />

Keratin filaments are [[intermediate filament]]s. 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 (biology)|annealing]] end-to-end into long filaments.

===Pairing===

{| class="wikitable" style="margin:1em auto 1em auto"
! '''A''' (neutral-basic)
! '''B''' (acidic)
!Occurrence
|-
| [[keratin 1]], [[keratin 2]]
| [[keratin 9]], [[keratin 10]]
| [[stratum corneum]], [[keratinocyte]]s
|-
| [[keratin 3]]
| [[keratin 12]]
| [[cornea]]
|-
| [[keratin 4]]
| [[keratin 13]]
| [[stratified squamous epithelium|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 [[Corneocyte#Cornified envelope|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 [[cell death|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==
{{More citations needed|date=January 2022}}
The [[silk]] [[fibroin]]s produced by [[insect]]s and [[spider]]s are often classified as keratins, though it is unclear whether they are phylogenetically related to vertebrate keratins.

Silk found in insect [[pupa]]e, and in [[spider web]]s and egg casings, also has twisted β-pleated sheets incorporated into fibers wound into larger supermolecular aggregates. The structure of the [[spinneret (spider)|spinneret]]s on spiders' tails, and the contributions of their interior [[gland]]s, provide remarkable control of fast [[extrusion]]. Spider silk is typically about 1 to 2 micrometers (μm) thick, compared with about 60&nbsp;μm for human hair, and more for some mammals. The [[biology|biologically]] and [[commerce|commercially]] useful properties of [[spider silk#Properties|silk fibers]] depend on the organization of multiple adjacent protein chains into hard, [[crystal]]line regions of varying size, alternating with flexible, [[amorphous]] regions where the chains are [[random coil|randomly coiled]].<ref>{{cite web | vauthors = Australia | title = Spiders – Silk structure | url = http://www.amonline.net.au/spiders/toolkit/silk/structure.htm | publisher = Amonline.net.au | access-date = 2010-09-23 | url-status = dead | archive-url = https://web.archive.org/web/20090508161836/http://www.amonline.net.au/spiders/toolkit/silk/structure.htm | archive-date = 2009-05-08 }}</ref> A somewhat analogous situation occurs with [[chemical synthesis|synthetic]] [[polymer]]s such as [[nylon]], developed as a silk substitute. Silk from the [[hornet]] [[Silkworm cocoons|cocoon]] contains doublets about 10&nbsp;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 [[adhesive|glue]], as do spiders.

==Clinical significance==
Abnormal growth of keratin can occur in a variety of conditions including [[keratosis]], [[hyperkeratosis]] and [[keratoderma]].

Mutations in keratin gene expression can lead to, among others:
* [[Alopecia areata]]
* [[Epidermolysis bullosa simplex]]
* [[Ichthyosis bullosa of Siemens]]
* [[Epidermolytic hyperkeratosis]]
* [[Steatocystoma multiplex]]
* [[Keratosis pharyngis]]
* Rhabdoid cell formation in [[large cell lung carcinoma with rhabdoid phenotype]]<ref name="Shiratsuchi_2002">{{cite journal | vauthors = Shiratsuchi H, Saito T, Sakamoto A, Itakura E, Tamiya S, Oshiro Y, Oda Y, Toh S, Komiyama S, Tsuneyoshi M | title = Mutation Analysis of Human Cytokeratin 8 Gene in Malignant Rhabdoid Tumor: A Possible Association with Intracytoplasmic Inclusion Body Formation | journal = Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc | volume = 15 | issue = 2 | pages = 146–153 | date = February 2002 | pmid = 11850543 | doi = 10.1038/modpathol.3880506 | doi-access = free }}</ref><ref name="Itakura_2001">{{cite journal | vauthors = Itakura E, Tamiya S, Morita K, Shiratsuchi H, Kinoshita Y, Oshiro Y, Oda Y, Ohta S, Furue M, Tsuneyoshi M | title = Subcellular Distribution of Cytokeratin and Vimentin in Malignant Rhabdoid Tumor: Three-Dimensional Imaging with Confocal Laser Scanning Microscopy and Double Immunofluorescence | journal = Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc | volume = 14 | issue = 9 | pages = 854–861 | date = September 2001 | pmid = 11557780 | doi = 10.1038/modpathol.3880401 | doi-access = free }}</ref>

Several diseases, such as [[athlete's foot]] and [[ringworm]], are caused by [[dermatophytes|infectious fungi]] that feed on keratin.<ref>{{cite journal | vauthors = Mercer DK, Stewart CS | title = Keratin hydrolysis by dermatophytes | journal = Medical Mycology | volume = 57 | issue = 1 | pages = 13–22 | date = 1 January 2019 | pmid = 29361043 | doi = 10.1093/mmy/myx160 }}</ref>

Keratin is highly resistant to digestive acids if ingested. [[Cat]]s regularly ingest hair as part of their [[Cat behavior#Grooming|grooming behavior]], leading to the gradual formation of [[hairball]]s 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 [[carcinoma]]s, [[thymoma]]s, [[sarcoma]]s and [[trophoblastic neoplasm]]s. Furthermore, the precise expression-pattern of keratin subtypes allows prediction of the origin of the primary tumor when assessing [[metastasis|metastases]]. For example, [[hepatocellular carcinoma]]s typically express CK8 and CK18, and [[cholangiocarcinoma]]s express CK7, CK8 and CK18, while metastases of [[colorectal carcinoma]]s express CK20, but not CK7.<ref>{{cite journal | vauthors = Omary MB, Ku NO, Strnad P, Hanada S | title = Toward unraveling the complexity of simple epithelial keratins in human disease | journal = The Journal of Clinical Investigation | volume = 119 | issue = 7 | pages = 1794–1805 | date = 1 July 2009 | pmid = 19587454 | pmc = 2701867 | doi = 10.1172/JCI37762 }}</ref>

== 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 ==
{{reflist|30em}}

==External links==
{{Americana Poster}}
*[https://web.archive.org/web/20060220123505/http://www.elmhurst.edu/~chm/vchembook/566secprotein.html Composition and β-sheet structure of silk]
*[https://web.archive.org/web/20060113171639/http://www.hair-science.com/_int/_en/topic/topic_sousrub.aspx?tc=ROOT-HAIR-SCIENCE%5EPORTRAIT-OF-AN-UNKNOWN-ELEMENT%5ESUPERB-CHEMISTRY&cur=SUPERB-CHEMISTRY Hair-Science.com's entry on the microscopic elements of hair]
* [http://www.proteopedia.org/w/Keratins Proteopedia page on keratins]

{{Fibrous proteins}}
{{Cytoskeletal proteins}}

{{Authority control}}

[[Category:Keratins]]
[[Category:Cytoskeleton]]
[[Category:Skin anatomy]]