AMBN (ameloblastin (enamel matrix protein))

2011-12-01   Marina Gonçalves Diniz , Ricardo Santiago Gomez , Carolina Cavalieri Gomes , André Luiz Sena Guimarães 





The putative start codon location and exon-intron sizes differs among reports in literature.
Atlas Image
The genomic organization of the human ameloblastin gene according to Mardh et al., 2001. The map is drawn to scale. Filled boxes represent exons and the thin lines indicate introns. Sequencing of AMBN intron 11 revealed an interrupted dinucleotide repeat (CA)n.


13 exons and 12 introns (Toyosawa et al., 2000; Macdougall et al., 2000) encompassing approximately 15005 bp. Until 2011, 44 SNP were described (NCBI dbSNP).


Alternatively spliced. Exon 6 can be excluded by the use of an alternative splice site (Macdougall et al., 2000). There are 2 validated alternative polyadenylation sites.



The predicted protein has 447 aa (48,3 kDa). There are 3 protein isoforms. The human precursor protein contains a phosphorylation site for tyrosine kinase, a SH3 binding region, an O-linked glycosylation, and a heparin binding domain (Kobayashi et al., 2007; Krebsbach et al., 1996; Yamakoshi et al., 2001; Sonoda et al., 2009). Ameloblastin is cleaved after secretion into several lower-molecular-mass proteins that are developmentally expressed (Ravindranath et al., 2007).


Tomes processes of secretory ameloblasts (Krebsbach et al., 1996; Cerny et al., 1996; Fong et al., 1996), odontoblasts and pre-odontoblasts (Fong et al., 1996; Nagano et al., 2003). Outer enamel, and sheath space between rod and interrod enamel (Uchida et al., 1995; Macdougall et al., 2000). Early bone and cartilage extracellular matrices during embryogenesis (Spahr et al., 2006).


Extracellular matrix.


Tooth enamel biomineralization (Uchida et al., 1997). Interactions between the ameloblasts and the enamel extracellular matrix (Fukumoto et al., 2004). Dental epithelium cell adhesion (Sonoda et al., 2009). Early bone formation and repair (Iizuza et al., 2011; Tamburstuen et al., 2011).


Pig (sheathlin), cattle, rat, and mouse AMBN sequences showed a high amino acid sequence similarity.



AMBN gene mutations have been observed in several epithelial odontogenic tumor entities: unicystic ameloblastoma, solid ameloblastoma, adenomatoid odontogenic tumor, squamous odontogenic tumor, and calcifying epithelial odontogenic tumor (Toyosawa et al., 2000; Perdigão et al., 2004; Perdigão et al., 2009).

Implicated in

Entity name
Odontogenic tumors
Odontogenic tumours arise from the residues of odontogenic epithelium and/or ectomesenchyme, as a result of disturbances in the development of teeth and associated structures.
AMBN gene is mutated in ameloblastomas and others odontogenic tumors (Toyosawa et al., 2000; Perdigão et al., 2004; Perdigão et al., 2009). Ambn-null mice develop odontogenic tumors of dental epithelium origin (Fukumoto et al., 2004). AMBN expression prevents odontogenic tumor development by suppressing cell proliferation and maintaining differentiation phenotype through Msx2, p21, and p27 (Sonoda et al., 2009). The absence of ameloblastin in epithelial odontogenic tumors has been considered a useful marker for the functional differentiation of secretory ameloblast (Takata et al., 2000).
Entity name
Amelogenesis imperfecta
Amelogenesis imperfect is a common group of inherited defects such as hypoplastic or hypomineralized enamel. Autosomal dominant, autosomal recessive, and X-linked forms of amelogenesis imperfect are recognized.
Amelogenin and ameloblastin have an impaired secretion in ameloblasts of phenocopies human X-linked amelogenesis imperfect mice, which results in severe enamel bio-mineralization defects, loss of ameloblast phenotype, increased ameloblast apoptosis, and formation of multi-cellular masses (Barron et al., 2010). AMBN mutations in the coding region or splice sites were discarted to be responsible for autosomal dominant amelogenesis imperfecta (Mardh et al., 2001).


