MESD_MOUSE
ID MESD_MOUSE Reviewed; 224 AA.
AC Q9ERE7; Q8C611; Q8CCX7; Q91WK8; Q9CVB9;
DT 25-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=LRP chaperone MESD {ECO:0000305};
DE AltName: Full=LDLR chaperone MESD;
DE AltName: Full=Mesoderm development candidate 2;
DE AltName: Full=Mesoderm development protein;
DE Flags: Precursor;
GN Name=Mesd {ECO:0000312|MGI:MGI:1891421}; Synonyms=Mesdc2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC STRAIN=129/SvJ;
RX PubMed=11247670; DOI=10.1006/geno.2000.6466;
RA Wines M.E., Lee L., Katari M.S., Zhang L., DeRossi C., Shi Y., Perkins S.,
RA Feldman M., McCombie W.R., Holdener B.C.;
RT "Identification of mesoderm development (mesd) candidate genes by
RT comparative mapping and genome sequence analysis.";
RL Genomics 72:88-98(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata, Stomach, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, INTERACTION WITH LRP5 AND LRP6, SUBCELLULAR LOCATION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=12581525; DOI=10.1016/s0092-8674(03)00045-x;
RA Hsieh J.-C., Lee L., Zhang L., Wefer S., Brown K., DeRossi C., Wines M.E.,
RA Rosenquist T., Holdener B.C.;
RT "Mesd encodes an LRP5/6 chaperone essential for specification of mouse
RT embryonic polarity.";
RL Cell 112:355-367(2003).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP STRUCTURE BY NMR OF 89-184, AND SUBUNIT.
RX PubMed=17342452; DOI=10.1007/s10969-007-9016-5;
RA Kohler C., Andersen O.M., Diehl A., Krause G., Schmieder P., Oschkinat H.;
RT "The solution structure of the core of mesoderm development (MESD), a
RT chaperone for members of the LDLR-family.";
RL J. Struct. Funct. Genomics 7:131-138(2006).
RN [7]
RP STRUCTURE BY NMR OF 41-185.
RX PubMed=20506034; DOI=10.1007/s10858-010-9426-8;
RA Chen J., Li Q., Liu C.C., Zhou B., Bu G., Wang J.;
RT "NMR structure note: solution structure of the core domain of MESD that is
RT essential for proper folding of LRP5/6.";
RL J. Biomol. NMR 47:283-288(2010).
RN [8]
RP STRUCTURE BY NMR OF 45-184, FUNCTION, AND DOMAINS CHAPERONE AND ESCORT.
RX PubMed=21397183; DOI=10.1016/j.str.2011.01.010;
RA Chen J., Liu C.C., Li Q., Nowak C., Bu G., Wang J.;
RT "Two structural and functional domains of MESD required for proper folding
RT and trafficking of LRP5/6.";
RL Structure 19:313-323(2011).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 98-183, AND SUBUNIT.
RX PubMed=21397184; DOI=10.1016/j.str.2010.11.017;
RA Collins M.N., Hendrickson W.A.;
RT "Structural characterization of the Boca/Mesd maturation factors for LDL-
RT receptor-type beta-propeller domains.";
RL Structure 19:324-336(2011).
RN [10]
RP STRUCTURE BY NMR OF 45-184.
RX PubMed=21397185; DOI=10.1016/j.str.2010.12.022;
RA Koehler C., Lighthouse J.K., Werther T., Andersen O.M., Diehl A.,
RA Schmieder P., Du J., Holdener B.C., Oschkinat H.;
RT "The structure of MESD45-184 brings light into the mechanism of LDLR family
RT folding.";
RL Structure 19:337-348(2011).
RN [11]
RP INTERACTION WITH LRP4, IDENTIFICATION BY MASS SPECTROMETRY, AND FUNCTION.
