{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q14126","secondaryAccessions":["Q4KKU6"],"uniProtkbId":"DSG2_HUMAN","entryAudit":{"firstPublicDate":"1997-11-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2007-05-29","entryVersion":222,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Desmoglein-2"}},"alternativeNames":[{"fullName":{"value":"Cadherin family member 5"}},{"fullName":{"value":"HDGC"}}],"flag":"Precursor"},"genes":[{"geneName":{"value":"DSG2"},"synonyms":[{"value":"CDHF5"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O55111"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17559062"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26918609"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27338829"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29910125"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38395410"}],"value":"A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:17559062, PubMed:38395410). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Required for proliferation and viability of embryonic stem cells in the blastocyst, thereby crucial for progression of post-implantation embryonic development (By similarity). Maintains pluripotency by regulating epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via interacting with and sequestering CTNNB1 to sites of cell-cell contact, thereby reducing translocation of CTNNB1 to the nucleus and subsequent transcription of CTNNB1/TCF-target genes (PubMed:29910125). Promotes pluripotency and the multi-lineage differentiation potential of hematopoietic stem cells (PubMed:27338829). Plays a role in endothelial cell sprouting and elongation via mediating the junctional-association of cortical actin fibers and CDH5 (PubMed:27338829). Promotes cardiomyocyte cell homeostasis and desmosome junction formation at intercalated disks, as a result plays a role in the maintenance of cardiac conduction and heart chamber integrity (By similarity). Positively regulates pancreatic islet development and maintenance of endothelial cell barrier integrity in the pancreas, therefore involved in the controlled release of insulin from islet cells into the circulation in response to glucose (By similarity). Plays a role in limiting inflammatory infiltration and the apoptotic response to injury in kidney tubular epithelial cells, potentially via its role in maintaining cell-cell adhesion and the epithelial barrier (PubMed:38395410). Acts as a positive modulator of CSK and EGFR activation via sequestering them away from lipid rafts, this is independent of its role in desmosome cell junctions (PubMed:26918609). Also disrupts the localization of CAV1 to lipid rafts resulting in its distribution throughout the cytoplasm (PubMed:26918609)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32581096"}],"value":"(Microbial infection) Required for fiber protein-mediated Human Adenovirus 55 and 14a infection; via its interaction with fiber protein"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11790773"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29910125"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31845994"}],"value":"Forms homodimers (PubMed:31845994). Interacts with PKP2 (PubMed:11790773). Interacts with CTNNB1; the interaction promotes localization of CTNNB1 at cell junctions thus reducing its nuclear localization and subsequent transcription of CTNNB1/TCF-target genes (PubMed:29910125)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29849084"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30862836"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32581096"}],"value":"(Microbial infection) Interacts (via Cadherin 3 domain) with human adenovirus B3 fiber protein (as a homotrimer) (PubMed:29849084, PubMed:30862836). Interacts with human adenovirus 55 fiber protein; the interaction is required for infection of host cells (PubMed:32581096)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q14126","intActId":"EBI-2556545"},"interactantTwo":{"uniProtKBAccession":"Q02487","geneName":"DSC2","intActId":"EBI-3048545"},"numberOfExperiments":2,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17559062"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30885746"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31845994"}],"value":"Localized to intercalated disks in the heart (PubMed:31845994). Localizes to the cytoplasm following cleavage by CASP3 in response to apoptosis (PubMed:17559062). Glycosylation promotes localization to the plasma membrane (PubMed:30885746)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17559062"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26918609"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27338829"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30885746"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31402609"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36309486"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"value":"Single-pass type I membrane protein","id":"SL-9905"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20859650"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25208567"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29999492"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31402609"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31845994"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33596089"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38375917"}],"value":"Cell junction, desmosome","id":"SL-0092"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17559062"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27338829"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38375917"}],"value":"Cytoplasm","id":"SL-0086"}}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34742300"}],"value":"(Microbial infection) Proteolytically cleaved at the cell membrane upon H.pylori infection"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34742300"}],"value":"Secreted","id":"SL-0243"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24220297"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27338829"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29910125"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31845994"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36309486"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38375917"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38395410"}],"value":"Expressed