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| | {{DISPLAYTITLE:Enamelin}} |
| | {{Infobox protein |
| | | name = Enamelin |
| | | image = |
| | | caption = |
| | | width = |
| | | symbol = ENAM |
| | | alt_symbols = |
| | | EntrezGene = 10117 |
| | | HGNCid = 3341 |
| | | OMIM = 606585 |
| | | RefSeq = NM_031889 |
| | | UniProt = Q9NRM1 |
| | | PDB = |
| | }} |
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| '''Enamelin''' is an enamel matrix [[protein]] (EMPs), that in humans is encoded by the ''ENAM'' [[gene]].<ref name="pmid11978766">{{cite journal | vauthors = Mårdh CK, Bäckman B, Holmgren G, Hu JC, Simmer JP, Forsman-Semb K | title = A nonsense mutation in the enamelin gene causes local hypoplastic autosomal dominant amelogenesis imperfecta (AIH2) | journal = Human Molecular Genetics | volume = 11 | issue = 9 | pages = 1069–74 | date = May 2002 | pmid = 11978766 | doi = 10.1093/hmg/11.9.1069 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ENAM enamelin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10117}}</ref> It is part of the non-[[amelogenin]]s, which comprise 10% of the total enamel matrix proteins.<ref name=":0">{{cite book | first1 = Antonio | last1 = Nanci | first2 = Arnold Richard | last2 = Ten Cate | name-list-style = vanc |title=Ten Cate's Oral Histology | edition = 8th | date=2012 |publisher= Elsevier India | isbn = 978-8131233436 |oclc=1027350695}}</ref> It is one of the key proteins thought to be involved in [[amelogenesis]] (enamel development). The formation of enamel's intricate architecture is thought to be rigorously controlled in ameloblasts through interactions of various organic matrix protein molecules that include: enamelin, [[amelogenin]], [[ameloblastin]], [[tuftelin]], dentine sialophosphoprotein, and a variety of enzymes. Enamelin is the largest protein (~168kDa) in the enamel matrix of developing teeth and is the least abundant (encompasses approximately 1-5%) of total enamel matrix proteins.<ref name="entrez" /> It is present predominantly at the growing enamel surface. | | ==Overview== |
| | '''Enamelin''' is a critical [[protein]] involved in the formation of [[dental enamel]], the hard outer layer of [[teeth]]. It is one of the largest enamel matrix proteins and plays a crucial role in the mineralization process during [[amelogenesis]]. |
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| == Structure == | | ==Structure== |
| Enamelin is thought to be the oldest member of the enamel matrix protein (EMP) family, with animal studies showing remarkable conservation of the gene phylogenetically.<ref>{{cite journal | vauthors = Al-Hashimi N, Lafont AG, Delgado S, Kawasaki K, Sire JY | title = The enamelin genes in lizard, crocodile, and frog and the pseudogene in the chicken provide new insights on enamelin evolution in tetrapods | journal = Molecular Biology and Evolution | volume = 27 | issue = 9 | pages = 2078–94 | date = September 2010 | pmid = 20403965 | doi = 10.1093/molbev/msq098 | doi-access = free }}</ref> All other EMPs are derived from enamelin, such as amelogenin.<ref>{{cite journal | vauthors = Sire JY, Davit-Béal T, Delgado S, Gu X | title = The origin and evolution of enamel mineralization genes | journal = Cells Tissues Organs | volume = 186 | issue = 1 | pages = 25–48 | date = 2007 | pmid = 17627117 | doi = 10.1159/000102679 | s2cid = 38992844 }}</ref> EMPs belong to a larger family of proteins termed 'secretory calcium-binding phosphoproteins' (SCPP).<ref>{{cite journal | vauthors = Hu JC, Lertlam R, Richardson AS, Smith CE, McKee MD, Simmer JP | title = Cell proliferation and apoptosis in enamelin null mice | journal = European Journal of Oral Sciences | volume = 119 Suppl 1 | pages = 329–37 | date = December 2011 | pmid = 22243264 | pmc = 3292790 | doi = 10.1111/j.1600-0722.2011.00860.x }}</ref> | | Enamelin is a large glycoprotein, initially synthesized as a precursor protein that undergoes extensive post-translational modifications. The protein is rich in [[proline]], [[glutamine]], and [[leucine]] residues, which contribute to its unique structure and function. Enamelin is secreted by [[ameloblasts]] during the secretory stage of enamel formation. |
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| Similar to other enamel matrix proteins, enamelin undergoes extensive post-translational modifications (mainly phosphorylation), processing, and secretion by proteases. Enamelin has three putative [[phosphoserine]]s (Ser<sup>54</sup>, Ser<sup>191</sup>, and Ser<sup>216</sup> in humans) phosphorylated by a Golgi-associated secretory pathway kinase ([[FAM20C]]) based on their distinctive Ser-x-Glu (S-x-E) motifs.<ref>{{cite journal | vauthors = Yan WJ, Ma P, Tian Y, Wang JY, Qin CL, Feng JQ, Wang XF | title = The importance of a potential phosphorylation site in enamelin on enamel formation | journal = International Journal of Oral Science | volume = 9 | issue = 11 | pages = e4 | date = November 2017 | pmid = 29593332 | pmc = 5775333 | doi = 10.1038/ijos.2017.41 }}</ref> The major secretory product of the ENAM gene has 1103 amino acids (post-secretion), and has an acidic isoelectric point ranging from 4.5–6.5 (depending on the fragment).<ref name="pmid14656895">{{cite journal | vauthors = Hu JC, Yamakoshi Y | title = Enamelin and autosomal-dominant amelogenesis imperfecta | journal = Critical Reviews in Oral Biology and Medicine | volume = 14 | issue = 6 | pages = 387–98 | date = 2003 | pmid = 14656895 | doi = 10.1177/154411130301400602 | doi-access = free }}</ref>
| | ==Function== |
| | The primary function of enamelin is to facilitate the growth and organization of [[hydroxyapatite]] crystals, which are the main mineral component of enamel. Enamelin interacts with other enamel matrix proteins, such as [[amelogenin]] and [[ameloblastin]], to regulate crystal nucleation and elongation. It is essential for the proper development of enamel's prismatic structure. |
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| At the secretory stage, the enzyme matrix metalloproteinase-20 ([[MMP20]]) proteolytically cleaves the secreted enamelin protein immediately upon release, into several smaller polypeptides; each having their own functions. However, the whole protein (~168 kDa) and its largest derivative fragment (~89 kDa) are undetectable in the secretory stage; these are existent only at the mineralisation front.<ref name=":0" /> Smaller polypeptide fragments remain embedded in the enamel, throughout the secretory stage enamel matrix. These strongly bind to the mineral and retard seeded crystal growth.
| | ==Genetics== |
| | The [[ENAM]] gene, located on [[chromosome 4]] in humans, encodes the enamelin protein. Mutations in the ENAM gene can lead to [[amelogenesis imperfecta]], a genetic condition characterized by defective enamel formation. This condition can result in enamel that is thin, soft, and prone to rapid wear and decay. |
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| == Function == | | ==Pathology== |
| The primary function of the proteins acts at the mineralisation front; growth sites where it is the interface between the ameloblast plasma membrane and lengthening extremity of crystals. The key activities of enamelin can be summarised:
| | Mutations in the ENAM gene are associated with various forms of amelogenesis imperfecta, including hypoplastic and hypomineralized types. These mutations can be inherited in an [[autosomal dominant]] or [[autosomal recessive]] manner, depending on the specific genetic alteration. Clinical manifestations include discolored, pitted, or grooved enamel, and increased susceptibility to dental caries. |
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| * Necessary for the adhesion of ameloblasts to the surface of the enamel in the secretory stage<ref name=":1">{{cite book |title= Fundamentals of oral histology and physiology |last1=Hand |first1=Arthur R |last2=Frank |first2=Marion E | name-list-style = vanc |date=2014-11-21 |isbn=9781118938317 |location=Ames, Iowa |oclc=891186059 }}</ref>
| | ==Research and Clinical Implications== |
| * Binds to hydroxyapatite and promotes crystallite elongation
| | Understanding the role of enamelin in enamel formation has significant implications for the development of novel dental treatments and regenerative therapies. Research into enamelin and its interactions with other enamel proteins may lead to advances in biomimetic materials for dental restoration and repair. |
| * Act as a modulator for ''de novo'' mineral formation<ref name=":0" />
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| It is speculated that this protein could interact with amelogenin or other enamel matrix proteins and be important in determining growth of the length of enamel crystallites. The mechanism of this proposed co-interaction is synergistic ("[[Goldilocks principle|Goldilocks effect]]"). With enamelin enhancing the rates of crystal nucleation via the creation of addition sites for EMPs, such as amelogenin, to template calcium phosphate nucleation.<ref>{{Cite journal| vauthors = Tao J, Fijneman A, Wan J, Prajapati S, Mukherjee K, Fernandez-Martinez A, Moradian-Oldak J, De Yoreo JJ |date=2018-12-05|title=Control of Calcium Phosphate Nucleation and Transformation through Interactions of Enamelin and Amelogenin Exhibits the "Goldilocks Effect" |journal=Crystal Growth & Design|volume=18|issue=12|pages=7391–7400|doi=10.1021/acs.cgd.8b01066 |pmid=32280310|url=https://research.tue.nl/nl/publications/control-of-calcium-phosphate-nucleation-and-transformation-through-interactions-of-enamelin-and-amelogenin-exhibits-the-goldilocks-effect(1cb6041f-11c8-415f-8c7a-86dda075be39).html|pmc=7152501}}</ref>
| | ==See Also== |
| | | * [[Amelogenesis imperfecta]] |
| It is best thought to understand the overarching function of enamelin as the proteins responsible for correct enamel thickness formation.
| | * [[Amelogenin]] |
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| == Clinical significance ==
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| Mutations in the ''ENAM'' gene can cause certain subtypes of [[amelogenesis imperfecta]] (AI), a heterogenous group of heritable conditions in which enamel in malformed.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/10117|title=ENAM enamelin [Homo sapiens (human)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2019-02-28}}</ref> Point mutations can cause autosomal-dominant hypoplastic AI, and novel ''ENAM'' mutations can cause autosomal-recessive hypoplastic AI.<ref>{{cite journal | vauthors = Pavlic A, Petelin M, Battelino T | title = Phenotype and enamel ultrastructure characteristics in patients with ENAM gene mutations g.13185-13186insAG and 8344delG | journal = Archives of Oral Biology | volume = 52 | issue = 3 | pages = 209–17 | date = March 2007 | pmid = 17125728 | doi = 10.1016/j.archoralbio.2006.10.010 }}</ref><ref>{{cite journal | vauthors = Hart TC, Hart PS, Gorry MC, Michalec MD, Ryu OH, Uygur C, Ozdemir D, Firatli S, Aren G, Firatli E | display-authors = 6 | title = Novel ENAM mutation responsible for autosomal recessive amelogenesis imperfecta and localised enamel defects | journal = Journal of Medical Genetics | volume = 40 | issue = 12 | pages = 900–6 | date = December 2003 | pmid = 14684688 | pmc = 1735344 | doi = 10.1136/jmg.40.12.900 }}</ref> However, mutations in the ''ENAM'' gene mainly tend to lead to the autosomal-dominant AI.<ref name=":1" /> The phenotype of the mutations are generalised thin enamel and no defined enamel layer.<ref name=":0" />
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| A moderately higher than usual ''ENAM'' expression leads to protrusive structures (often, horizontal grooves) on the surface of enamel, and with high transgene expression, the enamel layer is almost lost.<ref>{{cite journal | vauthors = Kim JW, Seymen F, Lin BP, Kiziltan B, Gencay K, Simmer JP, Hu JC | title = ENAM mutations in autosomal-dominant amelogenesis imperfecta | journal = Journal of Dental Research | volume = 84 | issue = 3 | pages = 278–82 | date = March 2005 | pmid = 15723871 | doi = 10.1177/154405910508400314 | s2cid = 464969 }}</ref>
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| == See also ==
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| * [[Ameloblastin]] | | * [[Ameloblastin]] |