RX PubMed=24140340; DOI=10.1016/j.febslet.2013.10.001;
RA Hoshi T., Tezuka T., Yokoyama K., Iemura S., Natsume T., Yamanashi Y.;
RT "Mesdc2 plays a key role in cell-surface expression of Lrp4 and
RT postsynaptic specialization in myotubes.";
RL FEBS Lett. 587:3749-3754(2013).
RN [12]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=27184668; DOI=10.1007/s10565-016-9339-8;
RA Chen X., Guo F., LeBlanc M.E., Ding Y., Zhang C., Shakya A., Li W.;
RT "Mesd extrinsically promotes phagocytosis by retinal pigment epithelial
RT cells.";
RL Cell Biol. Toxicol. 32:347-358(2016).
RN [13]
RP FUNCTION.
RX PubMed=31564437; DOI=10.1016/j.ajhg.2019.08.008;
RA Moosa S., Yamamoto G.L., Garbes L., Keupp K., Beleza-Meireles A.,
RA Moreno C.A., Valadares E.R., de Sousa S.B., Maia S., Saraiva J.,
RA Honjo R.S., Kim C.A., Cabral de Menezes H., Lausch E., Lorini P.V.,
RA Lamounier A. Jr., Carniero T.C.B., Giunta C., Rohrbach M., Janner M.,
RA Semler O., Beleggia F., Li Y., Yigit G., Reintjes N., Altmueller J.,
RA Nuernberg P., Cavalcanti D.P., Zabel B., Warman M.L., Bertola D.R.,
RA Wollnik B., Netzer C.;
RT "Autosomal-recessive mutations in MESD cause osteogenesis imperfecta.";
RL Am. J. Hum. Genet. 105:836-843(2019).
CC -!- FUNCTION: Chaperone specifically assisting the folding of beta-
CC propeller/EGF modules within the family of low-density lipoprotein
CC receptors (LDLRs) (PubMed:31564437). Acts as a modulator of the Wnt
CC pathway through chaperoning the coreceptors of the canonical Wnt
CC pathway, LRP5 and LRP6, to the plasma membrane. Essential for
CC specification of embryonic polarity and mesoderm induction
CC (PubMed:12581525, PubMed:21397183). Plays an essential role in
CC neuromuscular junction (NMJ) formation by promoting cell-surface
CC expression of LRP4 (PubMed:24140340). May regulate phagocytosis of
CC apoptotic retinal pigment epithelium (RPE) cells.
CC {ECO:0000269|PubMed:12581525, ECO:0000269|PubMed:21397183,
CC ECO:0000269|PubMed:24140340, ECO:0000269|PubMed:27184668,
CC ECO:0000269|PubMed:31564437}.
CC -!- SUBUNIT: Monomer. Interacts with LRP5; the interaction prevents LRP5
CC from forming aggregates and chaperones LRP6 to the plasma membrane.
CC Interacts with LRP6; the interaction prevents LRP6 from forming
CC aggregates and chaperones LRP6 to the plasma membrane. Interacts with
CC LRP4; the interaction promotes glycosylation of LRP4 and its cell-
CC surface expression (PubMed:24140340). {ECO:0000269|PubMed:12581525,
CC ECO:0000269|PubMed:17342452, ECO:0000269|PubMed:21397184,
CC ECO:0000269|PubMed:24140340}.
CC -!- INTERACTION:
CC Q9ERE7; Q8VI56: Lrp4; NbExp=2; IntAct=EBI-6662606, EBI-2106160;
CC Q9ERE7; Q9ERE7: Mesd; NbExp=3; IntAct=EBI-6662606, EBI-6662606;
CC Q9ERE7; O75581: LRP6; Xeno; NbExp=2; IntAct=EBI-6662606, EBI-910915;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:12581525}. Note=Released from apoptotic cells and
CC shed photoreceptor outer segments (PubMed:27184668).
CC {ECO:0000269|PubMed:27184668}.
