Junction plakoglobin (JUP)
The protein contains 745 amino acids for an estimated molecular weight of 81745 Da.
Common junctional plaque protein. The membrane-associated plaques are architectural elements in an important strategic position to influence the arrangement and function of both the cytoskeleton and the cells within the tissue. The presence of plakoglobin in both the desmosomes and in the intermediate junctions suggests that it plays a central role in the structure and function of submembranous plaques. Acts as a substrate for VE-PTP and is required by it to stimulate VE-cadherin function in endothelial cells. Can replace beta-catenin in E-cadherin/catenin adhesion complexes which are proposed to couple cadherins to the actin cytoskeleton (By similarity). (updated: April 1, 2015)
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.
- 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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| Variant | Description |
|---|---|
| ARVD12 | |
| dbSNP:rs41283425 | |
| dbSNP:rs143043662 | |
| dbSNP:rs1126821 |
Biological Process
Adherens junction assembly
Adherens junction organization
Bundle of His cell-Purkinje myocyte adhesion involved in cell communication
Cell junction assembly
Cell migration
Cell-cell adhesion
Cell-cell junction organization
Cellular response to indole-3-methanol
Cornification
Desmosome assembly
Detection of mechanical stimulus
Endothelial cell-cell adhesion
Establishment of protein localization to plasma membrane
Keratinization
Negative regulation of blood vessel endothelial cell migration
Neutrophil degranulation
Obsolete cytoskeletal anchoring at plasma membrane
Positive regulation of angiogenesis
Positive regulation of canonical Wnt signaling pathway
Positive regulation of cell-matrix adhesion
Positive regulation of DNA-binding transcription factor activity
Positive regulation of protein import into nucleus
Positive regulation of transcription by RNA polymerase II
Protein heterooligomerization
Protein localization to plasma membrane
Regulation of cell fate specification
Regulation of cell population proliferation
Regulation of heart rate by cardiac conduction
Regulation of ventricular cardiac muscle cell action potential
Single organismal cell-cell adhesion
Skin development
Vascular endothelial growth factor receptor signaling pathway
Cellular Component
Actin cytoskeleton
Adherens junction
Apicolateral plasma membrane
Catenin complex
Cell-cell adherens junction
Cell-cell junction
Cornified envelope
Cytoplasm
Cytoplasmic side of plasma membrane
Cytoskeleton
Cytosol
Desmosome
Extracellular exosome
Extracellular matrix
Extracellular region
Fascia adherens
Ficolin-1-rich granule lumen
Focal adhesion
Gamma-catenin-TCF7L2 complex
Intercalated disc
Intermediate filament
Lateral plasma membrane
Nucleus
Obsolete cell
Plasma membrane
Protein-DNA complex
Specific granule lumen
Z disc
Zonula adherens
Molecular Function
Alpha-catenin binding
Cadherin binding
Cell adhesion molecule binding
Cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication
Cytoskeletal protein-membrane anchor activity
Nuclear hormone receptor binding
Obsolete signal transducer activity
Protein homodimerization activity
Protein kinase binding
Protein phosphatase binding
Protein-containing complex binding
Structural constituent of cell wall
Structural molecule activity
Transcription coactivator activity
The reference OMIM entry for this protein is 173325
Junction plakoglobin; jup
Plakoglobin; pkgb
Desmoplakin iii; dp iii; dp3
Catenin, gamma
CLONING
Plakoglobin is a major cytoplasmic protein that occurs in a soluble and a membrane-associated form and is the only known constituent common to the submembranous plaques of both kinds of adhering junctions, the desmosomes and the intermediate junctions. It is a desmoplakin (see 125647) and is referred to as DP III. DP I and DP II are splice variants of the same gene. Using a partial cDNA clone for bovine plakoglobin, Franke et al. (1989) isolated cDNAs encoding human plakoglobin, determined its nucleotide sequence, and deduced the complete amino acid sequence. The polypeptide encoded by the cDNA was synthesized by in vitro transcription and translation and identified by its comigration with authentic plakoglobin in 2-dimensional gel electrophoresis. The protein, which has 744 amino acids and a molecular weight of 81,750 Da, is highly conserved between human and bovine tissues. Only one kind of plakoglobin mRNA (3.4 kb) was found in most tissues, but an additional mRNA (3.7 kb) was detected in certain human tumor cell lines.GENE FUNCTION
Plakoglobin associates with the cytoplasmic region of desmoglein I (125670), one of the transmembrane desmosomal proteins (Mathur et al., 1994). It also is a component of the cadherin (see 192090)-catenin complex, which is predominantly localized where actin filaments anchor in adherens junctions of epithelial cells (Knudsen and Wheelock, 1992). Aberle et al. (1995) stated that catenins are of central importance for cadherin function in that they mediate the connection of cadherins to actin filaments and are part of a higher order submembranous network by which cadherins are linked to other transmembrane and peripheral cytoplasmic proteins. Interaction of the cadherin-catenin complex with epidermal growth factor receptor (EGFR; 131550) and the finding that beta-catenin (CTNNB1; 116806) and plakoglobin are substrates for tyrosine phosphorylation following EGF stimulation of cells, together with the finding that catenins are associated with the tumor suppressor protein APC (611731), open the possibility that catenins are involved in signaling pathways and tumorigenesis. Beta-catenin and gamma-catenin, vertebrate homologs of Drosophila armadillo, function in cell adhesion and the Wnt (e.g., WNT1; 164820) signaling pathway. In colon and other cancers, mutations in the APC tumor suppressor protein or beta-catenin's N terminus stabilize beta-catenin, enhancing its ability to activate transcription of TCF (e.g., TCF7; 189908)/LEF (e.g., LEF1; 153245) target genes. Beta- and gamma-catenin have analogous structures and functions and like binding to APC. Kolligs et al. (2000) reported that APC regulates both beta- and gamma-catenin and gamma-catenin functions as an oncogene. In contrast to beta-catenin, for which only N-terminal mutated forms transform RK3E epithelial cells, wildtype and several N-terminal mutated forms of gamma-catenin had similar transforming activity. The transforming activity of gamma-catenin, like that of beta-catenin, was dependent on TCF/LEF function. However, in contrast to beta-catenin, gamma-catenin strongly activated c-myc (190080) expression and c-myc function was crucial for gamma-catenin transformation. Kolligs et al. (2000) suggested that APC mutations alter regulation of both beta- and gamma-catenin, perhaps explaining why the frequency of APC mutations in colon cancer far exceeds that of beta-catenin mutations. Elevated c-myc expression in cancers wit ... More on the omim web site
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 173325 was added.