| * [[Amelogenin]] | | * [[Hydroxyapatite]] |
| * [[Amelogenesis]]
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| * [[Amelogenesis imperfecta]]
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| == References == | | ==References== |
| {{reflist|30em}}
| | * Hu, J. C., & Simmer, J. P. (2007). Developmental biology and genetics of dental enamel. In: "Principles of Bone Biology". Academic Press. |
| | * Wright, J. T., & Hart, P. S. (2002). The genetics of enamel development. In: "Connective Tissue and Its Heritable Disorders". Wiley-Liss. |
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| == Further reading == | | ==External Links== |
| {{refbegin|30em}}
| | * [https://www.ncbi.nlm.nih.gov/gene/10117 ENAM gene - NCBI] |
| * {{cite journal | vauthors = Gutierrez SJ, Chaves M, Torres DM, Briceño I | title = Identification of a novel mutation in the enamalin gene in a family with autosomal-dominant amelogenesis imperfecta | journal = Archives of Oral Biology | volume = 52 | issue = 5 | pages = 503–6 | date = May 2007 | pmid = 17316551 | doi = 10.1016/j.archoralbio.2006.09.014 }} | | * [https://www.uniprot.org/uniprot/Q9NRM1 Enamelin - UniProt] |
| * {{cite journal | vauthors = Pavlic A, Petelin M, Battelino T | title = Phenotype and enamel ultrastructure characteristics in patients with ENAM gene mutations g.13185-13186insAG and 8344delG | journal = Archives of Oral Biology | volume = 52 | issue = 3 | pages = 209–17 | date = March 2007 | pmid = 17125728 | doi = 10.1016/j.archoralbio.2006.10.010 }}
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| * {{cite journal | vauthors = Ballif BA, Villén J, Beausoleil SA, Schwartz D, Gygi SP | title = Phosphoproteomic analysis of the developing mouse brain | journal = Molecular & Cellular Proteomics | volume = 3 | issue = 11 | pages = 1093–101 | date = November 2004 | pmid = 15345747 | doi = 10.1074/mcp.M400085-MCP200 | doi-access = free }}
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| * {{cite journal | vauthors = Hart TC, Hart PS, Gorry MC, Michalec MD, Ryu OH, Uygur C, Ozdemir D, Firatli S, Aren G, Firatli E | title = Novel ENAM mutation responsible for autosomal recessive amelogenesis imperfecta and localised enamel defects | journal = Journal of Medical Genetics | volume = 40 | issue = 12 | pages = 900–6 | date = December 2003 | pmid = 14684688 | pmc = 1735344 | doi = 10.1136/jmg.40.12.900 }}
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| * {{cite journal | vauthors = Hart PS, Michalec MD, Seow WK, Hart TC, Wright JT | title = Identification of the enamelin (g.8344delG) mutation in a new kindred and presentation of a standardized ENAM nomenclature | journal = Archives of Oral Biology | volume = 48 | issue = 8 | pages = 589–96 | date = August 2003 | pmid = 12828988 | doi = 10.1016/S0003-9969(03)00114-6 }}
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| * {{cite journal | vauthors = Kida M, Ariga T, Shirakawa T, Oguchi H, Sakiyama Y | title = Autosomal-dominant hypoplastic form of amelogenesis imperfecta caused by an enamelin gene mutation at the exon-intron boundary | journal = Journal of Dental Research | volume = 81 | issue = 11 | pages = 738–42 | date = November 2002 | pmid = 12407086 | doi = 10.1177/154405910208101103 }}
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| * {{cite journal | vauthors = Rajpar MH, Harley K, Laing C, Davies RM, Dixon MJ | title = Mutation of the gene encoding the enamel-specific protein, enamelin, causes autosomal-dominant amelogenesis imperfecta | journal = Human Molecular Genetics | volume = 10 | issue = 16 | pages = 1673–7 | date = August 2001 | pmid = 11487571 | doi = 10.1093/hmg/10.16.1673 | doi-access = free }} | |
| * {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = November 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
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| * {{cite journal | vauthors = Dong J, Gu TT, Simmons D, MacDougall M | title = Enamelin maps to human chromosome 4q21 within the autosomal dominant amelogenesis imperfecta locus | journal = European Journal of Oral Sciences | volume = 108 | issue = 5 | pages = 353–8 | date = October 2000 | pmid = 11037750 | doi = 10.1034/j.1600-0722.2000.108005353.x }}
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| * {{cite journal | vauthors = Hu CC, Hart TC, Dupont BR, Chen JJ, Sun X, Qian Q, Zhang CH, Jiang H, Mattern VL, Wright JT, Simmer JP | title = Cloning human enamelin cDNA, chromosomal localization, and analysis of expression during tooth development | journal = Journal of Dental Research | volume = 79 | issue = 4 | pages = 912–9 | date = April 2000 | pmid = 10831092 | doi = 10.1177/00220345000790040501 | s2cid = 24476486 }}
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| * {{cite journal | vauthors = Forsman K, Lind L, Bäckman B, Westermark E, Holmgren G | title = Localization of a gene for autosomal dominant amelogenesis imperfecta (ADAI) to chromosome 4q | journal = Human Molecular Genetics | volume = 3 | issue = 9 | pages = 1621–5 | date = September 1994 | pmid = 7833920 | doi = 10.1093/hmg/3.9.1621 }}
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| {{refend}}
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| == External links ==
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| * {{UCSC genome browser|ENAM}}
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| * {{UCSC gene details|ENAM}}
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| [[Category:Proteins]] | | [[Category:Proteins]] |
| [[Category:Dentistry]] | | [[Category:Dental enamel]] |
| [[Category:Biomineralization]] | | [[Category:Genetic disorders]] |
| [[Category:Teeth]] | | [[Category:Developmental biology]] |
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| {{adapted}}
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Overview
Enamelin is a critical protein involved in the formation of dental enamel, the hard outer layer of teeth. It is one of the largest enamel matrix proteins and plays a crucial role in the mineralization process during amelogenesis.
Structure
Enamelin is a large glycoprotein, initially synthesized as a precursor protein that undergoes extensive post-translational modifications. The protein is rich in proline, glutamine, and leucine residues, which contribute to its unique structure and function. Enamelin is secreted by ameloblasts during the secretory stage of enamel formation.
Function
The primary function of enamelin is to facilitate the growth and organization of hydroxyapatite crystals, which are the main mineral component of enamel. Enamelin interacts with other enamel matrix proteins, such as amelogenin and ameloblastin, to regulate crystal nucleation and elongation. It is essential for the proper development of enamel's prismatic structure.
Genetics
The ENAM gene, located on chromosome 4 in humans, encodes the enamelin protein. Mutations in the ENAM gene can lead to amelogenesis imperfecta, a genetic condition characterized by defective enamel formation. This condition can result in enamel that is thin, soft, and prone to rapid wear and decay.
Pathology
Mutations in the ENAM gene are associated with various forms of amelogenesis imperfecta, including hypoplastic and hypomineralized types. These mutations can be inherited in an autosomal dominant or autosomal recessive manner, depending on the specific genetic alteration. Clinical manifestations include discolored, pitted, or grooved enamel, and increased susceptibility to dental caries.
Research and Clinical Implications
Understanding the role of enamelin in enamel formation has significant implications for the development of novel dental treatments and regenerative therapies. Research into enamelin and its interactions with other enamel proteins may lead to advances in biomimetic materials for dental restoration and repair.
See Also
References
- Hu, J. C., & Simmer, J. P. (2007). Developmental biology and genetics of dental enamel. In: "Principles of Bone Biology". Academic Press.
- Wright, J. T., & Hart, P. S. (2002). The genetics of enamel development. In: "Connective Tissue and Its Heritable Disorders". Wiley-Liss.
External Links
