ENAM_HUMAN
ID ENAM_HUMAN Reviewed; 1142 AA.
AC Q9NRM1; Q17RI5; Q9H3D1;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 3.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Enamelin;
DE Flags: Precursor;
GN Name=ENAM;
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 [GENOMIC DNA], AND VARIANTS THR-648 AND GLN-763.
RX PubMed=18245370; DOI=10.1534/genetics.107.077123;
RA Kelley J.L., Swanson W.J.;
RT "Dietary change and adaptive evolution of enamelin in humans and among
RT primates.";
RL Genetics 178:1595-1603(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hu C.-C., Qian Q., Zhang C., Fukae M., Uchida T., Simmer J.P.;
RT "cDNA sequence of human enamelin.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 NUCLEOTIDE SEQUENCE [MRNA] OF 1014-1142.
RX PubMed=11037750; DOI=10.1034/j.1600-0722.2000.108005353.x;
RA Dong J., Gu T.T., Simmons D., MacDougall M.;
RT "Enamelin maps to human chromosome 4q21 within the autosomal dominant
RT amelogenesis imperfecta locus.";
RL Eur. J. Oral Sci. 108:353-358(2000).
RN [6]
RP INVOLVEMENT IN AI1B, AND TISSUE SPECIFICITY.
RX PubMed=11487571; DOI=10.1093/hmg/10.16.1673;
RA Rajpar M.H., Harley K., Laing C., Davies R.M., Dixon M.J.;
RT "Mutation of the gene encoding the enamel-specific protein, enamelin,
RT causes autosomal-dominant amelogenesis imperfecta.";
RL Hum. Mol. Genet. 10:1673-1677(2001).
RN [7]
RP INVOLVEMENT IN AI1B.
RX PubMed=11978766; DOI=10.1093/hmg/11.9.1069;
RA Mardh C.K., Backman B., Holmgren G., Hu J.C., Simmer J.P., Forsman-Semb K.;
RT "A nonsense mutation in the enamelin gene causes local hypoplastic
RT autosomal dominant amelogenesis imperfecta (AIH2).";
RL Hum. Mol. Genet. 11:1069-1074(2002).
RN [8]
RP INVOLVEMENT IN AI1C.
RX PubMed=14684688; DOI=10.1136/jmg.40.12.900;
RA Hart T.C., Hart P.S., Gorry M.C., Michalec M.D., Ryu O.H., Uygur C.,
RA Ozdemir D., Firatli S., Aren G., Firatli E.;
RT "Novel ENAM mutation responsible for autosomal recessive amelogenesis
RT imperfecta and localised enamel defects.";
RL J. Med. Genet. 40:900-906(2003).
RN [9]
RP PHOSPHORYLATION AT SER-191 AND SER-216, VARIANT AI1B LEU-216, VARIANT AI1C
RP LEU-216, CHARACTERIZATION OF VARIANT AI1B LEU-216, CHARACTERIZATION OF
RP VARIANT AI1C LEU-216, AND MUTAGENESIS OF SER-191.
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 AI1B LEU-216, AND VARIANT AI1C LEU-216.
RX PubMed=20439930; DOI=10.1177/0022034510365662;
RA Chan H.C., Mai L., Oikonomopoulou A., Chan H.L., Richardson A.S.,
RA Wang S.K., Simmer J.P., Hu J.C.;
RT "Altered enamelin phosphorylation site causes amelogenesis imperfecta.";
RL J. Dent. Res. 89:695-699(2010).
CC -!- FUNCTION: Involved in the mineralization and structural organization of
CC enamel. Involved in the extension of enamel during the secretory stage
CC of dental enamel formation. {ECO:0000250|UniProtKB:O97939}.
CC -!- INTERACTION:
CC Q9NRM1; Q8IXL6: FAM20C; NbExp=2; IntAct=EBI-11892601, EBI-7147442;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250|UniProtKB:O97939}.
CC -!- TISSUE SPECIFICITY: Expressed in tooth particularly in odontoblast,
CC ameloblast and cementoblast. {ECO:0000269|PubMed:11487571}.
CC -!- PTM: Phosphorylated by FAM20C in vitro. {ECO:0000269|PubMed:25789606}.
CC -!- DISEASE: Amelogenesis imperfecta 1B (AI1B) [MIM:104500]: An autosomal
CC dominant defect of enamel formation. Clinical manifestations may be
CC variable. Some cases present with generalized enamel hypoplasia
CC resulting in small, smooth, yellow and widely spaced teeth (smooth
CC hypoplastic AI). Others show horizontal rows of pits, grooves or a
CC hypoplastic area in the enamel (local hypoplastic AI).
CC {ECO:0000269|PubMed:11487571, ECO:0000269|PubMed:11978766,
CC ECO:0000269|PubMed:20439930, ECO:0000269|PubMed:25789606}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Amelogenesis imperfecta 1C (AI1C) [MIM:204650]: An autosomal
CC recessive defect of dental enamel formation. Teeth show local
CC hypoplastic and unmineralized enamel, and a yellow-brown discoloration.
