AMTN_HUMAN
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 03-AUG-2022, entry version 131.
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_001286731.1. [Q6UX39-2]
DR RefSeq; NP_997722.1; NM_212557.3. [Q6UX39-1]
DR AlphaFoldDB; Q6UX39; -.
DR BioGRID; 134946; 28.
DR IntAct; Q6UX39; 12.
DR STRING; 9606.ENSP00000341013; -.
DR iPTMnet; Q6UX39; -.
DR PhosphoSitePlus; Q6UX39; -.
DR BioMuta; AMTN; -.
DR DMDM; 55976710; -.
DR MassIVE; Q6UX39; -.
DR PaxDb; Q6UX39; -.
DR PeptideAtlas; Q6UX39; -.
DR PRIDE; Q6UX39; -.
DR ProteomicsDB; 67556; -. [Q6UX39-1]
DR ProteomicsDB; 67557; -. [Q6UX39-2]
DR Antibodypedia; 50435; 192 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 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 neXtProt; NX_Q6UX39; -.
DR OpenTargets; ENSG00000187689; -.
DR Orphanet; 100032; Hypocalcified amelogenesis imperfecta.
DR PharmGKB; PA162376390; -.
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 PhylomeDB; Q6UX39; -.
DR TreeFam; TF337677; -.
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 BioGRID-ORCS; 401138; 12 hits in 1063 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 29 other 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; IEA:UniProtKB-SubCell.
DR GO; GO:0031214; P:biomineral tissue development; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
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; PTHR36858; 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; Reference proteome;
KW 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 COMPBIAS 187..209
FT /note="Polar residues"
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
