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Protein

Matrix extracellular phosphoglycoprotein

Gene

Mepe

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Regulates renal phosphate and uric acid excretion (PubMed:26051469). Regulates bone mineralization by osteoblasts and cartilage mineralization by chondrocytes (PubMed:11414762, PubMed:12421822, PubMed:15843468, PubMed:22766095). Regulates the mineralization of the extracellular matrix of the craniofacial complex, such as teeth, bone and cartilage (PubMed:26927967). Increases dental pulp stem cell proliferation (By similarity).By similarity6 Publications

Miscellaneous

It has been proposed that MEPE is cleaved and generate 2 peptides dentonin and ASARM peptide.Curated

GO - Molecular functioni

  • extracellular matrix protein binding Source: GO_Central

GO - Biological processi

  • biomineral tissue development Source: UniProtKB-KW
  • negative regulation of bone mineralization Source: MGI
  • skeletal system development Source: MGI

Keywordsi

Biological processBiomineralization

Enzyme and pathway databases

ReactomeiR-MMU-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-MMU-8957275 Post-translational protein phosphorylation

Names & Taxonomyi

Protein namesi
Recommended name:
Matrix extracellular phosphoglycoprotein1 Publication
Alternative name(s):
Osteoblast/osteocyte factor 451 Publication
Short name:
OF451 Publication
OsteoregulinBy similarity
Gene namesi
Name:MepeImported
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:2137384 Mepe

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Disruption phenotypei

Mutant mice exhibit increased cancellous bone mass and no loss of trabecular bone characteristics (PubMed:12421822, PubMed:26051469). They also exhibit decreased biomechanical strength in their bones and increased skeletal mineralization (PubMed:15843468). In craniofacial complex development, mutant mice also exhibit hypermineralization in predentin, dentin and enamel of teeth and decreased expression of AMBN, ENAM, IBSP, DMP1, DSPP and SPP1 (PubMed:26927967). Mutant mice also exhibit hyperphostatemia and increased expression of SLC34A1/NPT2a, SLC34A3/NPT2c and VEGF in the kidney (PubMed:26051469). Hyperuricemia and reduced fractional excretion of uric acid was also exhibited (PubMed:26051469). As mutant mice age, bone mineral density and content is increased (PubMed:26051469).4 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_501410744125 – 441Matrix extracellular phosphoglycoproteinSequence analysisAdd BLAST417

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi82N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Phosphorylated on serine residues in the ASARM motif; the phosphorylation is important for the inhibition of bone mineralization.3 Publications
Cleaved by CTSB/cathepsin B; the cleavage is blocked by metalloprotease PHEX.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ8K4L6
PRIDEiQ8K4L6

PTM databases

iPTMnetiQ8K4L6
PhosphoSitePlusiQ8K4L6

Expressioni

Tissue specificityi

Expressed in osteocytes (at protein level) (PubMed:12421822, PubMed:15221418). Expressed by chondrocytes, specifically in the hypertrophic zone of the bone growth plate (at protein level) (PubMed:22766095). Expressed in osteoblasts in bone (at protein level) (PubMed:11414762, PubMed:15221418, PubMed:18597632). Expressed by osteoblasts within the metaphysis (at protein level) (PubMed:15221418, PubMed:22766095). Expressed at low levels in white fat, brown fat, testes, brain and aorta (PubMed:12421822). Expressed in the craniofacial complex (at protein level) (PubMed:26927967). Expressed in odontoblasts, ameloblasts and in predentin during tooth development (at protein level) (PubMed:22042093). Expressed in the kidney (at protein level) (PubMed:26051469). Expressed in osteocytes in mandibular condylar cartilage and tibial cartilage (at protein level) (PubMed:26428891). Expressed in salivary glands (PubMed:15329369).9 Publications

Developmental stagei

Detected at 16 days post coitum (dpc) in both epithelial and mesenchymal components of the tooth organ (PubMed:26927967). Also detected at 16 dpc and 18 dpc in mandibular bone osteocytes (PubMed:26428891). Detected at 15 dpc in the bone collar (PubMed:26428891). Detected at 13 dpc in the cartilage matrix (PubMed:26428891). Detected at postnatal day 3 in odontoblasts and ameloblasts (PubMed:22042093). At postnatal day 5, expression is decreased in dental papilla cells, but increased in the predentin (PubMed:22042093). By postnatal day 9, is only detected in the predentin (PubMed:22042093). Detected at postnatal day 2 in osteoblasts, the calcified cartilage cores in primary metaphyseal bone and in osterocytes embedded in cortical bone matrix (PubMed:15221418). At postnatal day 84 expression is detected in the osteocytes of cortical and trabecular bone (PubMed:15221418).4 Publications

Inductioni

Induced by ascorbate and beta-glycerophosphate (PubMed:11414762, PubMed:12421822). Induced expression during bone fracture healing, with low levels of expression being detected in fibroblast-like cells at 6 days post-fracture, and increased expression at 10 days post-fracture in late hypertrophic chondrocytes. At 14 days post-fracture, expression is detected in osteocytes, osteoblasts, and hypertrophic chondrocytes. By 28 days post-fracture, expression was highest in osteocytes and lower in osteoblasts (PubMed:15221418). Down-regulated by 1-alpha-25-dihydroxyvitamin D3 (calcitriol) (PubMed:11414762).3 Publications

Gene expression databases

BgeeiENSMUSG00000053863 Expressed in 71 organ(s), highest expression level in hindlimb long bone

Interactioni

Subunit structurei

Interacts (via ASARM motif) with PHEX; the interaction is zinc-dependent.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000065200

Structurei

3D structure databases

ProteinModelPortaliQ8K4L6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni178 – 200DentoninBy similarityAdd BLAST23
Regioni424 – 441ASARM motif; interaction with PHEX1 PublicationAdd BLAST18

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi183 – 185Cell attachment siteBy similarity3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi426 – 438Poly-SerSequence analysisAdd BLAST13

Domaini

The acidic serine aspartate-rich MEPE-associated (ASARM) motif is sufficient when phosphorylated to inhibit bone mineralization by osteoblasts and cartilage mineralization by chondrocytes by binding hydroxyapatite crystals during the mineralization stage (PubMed:15843468, PubMed:22766095, PubMed:26051469). It can also inhibit dentin mineralization (By similarity).By similarity3 Publications
The dentonin region is sufficient to promote dental pulp stem cell proliferation. It can also stimulate bone formation, osteoblast differentiation, and activate integrin signaling pathways.By similarity

Sequence similaritiesi

Belongs to the PF07175/osteoregulin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IIFI Eukaryota
ENOG41118PA LUCA
GeneTreeiENSGT00390000010702
HOGENOMiHOG000115910
HOVERGENiHBG004786
InParanoidiQ8K4L6
OMAiVPHRQNN
OrthoDBiEOG091G0HA8
PhylomeDBiQ8K4L6
TreeFamiTF338655

Family and domain databases

InterProiView protein in InterPro
IPR009837 Osteoregulin
PANTHERiPTHR16510 PTHR16510, 1 hit
PfamiView protein in Pfam
PF07175 Osteoregulin, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD338624 Osteoregulin, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8K4L6-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTPEGLMKMQ AVSVGLLLFS MTWAAPMPNE DRSSCGNQDS IHKDLAASVY
60 70 80 90 100
PDPTVDEGTE DGQGALLHPP GQDRYGAALL RNITQPVKSL VTGAELRREG
110 120 130 140 150
NQEKRPQSVL SVIPADVNDA KVSLKDIKNQ ESYLLTQSSP VKSKHTKHTR
160 170 180 190 200
QTRRSTHYLT HLPQIKKTPS DLEGSGSPDL LVRGDNDVPP FSGDGQHFMH
210 220 230 240 250
IPGKGGAGSG PESSTSRPLS GSSKAEVIDP HMSGLGSNEI PGREGHGGSA
260 270 280 290 300
YATRDKAAQG AGSAGGSLVG GSNEITGSTN FRELPGKEGN RINAGSQNAH
310 320 330 340 350
QGKVEFHYPQ VASREKVKGG VEHAGRAGYN EIPKSSKGSS SKDAEESKGN
360 370 380 390 400
QLTLTASQRF PGKGKSQGPA LPSHSLSNEV KSEENHYVFH GQNNLTPNKG
410 420 430 440
MSQRRGSWPS RRPNSHRRAS TRQRDSSESS SSGSSSESHG D
Length:441
Mass (Da):46,872
Last modified:October 1, 2002 - v1
Checksum:iAA1947BFE9F2E300
GO

Sequence cautioni

The sequence AAI19163 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAK70342 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence ACS37545 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2T → M in BAE34415 (PubMed:16141072).Curated1
Sequence conflicti14V → A in BAE34415 (PubMed:16141072).Curated1
Sequence conflicti81R → G in BAE34415 (PubMed:16141072).Curated1
Sequence conflicti120A → V in BAE34415 (PubMed:16141072).Curated1
Sequence conflicti132S → T in BAE34415 (PubMed:16141072).Curated1
Sequence conflicti219L → V in BAE34415 (PubMed:16141072).Curated1
Sequence conflicti293N → D in BAE34415 (PubMed:16141072).Curated1
Sequence conflicti340S → A in BAE34415 (PubMed:16141072).Curated1
Sequence conflicti414N → H in BAE34415 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF314964 mRNA Translation: AAK70342.1 Different initiation.
AF298661 mRNA Translation: AAM87687.1
AC122775 Genomic DNA No translation available.
AK158231 mRNA Translation: BAE34415.1
FJ999695 Genomic DNA Translation: ACS37545.1 Sequence problems.
BC119162 mRNA Translation: AAI19163.1 Different initiation.
CCDSiCCDS51578.1
RefSeqiNP_444402.2, NM_053172.2
UniGeneiMm.196672

Genome annotation databases

EnsembliENSMUST00000066207; ENSMUSP00000065200; ENSMUSG00000053863
GeneIDi94111
KEGGimmu:94111
UCSCiuc008ykh.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF314964 mRNA Translation: AAK70342.1 Different initiation.
AF298661 mRNA Translation: AAM87687.1
AC122775 Genomic DNA No translation available.
AK158231 mRNA Translation: BAE34415.1
FJ999695 Genomic DNA Translation: ACS37545.1 Sequence problems.
BC119162 mRNA Translation: AAI19163.1 Different initiation.
CCDSiCCDS51578.1
RefSeqiNP_444402.2, NM_053172.2
UniGeneiMm.196672

3D structure databases

ProteinModelPortaliQ8K4L6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000065200

PTM databases

iPTMnetiQ8K4L6
PhosphoSitePlusiQ8K4L6

Proteomic databases

PaxDbiQ8K4L6
PRIDEiQ8K4L6

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000066207; ENSMUSP00000065200; ENSMUSG00000053863
GeneIDi94111
KEGGimmu:94111
UCSCiuc008ykh.2 mouse

Organism-specific databases

CTDi56955
MGIiMGI:2137384 Mepe

Phylogenomic databases

eggNOGiENOG410IIFI Eukaryota
ENOG41118PA LUCA
GeneTreeiENSGT00390000010702
HOGENOMiHOG000115910
HOVERGENiHBG004786
InParanoidiQ8K4L6
OMAiVPHRQNN
OrthoDBiEOG091G0HA8
PhylomeDBiQ8K4L6
TreeFamiTF338655

Enzyme and pathway databases

ReactomeiR-MMU-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-MMU-8957275 Post-translational protein phosphorylation

Miscellaneous databases

SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000053863 Expressed in 71 organ(s), highest expression level in hindlimb long bone

Family and domain databases

InterProiView protein in InterPro
IPR009837 Osteoregulin
PANTHERiPTHR16510 PTHR16510, 1 hit
PfamiView protein in Pfam
PF07175 Osteoregulin, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD338624 Osteoregulin, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMEPE_MOUSE
AccessioniPrimary (citable) accession number: Q8K4L6
Secondary accession number(s): D6C6N6, Q3TYZ5, Q924I1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 12, 2018
Last sequence update: October 1, 2002
Last modified: November 7, 2018
This is version 99 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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