CC -!- TISSUE SPECIFICITY: Expressed in many tissues, but not in skeletal
CC muscles (PubMed:11247670). In the retina expressed in retinal ganglion
CC cells, inner and outer plexiform layers, photoreceptor inner and outer
CC segments and retinal pigment epithelium (at protein level)
CC (PubMed:27184668). {ECO:0000269|PubMed:11247670,
CC ECO:0000269|PubMed:27184668}.
CC -!- DOMAIN: The chaperone domain provides a folding template for proper
CC folding of the beta-propeller (BP) domains of LRP5/6.
CC {ECO:0000269|PubMed:21397183}.
CC -!- DOMAIN: The escort domain ensures LRP5/6 safe-trafficking from the ER
CC to the Golgi by preventing premature ligand-binding.
CC {ECO:0000269|PubMed:21397183}.
CC -!- DISRUPTION PHENOTYPE: Disruption of embryonic polarity and mesoderm
CC differentiation, likely resulting from a primary defect in Wnt
CC signaling. {ECO:0000269|PubMed:12581525}.
CC -!- SIMILARITY: Belongs to the MESD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH14742.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC36476.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF311213; AAG33621.1; -; Genomic_DNA.
DR EMBL; AK008735; BAB25865.1; -; mRNA.
DR EMBL; AK031949; BAC27617.1; -; mRNA.
DR EMBL; AK076760; BAC36471.1; -; mRNA.
DR EMBL; AK076773; BAC36476.1; ALT_FRAME; mRNA.
DR EMBL; BC014742; AAH14742.1; ALT_INIT; mRNA.
DR CCDS; CCDS21415.1; -.
DR RefSeq; NP_075892.3; NM_023403.3.
DR PDB; 2I9S; NMR; -; A=89-184.
DR PDB; 2KGL; NMR; -; A=30-224.
DR PDB; 2KMI; NMR; -; A=41-185.
DR PDB; 2RQK; NMR; -; A=45-184.
DR PDB; 2RQM; NMR; -; A=45-184.
DR PDB; 3OFH; X-ray; 2.01 A; A/B=98-183.
DR PDBsum; 2I9S; -.
DR PDBsum; 2KGL; -.
DR PDBsum; 2KMI; -.
DR PDBsum; 2RQK; -.
DR PDBsum; 2RQM; -.
DR PDBsum; 3OFH; -.
DR AlphaFoldDB; Q9ERE7; -.
DR BMRB; Q9ERE7; -.
DR SMR; Q9ERE7; -.
DR BioGRID; 212555; 12.
DR DIP; DIP-59114N; -.
DR IntAct; Q9ERE7; 5.
DR MINT; Q9ERE7; -.
DR STRING; 10090.ENSMUSP00000091768; -.
DR GlyGen; Q9ERE7; 1 site.
DR iPTMnet; Q9ERE7; -.
DR PhosphoSitePlus; Q9ERE7; -.
DR REPRODUCTION-2DPAGE; IPI00349285; -.
DR REPRODUCTION-2DPAGE; Q9ERE7; -.
DR EPD; Q9ERE7; -.
DR jPOST; Q9ERE7; -.
DR MaxQB; Q9ERE7; -.
DR PaxDb; Q9ERE7; -.
DR PeptideAtlas; Q9ERE7; -.
DR PRIDE; Q9ERE7; -.
DR ProteomicsDB; 292219; -.
DR ABCD; Q9ERE7; 1 sequenced antibody.
DR Antibodypedia; 27911; 183 antibodies from 34 providers.
DR DNASU; 67943; -.
DR Ensembl; ENSMUST00000094215; ENSMUSP00000091768; ENSMUSG00000038503.
DR GeneID; 67943; -.
DR KEGG; mmu:67943; -.
DR UCSC; uc009idx.2; mouse.
DR CTD; 23184; -.
DR MGI; MGI:1891421; Mesd.
DR VEuPathDB; HostDB:ENSMUSG00000038503; -.
DR eggNOG; KOG4357; Eukaryota.
