ID   DMP1_HUMAN              Reviewed;         513 AA.
AC   Q13316; A1L4L3; O43265;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 2.
DT   24-JAN-2024, entry version 175.
DE   RecName: Full=Dentin matrix acidic phosphoprotein 1;
DE            Short=DMP-1;
DE            Short=Dentin matrix protein 1;
DE   Flags: Precursor;
GN   Name=DMP1;
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=Molar;
RX   PubMed=9177774; DOI=10.1006/geno.1997.4700;
RA   Hirst K.L., Simmons D., Feng J., Aplin H., Dixon M.J., McDougall M.;
RT   "Elucidation of the sequence and the genomic organization of the human
RT   dentin matrix acidic phosphoprotein 1 (DMP1) gene: exclusion of the locus
RT   from a causative role in the pathogenesis of dentinogenesis imperfecta type
RT   II.";
RL   Genomics 42:38-45(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT CYS-69.
RA   McDougall M., Juan X., Simmons D., Feng J.;
RL   Submitted (JUL-1996) 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] (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   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 462-513, AND GENE MAPPING.
RX   PubMed=8586437; DOI=10.1006/geno.1995.9867;
RA   Aplin H.M., Hirst K.L., Crosby A.H., Dixon M.J.;
RT   "Mapping of the human dentin matrix acidic phosphoprotein gene (DMP1) to
RT   the dentinogenesis imperfecta type II critical region at chromosome 4q21.";
RL   Genomics 30:347-349(1995).
RN   [6]
RP   FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND INTERACTION WITH
RP   IMPORTIN ALPHA.
RX   PubMed=12615915; DOI=10.1074/jbc.m212700200;
RA   Narayanan K., Ramachandran A., Hao J., He G., Park K.W., Cho M., George A.;
RT   "Dual functional roles of dentin matrix protein 1. Implications in
RT   biomineralization and gene transcription by activation of intracellular
RT   Ca2+ store.";
RL   J. Biol. Chem. 278:17500-17508(2003).
RN   [7]
RP   INVOLVEMENT IN ARHR1, AND VARIANTS CYS-69; ASN-117 AND HIS-272.
RX   PubMed=17033625; DOI=10.1038/ng1868;
RA   Lorenz-Depiereux B., Bastepe M., Benet-Pages A., Amyere M.,
RA   Wagenstaller J., Mueller-Barth U., Badenhoop K., Kaiser S.M.,
RA   Rittmaster R.S., Shlossberg A.H., Olivares J.L., Loris C., Ramos F.J.,
RA   Glorieux F., Vikkula M., Jueppner H., Strom T.M.;
RT   "DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone
RT   matrix protein in the regulation of phosphate homeostasis.";
RL   Nat. Genet. 38:1248-1250(2006).
RN   [8]
RP   INVOLVEMENT IN ARHR1.
RX   PubMed=17033621; DOI=10.1038/ng1905;
RA   Feng J.Q., Ward L.M., Liu S., Lu Y., Xie Y., Yuan B., Yu X., Rauch F.,
RA   Davis S.I., Zhang S., Rios H., Drezner M.K., Quarles L.D., Bonewald L.F.,
RA   White K.E.;
RT   "Loss of DMP1 causes rickets and osteomalacia and identifies a role for
RT   osteocytes in mineral metabolism.";
RL   Nat. Genet. 38:1310-1315(2006).
RN   [9]
RP   PHOSPHORYLATION BY FAM20C.
RX   PubMed=22582013; DOI=10.1126/science.1217817;
RA   Tagliabracci V.S., Engel J.L., Wen J., Wiley S.E., Worby C.A., Kinch L.N.,
RA   Xiao J., Grishin N.V., Dixon J.E.;
RT   "Secreted kinase phosphorylates extracellular proteins that regulate
RT   biomineralization.";
RL   Science 336:1150-1153(2012).
CC   -!- FUNCTION: May have a dual function during osteoblast differentiation.
CC       In the nucleus of undifferentiated osteoblasts, unphosphorylated form
CC       acts as a transcriptional component for activation of osteoblast-
CC       specific genes like osteocalcin. During the osteoblast to osteocyte
CC       transition phase it is phosphorylated and exported into the
CC       extracellular matrix, where it regulates nucleation of hydroxyapatite.
CC       {ECO:0000269|PubMed:12615915}.
