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 02-OCT-2024, entry version 199. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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 and RT 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., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., 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., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., 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., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., 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., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., 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., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA 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 project: RT 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 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 Edman RT degradation and cDNA sequencing."; RL J. Dent. Res. 72:1566-1572(1993). RN [9] RP SUBCELLULAR LOCATION, AND 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 the RT 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 imperfecta RT (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 enamel CC development. Thought to play a major role in the structural CC organization and mineralization of developing enamel. CC -!- SUBUNIT: Interacts with KRT5. {ECO:0000250|UniProtKB:P63277}. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000305|PubMed:25789606}. 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 predominant CC protein in developing dental enamel. CC -!- PTM: Phosphorylated by FAM20C in vitro. {ECO:0000269|PubMed:25789606}. CC -!- DISEASE: Amelogenesis imperfecta 1E (AI1E) [MIM:301200]: An X-linked CC defect of dental enamel formation. Teeth have only a thin layer of CC enamel with normal hardness. The thinness of the enamel makes the teeth CC 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 variants affecting the gene represented in this CC 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 AlphaFoldDB; Q99217; -. DR IntAct; Q99217; 1. DR STRING; 9606.ENSP00000370088; -. DR PhosphoSitePlus; Q99217; -. DR BioMuta; AMELX; -. DR DMDM; 1168430; -. DR PaxDb; 9606-ENSP00000370088; -. DR PeptideAtlas; Q99217; -. DR ProteomicsDB; 78250; -. [Q99217-3] DR TopDownProteomics; Q99217-2; -. [Q99217-2] DR Antibodypedia; 23742; 172 antibodies from 22 providers. DR DNASU; 265; -. DR Ensembl; ENST00000348912.4; ENSP00000335312.5; ENSG00000125363.14. [Q99217-2] DR Ensembl; ENST00000380712.7; ENSP00000370088.3; ENSG00000125363.14. [Q99217-3] DR Ensembl; ENST00000380714.7; ENSP00000370090.3; ENSG00000125363.14. [Q99217-1] DR GeneID; 265; -. DR KEGG; hsa:265; -. DR MANE-Select; ENST00000380714.7; ENSP00000370090.3; NM_001142.2; NP_001133.1. DR UCSC; uc004cus.3; human. [Q99217-1] DR AGR; HGNC:461; -. DR CTD; 265; -. DR DisGeNET; 265; -. DR GeneCards; AMELX; -. DR HGNC; HGNC:461; AMELX. DR HPA; ENSG00000125363; Not detected. DR MalaCards; AMELX; -. DR MIM; 300391; gene. DR MIM; 301200; phenotype. DR neXtProt; NX_Q99217; -. DR OpenTargets; ENSG00000125363; -. DR Orphanet; 100033; Hypomaturation amelogenesis imperfecta. DR PharmGKB; PA24766; -. DR VEuPathDB; HostDB:ENSG00000125363; -. DR eggNOG; ENOG502S4XP; Eukaryota. DR GeneTree; ENSGT00390000009151; -. DR HOGENOM; CLU_120753_0_0_1; -. DR InParanoid; Q99217; -. DR OMA; FSYENSY; -. DR OrthoDB; 4520512at2759; -. DR PhylomeDB; Q99217; -. DR TreeFam; TF337092; -. DR PathwayCommons; Q99217; -. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR SignaLink; Q99217; -. DR BioGRID-ORCS; 265; 7 hits in 730 CRISPR screens. DR GeneWiki; AMELX; -. DR GenomeRNAi; 265; -. DR Pharos; Q99217; Tbio. DR PRO; PR:Q99217; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q99217; protein. DR Bgee; ENSG00000125363; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 25 other cell types or tissues. DR GO; GO:0009986; C:cell surface; ISS:BHF-UCL. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:BHF-UCL. DR GO; GO:0030139; C:endocytic vesicle; IEA:Ensembl. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW. 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:0097186; P:amelogenesis; ISS:ARUK-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: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: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:0042127; P:regulation of cell population proliferation; ISS:BHF-UCL. DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl. DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. 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 PANTHER; PTHR46794:SF2; AMELOGENIN, X ISOFORM; 1. DR PANTHER; PTHR46794; AMELOGENIN, Y ISOFORM; 1. 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 Direct protein sequencing; Disease variant; Extracellular matrix; KW Phosphoprotein; Reference proteome; Repeat; Secreted; Signal. FT SIGNAL 1..16 FT /evidence="ECO:0000269|PubMed:2509010" FT CHAIN 17..191 FT /note="Amelogenin, X isoform" FT /id="PRO_0000001199" FT REGION 95..191 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 115..170 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 32 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P02817" FT VAR_SEQ 19..34 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_000228" FT VAR_SEQ 34 FT /note="E -> ENSHSQAINVDRTAL (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11922868" FT /id="VSP_000229" FT VARIANT 4 FT /note="W -> S (in AI1E; dbSNP:rs104894738)" FT /evidence="ECO:0000269|PubMed:15111628" FT /id="VAR_037581" FT VARIANT 5..8 FT /note="ILFA -> T (in AI1E)" FT /evidence="ECO:0000269|PubMed:7782077" FT /id="VAR_000559" FT VARIANT 37 FT /note="T -> I (in AI1E; dbSNP:rs104894733)" FT /evidence="ECO:0000269|PubMed:7599636" FT /id="VAR_037582" FT VARIANT 56 FT /note="P -> T (in AI1E; dbSNP:rs104894736)" FT /evidence="ECO:0000269|PubMed:10669095, FT ECO:0000269|PubMed:9188994" FT /id="VAR_037583" FT CONFLICT 50..51 FT /note="PS -> SP (in Ref. 5; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 173 FT /note="D -> H (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 191 FT /note="D -> VSIF (in Ref. 7; AAA62826/CAA32613)" FT /evidence="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 //