This gene encodes a secreted calcium-binding phosphoprotein that belongs to the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family of proteins. Members of this family are components of the extracellular matrix of bone and dentin and regulate bone mineralization. Deficiency of a similar protein in mouse results in increased bone mass. Mice lacking this gene ar... See more...

Aliases for MEPE Gene

Aliases for MEPE Gene

  • Matrix Extracellular Phosphoglycoprotein 2 3 4 5
  • Matrix, Extracellular Phosphoglycoprotein With ASARM Motif (Bone) 2 3
  • Osteoblast/Osteocyte Factor 45 3 4
  • Osteoregulin 3 4
  • OF45 3 4
  • MEPE 5

External Ids for MEPE Gene

Previous GeneCards Identifiers for MEPE Gene

  • GC04P088911
  • GC04P089055
  • GC04P089212
  • GC04P089191
  • GC04P089099
  • GC04P088961
  • GC04P088754
  • GC04P084488

Summaries for MEPE Gene

Entrez Gene Summary for MEPE Gene

  • This gene encodes a secreted calcium-binding phosphoprotein that belongs to the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family of proteins. Members of this family are components of the extracellular matrix of bone and dentin and regulate bone mineralization. Deficiency of a similar protein in mouse results in increased bone mass. Mice lacking this gene are resistant to aging-related trabecular bone loss. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

GeneCards Summary for MEPE Gene

MEPE (Matrix Extracellular Phosphoglycoprotein) is a Protein Coding gene. Diseases associated with MEPE include Osteomalacia and Hypophosphatemic Rickets, Autosomal Dominant. Among its related pathways are Integrin Pathway and ERK Signaling. Gene Ontology (GO) annotations related to this gene include extracellular matrix structural constituent.

UniProtKB/Swiss-Prot Summary for MEPE Gene

  • Promotes renal phosphate excretion and inhibits intestinal phosphate absorption (PubMed:14962809, PubMed:19005008). Promotes bone mineralization by osteoblasts and cartilage mineralization by chondrocytes (PubMed:18162525, PubMed:19998030, PubMed:22766095). Regulates the mineralization of the extracellular matrix of the craniofacial complex, such as teeth, bone and cartilage (By similarity). Promotes dental pulp stem cell proliferation and differentiation (PubMed:22341070).

Gene Wiki entry for MEPE Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MEPE Gene

Genomics for MEPE Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for MEPE Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J087818 Enhancer 0.8 Ensembl ENCODE 600.7 -1.8 -1792 1.6 LEF1 BACH1 TAF9B NFE2 ZNF316 TRIM24 MAFG EHMT2 MAFK ZNF592 MEPE piR-53029-093 SPP1 IBSP
GH04J087832 Promoter 0.3 EPDnew 600.4 +11.6 11552 0.1 MEPE IBSP SPARCL1 lnc-MEPE-2 SPP1
GH04J087588 Enhancer 0.8 Ensembl ENCODE 10.2 -231.8 -231784 1.4 CREB1 ZNF629 ATF7 CEBPB CTBP1 JUN ZBTB17 ZNF217 ATF2 JUND DMP1 SPARCL1 MEPE DSPP hsa-miR-5095-371 ENSG00000249001
GH04J087909 Enhancer 1.1 ENCODE dbSUPER 7.2 +89.8 89848 3.7 HNRNPL GATAD2A TFE3 NFKBIZ RCOR2 GABPA RBFOX2 RXRB IRF2 SP1 SPP1 PKD2 MEPE piR-44484 piR-41245-194 lnc-MEPE-1
GH04J087843 Enhancer 0.6 FANTOM5 ENCODE 11.5 +22.9 22865 1 SPI1 JUN FOS SPP1 MEPE PKD2 HSD17B11 lnc-MEPE-2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MEPE on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MEPE

Top Transcription factor binding sites by QIAGEN in the MEPE gene promoter:
  • AML1a
  • AP-1
  • CBF(2)
  • CBF-A
  • FOXO1
  • FOXO1a
  • HOXA3
  • Nkx2-2
  • RSRFC4

Genomic Locations for MEPE Gene

Genomic Locations for MEPE Gene
chr4:87,821,398-87,846,817
(GRCh38/hg38)
Size:
25,420 bases
Orientation:
Plus strand
chr4:88,742,563-88,767,969
(GRCh37/hg19)
Size:
25,407 bases
Orientation:
Plus strand

Genomic View for MEPE Gene

Genes around MEPE on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MEPE Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MEPE Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MEPE Gene

Proteins for MEPE Gene

  • Protein details for MEPE Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NQ76-MEPE_HUMAN
    Recommended name:
    Matrix extracellular phosphoglycoprotein
    Protein Accession:
    Q9NQ76
    Secondary Accessions:
    • A1A4X9
    • A8MTA3
    • D2CFR4
    • F5H5C5

    Protein attributes for MEPE Gene

    Size:
    525 amino acids
    Molecular mass:
    58419 Da
    Quaternary structure:
    • Interacts (via the ASARM motif) with PHEX; the interaction is zinc-dependent.

    Alternative splice isoforms for MEPE Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MEPE Gene

Post-translational modifications for MEPE Gene

  • Phosphorylated on serine residues in the ASARM motif (in vitro) by FAM20C; the phosphorylation is important for the inhibition of bone mineralization (PubMed:19998030, PubMed:22582013).
  • Cleaved by CTSB/cathepsin B; the cleavage is blocked by metalloprotease PHEX.
  • Glycosylation at Asn477 and Asn478
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for MEPE Gene

Domains & Families for MEPE Gene

Gene Families for MEPE Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for MEPE Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for MEPE Gene

GenScript: Design optimal peptide antigens:
  • Matrix extracellular phosphoglycoprotein (D2CFR4_HUMAN)
  • Matrix extracellular phosphoglycoprotein (D6C6M7_HUMAN)
  • Osteoblast/osteocyte factor 45 (MEPE_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9NQ76

UniProtKB/Swiss-Prot:

MEPE_HUMAN :
  • 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:15664000, PubMed:18162525, PubMed:18597632, PubMed:19998030, PubMed:22766095). It can also inhibit dentin mineralization (PubMed:20581062).
  • Belongs to the PF07175/osteoregulin family.
Domain:
  • 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:15664000, PubMed:18162525, PubMed:18597632, PubMed:19998030, PubMed:22766095). It can also inhibit dentin mineralization (PubMed:20581062).
  • The dentonin region is sufficient to promote dental pulp stem cell proliferation (PubMed:15153459). It can also stimulate bone formation, osteoblast differentiation, and activate integrin signaling pathways (PubMed:15040834).
Family:
  • Belongs to the PF07175/osteoregulin family.
genes like me logo Genes that share domains with MEPE: view

Function for MEPE Gene

Molecular function for MEPE Gene

UniProtKB/Swiss-Prot Function:
Promotes renal phosphate excretion and inhibits intestinal phosphate absorption (PubMed:14962809, PubMed:19005008). Promotes bone mineralization by osteoblasts and cartilage mineralization by chondrocytes (PubMed:18162525, PubMed:19998030, PubMed:22766095). Regulates the mineralization of the extracellular matrix of the craniofacial complex, such as teeth, bone and cartilage (By similarity). Promotes dental pulp stem cell proliferation and differentiation (PubMed:22341070).

Phenotypes From GWAS Catalog for MEPE Gene

Gene Ontology (GO) - Molecular Function for MEPE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005201 extracellular matrix structural constituent TAS 10945470
GO:0005515 protein binding IPI 17474147
GO:1990430 extracellular matrix protein binding IBA 21873635
genes like me logo Genes that share ontologies with MEPE: view
genes like me logo Genes that share phenotypes with MEPE: view

Animal Models for MEPE Gene

MGI Knock Outs for MEPE:
  • Mepe Mepe<tm1Tbrw>

Animal Model Products

CRISPR Products

miRNA for MEPE Gene

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MEPE

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MEPE Gene

Localization for MEPE Gene

Subcellular locations from UniProtKB/Swiss-Prot for MEPE Gene

Secreted, extracellular space, extracellular matrix.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MEPE gene
Compartment Confidence
extracellular 4
endoplasmic reticulum 4
plasma membrane 2
nucleus 2
cytoskeleton 1
mitochondrion 1
cytosol 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for MEPE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005788 endoplasmic reticulum lumen TAS --
GO:0031012 extracellular matrix TAS,IBA 21873635
genes like me logo Genes that share ontologies with MEPE: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for MEPE Gene

Pathways & Interactions for MEPE Gene

PathCards logo

SuperPathways for MEPE Gene

SuperPathway Contained pathways
1 Integrin Pathway
.67
.67
.56
.56
.50
.38
2 ERK Signaling
.61
.61
.58
.51
.49
3 Phospholipase-C Pathway
.56
.56
genes like me logo Genes that share pathways with MEPE: view

Pathways by source for MEPE Gene

13 Qiagen pathways for MEPE Gene
  • ERK Signaling
  • FAK1 Signaling
  • GnRH Signaling
  • ILK Signaling
  • Inhibition of Angiogenesis by TSP1

Gene Ontology (GO) - Biological Process for MEPE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001501 skeletal system development TAS 10945470
GO:0031214 biomineral tissue development IBA 21873635
GO:0043687 post-translational protein modification TAS --
GO:0044267 cellular protein metabolic process TAS --
genes like me logo Genes that share ontologies with MEPE: view

No data available for SIGNOR curated interactions for MEPE Gene

Drugs & Compounds for MEPE Gene

(1) Drugs for MEPE Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with MEPE: view

Transcripts for MEPE Gene

mRNA/cDNA for MEPE Gene

6 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
9 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MEPE

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for MEPE Gene

No ASD Table

Relevant External Links for MEPE Gene

GeneLoc Exon Structure for
MEPE

Expression for MEPE Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MEPE Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MEPE Gene

This gene is overexpressed in Brain - Anterior cingulate cortex (BA24) (x14.3), Brain - Frontal Cortex (BA9) (x11.7), Brain - Cortex (x8.4), Brain - Amygdala (x6.0), and Brain - Hippocampus (x5.7).

