MEPE_RAT
ID MEPE_RAT Reviewed; 435 AA.
AC Q9ES02; A0A0G2K7K7; D6C6P2; Q8K3V0;
DT 12-SEP-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Matrix extracellular phosphoglycoprotein {ECO:0000303|PubMed:19924383};
DE AltName: Full=Osteoblast/osteocyte factor 45 {ECO:0000303|PubMed:10967096};
DE Short=OF45 {ECO:0000303|PubMed:10967096};
DE AltName: Full=Osteoregulin {ECO:0000250|UniProtKB:Q9NQ76};
DE Flags: Precursor;
GN Name=Mepe {ECO:0000312|RGD:71036};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000312|EMBL:AAG33366.1};
RN [1] {ECO:0000312|EMBL:AAG33366.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:AAG33366.1};
RX PubMed=10967096; DOI=10.1074/jbc.m003622200;
RA Petersen D.N., Tkalcevic G.T., Mansolf A.L., Rivera-Gonzalez R.,
RA Brown T.A.;
RT "Identification of osteoblast/osteocyte factor 45 (OF45), a bone-specific
RT cDNA encoding an RGD-containing protein that is highly expressed in
RT osteoblasts and osteocytes.";
RL J. Biol. Chem. 275:36172-36180(2000).
RN [2] {ECO:0000312|EMBL:AAM94403.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Fischer 344 {ECO:0000312|EMBL:AAM94403.1};
RA Hu B., Wang X., Wang Y.;
RT "Rattus norvegicus cDNA sequence highly expressed in A1-5 cell line
RT (identical to osteoregulin).";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:AAM94404.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=Fischer 344 {ECO:0000312|EMBL:AAM94404.1};
RA Wang X., Hu B., Wang Y.;
RT "Rattus norvegicus cDNA sequence expressed in B4 cell line (possible
RT subtype of osteoregulin).";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|EMBL:ACS37551.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=19924383; DOI=10.1007/s00018-009-0185-1;
RA Bardet C., Delgado S., Sire J.Y.;
RT "MEPE evolution in mammals reveals regions and residues of prime functional
RT importance.";
RL Cell. Mol. Life Sci. 67:305-320(2010).
RN [5] {ECO:0000312|Proteomes:UP000002494}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000312|Proteomes:UP000002494};
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [6] {ECO:0000312|EMBL:EDL99493.1, ECO:0000312|EMBL:EDL99494.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1 AND 2).
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Regulates renal phosphate excretion (By similarity).
CC Regulates bone mineralization by osteoblasts and cartilage
CC mineralization by chondrocytes (By similarity). Regulates the
CC mineralization of the extracellular matrix of the craniofacial complex,
CC such as teeth, bone and cartilage (By similarity). Increases dental
CC pulp stem cell proliferation. {ECO:0000250|UniProtKB:Q9NQ76}.
CC -!- SUBUNIT: Interacts (via ASARM motif) with PHEX; the interaction is
CC zinc-dependent. {ECO:0000250|UniProtKB:Q9NQ76}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250|UniProtKB:Q8K4L6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9ES02-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9ES02-2; Sequence=VSP_059757;
CC -!- TISSUE SPECIFICITY: Expressed in osteoblasts and osteocytes.
CC {ECO:0000269|PubMed:10967096}.
CC -!- INDUCTION: Induced by dexamethasone. {ECO:0000269|PubMed:10967096}.
CC -!- DOMAIN: The acidic serine aspartate-rich MEPE-associated (ASARM) motif
CC is sufficient when phosphorylated to inhibit bone mineralization by
CC osteoblasts and cartilage mineralization by chondrocytes by binding
CC hydroxyapatite crystals during the mineralization stage. It can also
CC inhibit dentin mineralization. {ECO:0000250|UniProtKB:Q9NQ76}.
CC -!- DOMAIN: The dentonin region is sufficient to promote dental pulp stem
CC cell proliferation. It can also stimulate bone formation, osteoblast
CC differentiation, and activate integrin signaling pathways.
CC {ECO:0000250|UniProtKB:Q9NQ76}.
CC -!- PTM: Phosphorylated on serine residues in the ASARM motif; the
CC phosphorylation is important for the inhibition of bone mineralization.
CC {ECO:0000250|UniProtKB:Q9NQ76}.
CC -!- PTM: Cleaved by CTSB/cathepsin B; the cleavage is blocked by
CC metalloprotease PHEX. {ECO:0000250|UniProtKB:Q9NQ76}.
CC -!- SIMILARITY: Belongs to the PF07175/osteoregulin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF260922; AAG33366.1; -; mRNA.
DR EMBL; AF530558; AAM94403.1; -; mRNA.
DR EMBL; AF530559; AAM94404.1; -; mRNA.
DR EMBL; FJ999701; ACS37551.1; -; Genomic_DNA.
DR EMBL; AC136829; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474022; EDL99493.1; -; Genomic_DNA.
DR EMBL; CH474022; EDL99494.1; -; Genomic_DNA.
DR RefSeq; NP_077056.1; NM_024142.1. [Q9ES02-1]
DR RefSeq; XP_006250697.1; XM_006250635.3.
DR AlphaFoldDB; Q9ES02; -.
DR STRING; 10116.ENSRNOP00000002927; -.
DR GlyGen; Q9ES02; 1 site.
DR GeneID; 79110; -.
DR KEGG; rno:79110; -.
DR CTD; 56955; -.
DR RGD; 71036; Mepe.
DR eggNOG; ENOG502SW2S; Eukaryota.
DR HOGENOM; CLU_039303_0_0_1; -.
DR OrthoDB; 962767at2759; -.
DR PhylomeDB; Q9ES02; -.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR PRO; PR:Q9ES02; -.
DR Proteomes; UP000002494; Unplaced.
DR Proteomes; UP000234681; Chromosome 14.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:1990430; F:extracellular matrix protein binding; IBA:GO_Central.
DR GO; GO:0031214; P:biomineral tissue development; IBA:GO_Central.
DR GO; GO:0030502; P:negative regulation of bone mineralization; ISO:RGD.
DR GO; GO:0046850; P:regulation of bone remodeling; IEP:RGD.
DR InterPro; IPR009837; MEPE.
DR PANTHER; PTHR16510; PTHR16510; 1.
DR Pfam; PF07175; Osteoregulin; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Biomineralization; Extracellular matrix;
KW Glycoprotein; Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..435
FT /note="Matrix extracellular phosphoglycoprotein"
FT /evidence="ECO:0000255"
FT /id="PRO_5010147977"
FT REGION 124..145
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 164..186
FT /note="Dentonin"
FT /evidence="ECO:0000250|UniProtKB:Q9NQ76"
FT REGION 166..435
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 418..435
FT /note="ASARM motif; interaction with PHEX"
FT /evidence="ECO:0000250|UniProtKB:Q8K4L6"
FT MOTIF 169..171
FT /note="Cell attachment site"
FT /evidence="ECO:0000250|UniProtKB:Q9NQ76"
FT COMPBIAS 202..218
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 296..316
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 334..361
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 419..435
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 3..18
FT /note="AVSVGLFLFSMTWAAP -> FLLSQNLKTENEHREPKTGWGKCH (in
FT isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_059757"
FT CONFLICT 43
FT /note="M -> T (in Ref. 4; ACS37551 and 6; AC136829/
FT EDL99493)"
FT /evidence="ECO:0000305"
FT CONFLICT 59
FT /note="L -> P (in Ref. 4; ACS37551 and 6; AC136829/
FT EDL99493)"
FT /evidence="ECO:0000305"
FT CONFLICT 109
FT /note="T -> A (in Ref. 4; ACS37551 and 6; AC136829/
FT EDL99493)"
FT /evidence="ECO:0000305"
FT CONFLICT 328
FT /note="A -> T (in Ref. 4; ACS37551 and 6; AC136829/
FT EDL99493)"
FT /evidence="ECO:0000305"
FT CONFLICT 403
FT /note="A -> P (in Ref. 4; ACS37551 and 6; AC136829/
FT EDL99493)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 435 AA; 46516 MW; D587F82968A26BCB CRC64;
MQAVSVGLFL FSMTWAAPKL NEDGSSGGNQ GNIHLASVKP EPMVGKGTEG GRDAPLHLLD
QNRQGATLLR NITQPVKSLV TGTEVQSDRN KEKKPQSVLS VIPTDVHNTN DYSEDTENQQ
RDLLLQNSPG QSKHTPRARR STHYLTHLPQ IRKILSDFED SASPDLLVRG DNDVPPFSGD
GQHFMHTPDR GGAVGSDPES SAGHPVSGSS NVEIVDPHTN GLGSNEIPGR EGHIGGAYAT
RGKTAQGAGS ADVSLVEGSN EITGSTKFRE LPGKEGNRVD ASSQNAHQGK VEFHYPQAPS
KEKVKGGSRE HTGKAGYNEI PKSSKGGASK DAEESKGNQV TLTESQRFPG KGKGQSSHSL
GNEVKSEEDS SNSLSREGIA IAHRRTSHPT RNRGMSQRRG SWASRRPHPH RRVSTRQRDS
SESSSSGSSS ESSGD
