Plakophilin-1 (PKP1)
The protein contains 747 amino acids for an estimated molecular weight of 82861 Da.
Seems to play a role in junctional plaques. Contributes to epidermal morphogenesis. (updated: March 4, 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 |
|---|---|
| dbSNP:rs34626929 | |
| dbSNP:rs34704938 | |
| dbSNP:rs35507614 | |
| dbSNP:rs1626370 | |
| dbSNP:rs10920171 |
Biological Process
Apoptotic process
Cell adhesion
Cell-cell adhesion
Cell-cell junction assembly
Cellular component disassembly involved in execution phase of apoptosis
Cornification
Intermediate filament bundle assembly
Keratinization
Multicellular organism development
Negative regulation of mRNA catabolic process
Neutrophil degranulation
Positive regulation of gene expression
Signal transduction
Single organismal cell-cell adhesion
Cellular Component
Adherens junction
Cell-cell adherens junction
Cell-cell junction
Cornified envelope
Cytoplasm
Desmosome
Extracellular exosome
Ficolin-1-rich granule membrane
Intermediate filament
Intracellular membrane-bounded organelle
Messenger ribonucleoprotein complex
Nucleoplasm
Nucleus
Plasma membrane
The reference OMIM entry for this protein is 601975
Plakophilin 1; pkp1
CLONING
Plakoglobin (JUP; 173325) was first identified as a protein of the desmosomal type of cell junction. It is a component of the plaque, i.e., that part of the desmosome in the cytoplasm with which the intermediate filaments interact. Another desmosomal component, plakophilin, originally known as band 6 protein, was cloned and sequenced in human and bovine by Hatzfeld et al. (1994) and Heid et al. (1994). Schmidt et al. (1999) determined that there are at least 2 isoforms of the PKP1 protein: PKP1a with 726 amino acids and PKP1b with 747 amino acids. PKP1b is located exclusively in nuclei, whereas PKP1a is located in nuclei as well as in desmosomal plaques of stratified and complex epithelia.GENE STRUCTURE
Schmidt et al. (1999) found that the primary PKP1 transcript spans approximately 50 kb and contains 15 exons, and identified exon 7 as the alternatively used exon, leading to splice variant PKP1b. Each mRNA splice form can occur in 2 polyadenylation forms of approximately 2.7 and 5.3 kb.GENE FUNCTION
Using immunohistochemistry and quantitative electron microscopy, McMillan et al. (2003) examined suprabasal desmosomes from 3 PKP1-deficient patients, an unaffected carrier with a PKP1-heterozygous acceptor splice site mutation, and 5 healthy control subjects. Compared with those in controls, desmosomes in PKP1-null patients were reduced dramatically both in size (49%) and frequency (61%) in the lower suprabasal layers (P less than 0.01). In the lower suprabasal compartment of the heterozygous carrier, corresponding reductions were 37% and 20%, respectively (P less than 0.01). Surprisingly, in the PKP1-null patients' upper suprabasal layer, desmosome size was larger (59%, P less than 0.01) than the control value, and showed increased desmoglein-1 (125670) and PKP2 (602861) staining. The upper suprabasal layer desmosome frequency in PKP1-null patients was similar to that seen in the lower suprabasal compartment but reduced by 43% compared to controls. The carrier showed no difference in the upper suprabasal layer desmosome size and frequency compared with the controls (P greater than 0.05). The PKP1-null patients showed poorly developed inner and outer desmosomal plaques. Thus, both the patients and unaffected carrier showed reductions in the lower suprabasal layer desmosome size and number, despite only PKP1-null patients exhibiting any phenotype. These findings attest to the molecular recruiting and stabilizing roles of PKP1 in desmosome formation, particularly in the lower suprabasal compartment.MAPPING
Cowley et al. (1997) used PCR analysis of monochromosomal somatic cell hybrids to map the PKP1 gene to chromosome 1; fluorescence in situ hybridization showed that the gene resides on the distal portion of 1q. By fluorescence in situ hybridization and analysis of a somatic cell hybrid mapping panel, Bonne et al. (1998) refined the mapping of the PKP1 gene to 1q32.MOLECULAR GENETICS
Members of the armadillo protein gene family, which includes plakoglobin and beta-catenin (116806), have important functions in cytoskeleton/cell membrane interactions. These proteins may act as linker molecules at adherens junctions and desmosomes at the plasma membrane; in addition, they may have pivotal roles in signal transduction pathways and significant effects on cell behavior during development. McGrath et al. (1997) described the first human mutations in 1 of these dual function proteins. ... 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
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for PKP1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601975 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed