ID   AMTN_HUMAN              Reviewed;         209 AA.
AC   Q6UX39; Q0P503; Q0P506;
DT   23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   02-SEP-2026, entry version 145.
DE   RecName: Full=Amelotin;
DE   Flags: Precursor;
GN   Name=AMTN; ORFNames=UNQ689/PRO1329;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA   Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA   Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA   Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA   Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA   Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT   identify novel human secreted and transmembrane proteins: a bioinformatics
RT   assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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   [3]
RP   PROTEIN SEQUENCE OF 17-31.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally verified
RT   cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [4]
RP   FUNCTION.
RX   PubMed=25407797; DOI=10.1002/jbmr.2411;
RA   Abbarin N., Miguel S.S., Holcroft J., Iwasaki K., Ganss B.;
RT   "The enamel protein amelotin is a promoter of hydroxyapatite
RT   mineralization.";
RL   J. Bone Miner. Res. 30:775-785(2015).
RN   [5]
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   [6]
RP   INVOLVEMENT IN AI3B.
RX   PubMed=27412008; DOI=10.1093/hmg/ddw203;
RA   Smith C.E., Murillo G., Brookes S.J., Poulter J.A., Silva S., Kirkham J.,
RA   Inglehearn C.F., Mighell A.J.;
RT   "Deletion of amelotin exons 3-6 is associated with amelogenesis
RT   imperfecta.";
RL   Hum. Mol. Genet. 25:3578-3587(2016).
RN   [7]
RP   VARIANT [LARGE SCALE ANALYSIS] SER-78.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Is a promoter of calcium phosphate mineralization, playing a
CC       critical role in the formation of the compact, mineralized, aprismatic
CC       enamel surface layer during the maturation stage of amelogenesis.
CC       {ECO:0000269|PubMed:25407797}.
CC   -!- INTERACTION:
CC       Q6UX39; P46379-2: BAG6; NbExp=3; IntAct=EBI-11892684, EBI-10988864;
CC       Q6UX39; Q8IXL6: FAM20C; NbExp=2; IntAct=EBI-11892684, EBI-7147442;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9D3J8}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q6UX39-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q6UX39-2; Sequence=VSP_023919;
CC   -!- PTM: Phosphorylated by FAM20C in vitro. {ECO:0000269|PubMed:25789606}.
CC   -!- PTM: O-glycosylated. {ECO:0000250|UniProtKB:Q3HS82}.
CC   -!- DISEASE: Amelogenesis imperfecta 3B (AI3B) [MIM:617607]: An autosomal
CC       dominant form of amelogenesis imperfecta, a defect of enamel formation.
CC       AI3B is characterized by hypomineralized enamel that has reduced
CC       tickness and exhibits structural defects.
CC       {ECO:0000269|PubMed:27412008}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the amelotin family. {ECO:0000305}.
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DR   EMBL; AY358528; AAQ88892.1; -; mRNA.
DR   EMBL; BC121812; AAI21813.1; -; mRNA.
DR   EMBL; BC121817; AAI21818.1; -; mRNA.
DR   CCDS; CCDS3542.1; -. [Q6UX39-1]
DR   CCDS; CCDS68716.1; -. [Q6UX39-2]
DR   RefSeq; NP_001273660.1; NM_001286731.2. [Q6UX39-2]
DR   RefSeq; NP_997722.1; NM_212557.4. [Q6UX39-1]
DR   AlphaFoldDB; Q6UX39; -.
DR   BioGRID; 134946; 28.
DR   FunCoup; Q6UX39; 11.
DR   IntAct; Q6UX39; 26.
DR   STRING; 9606.ENSP00000341013; -.
DR   GlyGen; Q6UX39; 1 site.
DR   iPTMnet; Q6UX39; -.
DR   PhosphoSitePlus; Q6UX39; -.
DR   BioMuta; AMTN; -.
DR   DMDM; 55976710; -.
DR   MassIVE; Q6UX39; -.
DR   PaxDb; 9606-ENSP00000341013; -.
DR   Antibodypedia; 50435; 196 antibodies from 23 providers.
DR   DNASU; 401138; -.
DR   Ensembl; ENST00000339336.9; ENSP00000341013.4; ENSG00000187689.10. [Q6UX39-1]
DR   Ensembl; ENST00000504451.1; ENSP00000422452.1; ENSG00000187689.10. [Q6UX39-2]
DR   GeneID; 401138; -.
