Enamelin

ENAM
Identifiers
Aliases	ENAM, AIH2, AI1C, ADAI, enamelin
External IDs	OMIM: 606585; MGI: 1333772; HomoloGene: 9698; GeneCards: ENAM; OMA:ENAM - orthologs
Gene location (Human) Chr. Chromosome 4 (human) Band 4q13.3 Start 70,628,744 bp End 70,646,824 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5|5 E1 Start 88,635,834 bp End 88,653,908 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle islet of Langerhans vastus lateralis muscle striated muscle tissue biceps brachii Skeletal muscle tissue of biceps brachii human kidney deltoid muscle corpus epididymis buccal mucosa cell Top expressed in molar tracheobronchial tree intestinal villus Ileal epithelium perirhinal cortex choroid plexus of fourth ventricle CA3 field lactiferous gland inferior colliculus superior colliculus More reference expression data BioGPS n/a
Gene ontology Molecular function structural constituent of tooth enamel protein binding Cellular component extracellular region endoplasmic reticulum lumen extracellular matrix Biological process odontogenesis of dentin-containing tooth biomineral tissue development amelogenesis regulation of cell morphogenesis ameloblast differentiation positive regulation of enamel mineralization post-translational protein modification Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 5: 88.64 – 88.65 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Enamelin
Identifiers
Symbol	Enamelin
Pfam	PF15362
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Enamelin is an enamel matrix protein, that in humans is encoded by the ENAM gene. It is part of the non amelogenins, which comprise 10% of the total enamel matrix proteins. It is one of the key proteins thought to be involved in amelogenesis (enamel development).

Template:PBB Summary It is present predominantly at the growing enamel surface.

Structure

Words

Major secretory product of ENAM gene is 1103 amino acids, and it is post-translationally modified, secreted, and processed by proteases. (hu and Yamakoshi)

The protein is involved in the mineralization and structural organization of enamel. Defects in this gene result in amelogenesis imperfect type 1C (2nd tab)

Believed to undergo extensive posttranslational modifications; it has N-linked sugars and is phosphorylated.

The full-length protein and its largest derivative fragments (to about 89 kDa) created as soon as the protein is secreted are not detected inside forming (secretory stage) enamel; these are present only at the growing enamel surface.

Small fragments from enamelin, however, do linger within enamel (e.g., 32 kDa and 25 kDa); these bind strongly to mineral and are inhibitory to crystal growth.

The EDTA-soluble protein described in older literature as “enamelin” turned out to be enamelin albumin derived from blood contamination - legacy protein (Nanci)

The protein is present in highest concentration at the mineralization front, but a proteolytic fragment of enamelin is located among the enamel crystals throughout the secretory stage enamel matrix. Molecular interactions between enamelin and amelo- genin have been shown in in vitro experiments and very likely are important for proper enamel crystal growth. Hand and Frank

AA sequence not known, but high in Glycine and Proline. Isoelectric point ranging from 4 to 6.5 (acidic). Anderson

Function

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

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.

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

Murine Studies

Words

Studies using knockout mice (which do not express a given protein), transgenic mice (overexpressing selected protein or ones with point mutations), and mutant mice (expressing altered/defective proteins) are providing us with invaluable information on the function of the various amelo- blast products. Transgenic mice expressing mutated forms of amelogenin and knockout mice exhibit major enamel struc- tural defects that affect overall thickness and enamel rod structure. Consistent with their proposed role in promoting and sustaining mineral formation, no structured enamel layer forms in mice expressing defective ameloblastin or enamelin. This is also the case when expression of enamelin is completely abrogated, attesting to the critical role of non- amelogenins. Nanci

Clinical significance

Words
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)

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.

Three different mutations ENAM gene mutations are associated with different AI types. Anderson

See also

Ameloblastin

Amelogenin

Amelogenesis

Amelogenesis imperfecta

External links

• ENAM human gene location in the UCSC Genome Browser.
• ENAM human gene details in the UCSC Genome Browser.