ID AMELX_HUMAN Reviewed; 191 AA. AC Q99217; Q96NW6; Q9UCA7; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 09-DEC-2015, entry version 150. DE RecName: Full=Amelogenin, X isoform; DE Flags: Precursor; GN Name=AMELX; Synonyms=AMG, AMGX; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Tooth bud; RX PubMed=1734713; RA Salido E.C., Yen P.H., Koprivnikar K., Yu L.-C., Shapiro L.J.; RT "The human enamel protein gene amelogenin is expressed from both the X RT and the Y chromosomes."; RL Am. J. Hum. Genet. 50:303-316(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3). RX PubMed=11922868; DOI=10.1016/S0003-9969(02)00005-5; RA Hart P.S., Hart T.C., Simmer J.P., Wright J.T.; RT "A nomenclature for X-linked amelogenesis imperfecta."; RL Arch. Oral Biol. 47:255-260(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP PROTEIN SEQUENCE OF 17-60. RX PubMed=2509010; DOI=10.1007/BF02556044; RA Fincham A.G., Hu Y., Pavlova Z., Slavkin H.C., Snead M.L.; RT "Human amelogenins: sequences of 'TRAP' molecules."; RL Calcif. Tissue Int. 45:243-250(1989). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 17-37. RX PubMed=8118759; DOI=10.1007/BF00316294; RA Catalano-Sherman J., Laskov R., Palmon A., David S., Deutsch D.; RT "Production of a monoclonal antibody against human amelogenin."; RL Calcif. Tissue Int. 54:76-80(1994). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 19-191 (ISOFORM 1). RX PubMed=2004775; DOI=10.1016/0888-7543(91)90251-9; RA Nakahori Y., Takenaka O., Nakagome Y.; RT "A human X-Y homologous region encodes 'amelogenin'."; RL Genomics 9:264-269(1991). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 49-190, AND PARTIAL PROTEIN RP SEQUENCE. RC TISSUE=Tooth bud; RX PubMed=8254123; DOI=10.1177/00220345930720120601; RA Catalano-Sherman J., Palmon A., Burstein Y., Deutsch D.; RT "Amino acid sequence of a major human amelogenin protein employing RT Edman degradation and cDNA sequencing."; RL J. Dent. Res. 72:1566-1572(1993). RN [9] RP PHOSPHORYLATION. RX PubMed=25789606; DOI=10.7554/eLife.06120; RA Cui J., Xiao J., Tagliabracci V.S., Wen J., Rahdar M., Dixon J.E.; RT "A secretory kinase complex regulates extracellular protein RT phosphorylation."; RL Elife 4:0-0(2015). RN [10] RP VARIANT AI1E 5-ILE--ALA-8 DELINS THR. RX PubMed=7782077; DOI=10.1016/0888-7543(95)80097-6; RA Lagerstroem-Fermer M., Nilddon M., Baeckman B., Salido E., Shapiro L., RA Pettersson U., Landergren U.; RT "Amelogenin signal peptide mutation: correlation between mutations in RT the amelogenin gene (AMGX) and manifestations of X-linked amelogenesis RT imperfecta."; RL Genomics 26:159-162(1995). RN [11] RP VARIANT AI1E ILE-37. RX PubMed=7599636; DOI=10.1002/humu.1380050310; RA Lench N.J., Winter G.B.; RT "Characterisation of molecular defects in X-linked amelogenesis RT imperfecta (AIH1)."; RL Hum. Mutat. 5:251-259(1995). RN [12] RP VARIANT AI1E THR-56. RX PubMed=10669095; DOI=10.1016/S0003-9969(99)00106-5; RA Hart S., Hart T., Gibson C., Wright J.T.; RT "Mutational analysis of X-linked amelogenesis imperfecta in multiple RT families."; RL Arch. Oral Biol. 45:79-86(2000). RN [13] RP VARIANT AI1E THR-56. RX PubMed=9188994; DOI=10.1016/S0003-9969(96)00099-4; RA Collier P.M., Sauk J.J., Rosenbloom S.J., Yuan Z.A., Gibson C.W.; RT "An amelogenin gene defect associated with human X-linked amelogenesis RT imperfecta."; RL Arch. Oral Biol. 42:235-242(1997). RN [14] RP VARIANT AI1E SER-4. RX PubMed=15111628; DOI=10.1177/154405910408300505; RA Kim J.