DSC2

DSC2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5J5J, 5ERP
Identifiers
Aliases	DSC2, ARVD11, CDHF2, DG2, DGII/III, DSC3, desmocollin 2
External IDs	OMIM: 125645; MGI: 103221; HomoloGene: 8397; GeneCards: DSC2; OMA:DSC2 - orthologs
Gene location (Human) Chr. Chromosome 18 (human)[1] Band 18q12.1 Start 31,058,840 bp[1] End 31,102,522 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18 A2|18 11.14 cM Start 20,163,690 bp[2] End 20,192,611 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gingival epithelium oral cavity mucosa of pharynx mucosa of sigmoid colon jejunal mucosa body of tongue human penis vulva parotid gland amniotic fluid Top expressed in conjunctival fornix corneal stroma epithelium of stomach esophagus pyloric antrum mucous cell of stomach cervix ileum jejunum left colon More reference expression data BioGPS More reference expression data
Gene ontology Molecular function cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication calcium ion binding protein binding metal ion binding Cellular component integral component of membrane cell junction desmosome extracellular exosome cytoplasmic vesicle membrane intercalated disc cornified envelope plasma membrane cell-cell junction Biological process cellular response to starvation cell adhesion bundle of His cell-Purkinje myocyte adhesion involved in cell communication regulation of heart rate by cardiac conduction regulation of ventricular cardiac muscle cell action potential homophilic cell adhesion via plasma membrane adhesion molecules cardiac muscle cell-cardiac muscle cell adhesion keratinization cornification cell-cell adhesion Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1824 13506 Ensembl ENSG00000134755 ENSMUSG00000024331 UniProt Q02487 P55292 RefSeq (mRNA) NM_004949 NM_024422 NM_013505 NM_001317363 NM_001317365 RefSeq (protein) NP_004940 NP_077740 NP_001304292 NP_001304294 NP_038533 Location (UCSC) Chr 18: 31.06 – 31.1 Mb Chr 18: 20.16 – 20.19 Mb PubMed search [3] [4]
Wikidata
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Desmocollin-2 is a protein that in humans is encoded by the DSC2 gene.^[5][6] Desmocollin-2 is a cadherin-type protein that functions to link adjacent cells together in specialized regions known as desmosomes. Desmocollin-2 is widely expressed, and is the only desmocollin isoform expressed in cardiac muscle, where it localizes to intercalated discs. Mutations in DSC2 have been causally linked to arrhythmogenic right ventricular cardiomyopathy.^[7]

Desmocollin-2 is a calcium-dependent glycoprotein that is a member of the desmocollin subfamily of the cadherin superfamily. Three different posttranslational modifications (N-Glycosylations, O-Mannosylations and disulfide bridges) were present in the extracellular domain of desmocollin-2.^[8] The desmocollin family members are arranged as closely linked genes on human chromosome 18q12.1. Human DSC2 consists of greater than 32 kb of DNA and has 17 exons, with exon 16 being alternatively spliced and encoding distinct isoforms.^[9] Desmocollin-2 contains five N-terminal extracellular domains, a transmembrane-spanning domain, and a C-terminal cytoplasmic tail.^[9] Desmocollin-2 binds to desmoglein family members through a calcium-dependent interaction with its extracellular domains,^[10] and to plakoglobin through its cytoplasmic tail.^[11] Desmocollin-2 is ubiquitously expressed in desmosomal tissues, such as skin epithelia, and is the only desmocollin isoform expressed in human cardiac muscle, where it localizes to desmosomes within intercalated discs.^[12]

Desmosomal cadherins, including the desmocollin family members and desmogleins, are found at desmosome cell-cell junctions and are required for cell adhesion and desmosome formation via interactions with their extracellular cadherin regions.^[13] Desmosomes function to anchor intermediate filaments at sites of strong adhesion, which undergo high mechanical stress, such as in cardiac muscle.^[14] Desmocollins are integral components to desmosomes and studies have shown that in addition to tensile strength, desmocollins also function as molecular sensors and facilitators of signal transduction.^[15] Studies in zebrafish expressing a mutant desmocollin-2 have shed light on its function in the myocardium as a pivotal component for normal myocardial structure and function. Knockdown of desmcollin-2 caused malformations in desmosomal plaques and bradycardia, dilation of the ventricular chamber and reduced fractional shortening.^[16]

Mutations in DSC2 are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC),^{[17][16][18][19][20][21][22][23][24][25]} including mutations with a recessive inheritance.^[25][26][27] Mutations in DSC2 as well as other desmosomal genes are frequent in patients with advanced dilated cardiomyopathy that are undergoing cardiac transplantation.^[28]

Hallmark features of ARVC include enlargement of the right ventricle, replacement of right ventricular cardiomyocytes with fibrofatty deposits, electrocardiographic abnormalities, and arrhythmias.^{[29][30][31][32]} Biopsies from patients with ARVC consistently show abnormalities in intercalated discs, with decreased numbers of desmosomes and widening of intercellular gaps between adjacent cardiomyocytes, suggesting that this disease is a disease of intercalated discs.^[33][34] Studies investigating two heterozygous DSC2 mutations have shown that certain mutations in the N-terminal region can modify the subcellular localization of desmocollin-2 from the desmosomal plaque to the cytoplasm.^[35]

Desmocollin-2 has been shown to interact with:

• DSG2^[10]
• JUP^[11]

• Transgenic mice with cardiac specific overexpression of desmocollin-2 develop severe cardiomyopathy.^[7]

• GeneReviews/NCBI/NIH/UW entry on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant
• OMIM entries on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant