DMP1_HUMAN
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 03-AUG-2022, entry version 167.
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 GlyGen; Q13316; 8 sites.
DR iPTMnet; Q13316; -.
DR PhosphoSitePlus; Q13316; -.
DR BioMuta; DMP1; -.
DR DMDM; 7673998; -.
DR MassIVE; Q13316; -.
DR PaxDb; Q13316; -.
DR PeptideAtlas; Q13316; -.
DR PRIDE; Q13316; -.
DR Antibodypedia; 25470; 322 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 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; GQPKNME; -.
DR OrthoDB; 1235561at2759; -.
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 1056 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 tissues.
DR Genevisible; Q13316; 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; 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: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; PTHR23400; 1.
DR Pfam; PF07263; DMP1; 1.
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
