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Protein

Matrix extracellular phosphoglycoprotein

Gene

MEPE

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity6 Publications

GO - Molecular functioni

  • extracellular matrix protein binding Source: GO_Central
  • extracellular matrix structural constituent Source: ProtInc

GO - Biological processi

Keywordsi

Biological processBiomineralization

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Matrix extracellular phosphoglycoprotein1 Publication
Alternative name(s):
Osteoblast/osteocyte factor 45By similarity
Short name:
OF45By similarity
Osteoregulin1 Publication
Gene namesi
Name:MEPE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000152595.16
HGNCiHGNC:13361 MEPE
MIMi605912 gene
neXtProtiNX_Q9NQ76

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

Organism-specific databases

DisGeNETi56955
OpenTargetsiENSG00000152595
PharmGKBiPA30755

Polymorphism and mutation databases

BioMutaiMEPE
DMDMi33112396

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
ChainiPRO_000002166818 – 525Matrix extracellular phosphoglycoproteinAdd BLAST508

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi477N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi478N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

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).2 Publications
Cleaved by CTSB/cathepsin B; the cleavage is blocked by metalloprotease PHEX.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9NQ76
PeptideAtlasiQ9NQ76
PRIDEiQ9NQ76
ProteomicsDBi82096
82097 [Q9NQ76-2]

PTM databases

iPTMnetiQ9NQ76
PhosphoSitePlusiQ9NQ76

Expressioni

Tissue specificityi

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).9 Publications

Gene expression databases

BgeeiENSG00000152595 Expressed in 39 organ(s), highest expression level in tibia
CleanExiHS_MEPE
ExpressionAtlasiQ9NQ76 baseline and differential
GenevisibleiQ9NQ76 HS

Organism-specific databases

HPAiHPA038003
HPA038004

Interactioni

Subunit structurei

Interacts (via the ASARM motif) with PHEX; the interaction is zinc-dependent.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
NCK1P163333EBI-1753293,EBI-389883

GO - Molecular functioni

Protein-protein interaction databases

BioGridi121279, 4 interactors
IntActiQ9NQ76, 10 interactors
STRINGi9606.ENSP00000354341

Structurei

3D structure databases

ProteinModelPortaliQ9NQ76
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni242 – 264Dentonin2 PublicationsAdd BLAST23
Regioni507 – 525ASARM motif; interaction with PHEX1 PublicationAdd BLAST19

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi247 – 249Cell attachment siteSequence analysis3

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:15664000, PubMed:18162525, PubMed:18597632, PubMed:19998030, PubMed:22766095). It can also inhibit dentin mineralization (PubMed:20581062).6 Publications
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).2 Publications

Sequence similaritiesi

Belongs to the PF07175/osteoregulin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IIFI Eukaryota
ENOG41118PA LUCA
GeneTreeiENSGT00390000010702
HOGENOMiHOG000115910
HOVERGENiHBG004786
InParanoidiQ9NQ76
OMAiVPHRQNN
OrthoDBiEOG091G0HA8
PhylomeDBiQ9NQ76
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

Sequences (3+)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9NQ76-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MRVFCVGLLL FSVTWAAPTF QPQTEKTKQS CVEEQRQEEK NKDNIGFHHL
60 70 80 90 100
GKRINQELSS KENIVQERKK DLSLSEASEN KGSSKSQNYF TNRQRLNKEY
110 120 130 140 150
SISNKENTHN GLRMSIYPKS TGNKGFEDGD DAISKLHDQE EYGAALIRNN
160 170 180 190 200
MQHIMGPVTA IKLLGEENKE NTPRNVLNII PASMNYAKAH SKDKKKPQRD
210 220 230 240 250
SQAQKSPVKS KSTHRIQHNI DYLKHLSKVK KIPSDFEGSG YTDLQERGDN
260 270 280 290 300
DISPFSGDGQ PFKDIPGKGE ATGPDLEGKD IQTGFAGPSE AESTHLDTKK
310 320 330 340 350
PGYNEIPERE ENGGNTIGTR DETAKEADAV DVSLVEGSND IMGSTNFKEL
360 370 380 390 400
PGREGNRVDA GSQNAHQGKV EFHYPPAPSK EKRKEGSSDA AESTNYNEIP
410 420 430 440 450
KNGKGSTRKG VDHSNRNQAT LNEKQRFPSK GKSQGLPIPS RGLDNEIKNE
460 470 480 490 500
MDSFNGPSHE NIITHGRKYH YVPHRQNNST RNKGMPQGKG SWGRQPHSNR
510 520
RFSSRRRDDS SESSDSGSSS ESDGD
Length:525
Mass (Da):58,419
Last modified:October 1, 2000 - v1
Checksum:i0977CA6E871CA9E5
GO
Isoform 2 (identifier: Q9NQ76-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     36-36: R → RITYKGHYEKHGHYVFKCVYMSPEKKNQTDVK

Show »
Length:556
Mass (Da):62,160
Checksum:iF475015A4923DA71
GO
Isoform 3 (identifier: Q9NQ76-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-113: Missing.

Note: Gene prediction based on EST data.
Show »
Length:412
Mass (Da):45,291
Checksum:iB93BA6DAFF1D5052
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RFW6D6RFW6_HUMAN
Matrix extracellular phosphoglycopr...
MEPE
96Annotation score:
D6RAC8D6RAC8_HUMAN
Matrix extracellular phosphoglycopr...
MEPE
501Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034094330V → I. Corresponds to variant dbSNP:rs17013285Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0468921 – 113Missing in isoform 3. CuratedAdd BLAST113
Alternative sequenceiVSP_04398636R → RITYKGHYEKHGHYVFKCVY MSPEKKNQTDVK in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ276396 mRNA Translation: CAB97250.1
AF325916 mRNA Translation: AAK70343.1
AC093768 Genomic DNA No translation available.
CH471057 Genomic DNA Translation: EAX06001.1
CH471057 Genomic DNA Translation: EAX06002.1
BC128158 mRNA Translation: AAI28159.1
DQ854717 mRNA Translation: ABI64294.1
CCDSiCCDS3625.1 [Q9NQ76-1]
CCDS54776.1 [Q9NQ76-3]
CCDS77940.1 [Q9NQ76-2]
RefSeqiNP_001171623.1, NM_001184694.2 [Q9NQ76-1]
NP_001171624.1, NM_001184695.1 [Q9NQ76-3]
NP_001171625.1, NM_001184696.1 [Q9NQ76-3]
NP_001171626.1, NM_001184697.1 [Q9NQ76-3]
NP_001278112.1, NM_001291183.1 [Q9NQ76-2]
NP_064588.1, NM_020203.3 [Q9NQ76-1]
XP_006714341.1, XM_006714278.2 [Q9NQ76-2]
UniGeneiHs.676357

Genome annotation databases

EnsembliENST00000361056; ENSP00000354341; ENSG00000152595 [Q9NQ76-1]
ENST00000395102; ENSP00000378534; ENSG00000152595 [Q9NQ76-2]
ENST00000424957; ENSP00000416984; ENSG00000152595 [Q9NQ76-1]
ENST00000540395; ENSP00000443491; ENSG00000152595 [Q9NQ76-3]
ENST00000560249; ENSP00000453994; ENSG00000152595 [Q9NQ76-3]
GeneIDi56955
KEGGihsa:56955
UCSCiuc003hqy.4 human [Q9NQ76-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ276396 mRNA Translation: CAB97250.1
AF325916 mRNA Translation: AAK70343.1
AC093768 Genomic DNA No translation available.
CH471057 Genomic DNA Translation: EAX06001.1
CH471057 Genomic DNA Translation: EAX06002.1
BC128158 mRNA Translation: AAI28159.1
DQ854717 mRNA Translation: ABI64294.1
CCDSiCCDS3625.1 [Q9NQ76-1]
CCDS54776.1 [Q9NQ76-3]
CCDS77940.1 [Q9NQ76-2]
RefSeqiNP_001171623.1, NM_001184694.2 [Q9NQ76-1]
NP_001171624.1, NM_001184695.1 [Q9NQ76-3]
NP_001171625.1, NM_001184696.1 [Q9NQ76-3]
NP_001171626.1, NM_001184697.1 [Q9NQ76-3]
NP_001278112.1, NM_001291183.1 [Q9NQ76-2]
NP_064588.1, NM_020203.3 [Q9NQ76-1]
XP_006714341.1, XM_006714278.2 [Q9NQ76-2]
UniGeneiHs.676357

3D structure databases

ProteinModelPortaliQ9NQ76
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121279, 4 interactors
IntActiQ9NQ76, 10 interactors
STRINGi9606.ENSP00000354341

PTM databases

iPTMnetiQ9NQ76
PhosphoSitePlusiQ9NQ76

Polymorphism and mutation databases

BioMutaiMEPE
DMDMi33112396

Proteomic databases

PaxDbiQ9NQ76
PeptideAtlasiQ9NQ76
PRIDEiQ9NQ76
ProteomicsDBi82096
82097 [Q9NQ76-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361056; ENSP00000354341; ENSG00000152595 [Q9NQ76-1]
ENST00000395102; ENSP00000378534; ENSG00000152595 [Q9NQ76-2]
ENST00000424957; ENSP00000416984; ENSG00000152595 [Q9NQ76-1]
ENST00000540395; ENSP00000443491; ENSG00000152595 [Q9NQ76-3]
ENST00000560249; ENSP00000453994; ENSG00000152595 [Q9NQ76-3]
GeneIDi56955
KEGGihsa:56955
UCSCiuc003hqy.4 human [Q9NQ76-1]

Organism-specific databases

CTDi56955
DisGeNETi56955
EuPathDBiHostDB:ENSG00000152595.16
GeneCardsiMEPE
HGNCiHGNC:13361 MEPE
HPAiHPA038003
HPA038004
MIMi605912 gene
neXtProtiNX_Q9NQ76
OpenTargetsiENSG00000152595
PharmGKBiPA30755
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IIFI Eukaryota
ENOG41118PA LUCA
GeneTreeiENSGT00390000010702
HOGENOMiHOG000115910
HOVERGENiHBG004786
InParanoidiQ9NQ76
OMAiVPHRQNN
OrthoDBiEOG091G0HA8
PhylomeDBiQ9NQ76
TreeFamiTF338655

Enzyme and pathway databases

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

Miscellaneous databases

GeneWikiiMEPE
GenomeRNAii56955
PROiPR:Q9NQ76
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000152595 Expressed in 39 organ(s), highest expression level in tibia
CleanExiHS_MEPE
ExpressionAtlasiQ9NQ76 baseline and differential
GenevisibleiQ9NQ76 HS

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_HUMAN
AccessioniPrimary (citable) accession number: Q9NQ76
Secondary accession number(s): A1A4X9
, A8MTA3, D2CFR4, F5H5C5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2003
Last sequence update: October 1, 2000
Last modified: November 7, 2018
This is version 118 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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