Protein differential expression in normal tissues from HIPED for MEPE Gene

This gene is overexpressed in Fetal ovary (50.7) and Testis (6.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for MEPE Gene



Protein tissue co-expression partners for MEPE Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MEPE

SOURCE GeneReport for Unigene cluster for MEPE Gene:

Hs.676357

mRNA Expression by UniProt/SwissProt for MEPE Gene:

Q9NQ76-MEPE_HUMAN
Tissue specificity: Expressed by osteoblasts (PubMed:10945470, PubMed:11414762, PubMed:15108058). Expressed by stem cells in dental pulp (PubMed:15153459). Expressed by mesenchymal cells in dental papilla and dental pulp (PubMed:18547474, PubMed:22341070). Expressed in teeth, specifically in decidious dentin (PubMed:20581062). Expressed in ondotoblasts (PubMed:12489176). Expressed in salivary glands (PubMed:15329369). Secreted from oncogenic hypophosphatemic tumors (PubMed:11414762).

Evidence on tissue expression from TISSUES for MEPE Gene

  • Bone(4.6)
  • Kidney(2.3)
  • Nervous system(2)
  • Blood(2)
genes like me logo Genes that share expression patterns with MEPE: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for MEPE Gene

Orthologs for MEPE Gene

This gene was present in the common ancestor of mammals.

Orthologs for MEPE Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia MEPE 30 31
  • 99.2 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia MEPE 30
  • 83.1 (n)
Cow
(Bos Taurus)
Mammalia MEPE 30 31
  • 78.92 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Mepe 30
  • 67.93 (n)
Mouse
(Mus musculus)
Mammalia Mepe 30 17 31
  • 67.81 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia MEPE 31
  • 35 (a)
OneToOne
Species where no ortholog for MEPE was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for MEPE Gene

ENSEMBL:
Gene Tree for MEPE (if available)
TreeFam:
Gene Tree for MEPE (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MEPE: view image

Paralogs for MEPE Gene

No data available for Paralogs for MEPE Gene

Variants for MEPE Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MEPE Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
767958 Benign: not provided 87,846,039(+) G/A MISSENSE_VARIANT
767959 Benign: not provided 87,846,053(+) C/G MISSENSE_VARIANT
767960 Benign: not provided 87,846,108(+) T/G MISSENSE_VARIANT
767961 Benign: not provided 87,846,214(+) A/C MISSENSE_VARIANT
767962 Benign: not provided 87,846,309(+) C/T MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for MEPE Gene

Structural Variations from Database of Genomic Variants (DGV) for MEPE Gene

Variant ID Type Subtype PubMed ID
dgv94n17 CNV loss 16327808
esv275333 CNV gain+loss 21479260
esv3575757 CNV gain 25503493
nsv822637 CNV gain 20364138

Variation tolerance for MEPE Gene

Residual Variation Intolerance Score: 89.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.16; 51.64% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MEPE Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
MEPE

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MEPE Gene

Disorders for MEPE Gene

MalaCards: The human disease database

(28) MalaCards diseases for MEPE Gene - From: DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search MEPE in MalaCards View complete list of genes associated with diseases

Additional Disease Information for MEPE

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with MEPE: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MEPE Gene

Publications for MEPE Gene

  1. MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia. (PMID: 10945470) Rowe PS … Oudet CL (Genomics 2000) 2 3 4 23
  2. MEPE's diverse effects on mineralization. (PMID: 19998030) Boskey AL … Rowe PS (Calcified tissue international 2010) 3 4 23
  3. Changes in matrix extracellular phosphoglycoprotein expression before and during in vitro osteogenic differentiation of human dental papilla mesenchymal cells. (PMID: 18547474) Tetè S … Ciccarelli R (International journal of immunopathology and pharmacology 2008) 3 4 23
  4. Matrix extracellular phosphoglycoprotein inhibits phosphate transport. (PMID: 19005008) Marks J … Unwin RJ (Journal of the American Society of Nephrology : JASN 2008) 3 4 23
  5. Matrix extracellular phosphoglycoprotein (MEPE) is highly expressed in osteocytes in human bone. (PMID: 15108058) Nampei A … Yoshikawa H (Journal of bone and mineral metabolism 2004) 3 4 23

Products for MEPE Gene

  • Signalway ELISA kits for MEPE
  • Signalway Proteins for MEPE

Sources for MEPE Gene