| Written | 2011-12 | Marina Gonçalves Diniz, Ricardo Santiago Gomez, Carolina Cavalieri Gomes, André Luiz Sena Guimarães |
| Department of Oral Surgery, Pathology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Belo Horizonte-MG CEP 31270, Brazil (MGD, RSG); Department of Pathology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Belo Horizonte-MG CEP 31270, Brazil (CCG); Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Brazil (ALSG) |
| Identity |
| Alias_names | ameloblastin, enamel matrix protein |
| ameloblastin (enamel matrix protein) | |
| Other alias | |
| HGNC (Hugo) | AMBN |
| LocusID (NCBI) | 258 |
| Atlas_Id | 51161 |
| Location | 4q13.3 [Link to chromosome band 4q13] |
| Location_base_pair | Starts at 70592258 and ends at 70607287 bp from pter ( according to hg19-Feb_2009) [Mapping AMBN.png] |
| Local_order | AMBN is between the sequence tagged site markers D4S409 and D4S1558 (Karrman et al., 1997). |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| DNA/RNA |
| Note | The putative start codon location and exon-intron sizes differs among reports in literature. |
 | |
| 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. | |
| Description | 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). |
| Transcription | 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. |
| Protein |
| Description | 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). |
| Expression | 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). |
| Localisation | Extracellular matrix. |
| Function | 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). |
| Homology | Pig (sheathlin), cattle, rat, and mouse AMBN sequences showed a high amino acid sequence similarity. |
| Mutations |
| Somatic | 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 |
| Note | |
| Entity | Odontogenic tumors |
| Disease | 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. |
| Oncogenesis | 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 | Amelogenesis imperfecta |
| Disease | 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. |
| Oncogenesis | 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). |
| Bibliography |
| A mutation in the mouse Amelx tri-tyrosyl domain results in impaired secretion of amelogenin and phenocopies human X-linked amelogenesis imperfecta. |
| Barron MJ, Brookes SJ, Kirkham J, Shore RC, Hunt C, Mironov A, Kingswell NJ, Maycock J, Shuttleworth CA, Dixon MJ. |
| Hum Mol Genet. 2010 Apr 1;19(7):1230-47. Epub 2010 Jan 12. |
| PMID 20067920 |
| A novel gene expressed in rat ameloblasts codes for proteins with cell binding domains. |
| Cerny R, Slaby I, Hammarstrom L, Wurtz T. |
| J Bone Miner Res. 1996 Jul;11(7):883-91. |
| PMID 8797107 |
| Amelin: an enamel-related protein, transcribed in the cells of epithelial root sheath. |
| Fong CD, Slaby I, Hammarstrom L. |
| J Bone Miner Res. 1996 Jul;11(7):892-8. |
| PMID 8797108 |
| Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts. |
| Fukumoto S, Kiba T, Hall B, Iehara N, Nakamura T, Longenecker G, Krebsbach PH, Nanci A, Kulkarni AB, Yamada Y. |
| J Cell Biol. 2004 Dec 6;167(5):973-83. |
| PMID 15583034 |
| Ameloblastin regulates osteogenic differentiation by inhibiting Src kinase via cross talk between integrin beta1 and CD63. |
| Iizuka S, Kudo Y, Yoshida M, Tsunematsu T, Yoshiko Y, Uchida T, Ogawa I, Miyauchi M, Takata T. |
| Mol Cell Biol. 2011 Feb;31(4):783-92. Epub 2010 Dec 13. |
| PMID 21149578 |
| Splicing determines the glycosylation state of ameloblastin. |
| Kobayashi K, Yamakoshi Y, Hu JC, Gomi K, Arai T, Fukae M, Krebsbach PH, Simmer JP. |
| J Dent Res. 2007 Oct;86(10):962-7. |
| PMID 17890672 |
| Full-length sequence, localization, and chromosomal mapping of ameloblastin. A novel tooth-specific gene. |