Pubmed IDLast YearTitleAuthors
200679202010A mutation in the mouse Amelx tri-tyrosyl domain results in impaired secretion of amelogenin and phenocopies human X-linked amelogenesis imperfecta.Barron MJ et al
87971071996A novel gene expressed in rat ameloblasts codes for proteins with cell binding domains.Cerný R et al
87971081996Amelin: an enamel-related protein, transcribed in the cells of epithelial root sheath.Fong CD et al
155830342004Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts.Fukumoto S et al
211495782011Ameloblastin regulates osteogenic differentiation by inhibiting Src kinase via cross talk between integrin beta1 and CD63.Iizuka S et al
178906722007Splicing determines the glycosylation state of ameloblastin.Kobayashi K et al
86267941996Full-length sequence, localization, and chromosomal mapping of ameloblastin. A novel tooth-specific gene.Krebsbach PH et al
109467652000Cloning, characterization and immunolocalization of human ameloblastin.MacDougall M et al
113309372001Human ameloblastin gene: genomic organization and mutation analysis in amelogenesis imperfecta patients.Mårdh CK et al
146308992003Relative levels of mRNA encoding enamel proteins in enamel organ epithelia and odontoblasts.Nagano T et al
196613172009Mutation of ameloblastin gene in calcifying epithelial odontogenic tumor.Perdigão PF et al
179214542007Spatiotemporal expression of ameloblastin isoforms during murine tooth development.Ravindranath RM et al
196481212009Critical role of heparin binding domains of ameloblastin for dental epithelium cell adhesion and ameloblastoma proliferation.Sonoda A et al
171842332006Ameloblastin expression during craniofacial bone formation in rats.Spahr A et al
108345342000Immunohistochemical demonstration of an enamel sheath protein, sheathlin, in odontogenic tumors.Takata T et al
208549432011Ameloblastin expression and putative autoregulation in mesenchymal cells suggest a role in early bone formation and repair.Tamburstuen MV et al
110545292000Cloning and characterization of the human ameloblastin gene.Toyosawa S et al
93137951997Synthesis, secretion, degradation, and fate of ameloblastin during the matrix formation stage of the rat incisor as shown by immunocytochemistry and immunochemistry using region-specific antibodies.Uchida T et al
115437072001Calcium binding of enamel proteins and their derivatives with emphasis on the calcium-binding domain of porcine sheathlin.Yamakoshi Y et al

Other Information

Locus ID:

NCBI: 258
MIM: 601259
HGNC: 452
Ensembl: ENSG00000178522


dbSNP: 258
ClinVar: 258
TCGA: ENSG00000178522


Gene IDTranscript IDUniprot

Expression (GTEx)



Pubmed IDYearTitleCitations
187810682008Enamel formation genes are associated with high caries experience in Turkish children.41
248589072014Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta.41
211495782011Ameloblastin regulates osteogenic differentiation by inhibiting Src kinase via cross talk between integrin beta1 and CD63.23
183530052008Bioinformatic analysis and molecular modelling of human ameloblastin suggest a two-domain intrinsically unstructured calcium-binding protein.21
200439042010Identification of a fibronectin interaction site in the extracellular matrix protein ameloblastin.21
237905032013Genes expressed in dental enamel development are associated with molar-incisor hypomineralization.21
237826912013Intrinsically disordered enamel matrix protein ameloblastin forms ribbon-like supramolecular structures via an N-terminal segment encoded by exon 5.19
208315782010Ameloblastin promotes bone growth by enhancing proliferation of progenitor cells and by stimulating immunoregulators.18
208549432011Ameloblastin expression and putative autoregulation in mesenchymal cells suggest a role in early bone formation and repair.17
262232662015Evolutionary analysis of selective constraints identifies ameloblastin (AMBN) as a potential candidate for amelogenesis imperfecta.14


Marina Gonçalves Diniz ; Ricardo Santiago Gomez ; Carolina Cavalieri Gomes ; André Luiz Sena Guimarães

AMBN (ameloblastin (enamel matrix protein))

Atlas Genet Cytogenet Oncol Haematol. 2011-12-01

Online version: