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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 | url = https://academic.oup.com/mbe/article/27/9/2078/1009898 }}</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 | url = https://www.karger.com/Article/FullText/102679 }}</ref> EMPs belong to a larger family of proteins termed 'secretory calcium-binding phosphoproteins' (SCPP).<ref>{{Cite journal|last=Hu|first=Jan C-C.|last2=Lertlam|first2=Rangsiyakorn|last3=Richardson|first3=Amelia S.|last4=Smith|first4=Charles E.|last5=McKee|first5=Marc D.|last6=Simmer|first6=James P.|date=2011-12|title=Cell proliferation and apoptosis in enamelin null mice: Enam null mice|url=http://doi.wiley.com/10.1111/j.1600-0722.2011.00860.x|journal=European Journal of Oral Sciences|language=en|volume=119|pages=329–337|doi=10.1111/j.1600-0722.2011.00860.x|pmc=PMC3292790|pmid=22243264}}</ref>
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 | url = https://academic.oup.com/mbe/article/27/9/2078/1009898 }}</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 | url = https://www.karger.com/Article/FullText/102679 }}</ref> EMPs belong to a larger family of proteins termed 'secretory calcium-binding phosphoproteins' (SCPP).<ref>{{Cite journal|last=Hu|first=Jan C-C.|last2=Lertlam|first2=Rangsiyakorn|last3=Richardson|first3=Amelia S.|last4=Smith|first4=Charles E.|last5=McKee|first5=Marc D.|last6=Simmer|first6=James P.|date=2011-12|title=Cell proliferation and apoptosis in enamelin null mice: Enam null mice|url=http://doi.wiley.com/10.1111/j.1600-0722.2011.00860.x|journal=European Journal of Oral Sciences|language=en|volume=119|pages=329–337|doi=10.1111/j.1600-0722.2011.00860.x|pmc=PMC3292790|pmid=22243264}}</ref>


Similar to other enamel matrix proteins, enamelin undergoes extensive post-translational modifications (mainly phosphorylation), processing, and secretion by proteases. Enamelin has three putative [[Phosphoserine|phosphoserines]] (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 | url = https://www.nature.com/articles/ijos201741 }}</ref> The major secretory product of the ENAM gene has 1103 amino acids (post-secretion), and has an isoelectric point ranging from 4.5 to 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 : an Official Publication of the American Association of Oral Biologists | volume = 14 | issue = 6 | pages = 387–98 | date = 2003 | pmid = 14656895 | doi = 10.1177/154411130301400602 }}</ref>
Similar to other enamel matrix proteins, enamelin undergoes extensive post-translational modifications (mainly phosphorylation), processing, and secretion by proteases. Enamelin has three putative [[Phosphoserine|phosphoserines]] (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 | url = https://www.nature.com/articles/ijos201741 }}</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 : an Official Publication of the American Association of Oral Biologists | volume = 14 | issue = 6 | pages = 387–98 | date = 2003 | pmid = 14656895 | doi = 10.1177/154411130301400602 }}</ref>


Enzymes proteolytically cleave the secreted enamelin protein 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.
Matrix metalloproteinase-20 ([[MMP20]]) proteolytically cleaves the secreted enamelin protein 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.


== Function ==
== Function ==
Primary function acts at mineralisation front; growth sites where it is the interface between ameloblast plasma membrane and lengthening extremity of crystals. It is critical for enamel mineralisation and thought to be imperative for correct elongation of the enamel crystallites during the secretory stage. <ref>{{Cite book|url=https://www.worldcat.org/oclc/891186059|title=Fundamentals of oral histology and physiology|last=1943-|first=Hand, Arthur R.,|others=Frank, Marion E. (Marion Elizabeth), 1940-|isbn=9781118938317|location=Ames, Iowa|oclc=891186059}}</ref>
Words

Believed to function in part as a modulator for de novo formation of mineral and to promote crystal elongation. Ted Cate's

Concentrated near the cell surface at sites where they are secreted (mineralisation front). At these growth sites, the interface between the membrane and the lengthening extremity of crystals can in fact be regarded as a mineralization front. Primary function at mineralisation front.

Critical for enamel mineralization and adhesion of ameloblasts to enamel surface during the secretory stage. Hand and Frank


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.
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.

Binds to HAP. It is known to retard seeded growth. Anderson

<br />


== Clinical significance ==
== Clinical significance ==
Mutations in ''ENAM'' gene can cause certain forms of [[Amelogenesis imperfecta|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> The forms are autosomal-dominant hypoplastic AI; generalised thin enamel and no defined enamel layer.<ref name=":0" />
⚫
Higher - protrusive structure on the surface of enamel; with high transgene expression, the enamel layer is almost lost.

The protein is involved in the mineralization and structural organization of enamel. Defects in this gene result in amelogenesis imperfect type 1C (<nowiki>https://www.ncbi.nlm.nih.gov/gene/10117</nowiki>)

Loss of function & mutant protein: No defined enamel layer. Nanci

Mutations in ENAM cause a severe form of autosomal-dominant smooth hypoplastic AI that represents 1.5%, and a mild form of autosomal-dominant local hypoplastic AI that accounts for 27% of AI cases in Sweden. (Hu and Yamakoshi)

Enamelin mutations have been found to cause certain forms of amelogenesis imperfecta, a condition in which enamel is malformed

Autosomal Dominant Hypoplastic AI - ENAM (Hand and Frank)

Mutations in the genes for enamel matrix proteins such as amelogenin (''AMELX'') and enamelin (''ENAM'') result in varying degrees of enamel hypoplasia and hypomineralization. These include pit- ting and grooves, as well as generalized thin enamel, and disruption of the normal rod structure.


⚫
A moderately higher than usual ''ENAM'' expression leads to protrusive structures (grooves) on the surface of enamel; with high transgene expression, the enamel layer is almost lost.
Three different mutations ENAM gene mutations are associated with different AI types. Anderson


== See also ==
== See also ==

Revision as of 00:00, 1 March 2019

ENAM
Identifiers
AliasesENAM, AIH2, AI1C, ADAI, enamelin
External IDsOMIM: 606585; MGI: 1333772; HomoloGene: 9698; GeneCards: ENAM; OMA:ENAM - orthologs
Orthologs
SpeciesHumanMouse
Entrez

10117

13801

Ensembl

ENSG00000132464

ENSMUSG00000029286

UniProt

Q9NRM1

O55196

RefSeq (mRNA)

NM_031889
NM_001368133

NM_017468

RefSeq (protein)

NP_114095
NP_001355062

NP_059496

Location (UCSC)Chr 4: 70.63 – 70.65 MbChr 5: 88.64 – 88.65 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Enamelin
Identifiers
SymbolEnamelin
PfamPF15362
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Enamelin is an enamel matrix protein (EMPs), that in humans is encoded by the ENAM gene.[5][6] It is part of the non-amelogenins, which comprise 10% of the total enamel matrix proteins.[7] It is one of the key proteins thought to be involved in amelogenesis (enamel development). Dental enamel is a highly mineralized tissue with 96% of its volume occupied by unusually large, highly organised, hydroxyapatite crystals. 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 5%) of total enamel matrix proteins.[6] It is present predominantly at the growing enamel surface.

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.[8] All other EMPs are derived from enamelin, such as amelogenin.[9] EMPs belong to a larger family of proteins termed 'secretory calcium-binding phosphoproteins' (SCPP).[10]

Similar to other enamel matrix proteins, enamelin undergoes extensive post-translational modifications (mainly phosphorylation), processing, and secretion by proteases. Enamelin has three putative phosphoserines (Ser54, Ser191, and Ser216 in humans) phosphorylated by a Golgi-associated secretory pathway kinase (FAM20C) based on their distinctive Ser-x-Glu (S-x-E) motifs.[11] 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).[12]

Matrix metalloproteinase-20 (MMP20) proteolytically cleaves the secreted enamelin protein 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.[7] 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.

