LRP chaperone MESD (MESDC2)
The protein contains 234 amino acids for an estimated molecular weight of 26077 Da.
Chaperone specifically assisting the folding of beta-propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs) (PubMed:15014448). Acts as a modulator of the Wnt pathway through chaperoning the coreceptors of the canonical Wnt pathway, LRP5 and LRP6, to the plasma membrane (PubMed:17488095). Essential for specification of embryonic polarity and mesoderm induction. Plays an essential role in neuromuscular junction (NMJ) formation by promoting cell-surface expression of LRP4 (By similarity). May regulate phagocytosis of apoptotic retinal pigment epithelium (RPE) cells (By similarity). (updated: June 17, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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The reference OMIM entry for this protein is 607783
Mesoderm development candidate gene 2; mesdc2
Mesoderm development gene; mesd
Kiaa0081
Boca, drosophila, homolog of; boca mesdc2/senp1 fusion gene, included
CLONING
By sequencing cDNAs randomly selected from a cDNA library derived from the human immature myeloid cell line KG-1, Nagase et al. (1995) isolated a cDNA encoding MESDC2, which they designated KIAA0081. The predicted 233-amino acid protein contains at least 1 putative transmembrane region. Northern blot analysis detected expression in all tissues tested except peripheral blood leukocytes. Wines et al. (2001) cloned mouse Mesdc2, which encodes a 223-amino acid protein that shares 82% identity with the 234-amino acid human protein. MESDC2 was predicted to have an N-terminal transmembrane domain. Northern blot analysis detected a 1.8-kb transcript in mouse embryos throughout development and in all adult mouse tissues tested, except skeletal muscle.GENE FUNCTION
Hsieh et al. (2003) demonstrated that Mesdc2, a gene identified in the mesoderm development (Mesd) deletion interval on mouse chromosome 7, is essential for specification of embryonic polarity and mesoderm induction. They determined that the patterning and cell differentiation defects observed in Mesd deletion homozygotes result solely from loss of the Mesdc2 gene, and therefore they renamed the gene Mesd. Hsieh et al. (2003) showed that Mesd functions in the endoplasmic reticulum (ER) as a specific chaperone for Lrp5 (603506) and Lrp6 (603507), which in conjunction with frizzled (see 603408) are coreceptors for canonical Wnt signal transduction. The authors proposed that disruption of embryonic polarity and mesoderm differentiation in Mesd-deficient embryos likely results from a primary defect in Wnt signaling. However, phenotypic differences between Mesd-deficient and Wnt3 (165330) -/- embryos suggested that Mesd may function on related members of the LDLR family. LDLR family members mediate diverse cellular processes ranging from cargo transport to signaling. Culi and Mann (2003) described boca, an evolutionarily conserved gene in Drosophila melanogaster that encodes an ER protein homologous to the mouse Mesdc2 protein. They showed that boca is specifically required for the intracellular trafficking of members of the LDLR family. Two LDLRs in flies, arrow (see 603507), which is required for wingless signal transduction, and yolkless, which is required for yolk protein uptake during oogenesis, were found to require boca function. Culi and Mann (2003) concluded that boca is an essential component of the wingless pathway but is more generally required for the activities of multiple LDLR family members. Veltman et al. (2005) identified a patient with an infantile sacrococcygeal teratoma and a constitutional t(12;15)(q13;q25) chromosomal translocation, resulting SENP1 (612157)/MESDC2 fusion gene. Both reciprocal SENP1/MESDC2 (SEME) and MESDC2/SENP1 (MESE) fusion genes were transcribed in tumor-derived cells, and their open reading frames encoded aberrant proteins. In contrast to wildtype MESDC2, the translocation-associated SEME protein was no longer targeted to the endoplasmic reticulum, leading to a presumed loss-of-function as a chaperone for the WNT coreceptors LRP5 (603506) and/or LRP6 (603507). SUMO, a posttranslational modifier, plays an important role in several cellular key processes and is cleaved from its substrates by wildtype SENP1. In vitro studies revealed that translocation-associated MESE proteins exhibited desumoylation capacities similar to those observed for wildtype SENP1. Veltman et al. (2005) speculated that spatiotemporal disturbance ... More on the omim web site
June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 607783 was added.