DR   KEGG; hsa:401138; -.
DR   MANE-Select; ENST00000339336.9; ENSP00000341013.4; NM_212557.4; NP_997722.1.
DR   UCSC; uc003hfk.3; human. [Q6UX39-1]
DR   AGR; HGNC:33188; -.
DR   ClinPGx; PA162376390; -.
DR   CTD; 401138; -.
DR   DisGeNET; 401138; -.
DR   GeneCards; AMTN; -.
DR   HGNC; HGNC:33188; AMTN.
DR   HPA; ENSG00000187689; Tissue enhanced (lymphoid tissue, salivary gland, stomach).
DR   MalaCards; AMTN; -.
DR   MIM; 610912; gene.
DR   MIM; 617607; phenotype.
DR   OpenTargets; ENSG00000187689; -.
DR   Orphanet; 100032; Hypocalcified amelogenesis imperfecta.
DR   VEuPathDB; HostDB:ENSG00000187689; -.
DR   eggNOG; ENOG502SFV7; Eukaryota.
DR   GeneTree; ENSGT00390000006715; -.
DR   HOGENOM; CLU_082745_0_0_1; -.
DR   InParanoid; Q6UX39; -.
DR   OMA; PQMLPIF; -.
DR   OrthoDB; 9837242at2759; -.
DR   PAN-GO; Q6UX39; 4 GO annotations based on evolutionary models.
DR   PhylomeDB; Q6UX39; -.
DR   PathwayCommons; Q6UX39; -.
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; Q6UX39; -.
DR   Agora; ENSG00000187689; -.
DR   BioGRID-ORCS; 401138; 12 hits in 1149 CRISPR screens.
DR   ChiTaRS; AMTN; human.
DR   GenomeRNAi; 401138; -.
DR   Pharos; Q6UX39; Tbio.
DR   PRO; PR:Q6UX39; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; Q6UX39; protein.
DR   Bgee; ENSG00000187689; Expressed in tonsil and 30 other cell types or tissues.
DR   ExpressionAtlas; Q6UX39; baseline and differential.
DR   GO; GO:0005604; C:basement membrane; ISS:HGNC-UCL.
DR   GO; GO:0005911; C:cell-cell junction; ISS:HGNC-UCL.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0031012; C:extracellular matrix; ISS:HGNC-UCL.
DR   GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR   GO; GO:0042475; P:odontogenesis of dentin-containing tooth; ISS:HGNC-UCL.
DR   GO; GO:0070169; P:positive regulation of biomineral tissue development; IDA:UniProtKB.
DR   GO; GO:0070175; P:positive regulation of enamel mineralization; IBA:GO_Central.
DR   InterPro; IPR031501; Amelotin.
DR   PANTHER; PTHR36858; AMELOTIN; 1.
DR   PANTHER; PTHR36858:SF1; AMELOTIN; 1.
DR   Pfam; PF15757; Amelotin; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Amelogenesis imperfecta; Biomineralization;
KW   Cell adhesion; Direct protein sequencing; Glycoprotein;
KW   Proteomics identification; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000269|PubMed:15340161"
FT   CHAIN           17..209
FT                   /note="Amelotin"
FT                   /id="PRO_0000022613"
FT   REGION          142..209
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         19
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_023919"
FT   VARIANT         45
FT                   /note="N -> S (in dbSNP:rs7660807)"
FT                   /id="VAR_050661"
FT   VARIANT         50
FT                   /note="S -> P (in dbSNP:rs34803339)"
FT                   /id="VAR_050662"
FT   VARIANT         78
FT                   /note="G -> S (in a colorectal cancer sample; somatic
FT                   mutation; dbSNP:rs151041998)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_035791"
SQ   SEQUENCE   209 AA;  21588 MW;  5DD8991674DB8457 CRC64;
     MRSTILLFCL LGSTRSLPQL KPALGLPPTK LAPDQGTLPN QQQSNQVFPS LSLIPLTQML
     TLGPDLHLLN PAAGMTPGTQ THPLTLGGLN VQQQLHPHVL PIFVTQLGAQ GTILSSEELP
     QIFTSLIIHS LFPGGILPTS QAGANPDVQD GSLPAGGAGV NPATQGTPAG RLPTPSGTDD
     DFAVTTPAGI QRSTHAIEEA TTESANGIQ
//