Function

Primary function acts at mineralisation front; growth sites where it is the interface between ameloblast plasma membrane and lengthening extremity of crystals. It is critical for enamel mineralisation and thought to be imperative for correct elongation of the enamel crystallites during the secretory stage. [13]

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.

Clinical significance

Mutations in ENAM gene can cause certain forms of amelogenesis imperfecta (AI), a heterogenous group of heritable conditions in which enamel in malformed.[14] The forms are autosomal-dominant hypoplastic AI; generalised thin enamel and no defined enamel layer.[7]

A moderately higher than usual ENAM expression leads to protrusive structures (grooves) on the surface of enamel; with high transgene expression, the enamel layer is almost lost.

See also

Ameloblastin

Amelogenin

Amelogenesis

Amelogenesis imperfecta

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000132464 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029286 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Mårdh CK, Bäckman B, Holmgren G, Hu JC, Simmer JP, Forsman-Semb K (May 2002). "A nonsense mutation in the enamelin gene causes local hypoplastic autosomal dominant amelogenesis imperfecta (AIH2)". Human Molecular Genetics. 11 (9): 1069–74. doi:10.1093/hmg/11.9.1069. PMID 11978766.
  6. ^ a b "Entrez Gene: ENAM enamelin".
  7. ^ a b c ANTONIO., NANCI, (2012). TEN CATE'S ORAL HISTOLOGY, 8E. [Place of publication not identified],: ELSEVIER INDIA. ISBN 813123343X. OCLC 1027350695.{{cite book}}: CS1 maint: extra punctuation (link) CS1 maint: multiple names: authors list (link)
  8. ^ Al-Hashimi N, Lafont AG, Delgado S, Kawasaki K, Sire JY (September 2010). "The enamelin genes in lizard, crocodile, and frog and the pseudogene in the chicken provide new insights on enamelin evolution in tetrapods". Molecular Biology and Evolution. 27 (9): 2078–94. doi:10.1093/molbev/msq098. PMID 20403965.
  9. ^ Sire JY, Davit-Béal T, Delgado S, Gu X (2007). "The origin and evolution of enamel mineralization genes". Cells, Tissues, Organs. 186 (1): 25–48. doi:10.1159/000102679. PMID 17627117.
  10. ^ Hu, Jan C-C.; Lertlam, Rangsiyakorn; Richardson, Amelia S.; Smith, Charles E.; McKee, Marc D.; Simmer, James P. (2011-12). "Cell proliferation and apoptosis in enamelin null mice: Enam null mice". European Journal of Oral Sciences. 119: 329–337. doi:10.1111/j.1600-0722.2011.00860.x. PMC 3292790. PMID 22243264. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  11. ^ Yan WJ, Ma P, Tian Y, Wang JY, Qin CL, Feng JQ, Wang XF (November 2017). "The importance of a potential phosphorylation site in enamelin on enamel formation". International Journal of Oral Science. 9 (11): e4. doi:10.1038/ijos.2017.41. PMC 5775333. PMID 29593332.
  12. ^ Hu JC, Yamakoshi Y (2003). "Enamelin and autosomal-dominant amelogenesis imperfecta". Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists. 14 (6): 387–98. doi:10.1177/154411130301400602. PMID 14656895.
  13. ^ 1943-, Hand, Arthur R.,. Fundamentals of oral histology and physiology. Frank, Marion E. (Marion Elizabeth), 1940-. Ames, Iowa. ISBN 9781118938317. OCLC 891186059. {{cite book}}: |last= has numeric name (help)CS1 maint: extra punctuation (link) CS1 maint: multiple names: authors list (link)
  14. ^ "ENAM enamelin [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-02-28.

Further reading

External links


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