LOCUS       NM_020203               1982 bp    mRNA    linear   PRI 03-OCT-2024
DEFINITION  Homo sapiens matrix extracellular phosphoglycoprotein (MEPE),
            transcript variant 2, mRNA.
ACCESSION   NM_020203
VERSION     NM_020203.6
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 1982)
  AUTHORS   Minamizaki,T., Sakurai,K., Hayashi,I., Toshishige,M., Yoshioka,H.,
            Kozai,K. and Yoshiko,Y.
  TITLE     Active sites of human MEPE-ASARM regulating bone matrix
            mineralization
  JOURNAL   Mol Cell Endocrinol 517, 110931 (2020)
   PUBMED   32712387
  REMARK    GeneRIF: Active sites of human MEPE-ASARM regulating bone matrix
            mineralization.
REFERENCE   2  (bases 1 to 1982)
  AUTHORS   Surakka,I., Fritsche,L.G., Zhou,W., Backman,J., Kosmicki,J.A.,
            Lu,H., Brumpton,B., Nielsen,J.B., Gabrielsen,M.E., Skogholt,A.H.,
            Wolford,B., Graham,S.E., Chen,Y.E., Lee,S., Kang,H.M.,
            Langhammer,A., Forsmo,S., Asvold,B.O., Styrkarsdottir,U., Holm,H.,
            Gudbjartsson,D., Stefansson,K., Baras,A., Abecasis,G.R., Hveem,K.
            and Willer,C.J.
  CONSRTM   Regeneron Genetics Center
  TITLE     MEPE loss-of-function variant associates with decreased bone
            mineral density and increased fracture risk
  JOURNAL   Nat Commun 11 (1), 4093 (2020)
   PUBMED   33097703
  REMARK    GeneRIF: MEPE loss-of-function variant associates with decreased
            bone mineral density and increased fracture risk.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 1982)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   4  (bases 1 to 1982)
  AUTHORS   Schrauwen,I., Valgaeren,H., Tomas-Roca,L., Sommen,M., Altunoglu,U.,
            Wesdorp,M., Beyens,M., Fransen,E., Nasir,A., Vandeweyer,G.,
            Schepers,A., Rahmoun,M., van Beusekom,E., Huentelman,M.J.,
            Offeciers,E., Dhooghe,I., Huber,A., Van de Heyning,P., Zanetti,D.,
            De Leenheer,E.M.R., Gilissen,C., Hoischen,A., Cremers,C.W.,
            Verbist,B., de Brouwer,A.P.M., Padberg,G.W., Pennings,R.,
            Kayserili,H., Kremer,H., Van Camp,G. and van Bokhoven,H.
  TITLE     Variants affecting diverse domains of MEPE are associated with two
            distinct bone disorders, a craniofacial bone defect and
            otosclerosis
  JOURNAL   Genet Med 21 (5), 1199-1208 (2019)
   PUBMED   30287925
  REMARK    GeneRIF: sequencing identified a rare segregating heterozygous
            frameshift variant p.(Gln425Lysfs*38) in MEPE. We performed variant
            burden and variance components analyses in a large otosclerosis
            cohort and demonstrated that nonsense and frameshift MEPE variants
            were significantly enriched in affected subjects (p =
            0.0006-0.0060).
REFERENCE   5  (bases 1 to 1982)
  AUTHORS   Tagliabracci,V.S., Engel,J.L., Wen,J., Wiley,S.E., Worby,C.A.,
            Kinch,L.N., Xiao,J., Grishin,N.V. and Dixon,J.E.
  TITLE     Secreted kinase phosphorylates extracellular proteins that regulate
            biomineralization
  JOURNAL   Science 336 (6085), 1150-1153 (2012)
   PUBMED   22582013
REFERENCE   6  (bases 1 to 1982)
  AUTHORS   Quarles,L.D.
  TITLE     FGF23, PHEX, and MEPE regulation of phosphate homeostasis and
            skeletal mineralization
  JOURNAL   Am J Physiol Endocrinol Metab 285 (1), E1-E9 (2003)
   PUBMED   12791601
  REMARK    GeneRIF: There is evidence for a hormone/enzyme/extracellular
            matrix protein cascade involving fibroblastic growth factor 23
            (FGF23), a phosphate-regulating gene with homologies to (PHEX) and
            (MEPE)--REVIEW
            Review article
REFERENCE   7  (bases 1 to 1982)
  AUTHORS   Gowen,L.C., Petersen,D.N., Mansolf,A.L., Qi,H., Stock,J.L.,
            Tkalcevic,G.T., Simmons,H.A., Crawford,D.T., Chidsey-Frink,K.L.,
            Ke,H.Z., McNeish,J.D. and Brown,T.A.
  TITLE     Targeted disruption of the osteoblast/osteocyte factor 45 gene
            (OF45) results in increased bone formation and bone mass
  JOURNAL   J Biol Chem 278 (3), 1998-2007 (2003)
   PUBMED   12421822
  REMARK    GeneRIF: Mice deficient in an ortholog of MEPE show increased bone
            mass and are resistant to aging-related bone loss.
REFERENCE   8  (bases 1 to 1982)
  AUTHORS   MacDougall,M., Simmons,D., Gu,T.T. and Dong,J.
  TITLE     MEPE/OF45, a new dentin/bone matrix protein and candidate gene for
            dentin diseases mapping to chromosome 4q21
  JOURNAL   Connect Tissue Res 43 (2-3), 320-330 (2002)
   PUBMED   12489176
  REMARK    GeneRIF: MEPE/OF45, a new dentin/bone matrix protein and candidate
            gene for dentin diseases mapping to chromosome 4q21. Expressed
            during odontogenesis.
REFERENCE   9  (bases 1 to 1982)
  AUTHORS   Argiro,L., Desbarats,M., Glorieux,F.H. and Ecarot,B.
  TITLE     Mepe, the gene encoding a tumor-secreted protein in oncogenic
            hypophosphatemic osteomalacia, is expressed in bone
  JOURNAL   Genomics 74 (3), 342-351 (2001)
   PUBMED   11414762
REFERENCE   10 (bases 1 to 1982)
  AUTHORS   Rowe,P.S., de Zoysa,P.A., Dong,R., Wang,H.R., White,K.E.,
            Econs,M.J. and Oudet,C.L.
  TITLE     MEPE, a new gene expressed in bone marrow and tumors causing
            osteomalacia
  JOURNAL   Genomics 67 (1), 54-68 (2000)
   PUBMED   10945470
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC093768.3.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Feb 19, 2021 this sequence version replaced NM_020203.5.
            
            Summary: 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].
            
            Sequence Note:.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AJ276396.1, BC128158.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2145743, SAMN02400308
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000361056.4/ ENSP00000354341.3
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-46                AC093768.3         63668-63713
            47-112              AC093768.3         65402-65467
            113-166             AC093768.3         69331-69384
            167-1982            AC093768.3         75676-77491
FEATURES             Location/Qualifiers
     source          1..1982
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4q22.1"
     gene            1..1982
                     /gene="MEPE"
                     /gene_synonym="OF45"
                     /note="matrix extracellular phosphoglycoprotein"
                     /db_xref="GeneID:56955"
                     /db_xref="HGNC:HGNC:13361"
                     /db_xref="MIM:605912"
     exon            1..46
                     /gene="MEPE"
                     /gene_synonym="OF45"
                     /inference="alignment:Splign:2.1.0"
     exon            47..112
                     /gene="MEPE"
                     /gene_synonym="OF45"
                     /inference="alignment:Splign:2.1.0"
     CDS             59..1636
                     /gene="MEPE"
                     /gene_synonym="OF45"
                     /note="isoform a precursor is encoded by transcript
                     variant 2; matrix, extracellular phosphoglycoprotein with
                     ASARM motif (bone); osteoblast/osteocyte factor 45;
                     osteoregulin"
                     /codon_start=1
                     /product="matrix extracellular phosphoglycoprotein isoform
                     a precursor"
                     /protein_id="NP_064588.1"
                     /db_xref="CCDS:CCDS3625.1"
                     /db_xref="GeneID:56955"
                     /db_xref="HGNC:HGNC:13361"
                     /db_xref="MIM:605912"
                     /translation="MRVFCVGLLLFSVTWAAPTFQPQTEKTKQSCVEEQRQEEKNKDN