| Krebsbach PH, Lee SK, Matsuki Y, Kozak CA, Yamada KM, Yamada Y. |
| J Biol Chem. 1996 Feb 23;271(8):4431-5. |
| PMID 8626794 |
| Cloning, characterization and immunolocalization of human ameloblastin. |
| MacDougall M, Simmons D, Gu TT, Forsman-Semb K, Mardh CK, Mesbah M, Forest N, Krebsbach PH, Yamada Y, Berdal A. |
| Eur J Oral Sci. 2000 Aug;108(4):303-10. |
| PMID 10946765 |
| Human ameloblastin gene: genomic organization and mutation analysis in amelogenesis imperfecta patients. |
| Mardh CK, Backman B, Simmons D, Golovleva I, Gu TT, Holmgren G, MacDougall M, Forsman-Semb K. |
| Eur J Oral Sci. 2001 Feb;109(1):8-13. |
| PMID 11330937 |
| Relative levels of mRNA encoding enamel proteins in enamel organ epithelia and odontoblasts. |
| Nagano T, Oida S, Ando H, Gomi K, Arai T, Fukae M. |
| J Dent Res. 2003 Dec;82(12):982-6. |
| PMID 14630899 |
| Mutation of ameloblastin gene in calcifying epithelial odontogenic tumor. |
| Perdigao PF, Carvalho VM, DE Marco L, Gomez RS. |
| Anticancer Res. 2009 Aug;29(8):3065-7. |
| PMID 19661317 |
| Spatiotemporal expression of ameloblastin isoforms during murine tooth development. |
| Ravindranath RM, Devarajan A, Uchida T. |
| J Biol Chem. 2007 Dec 14;282(50):36370-6. Epub 2007 Oct 5. |
| PMID 17921454 |
| Critical role of heparin binding domains of ameloblastin for dental epithelium cell adhesion and ameloblastoma proliferation. |
| Sonoda A, Iwamoto T, Nakamura T, Fukumoto E, Yoshizaki K, Yamada A, Arakaki M, Harada H, Nonaka K, Nakamura S, Yamada Y, Fukumoto S. |
| J Biol Chem. 2009 Oct 2;284(40):27176-84. Epub 2009 Jul 31. |
| PMID 19648121 |
| Ameloblastin expression during craniofacial bone formation in rats. |
| Spahr A, Lyngstadaas SP, Slaby I, Pezeshki G. |
| Eur J Oral Sci. 2006 Dec;114(6):504-11. |
| PMID 17184233 |
| Immunohistochemical demonstration of an enamel sheath protein, sheathlin, in odontogenic tumors. |
| Takata T, Zhao M, Uchida T, Kudo Y, Sato S, Nikai H. |
| Virchows Arch. 2000 Apr;436(4):324-9. |
| PMID 10834534 |
| Ameloblastin expression and putative autoregulation in mesenchymal cells suggest a role in early bone formation and repair. |
| Tamburstuen MV, Reseland JE, Spahr A, Brookes SJ, Kvalheim G, Slaby I, Snead ML, Lyngstadaas SP. |
| Bone. 2011 Feb;48(2):406-13. Epub 2010 Sep 18. |
| PMID 20854943 |
| Cloning and characterization of the human ameloblastin gene. |
| Toyosawa S, Fujiwara T, Ooshima T, Shintani S, Sato A, Ogawa Y, Sobue S, Ijuhin N. |
| Gene. 2000 Oct 3;256(1-2):1-11. |
| PMID 11054529 |
| Immunochemical and immunocytochemical study of a 15 kDa non-amelogenin and related proteins in the porcine immature enamel: proposal of a new group of enamel proteins sheath proteins. |
| Uchida T, Fukae M, Tanabe T, Yamakoshi Y, Satoda T, Murakami C, et al. |
| Biomed Res. 1995; 16:131-140. |
| Synthesis, 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, Murakami C, Dohi N, Wakida K, Satoda T, Takahashi O. |
| J Histochem Cytochem. 1997 Oct;45(10):1329-40. |
| PMID 9313795 |
| Calcium binding of enamel proteins and their derivatives with emphasis on the calcium-binding domain of porcine sheathlin. |
| Yamakoshi Y, Tanabe T, Oida S, Hu CC, Simmer JP, Fukae M. |
| Arch Oral Biol. 2001 Nov;46(11):1005-14. |
| PMID 11543707 |
| Citation |
| This paper should be referenced as such : |
| Diniz, MG ; Gomez, RS ; Gomes, CC ; Guimares, ALS |
| AMBN (ameloblastin (enamel matrix protein)) |
| Atlas Genet Cytogenet Oncol Haematol. 2012;16(5):326-328. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/AMBNID51161ch4q13.html |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Aug 26 18:39:11 CEST 2019 |
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