JUP
Available structures PDB Ortholog search:PDBeRCSB List of PDB id codes 3IFQ
Identifiers
Aliases	JUP, ARVD12, CTNNG, DP3, DPIII, PDGB, PKGB, Plakoglobin, junction plakoglobin, PG
External IDs	OMIM:173325;MGI:96650;HomoloGene:1680;GeneCards:JUP;OMA:JUP - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q21.2 Start 41,754,604bp[1] End 41,786,931bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 D|11 63.47 cM Start 100,259,784bp[2] End 100,288,589bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of leg skin of abdomen mucosa of pharynx nipple gingival epithelium skin of arm human penis vulva skin of thigh apex of heart Top expressed in lip esophagus corneal stroma skin of back muscle of thigh skin of external ear stomach pyloric antrum epithelium of stomach yolk sac More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein homodimerization activity transcription coactivator activity structural constituent of cell wall structural molecule activity signal transducer activity protein binding cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication protein phosphatase binding protein kinase binding alpha-catenin binding cell adhesion molecule binding cadherin binding Cellular component cytoplasm cytosol gamma-catenin-TCF7L2 complex lateral plasma membrane membrane intercalated disc cell-cell junction focal adhesion adherens junction plasma membrane desmosome hemidesmosome cell junction apicolateral plasma membrane protein-DNA complex Z discdkac actin cytoskeleton zonula adherens cytoplasmic side of plasma membrane catenin complex fascia adherens cytoskeleton intermediate filament extracellular exosome nucleus extracellular matrix cornified envelope extracellular region specific granule lumen ficolin-1-rich granule lumen Biological process adherens junction assembly protein heterooligomerization positive regulation of canonical Wnt signaling pathway positive regulation of DNA-binding transcription factor activity bundle of His cell-Purkinje myocyte adhesion involved in cell communication endothelial cell-cell adhesion cellular response to indole-3-methanol desmosome assembly cell adhesion regulation of cell population proliferation detection of mechanical stimulus positive regulation of protein import into nucleus adherens junction organization regulation of heart rate by cardiac conduction cell migration regulation of ventricular cardiac muscle cell action potential skin development signal transduction keratinization neutrophil degranulation cornification protein localization to plasma membrane cell-cell adhesion positive regulation of cell-matrix adhesion negative regulation of blood vessel endothelial cell migration positive regulation of angiogenesis positive regulation of transcription by RNA polymerase II Sources:Amigo /QuickGO
Orthologs Species Human Mouse Entrez 3728 16480 Ensembl ENSG00000173801 ENSMUSG00000001552 UniProt P14923 Q02257 RefSeq (mRNA) NM_002230 NM_021991 NM_001352773 NM_001352774 NM_001352775 NM_001352776 NM_001352777 NM_010593 RefSeq (protein) NP_002221 NP_068831 NP_001339702 NP_001339703 NP_001339704 NP_001339705 NP_001339706 NP_034723 Location (UCSC) Chr 17: 41.75 – 41.79 Mb Chr 11: 100.26 – 100.29 Mb PubMed search [3] [4]
Wikidata
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Plakoglobin, also known asjunction plakoglobin orgamma-catenin, is aprotein that in humans is encoded by theJUPgene.^[5] Plakoglobin is a member of thecatenin protein family and homologous toβ-catenin. Plakoglobin is acytoplasmic component ofdesmosomes andadherens junctions structures located withinintercalated discs ofcardiac muscle that function to anchorsarcomeres and join adjacent cells incardiac muscle. Mutations in plakoglobin are associated witharrhythmogenic right ventricular dysplasia.

Human plakoglobin is 81.7 kDa in molecular weight and 745 amino acids long.^[6] TheJUP gene contains 13 exons spanning 17 kb on chromosome 17q21.^[7] Plakoglobin is a member of thecatenin family, since it contains a distinct repeating amino acid motif called thearmadillo repeat.^[5] Plakoglobin is highly similar toβ-catenin; both have 12armadillo repeats as well asN-terminal andC-terminal globular domains of unknown structure.^[8] Plakoglobin was originally identified as a component ofdesmosomes, where it can bind to thecadherin family memberdesmoglein I. Plakoglobin also associates with classical cadherins such asE-cadherin; in that context, it was called gamma-catenin. Plakoglobin forms distinct complexes withcadherins anddesmosomal cadherins.

Plakoglobin is a majorcytoplasmic component of bothdesmosomes andadherens junctions, and is the only known constituent common to submembranous plaques in both of these structures,^[9] which are located at the intercalated disc (ICD) of cardiomyocytes. Plakoglobin linkscadherins to theactincytoskeleton. Plakoglobin binds to conserved regions ofdesmoglein anddesmocollin atintracellularcatenin-binding sites to assembledesmosomes.^[10][11]

Plakoglobin is essential for normal development ofintercalated discs and stability ofcardiac muscle. Transgenic mice homozygous for a null mutation of theJUP gene die around embryonic day 12 from substantial defects inadherens junctions and a lack of functional desmosomes in the heart.^[12][13] Further studies showed thatcardiac fibers obtained fromJUP-null embryonic mice had decreased passive compliance albeit normal attachment ofsarcomeres toadherens junctions.^[14]

In additional studies, an induciblecardiac-specific plakoglobin knockout mice were generated. Transgenic mice displayed a similar phenotype asarrhythmogenic right ventricular cardiomyopathy patients, with loss ofcardiomyocytes,fibrosis and cardiac dysfunction, as well as alterations indesmosome protein content andgap junction remodeling. Hearts also exhibited increases inβ-catenin signaling.^[15][16] Further investigations on the role ofβ-catenin and plakoglobin in the heart generated a double knockout of these two proteins. Mice exhibitedcardiomyopathy,fibrosis, conduction abnormalities andsudden cardiac death, presumably via spontaneous lethal ventriculararrhythmias. Mice also showed a decrease ingap junction structures atintercalated discs.^[17]

Intracellular plakoglobin expression is controlled byWnt signaling and ubiquitin-proteasome-dependent degradation.Phosphorylation ofN-terminalSerines by a “destruction complex” composed ofglycogen synthase kinase 3β (GSK3β) and scaffold proteinsadenomatous polyposis coli (APC) andaxin targets plakoglobin for degradation.^[18][19][20][31–33]. Thephosphorylated motif is recognized by β-TrCP, a ubiquitin ligase that targets plakoglobin 26S proteasome-dependent degradation.^[21] Plakoglobin is alsoO-glycosylated near itsN-terminal destruction box.

Mutation of theJUP gene encoding plakoglobin has been implicated as one of the causes of thecardiomyopathy known asarrhythmogenic right ventricular dysplasia (ARVD) orarrhythmogenic right ventricular cardiomyopathy; mutations inJUP specifically causes anautosomal recessive form referred to asNaxos disease.^[22][23][24] This form of was first identified in a small cluster of families on the Greek island ofNaxos. The phenotype of theNaxos disease variant ofARVD is unique in that it involves the hair and skin as well as the rightventricle. Affected individuals have kinky,wooly hair; there is also palmar and plantarerythema at birth that progresses tokeratosis as the palms and soles of the feet are used in crawling and walking.^[25][26][27] These findings co-segregate 100% with the development ofARVD by early adolescence.

It has become clear thatARVD/ARVC is a disease of thecardiac muscledesmosome; advances in molecular genetics have illuminated this notion.^{[28][29][30][31][32][33][34][35][36]}

Studies investigating the role of plakoglobin in disease pathology have found that suppression ofdesmoplakin expression bysiRNA led to thenuclear localization of plakoglobin, resulting in a reduction inWnt signaling via Tcf/Lef1 and ensued pathogenesis of ARVC.^[37] Specifically, adipogenic factor expression was induced and cardiac progenitor cells at the epicardium were differentiated to adipocytes.^[38]

Non-invasivecardiac screening identified T-wave inversion, abnormalities in rightventricular wall motion, and frequent ventricular extrasystoles as sensitive and specific markers of aJUP mutation.^[39] Additional studies have shown that immunohistochemical analysis ofcardiac muscledesmosomal proteins is also a sensitive and specific diagnostic text forARVD/ARVC.^[40]

Abnormal distribution of plakoglobin due to mutations in genes encoding forDesmoglein 1 and 3 have also been implicated inPemphigus vulgaris.^[41][42]

Plakoglobin has been shown tointeract with:

• Catenin
• List of conditions caused by problems with junctional proteins

• GeneReviews/NCBI/NIH/UW entry on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant
• OMIM entries on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant
• gamma-Catenin at the U.S. National Library of MedicineMedical Subject Headings (MeSH)

• Genes on human chromosome 17
• Catenins
• Armadillo-repeat-containing proteins

• CS1 maint: DOI inactive as of July 2025
• Articles with short description
• Short description matches Wikidata