                     IGFHHLGKRINQELSSKENIVQERKKDLSLSEASENKGSSKSQNYFTNRQRLNKEYSI
                     SNKENTHNGLRMSIYPKSTGNKGFEDGDDAISKLHDQEEYGAALIRNNMQHIMGPVTA
                     IKLLGEENKENTPRNVLNIIPASMNYAKAHSKDKKKPQRDSQAQKSPVKSKSTHRIQH
                     NIDYLKHLSKVKKIPSDFEGSGYTDLQERGDNDISPFSGDGQPFKDIPGKGEATGPDL
                     EGKDIQTGFAGPSEAESTHLDTKKPGYNEIPEREENGGNTIGTRDETAKEADAVDVSL
                     VEGSNDIMGSTNFKELPGREGNRVDAGSQNAHQGKVEFHYPPAPSKEKRKEGSSDAAE
                     STNYNEIPKNGKGSTRKGVDHSNRNQATLNEKQRFPSKGKSQGLPIPSRGLDNEIKNE
                     MDSFNGPSHENIITHGRKYHYVPHRQNNSTRNKGMPQGKGSWGRQPHSNRRFSSRRRD
                     DSSESSDSGSSSESDGD"
     exon            113..166
                     /gene="MEPE"
                     /gene_synonym="OF45"
                     /inference="alignment:Splign:2.1.0"
     exon            167..1982
                     /gene="MEPE"
                     /gene_synonym="OF45"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1958..1963
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MEPE"
                     /gene_synonym="OF45"
                     /note="hexamer: AATAAA"
     polyA_site      1982
                     /gene="MEPE"
                     /gene_synonym="OF45"
                     /note="major polyA site"
ORIGIN      
        1 aatcctgcaa caagaagcca ggtattctga aggtgaaaga taccagagat tctcaaagat
       61 gcgagttttc tgtgtgggac tactcctttt cagtgtgacc tgggcagcac caacatttca
      121 accacagact gagaaaacta agcaaagctg tgtggaagag cagaggcagg aagaaaaaaa
      181 caaagacaat attggttttc accatttggg caagagaata aatcaagagc tatcatctaa
      241 agaaaatatt gtccaggaaa gaaagaaaga tttgtccctt tctgaagcca gtgagaataa
      301 gggaagtagt aaatctcaaa attatttcac aaatagacag agactgaata aagaatatag
      361 tatcagtaac aaagagaata ctcacaatgg cctgaggatg tcaatttatc ctaagtcaac
      421 tgggaataaa gggtttgagg atggagatga tgctatcagc aaactacatg accaagaaga
      481 atatggcgca gctctcatca gaaataacat gcaacatata atggggccag tgactgcgat
      541 taaactcctg ggggaagaaa acaaagagaa cacacctagg aatgttctaa acataatccc
      601 agcaagtatg aattatgcta aagcacactc gaaggataaa aagaagcctc aaagagattc
      661 ccaagcccag aaaagtccag taaaaagcaa aagcacccat cgtattcaac acaacattga
      721 ctacctaaaa catctctcaa aagtcaaaaa aatccccagt gattttgaag gcagcggtta
      781 tacagatctt caagagagag gggacaatga tatatctcct ttcagtgggg acggccaacc
      841 ttttaaggac attcctggta aaggagaagc tactggtcct gacctagaag gcaaagatat
      901 tcaaacaggg tttgcaggcc caagtgaagc tgagagtact catcttgaca caaaaaagcc
      961 aggttataat gagatcccag agagagaaga aaatggtgga aataccattg gaactaggga
     1021 tgaaactgcg aaagaggcag atgctgttga tgtcagcctt gtagagggca gcaacgatat
     1081 catgggtagt accaatttta aggagctccc tggaagagaa ggaaacagag tggatgctgg
     1141 cagccaaaat gctcaccaag ggaaggttga gtttcattac cctcctgcac cctcaaaaga
     1201 gaaaagaaaa gaaggcagta gtgatgcagc tgaaagtacc aactataatg aaattcctaa
     1261 aaatggcaaa ggcagtacca gaaagggtgt agatcattct aataggaacc aagcaacctt
     1321 aaatgaaaaa caaaggtttc ctagtaaggg caaaagtcag ggcctgccca ttccttctcg
     1381 tggtcttgat aatgaaatca aaaacgaaat ggattccttt aatggcccca gtcatgagaa
     1441 tataataaca catggcagaa aatatcatta tgtaccccac agacaaaata attctacacg
     1501 gaataagggt atgccacaag ggaaaggctc ctggggtaga caaccccatt ccaacaggag
     1561 gtttagttcc cgtagaaggg atgacagtag tgagtcatct gacagtggca gttcaagtga
     1621 gagcgatggt gactagtcca ccaggagttc ccagcggggt gacagtctga agacctcgtc
     1681 acctgtgagt tgatgtagag gagagccacc tgacagctga ccaggtgaag agaggataga
     1741 gtgaagaact gagtgagcca agaatcctgg tctccttggg ggaatttttg ctatcttaat
     1801 agtcacagta taaaattcta ttaaaggcta taatgttttt aagcaaaaaa aaatcattac
     1861 agatctatga aataggtaac atttgagtag gtgtcattta aaaatagttg gtgaatgtca
     1921 caaatgcctt ctatgttgtt tgctctgtag acatgaaaat aaacaatatc tctcgatgat
     1981 aa
//