-W., Simmer J.P., Hu Y.Y., Lin B.P.-L., Boyd C., Wright J.T., RA Yamada C.J.M., Rayes S.K., Feigal R.J., Hu J.C.-C.; RT "Amelogenin p.M1T and p.W4S mutations underlying hypoplastic X-linked RT amelogenesis imperfecta."; RL J. Dent. Res. 83:378-383(2004). CC -!- FUNCTION: Plays a role in biomineralization. Seems to regulate the CC formation of crystallites during the secretory stage of tooth CC enamel development. Thought to play a major role in the structural CC organization and mineralization of developing enamel. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Comment=Additional isoforms seem to exist.; CC Name=1; CC IsoId=Q99217-1; Sequence=Displayed; CC Name=2; CC IsoId=Q99217-2; Sequence=VSP_000228; CC Name=3; Synonyms=Rare; CC IsoId=Q99217-3; Sequence=VSP_000229; CC -!- DEVELOPMENTAL STAGE: Transiently but abundantly expressed by CC ameloblasts during tooth development. Amelogenin is the CC predominant protein in developing dental enamel. CC -!- PTM: Phosphorylated by FAM20C in vitro. CC {ECO:0000269|PubMed:25789606}. CC -!- DISEASE: Amelogenesis imperfecta 1E (AI1E) [MIM:301200]: A X- CC linked defect of dental enamel formation. Teeth have only a thin CC layer of enamel with normal hardness. The thinness of the enamel CC makes the teeth appear small. {ECO:0000269|PubMed:10669095, CC ECO:0000269|PubMed:15111628, ECO:0000269|PubMed:7599636, CC ECO:0000269|PubMed:7782077, ECO:0000269|PubMed:9188994}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- SIMILARITY: Belongs to the amelogenin family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M86932; AAA51717.1; -; mRNA. DR EMBL; AF436849; AAL30432.1; -; mRNA. DR EMBL; AY040206; AAK77213.1; -; Genomic_DNA. DR EMBL; AC002366; AAC21581.1; -; Genomic_DNA. DR EMBL; BC074951; AAH74951.1; -; mRNA. DR EMBL; M55418; AAA62826.1; -; Genomic_DNA. DR EMBL; X14440; CAA32613.1; -; Genomic_DNA. DR EMBL; S67147; AAB29184.1; -; mRNA. DR CCDS; CCDS14144.1; -. [Q99217-1] DR CCDS; CCDS14145.1; -. [Q99217-3] DR CCDS; CCDS14146.1; -. [Q99217-2] DR PIR; B41816; A41816. DR RefSeq; NP_001133.1; NM_001142.2. [Q99217-1] DR RefSeq; NP_872621.1; NM_182680.1. [Q99217-3] DR RefSeq; NP_872622.1; NM_182681.1. [Q99217-2] DR RefSeq; XP_011543791.1; XM_011545489.1. [Q99217-3] DR UniGene; Hs.654436; -. DR ProteinModelPortal; Q99217; -. DR BioMuta; AMELX; -. DR DMDM; 1168430; -. DR PRIDE; Q99217; -. DR DNASU; 265; -. DR Ensembl; ENST00000348912; ENSP00000335312; ENSG00000125363. [Q99217-2] DR Ensembl; ENST00000380712; ENSP00000370088; ENSG00000125363. [Q99217-3] DR Ensembl; ENST00000380714; ENSP00000370090; ENSG00000125363. [Q99217-1] DR GeneID; 265; -. DR KEGG; hsa:265; -. DR UCSC; uc004cus.3; human. [Q99217-3] DR UCSC; uc004cut.3; human. [Q99217-1] DR UCSC; uc004cuu.3; human. [Q99217-2] DR CTD; 265; -. DR GeneCards; AMELX; -. DR H-InvDB; HIX0176766; -. DR HGNC; HGNC:461; AMELX. DR HPA; HPA005988; -. DR MalaCards; AMELX; -. DR MIM; 300391; gene. DR MIM; 301200; phenotype. DR neXtProt; NX_Q99217; -. DR Orphanet; 100033; Hypomaturation amelogenesis imperfecta. DR