Mesd mesoderm development LRP chaperone [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Mesdprovided by MGI
Official Full Name: mesoderm development LRP chaperoneprovided by MGI
Primary source: MGI:MGI:1891421
See related: Ensembl:ENSMUSG00000038503 AllianceGenome:MGI:1891421
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: msd; mesd; Mesdc2; mKIAA0081; 2210015O11Rik
Summary: Enables identical protein binding activity and low-density lipoprotein particle receptor binding activity. Involved in phagocytosis and positive regulation of skeletal muscle acetylcholine-gated channel clustering. Acts upstream of or within protein folding and protein localization to cell surface. Located in plasma membrane. Is expressed in several structures, including genitourinary system; hemolymphoid system; liver; lung; and ventricular layer. Human ortholog(s) of this gene implicated in osteogenesis imperfecta type 20. Orthologous to human MESD (mesoderm development LRP chaperone). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in CNS E11.5 (RPKM 3.6), adrenal adult (RPKM 2.8) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 7 48.35 cM; 7 D3

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	7	NC_000073.7 (83533074..83549519)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	7	NC_000073.6 (83883866..83900311)

Chromosome 7 - NC_000073.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Mescd2 binds to Lrp4 and regulates Lrp4 surface expression in myotubes.
Title: Mesdc2 plays a key role in cell-surface expression of Lrp4 and postsynaptic specialization in myotubes.
Mesd C-terminal region constitutes the major LRP5/6-binding domain, and that Mesd protein and its C-terminal region peptide have a potential therapeutic value in cancer
Title: The C-terminal region Mesd peptide mimics full-length Mesd and acts as an inhibitor of Wnt/β-catenin signaling in cancer cells.
The region 45-184 of MESD is essential and sufficient to act as a molecular chaperone for the low-density lipoprotein receptor (LDLR) family.
Title: The structure of MESD45-184 brings light into the mechanism of LDLR family folding.
Mesd not only blocks binding of Dickkopf (DKK)-1 and sclerostin proteins to low-density lipoprotein receptor-related protein (LRP)5 and LRP6 but also inhibits Wnt/beta-catenin signaling in LRP5- or LRP6- expressing cancer cells.
Title: Mesd is a universal inhibitor of Wnt coreceptors LRP5 and LRP6 and blocks Wnt/beta-catenin signaling in cancer cells.
Secondary structure prediction using chemical shift data indicates that MESD(12-155) contains four a-helices and five b-sheets.
Title: A complete NMR spectral assignment of the conserved region of the MESD protein, MESD(12-155).
Functional analyses of the Lrp6 rs mutant showed decreased targeting to plasma membrane because of reduced interaction with Mesoderm development (Mesd), a chaperone for Lrp6, leading to impaired Wnt/beta-catenin signaling
Title: Lrp6 hypomorphic mutation affects bone mass through bone resorption in mice and impairs interaction with Mesd.
We show that MESD contains a central folded domain flanked by unstructured regions required to facilitate maturation of LRP6. Enforced expression of human MESD promotes the secretion of soluble minireceptors derived from LRP6.
Title: Requirement for natively unstructured regions of mesoderm development candidate 2 in promoting low-density lipoprotein receptor-related protein 6 maturation.
Together our results show that in addition to serving as a folding chaperone, Mesd can function as a receptor antagonist by inhibiting ligand binding to mature LRP6.
Title: Mesd binds to mature LDL-receptor-related protein-6 and antagonizes ligand binding.

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Phenotypes

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Associated conditions

Description	Tests
mesoderm development GeneReviews: Not available

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (4) 1 citation
Radiation induced (1) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables low-density lipoprotein particle receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables low-density lipoprotein particle receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in mesoderm development	NAS Non-traceable Author Statement more info	PubMed
involved_in ossification	ISO Inferred from Sequence Orthology more info
involved_in phagocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of skeletal muscle acetylcholine-gated channel clustering	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein folding	IDA Inferred from Direct Assay more info	PubMed
involved_in protein folding	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein folding	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein localization to cell surface	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: LRP chaperone MESD

Names: LDLR chaperone MESD; mesoderm development candidate 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.