CC   -!- SUBUNIT: Interacts with importin alpha. {ECO:0000269|PubMed:12615915}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12615915}. Cytoplasm
CC       {ECO:0000269|PubMed:12615915}. Secreted, extracellular space,
CC       extracellular matrix {ECO:0000269|PubMed:12615915}. Note=In
CC       proliferating preosteoblasts it is nuclear, during early maturation
CC       stage is cytoplasmic and in mature osteoblast localizes in the
CC       mineralized matrix. Export from the nucleus of differentiating
CC       osteoblast is triggered by the release of calcium from intracellular
CC       stores followed by a massive influx of this pool of calcium into the
CC       nucleus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q13316-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q13316-2; Sequence=VSP_004191;
CC   -!- TISSUE SPECIFICITY: Expressed in tooth particularly in odontoblast,
CC       ameloblast and cementoblast.
CC   -!- PTM: Phosphorylated in the cytosol and extracellular matrix and
CC       unphosphorylated in the nucleus. Phosphorylation is necessary for
CC       nucleocytoplasmic transport and may be catalyzed by a nuclear isoform
CC       of CK2 and can be augmented by calcium. Phosphorylated (in vitro) by
CC       FAM20C in the extracellular medium at sites within the S-x-E/pS motif.
CC       {ECO:0000269|PubMed:12615915, ECO:0000269|PubMed:22582013}.
CC   -!- DISEASE: Hypophosphatemic rickets, autosomal recessive, 1 (ARHR1)
CC       [MIM:241520]: A hereditary form of hypophosphatemic rickets, a disorder
CC       of proximal renal tubule function that causes phosphate loss,
CC       hypophosphatemia and skeletal deformities, including rickets and
CC       osteomalacia unresponsive to vitamin D. Symptoms are bone pain,
CC       fractures and growth abnormalities. {ECO:0000269|PubMed:17033621,
CC       ECO:0000269|PubMed:17033625}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
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DR   EMBL; U89012; AAC51332.1; -; mRNA.
DR   EMBL; U34037; AAA97602.1; -; Genomic_DNA.
DR   EMBL; CH471057; EAX05996.1; -; Genomic_DNA.
DR   EMBL; BC130581; AAI30582.1; -; mRNA.
DR   EMBL; BC132865; AAI32866.1; -; mRNA.
DR   EMBL; U65378; AAB87728.1; -; mRNA.
DR   CCDS; CCDS3623.1; -. [Q13316-1]
DR   CCDS; CCDS43249.1; -. [Q13316-2]
DR   RefSeq; NP_001073380.1; NM_001079911.2. [Q13316-2]
DR   RefSeq; NP_004398.1; NM_004407.3. [Q13316-1]
DR   AlphaFoldDB; Q13316; -.
DR   BioGRID; 108098; 2.
DR   IntAct; Q13316; 1.
DR   STRING; 9606.ENSP00000340935; -.
DR   GlyCosmos; Q13316; 8 sites, No reported glycans.
DR   GlyGen; Q13316; 8 sites.
DR   iPTMnet; Q13316; -.
DR   PhosphoSitePlus; Q13316; -.
DR   BioMuta; DMP1; -.
DR   DMDM; 7673998; -.
DR   MassIVE; Q13316; -.
DR   PaxDb; 9606-ENSP00000340935; -.
DR   PeptideAtlas; Q13316; -.
DR   ProteomicsDB; 59304; -. [Q13316-1]
DR   ProteomicsDB; 59305; -. [Q13316-2]
DR   Antibodypedia; 25470; 338 antibodies from 36 providers.
DR   DNASU; 1758; -.
DR   Ensembl; ENST00000282479.8; ENSP00000282479.6; ENSG00000152592.15. [Q13316-2]
DR   Ensembl; ENST00000339673.11; ENSP00000340935.6; ENSG00000152592.15. [Q13316-1]
DR   GeneID; 1758; -.
DR   KEGG; hsa:1758; -.
DR   MANE-Select; ENST00000339673.11; ENSP00000340935.6; NM_004407.4; NP_004398.1.
DR   UCSC; uc003hqv.4; human. [Q13316-1]
DR   AGR; HGNC:2932; -.
DR   CTD; 1758; -.
DR   DisGeNET; 1758; -.
DR   GeneCards; DMP1; -.
DR   HGNC; HGNC:2932; DMP1.
DR   HPA; ENSG00000152592; Not detected.
DR   MalaCards; DMP1; -.
DR   MIM; 241520; phenotype.
DR   MIM; 600980; gene.
DR   neXtProt; NX_Q13316; -.
DR   OpenTargets; ENSG00000152592; -.
DR   Orphanet; 289176; Autosomal recessive hypophosphatemic rickets.
DR   PharmGKB; PA27379; -.
DR   VEuPathDB; HostDB:ENSG00000152592; -.
DR   eggNOG; KOG1181; Eukaryota.
DR   GeneTree; ENSGT00730000111375; -.
DR   HOGENOM; CLU_040174_0_0_1; -.
