Atlas of Genetics and Cytogenetics in Oncology and Haematology

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AMBN (ameloblastin (enamel matrix protein))

Written2011-12Marina 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)

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HGNC Alias nameenamel matrix protein
HGNC Previous nameameloblastin, enamel matrix protein
 ameloblastin (enamel matrix protein)
LocusID (NCBI) 258
Atlas_Id 51161
Location 4q13.3  [Link to chromosome band 4q13]
Location_base_pair Starts at 70592256 and ends at 70607287 bp from pter ( according to GRCh38/hg38-Dec_2013)  [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)


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.


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.


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

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).


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


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 ]

External links


HGNC (Hugo)AMBN   452
Entrez_Gene (NCBI)AMBN    ameloblastin
GeneCards (Weizmann)AMBN
Ensembl hg19 (Hinxton)ENSG00000178522 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000178522 [Gene_View]  ENSG00000178522 [Sequence]  chr4:70592256-70607287 [Contig_View]  AMBN [Vega]
ICGC DataPortalENSG00000178522
Genatlas (Paris)AMBN
SOURCE (Princeton)AMBN
Genetics Home Reference (NIH)AMBN
Genomic and cartography
GoldenPath hg38 (UCSC)AMBN  -     chr4:70592256-70607287 +  4q13.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)AMBN  -     4q13.3   [Description]    (hg19-Feb_2009)
GoldenPathAMBN - 4q13.3 [CytoView hg19]  AMBN - 4q13.3 [CytoView hg38]
Genome Data Viewer NCBIAMBN [Mapview hg19]  
OMIM601259   616270   
Gene and transcription
Genbank (Entrez)AF209780 AF219994 AF263464 AJ537437 AK314918
RefSeq transcript (Entrez)NM_016519
Consensus coding sequences : CCDS (NCBI)AMBN
Gene ExpressionAMBN [ NCBI-GEO ]   AMBN [ EBI - ARRAY_EXPRESS ]   AMBN [ SEEK ]   AMBN [ MEM ]
Gene Expression Viewer (FireBrowse)AMBN [ Firebrowse - Broad ]
GenevisibleExpression of AMBN in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)258
GTEX Portal (Tissue expression)AMBN
Human Protein AtlasENSG00000178522-AMBN [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9NP70   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9NP70  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9NP70
Domains : Interpro (EBI)Amelin   
Domain families : Pfam (Sanger)Amelin (PF05111)   
Domain families : Pfam (NCBI)pfam05111   
Domain families : Smart (EMBL)Amelin (SM00817)  
Conserved Domain (NCBI)AMBN
AlphaFold pdb e-kbQ9NP70   
Human Protein Atlas [tissue]ENSG00000178522-AMBN [tissue]
Protein Interaction databases
IntAct (EBI)Q9NP70
Ontologies - Pathways
Ontology : AmiGOprotein binding  extracellular region  endoplasmic reticulum lumen  cell adhesion  cell adhesion  signal transduction  growth factor activity  growth factor activity  structural constituent of tooth enamel  biomineral tissue development  regulation of cell population proliferation  odontogenesis of dentin-containing tooth  post-translational protein modification  cellular protein metabolic process  
Ontology : EGO-EBIprotein binding  extracellular region  endoplasmic reticulum lumen  cell adhesion  cell adhesion  signal transduction  growth factor activity  growth factor activity  structural constituent of tooth enamel  biomineral tissue development  regulation of cell population proliferation  odontogenesis of dentin-containing tooth  post-translational protein modification  cellular protein metabolic process  
REACTOMEQ9NP70 [protein]
REACTOME PathwaysR-HSA-8957275 [pathway]   
NDEx NetworkAMBN
Atlas of Cancer Signalling NetworkAMBN
Wikipedia pathwaysAMBN
Orthology - Evolution
GeneTree (enSembl)ENSG00000178522
Phylogenetic Trees/Animal Genes : TreeFamAMBN
Homologs : HomoloGeneAMBN
Homology/Alignments : Family Browser (UCSC)AMBN
Gene fusions - Rearrangements
Fusion : QuiverAMBN
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerAMBN [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)AMBN
Exome Variant ServerAMBN
GNOMAD BrowserENSG00000178522
Varsome BrowserAMBN
ACMGAMBN variants
Genomic Variants (DGV)AMBN [DGVbeta]
DECIPHERAMBN [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisAMBN 
ICGC Data PortalAMBN 
TCGA Data PortalAMBN 
Broad Tumor PortalAMBN
OASIS PortalAMBN [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICAMBN  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DAMBN
Mutations and Diseases : HGMDAMBN
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)AMBN
DoCM (Curated mutations)AMBN
CIViC (Clinical Interpretations of Variants in Cancer)AMBN
NCG (London)AMBN
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM601259    616270   
Genetic Testing Registry AMBN
NextProtQ9NP70 [Medical]
Target ValidationAMBN
Huge Navigator AMBN [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDAMBN
Pharm GKB GenePA24758
Clinical trialAMBN
DataMed IndexAMBN
PubMed34 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:12:26 CEST 2021

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