DSG2 (desmoglein 2)

2009-11-01   Masakazu Yashiro 

The Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan

Identity

HGNC
LOCATION
18q12.1
LOCUSID
ALIAS
CDHF5,HDGC
FUSION GENES

DNA/RNA

Description

Desmoglein-2 gene maps on chromosome 18q12.1.

Transcription

15 exons; Transcript length: 5,652 bps.

Proteins

Description

A transmembrane glycoprotein of 1,118 amino acids, which has a molecular mass ranging 97 to 18 kDa. Desmoglein-2 is a calcium-binding transmembrane glycoprotein component of desmosomes.

Expression

Desmoglein-2 (DSG2) is expressed on various cells including simple epithelia and myocardium, tumors and and many cell cultures. By contrast, the epidermal isoforms DSG1 and DSG3 are restricted to certain specialized epithelia, mostly stratified squamous ones (Schafer et al., 1994).

Function

Epithelial cell-cell adhesion is important in tumor development. Dsgs are transmembrane glycoproteins of the desmosome, a cell-cell adhesive structure prominent in epithelial tissues, which have been reported to be associated with tumor development (Tselepis et al., 1998). cDNA and protein studies have revealed that there are subfamilies of DSG (types 1, 2 and 3) and DSC (types 1, 2 and 3) (Buxton et al., 1993). DSG2 and DSC2 are widely expressed and are found together in desmosomes of the basal layer of stratified epithelia, simple epithelia, and nonepithelial cells such as in the myocardium of the heart and lymph node follicles, whereas DSG3/DSC3 and DSG1/DSC1 are more restricted to complex epithelial tissues. Although considerable overlap is exhibited in the distribution of these isoforms in stratified tissues, their expression is clearly differentiation-dependent. DSG2, but not DSG1 or DSG3, is expressed in stomach epithelia.

Implicated in

Entity name
Gastric cancer
Disease
DSG2, but not type 1 or 3, is expressed in stomach epithelia. Decreased expression of DSG2 is involved in a subset of gastric carcinomas, in particular diffuse-type gastric cancers, and poor prognosis in gastric carcinoma (Biedermann et al., 2005; Yashiro et al., 2006).
Entity name
Skin cancer
Disease
DSG2 is highly regulated in cutaneous squamous cell carcinoma, and correlates with risk of metastasis (Kurzen et al., 2003). Overexpression of DSG2 in epidermal keratinocytes deregulates multiple signaling pathways associated with increased growth rate, and the enhanced activation of multiple growth and survival pathways, including the phosphatidylinositol 3-kinase, mitogen activated protein kinase, STAT3 and NF-kB pathways, is observed (Brennan et al., 2007).
Entity name
Pancreas cancer
Disease
Levels of DSG1 and DSG2 are reduced in pancreatic tumors (Ramani et al., 2008).
Entity name
Arrhythmogenic right ventricular dysplasia
Disease
Mutations in DSG2 contribute to the development of arrhythmogenic right ventricular dysplasia/cardiomyopathy (Pilichou et al., 2006; Awad et al., 2006).
Entity name
Pemphigus
Disease
Pemphigus represents a distinct organ-specific acquired autoimmune disease characterized by intra-epidermal blistering, which is induced by autoantibodies against desmosomal cadherins, DSG1 and DSG3 (Kitajima and Aoyama, 2007).

Bibliography

Pubmed IDLast YearTitleAuthors
167735732006DSG2 mutations contribute to arrhythmogenic right ventricular dysplasia/cardiomyopathy.Awad MM et al
160254352005Desmoglein 2 is expressed abnormally rather than mutated in familial and sporadic gastric cancer.Biedermann K et al
172845152007Suprabasal Dsg2 expression in transgenic mouse skin confers a hyperproliferative and apoptosis-resistant phenotype to keratinocytes.Brennan D et al
84867291993Nomenclature of the desmosomal cadherins.Buxton RS et al
180949472007A perspective of pemphigus from bedside and laboratory-bench.Kitajima Y et al
147440872003Expression of desmosomal proteins in squamous cell carcinomas of the skin.Kurzen H et al
165051732006Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy.Pilichou K et al
190911212008Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer.Ramani VC et al
81437881994Identification of the ubiquitous human desmoglein, Dsg2, and the expression catalogue of the desmoglein subfamily of desmosomal cadherins.Schäfer S et al
96531401998Desmosomal adhesion inhibits invasive behavior.Tselepis C et al
168904242006Decreased expression of the adhesion molecule desmoglein-2 is associated with diffuse-type gastric carcinoma.Yashiro M et al

Other Information

Locus ID:

NCBI: 1829
MIM: 125671
HGNC: 3049
Ensembl: ENSG00000046604

Variants:

dbSNP: 1829
ClinVar: 1829
TCGA: ENSG00000046604
COSMIC: DSG2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000046604ENST00000261590Q14126
ENSG00000046604ENST00000585206J3KSI6

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45

Pathways

PathwaySourceExternal ID
Arrhythmogenic right ventricular cardiomyopathy (ARVC)KEGGko05412
Arrhythmogenic right ventricular cardiomyopathy (ARVC)KEGGhsa05412
Programmed Cell DeathREACTOMER-HSA-5357801
ApoptosisREACTOMER-HSA-109581
Apoptotic execution phaseREACTOMER-HSA-75153
Apoptotic cleavage of cellular proteinsREACTOMER-HSA-111465
Apoptotic cleavage of cell adhesion proteinsREACTOMER-HSA-351906
Developmental BiologyREACTOMER-HSA-1266738
KeratinizationREACTOMER-HSA-6805567
Formation of the cornified envelopeREACTOMER-HSA-6809371

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA134871907TMEM43GeneDataAnnotationassociated
PA27489DSC2GeneDataAnnotationassociated
PA27505DSPGeneDataAnnotationassociated
PA33357PKP2GeneDataAnnotationassociated
PA446847Arrhythmogenic Right Ventricular DysplasiaDiseaseDataAnnotation, Literature, MultilinkAnnotationassociated23788249

References

Pubmed IDYearTitleCitations
165051732006Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy.129
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
167735732006DSG2 mutations contribute to arrhythmogenic right ventricular dysplasia/cardiomyopathy.63
200316172009Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy.61
178048172007Desmoglein-2: a novel regulator of apoptosis in the intestinal epithelium.52
221897872012Desmoglein as a target in skin disease and beyond.52
204004432010Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice.48
202240062010Desmoglein 2-mediated adhesion is required for intestinal epithelial barrier integrity.40
194584822009Increased expression of Dsg2 in malignant skin carcinomas: A tissue-microarray based study.39
221842012011Desmosomal cadherins utilize distinct kinesins for assembly into desmosomes.37

Citation

Masakazu Yashiro

DSG2 (desmoglein 2)

Atlas Genet Cytogenet Oncol Haematol. 2009-11-01

Online version: http://atlasgeneticsoncology.org/gene/40367/dsg2