DR   InParanoid; Q13316; -.
DR   OMA; HDDNDCQ; -.
DR   OrthoDB; 4642623at2759; -.
DR   PhylomeDB; Q13316; -.
DR   TreeFam; TF337029; -.
DR   PathwayCommons; Q13316; -.
DR   Reactome; R-HSA-3000178; ECM proteoglycans.
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; Q13316; -.
DR   BioGRID-ORCS; 1758; 6 hits in 1132 CRISPR screens.
DR   GeneWiki; DMP1_(gene); -.
DR   GenomeRNAi; 1758; -.
DR   Pharos; Q13316; Tbio.
DR   PRO; PR:Q13316; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; Q13316; Protein.
DR   Bgee; ENSG00000152592; Expressed in periodontal ligament and 37 other cell types or tissues.
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; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR   GO; GO:0050840; F:extracellular matrix binding; IBA:GO_Central.
DR   GO; GO:0005178; F:integrin binding; TAS:ProtInc.
DR   GO; GO:0043167; F:ion binding; EXP:DisProt.
DR   GO; GO:0031214; P:biomineral tissue development; IEA:UniProtKB-KW.
DR   GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR   GO; GO:0001503; P:ossification; TAS:ProtInc.
DR   GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IEA:Ensembl.
DR   GO; GO:0070173; P:regulation of enamel mineralization; IEA:Ensembl.
DR   InterPro; IPR009889; DMP1.
DR   PANTHER; PTHR23400; DENTIN MATRIX ACIDIC PHOSPHOPROTEIN 1; 1.
DR   PANTHER; PTHR23400:SF0; DENTIN MATRIX ACIDIC PHOSPHOPROTEIN 1; 1.
DR   Pfam; PF07263; DMP1; 1.
DR   Genevisible; Q13316; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Biomineralization; Cytoplasm; Extracellular matrix;
KW   Glycoprotein; Nucleus; Phosphoprotein; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000255"
FT   CHAIN           17..513
FT                   /note="Dentin matrix acidic phosphoprotein 1"
FT                   /id="PRO_0000021110"
FT   REGION          23..513
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           364..366
FT                   /note="Cell attachment site"
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        43..57
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        63..77
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        101..115
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        117..140
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        146..161
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        162..197
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        204..226
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        227..259
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        263..297
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        307..327
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        328..356
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        385..407
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        425..442
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        454..506
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        25
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        285
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        324
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        345
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        351
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        413
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        426
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        467
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         46..61
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_004191"
FT   VARIANT         69
FT                   /note="S -> C (in dbSNP:rs10019009)"
FT                   /evidence="ECO:0000269|PubMed:17033625, ECO:0000269|Ref.2"
FT                   /id="VAR_030750"
FT   VARIANT         117
FT                   /note="D -> N (in one individual with tumoral calcinosis;
FT                   dbSNP:rs140719182)"
FT                   /evidence="ECO:0000269|PubMed:17033625"
FT                   /id="VAR_030751"
FT   VARIANT         272
FT                   /note="R -> H (in dbSNP:rs145237146)"
FT                   /evidence="ECO:0000269|PubMed:17033625"
FT                   /id="VAR_030752"
FT   VARIANT         463
FT                   /note="K -> R (in dbSNP:rs34661425)"
FT                   /id="VAR_033848"
SQ   SEQUENCE   513 AA;  55782 MW;  2C1FDE319A5D106F CRC64;
     MKISILLMFL WGLSCALPVT RYQNNESEDS EEWKGHLAQA PTPPLESSES SEGSKVSSEE
     QANEDPSDST QSEEGLGSDD HQYIYRLAGG FSRSTGKGGD DKDDDEDDSG DDTFGDDDSG
     PGPKDRQEGG NSRLGSDEDS DDTIQASEES APQGQDSAQD TTSESRELDN EDRVDSKPEG
     GDSTQESESE EHWVGGGSDG ESSHGDGSEL DDEGMQSDDP ESIRSERGNS RMNSAGMKSK
     ESGENSEQAN TQDSGGSQLL EHPSRKIFRK SRISEEDDRS ELDDNNTMEE VKSDSTENSN
     SRDTGLSQPR RDSKGDSQED SKENLSQEES QNVDGPSSES SQEANLSSQE NSSESQEEVV
     SESRGDNPDP TTSYVEDQED SDSSEEDSSH TLSHSKSESR EEQADSESSE SLNFSEESPE
     SPEDENSSSQ EGLQSHSSSA ESQSEESHSE EDDSDSQDSS RSKEDSNSTE SKSSSEEDGQ
     LKNIEIESRK LTVDAYHNKP IGDQDDNDCQ DGY
//