CC Enamel defects can be associated with facial and oral features
CC including vertical dysgnathia and anterior openbite malocclusion.
CC {ECO:0000269|PubMed:14684688, ECO:0000269|PubMed:20439930,
CC ECO:0000269|PubMed:25789606}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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; EU482096; ACA43029.1; -; Genomic_DNA.
DR EMBL; AF125373; AAG43242.1; -; mRNA.
DR EMBL; CH471057; EAX05625.1; -; Genomic_DNA.
DR EMBL; BC117308; AAI17309.1; -; mRNA.
DR EMBL; BC117310; AAI17311.1; -; mRNA.
DR EMBL; AF210247; AAF73847.1; -; mRNA.
DR CCDS; CCDS3544.2; -.
DR RefSeq; NP_114095.2; NM_031889.2.
DR RefSeq; XP_006714119.1; XM_006714056.3.
DR AlphaFoldDB; Q9NRM1; -.
DR BioGRID; 115422; 3.
DR IntAct; Q9NRM1; 4.
DR MINT; Q9NRM1; -.
DR STRING; 9606.ENSP00000379383; -.
DR GlyGen; Q9NRM1; 10 sites.
DR iPTMnet; Q9NRM1; -.
DR PhosphoSitePlus; Q9NRM1; -.
DR BioMuta; ENAM; -.
DR DMDM; 212276506; -.
DR EPD; Q9NRM1; -.
DR MassIVE; Q9NRM1; -.
DR PaxDb; Q9NRM1; -.
DR PeptideAtlas; Q9NRM1; -.
DR PRIDE; Q9NRM1; -.
DR ProteomicsDB; 82388; -.
DR Antibodypedia; 24350; 79 antibodies from 15 providers.
DR DNASU; 10117; -.
DR Ensembl; ENST00000396073.4; ENSP00000379383.4; ENSG00000132464.13.
DR GeneID; 10117; -.
DR KEGG; hsa:10117; -.
DR MANE-Select; ENST00000396073.4; ENSP00000379383.4; NM_031889.3; NP_114095.2.
DR UCSC; uc011caw.2; human.
DR CTD; 10117; -.
DR DisGeNET; 10117; -.
DR GeneCards; ENAM; -.
DR HGNC; HGNC:3344; ENAM.
DR HPA; ENSG00000132464; Tissue enhanced (epididymis, heart muscle, kidney, skeletal muscle).
DR MalaCards; ENAM; -.
DR MIM; 104500; phenotype.
DR MIM; 204650; phenotype.
DR MIM; 606585; gene.
DR neXtProt; NX_Q9NRM1; -.
DR OpenTargets; ENSG00000132464; -.
DR Orphanet; 100031; Hypoplastic amelogenesis imperfecta.
DR PharmGKB; PA27781; -.
DR VEuPathDB; HostDB:ENSG00000132464; -.
DR eggNOG; ENOG502R69E; Eukaryota.
DR GeneTree; ENSGT00440000037826; -.
DR HOGENOM; CLU_280412_0_0_1; -.
DR InParanoid; Q9NRM1; -.
DR OMA; WNSWDHR; -.
DR OrthoDB; 201332at2759; -.
DR PhylomeDB; Q9NRM1; -.
DR TreeFam; TF337278; -.
DR PathwayCommons; Q9NRM1; -.
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; Q9NRM1; -.
DR BioGRID-ORCS; 10117; 9 hits in 1064 CRISPR screens.
DR GeneWiki; ENAM; -.
DR GenomeRNAi; 10117; -.
DR Pharos; Q9NRM1; Tbio.
DR PRO; PR:Q9NRM1; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9NRM1; protein.
DR Bgee; ENSG00000132464; Expressed in islet of Langerhans and 69 other tissues.
DR ExpressionAtlas; Q9NRM1; baseline and differential.
DR Genevisible; Q9NRM1; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0030345; F:structural constituent of tooth enamel; IBA:GO_Central.
DR GO; GO:0036305; P:ameloblast differentiation; IBA:GO_Central.
DR GO; GO:0097186; P:amelogenesis; IBA:GO_Central.
DR GO; GO:0031214; P:biomineral tissue development; IEA:UniProtKB-KW.
DR GO; GO:0070175; P:positive regulation of enamel mineralization; IBA:GO_Central.
DR InterPro; IPR015673; Enamelin.
DR PANTHER; PTHR16784; PTHR16784; 1.
DR Pfam; PF15362; Enamelin; 1.
PE 1: Evidence at protein level;
KW Amelogenesis imperfecta; Biomineralization; Disease variant;
KW Extracellular matrix; Glycoprotein; Phosphoprotein; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..39
FT /evidence="ECO:0000255"
FT CHAIN 40..1142
FT /note="Enamelin"
FT /id="PRO_0000021174"
FT REGION 88..193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 214..326
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 398..671
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 874..955
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1020..1048
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1062..1092
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 90..104
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 120..152
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 174..188
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 218..236
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 239..286
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 299..320
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 449..470
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..519
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 528..542
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 571..591
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 897..938
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1028..1048
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1063..1092
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 191
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:25789606"
FT MOD_RES 216
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:25789606"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 252
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 265
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 467
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 534
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 934
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1040
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 216
FT /note="S -> L (in AI1B and AI1C; decreased phosphorylation
FT by FAM20C; dbSNP:rs867263935)"
FT /evidence="ECO:0000269|PubMed:20439930,
FT ECO:0000305|PubMed:25789606"
FT /id="VAR_073665"
FT VARIANT 576
FT /note="F -> L (in dbSNP:rs2609428)"
FT /id="VAR_024311"
FT VARIANT 648
FT /note="I -> T (in dbSNP:rs7671281)"
FT /evidence="ECO:0000269|PubMed:18245370"
FT /id="VAR_024312"
FT VARIANT 724
FT /note="P -> L (in dbSNP:rs3796703)"
FT /id="VAR_020105"
FT VARIANT 763
FT /note="R -> Q (in dbSNP:rs3796704)"
FT /evidence="ECO:0000269|PubMed:18245370"
FT /id="VAR_024313"
FT VARIANT 767
FT /note="D -> G (in dbSNP:rs3796705)"
FT /id="VAR_047076"
FT MUTAGEN 191
FT /note="S->A: Decreased phosphorylation by FAM20C."
FT /evidence="ECO:0000269|PubMed:25789606"
FT CONFLICT 284
FT /note="P -> S (in Ref. 2; AAG43242)"
FT /evidence="ECO:0000305"
FT CONFLICT 286
FT /note="Q -> R (in Ref. 2; AAG43242)"
FT /evidence="ECO:0000305"
FT CONFLICT 948
FT /note="D -> G (in Ref. 2; AAG43242)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1142 AA; 128785 MW; 28274A71BE947EB1 CRC64;
MLVLRCRLGT SFPKLDNLVP KGKMKILLVF LGLLGNSVAM PMHMPRMPGF SSKSEEMMRY
NQFNFMNGPH MAHLGPFFGN GLPQQFPQYQ MPMWPQPPPN TWHPRKSSAP KRHNKTDQTQ
ETQKPNQTQS KKPPQKRPLK QPSHNQPQPE EEAQPPQAFP PFGNGLFPYQ QPPWQIPQRL
PPPGYGRPPI SNEEGGNPYF GYFGYHGFGG RPPYYSEEMF EQDFEKPKEE DPPKAESPGT
EPTANSTVTE TNSTQPNPKG SQGGNDTSPT GNSTPGLNTG NNPPAQNGIG PLPAVNASGQ
GGPGSQIPWR PSQPNIRENH PYPNIRNFPS GRQWYFTGTV MGHRQNRPFY RNQQVQRGPR
WNFFAWERKQ VARPGNPVYH KAYPPTSRGN YPNYAGNPAN LRRKPQGPNK HPVGTTVAPL
GPKPGPVVRN EKIQNPKEKP LGPKEQIIVP TKNPTSPWRN SQQYEVNKSN YKLPHSEGYM
PVPNFNSVDQ HENSYYPRGD SRKVPNSDGQ TQSQNLPKGI VLGSRRMPYE SETNQSELKH
SSYQPAVYPE EIPSPAKEHF PAGRNTWDHQ EISPPFKEDP GRQEEHLPHP SHGSRGSVFY
PEYNPYDPRE NSPYLRGNTW DERDDSPNTM GQKESPLYPI NTPDQKEIVP YNEEDPVDPT
GDEVFPGQNR WGEELSFKGG PTVRHYEGEQ YTSNQPKEYL PYSLDNPSKP REDFYYSEFY
PWSPDENFPS YNTASTMPPP IESRGYYVNN AAGPEESTLF PSRNSWDHRI QAQGQRERRP
YFNRNIWDQA THLQKAPARP PDQKGNQPYY SNTPAGLQKN PIWHEGENLN YGMQITRMNS
PEREHSSFPN FIPPSYPSGQ KEAHLFHLSQ RGSCCAGSST GPKDNPLALQ DYTPSYGLAP
GENQDTSPLY TDGSHTKQTR DIISPTSILP GQRNSSEKRE SQNPFRDDVS TLRRNTPCSI
KNQLGQKEIM PFPEASSLQS KNTPCLKNDL GGDGNNILEQ VFEDNQLNER TVDLTPEQLV
IGTPDEGSNP EGIQSQVQEN ESERQQQRPS NILHLPCFGS KLAKHHSSTT GTPSSDGRQS
PFDGDSITPT ENPNTLVELA TEEQFKSINV DPLDADEHSP FEFLQRGTNV QDQVQDCLLL
QA