PharmGKB; PA24766; -. DR GeneTree; ENSGT00390000009151; -. DR HOGENOM; HOG000231643; -. DR HOVERGEN; HBG016835; -. DR InParanoid; Q99217; -. DR OMA; HSMTPTQ; -. DR OrthoDB; EOG7JQBQ8; -. DR PhylomeDB; Q99217; -. DR TreeFam; TF337092; -. DR GeneWiki; AMELX; -. DR GenomeRNAi; 265; -. DR NextBio; 1037; -. DR PMAP-CutDB; Q99217; -. DR PRO; PR:Q99217; -. DR Proteomes; UP000005640; Chromosome X. DR Bgee; Q99217; -. DR CleanEx; HS_AMELX; -. DR Genevisible; Q99217; HS. DR GO; GO:0009986; C:cell surface; ISS:BHF-UCL. DR GO; GO:0005578; C:proteinaceous extracellular matrix; IDA:BHF-UCL. DR GO; GO:0008083; F:growth factor activity; ISS:BHF-UCL. DR GO; GO:0046848; F:hydroxyapatite binding; ISS:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; ISS:BHF-UCL. DR GO; GO:0030345; F:structural constituent of tooth enamel; IDA:BHF-UCL. DR GO; GO:0031214; P:biomineral tissue development; TAS:BHF-UCL. DR GO; GO:0007155; P:cell adhesion; ISS:BHF-UCL. DR GO; GO:0008283; P:cell proliferation; ISS:BHF-UCL. DR GO; GO:0002062; P:chondrocyte differentiation; ISS:BHF-UCL. DR GO; GO:0070166; P:enamel mineralization; IMP:BHF-UCL. DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISS:BHF-UCL. DR GO; GO:0050801; P:ion homeostasis; TAS:BHF-UCL. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; ISS:BHF-UCL. DR GO; GO:0001649; P:osteoblast differentiation; ISS:BHF-UCL. DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISS:BHF-UCL. DR GO; GO:0070172; P:positive regulation of tooth mineralization; TAS:BHF-UCL. DR GO; GO:0007165; P:signal transduction; TAS:BHF-UCL. DR GO; GO:0034505; P:tooth mineralization; IMP:BHF-UCL. DR InterPro; IPR004116; Amelogenin. DR Pfam; PF02948; Amelogenin; 1. DR PRINTS; PR01757; AMELOGENIN. DR SMART; SM00818; Amelogenin; 1. PE 1: Evidence at protein level; KW Alternative splicing; Amelogenesis imperfecta; Biomineralization; KW Complete proteome; Direct protein sequencing; Disease mutation; KW Extracellular matrix; Phosphoprotein; Reference proteome; Repeat; KW Secreted; Signal. FT SIGNAL 1 16 {ECO:0000269|PubMed:2509010}. FT CHAIN 17 191 Amelogenin, X isoform. FT /FTId=PRO_0000001199. FT MOD_RES 32 32 Phosphoserine. FT {ECO:0000250|UniProtKB:P02817}. FT VAR_SEQ 19 34 Missing (in isoform 2). {ECO:0000305}. FT /FTId=VSP_000228. FT VAR_SEQ 34 34 E -> ENSHSQAINVDRTAL (in isoform 3). FT {ECO:0000303|PubMed:11922868}. FT /FTId=VSP_000229. FT VARIANT 4 4 W -> S (in AI1E). FT {ECO:0000269|PubMed:15111628}. FT /FTId=VAR_037581. FT VARIANT 5 8 ILFA -> T (in AI1E). FT {ECO:0000269|PubMed:7782077}. FT /FTId=VAR_000559. FT VARIANT 37 37 T -> I (in AI1E). FT {ECO:0000269|PubMed:7599636}. FT /FTId=VAR_037582. FT VARIANT 56 56 P -> T (in AI1E). FT {ECO:0000269|PubMed:10669095, FT ECO:0000269|PubMed:9188994}. FT /FTId=VAR_037583. FT CONFLICT 50 51 PS -> SP (in Ref. 5; AA sequence). FT {ECO:0000305}. FT CONFLICT 173 173 D -> H (in Ref. 8; AA sequence). FT {ECO:0000305}. FT CONFLICT 191 191 D -> VSIF (in Ref. 7; AAA62826/CAA32613). FT {ECO:0000305}. SQ SEQUENCE 191 AA; 21603 MW; 322C88DA3F7155DC CRC64; MGTWILFACL LGAAFAMPLP PHPGHPGYIN FSYEVLTPLK WYQSIRPPYP SYGYEPMGGW LHHQIIPVLS QQHPPTHTLQ PHHHIPVVPA QQPVIPQQPM MPVPGQHSMT PIQHHQPNLP PPAQQPYQPQ PVQPQPHQPM QPQPPVHPMQ PLPPQPPLPP MFPMQPLPPM LPDLTLEAWP STDKTKREEV D //