AMELX_HUMAN
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 03-AUG-2022, entry version 187.
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}.
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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 PeptideAtlas; Q99217; -.
DR PRIDE; Q99217; -.
DR TopDownProteomics; Q99217-2; -. [Q99217-2]
DR Antibodypedia; 23742; 162 antibodies from 21 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 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; IPIMAAQ; -.
DR OrthoDB; 1509730at2759; -.
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 656 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 colonic epithelium and 24 other tissues.
DR Genevisible; Q99217; HS.
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:0005794; C:Golgi apparatus; IEA:Ensembl.
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; PTHR46794; 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