DR GeneTree; ENSGT00390000000993; -.
DR HOGENOM; CLU_111621_0_0_1; -.
DR InParanoid; Q9ERE7; -.
DR OMA; NRATKQR; -.
DR OrthoDB; 1590303at2759; -.
DR PhylomeDB; Q9ERE7; -.
DR TreeFam; TF315614; -.
DR BioGRID-ORCS; 67943; 15 hits in 73 CRISPR screens.
DR ChiTaRS; Mesd; mouse.
DR EvolutionaryTrace; Q9ERE7; -.
DR PRO; PR:Q9ERE7; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9ERE7; protein.
DR Bgee; ENSMUSG00000038503; Expressed in saccule of membranous labyrinth and 260 other tissues.
DR ExpressionAtlas; Q9ERE7; baseline and differential.
DR Genevisible; Q9ERE7; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IPI:MGI.
DR GO; GO:0007498; P:mesoderm development; NAS:UniProtKB.
DR GO; GO:0001503; P:ossification; ISS:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; IMP:UniProtKB.
DR GO; GO:1904395; P:positive regulation of skeletal muscle acetylcholine-gated channel clustering; IMP:UniProtKB.
DR GO; GO:0006457; P:protein folding; IDA:MGI.
DR GO; GO:0034394; P:protein localization to cell surface; IDA:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR DisProt; DP02314; -.
DR InterPro; IPR019330; MESD.
DR PANTHER; PTHR17600; PTHR17600; 1.
DR Pfam; PF10185; Mesd; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chaperone; Endoplasmic reticulum; Glycoprotein;
KW Reference proteome; Signal; Wnt signaling pathway.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..224
FT /note="LRP chaperone MESD"
FT /id="PRO_0000096444"
FT REGION 1..155
FT /note="Chaperone domain"
FT /evidence="ECO:0000269|PubMed:21397183"
FT REGION 28..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 156..195
FT /note="Escort domain"
FT /evidence="ECO:0000269|PubMed:21397183"
FT REGION 178..224
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 221..224
FT /note="Prevents secretion from ER"
FT COMPBIAS 188..224
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 206
FT /note="P -> R (in Ref. 2; BAC36471)"
FT /evidence="ECO:0000305"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:2KGL"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:2KGL"
FT HELIX 51..65
FT /evidence="ECO:0007829|PDB:2KGL"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:2KGL"
FT HELIX 93..99
FT /evidence="ECO:0007829|PDB:2I9S"
FT STRAND 105..113
FT /evidence="ECO:0007829|PDB:3OFH"
FT HELIX 117..133
FT /evidence="ECO:0007829|PDB:3OFH"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:3OFH"
FT STRAND 147..153
FT /evidence="ECO:0007829|PDB:3OFH"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:3OFH"
FT HELIX 158..166
FT /evidence="ECO:0007829|PDB:3OFH"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:2RQK"
FT STRAND 171..176
FT /evidence="ECO:0007829|PDB:3OFH"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:3OFH"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:2KGL"
FT HELIX 195..203
FT /evidence="ECO:0007829|PDB:2KGL"
FT STRAND 208..210
FT /evidence="ECO:0007829|PDB:2KGL"
FT HELIX 211..217
FT /evidence="ECO:0007829|PDB:2KGL"
SQ SEQUENCE 224 AA; 25207 MW; 6A94D5B315AE1D66 CRC64;
MAASRWLRAV LLFLCASDLL LLPPPNAYAA DTPGEATPPP RKKKDIRDYN DADMARLLEQ
WEKDDDIEEG DLPEHKRPSA PIDFSKLDPG KPESILKMTK KGKTLMMFVT VSGNPTEKET
EEITSLWQGS LFNANYDVQR FIVGSDRAIF MLRDGSYAWE IKDFLVSQDR CAEVTLEGQM
YPGKGGGSKE KNKTKPEKAK KKEGDPKPRA SKEDNRAGSR REDL