in undifferentiated pluripotent stem cells, expression decreases during differentiation (at protein level) (PubMed:29910125). Expressed in hematopoietic stem cells and circulating endothelial progenitor cells, expression decreases upon increasing cell lineage commitment (at protein level) (PubMed:27338829). Expressed on common myeloid progenitors, pro-myelocytes, pro-erythrocytes and B-cell linage progenitors (at protein level). Expression in mature cell types in the bone marrow and mature leukocyte populations is absent (PubMed:27338829). Expressed by foreskin fibroblasts, expression peaks during the early stage of differentiation reprogramming (at protein level) (PubMed:29910125). Expressed by endothelial cells in both arterioles and venules in the cervix (at protein level) (PubMed:27338829). Expressed in pancreatic alpha-cells, beta-cells and exocrine tissue (at protein level) (PubMed:36309486). Expressed in cardiomyocytes (at protein level) (PubMed:31845994, PubMed:38375917). Expressed in kidney tubular epithelial cells (PubMed:38395410). Expressed in the esophageal mucosa (PubMed:24220297)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34742300"}],"value":"(Microbial infection) Proteolytically cleaved by H.pylori HtrA at the cell membrane; cleavage is facilitated by host MMP and ADAM family members"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17559062"}],"value":"Cleaved by CASP3 in response to apoptosis which results in a loss of full length DSG2 at cell-cell adhesion junctions and a decrease in intercellular adhesion"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29849084"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30885746"}],"value":"N-glycosylated; promotes localization to the plasma membrane and cell-cell adhesion junction strength (PubMed:30885746). Not required for interaction with human adenovirus B 3 fiber protein (PubMed:29849084)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31402609"}],"value":"Palmitoylated by ZDHHC5 at the plasma membrane"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Arrhythmogenic right ventricular dysplasia, familial, 10","diseaseAccession":"DI-01554","acronym":"ARVD10","description":"A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias.","diseaseCrossReference":{"database":"MIM","id":"610193"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16505173"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16773573"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19635863"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19863551"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20031617"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21062920"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30391969"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30454721"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31845994"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33917638"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38375917"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Cardiomyopathy, dilated, 1BB","diseaseAccession":"DI-02483","acronym":"CMD1BB","description":"A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.","diseaseCrossReference":{"database":"MIM","id":"612877"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18678517"}]},"note":{"texts":[{"value":"Disease susceptibility is associated with variants affecting the gene represented in this entry"}]}},{"commentType":"WEB RESOURCE","resourceName":"Atlas of Genetics and Cytogenetics in Oncology and Haematology","resourceUrl":"https://atlasgeneticsoncology.org/gene/40367/DSG2","ftp":false}],"features":[{"type":"Signal","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":23,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Propeptide","location":{"start":{"value":24,"modifier":"EXACT"},"end":{"value":49,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255"}],"featureId":"PRO_0000003845"},{"type":"Chain","location":{"start":{"value":50,"modifier":"EXACT"},"end":{"value":1118,"modifier":"EXACT"}},"description":"Desmoglein-2","featureId":"PRO_0000003846"},{"type":"Topological 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asparagine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16335952"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19159218"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19349973"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30885746"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":309,"modifier":"EXACT"},"end":{"value":309,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30885746"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":462,"modifier":"EXACT"},"end":{"value":462,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) (complex) asparagine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19139490"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19349973"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30885746"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":514,"modifier":"EXACT"},"end":{"value":514,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30885746"}],"featureId":""},{"type":"Natural variant","location":{"start":{"value":46,"modifier":"EXACT"},"end":{"value":46,"modifier":"EXACT"}},"description":"in ARVD10; uncertain significance; propeptide present at intercellular junctions of cardiomyocytes; no effect on DSG2 expression at intercalated disks or at intercellular junctions; no effect on expression or localization of PKP2, JUP or CTNNB1; dbSNP:rs121913008","featureCrossReferences":[{"database":"dbSNP","id":"rs121913008"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16773573"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20031617"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31845994"}],"featureId":"VAR_029365","alternativeSequence":{"originalSequence":"R","alternativeSequences":["Q"]}},{"type":"Natural variant","location":{"start":{"value":46,"modifier":"EXACT"},"end":{"value":46,"modifier":"EXACT"}},"description":"in ARVD10; uncertain significance; propeptide present at intercellular junctions of cardiomyocytes; decrease in DSG2 protein abundance with smaller desmosome cell junctions and abnormal inter-membrane vacuoles in cardiomyocytes of both ventricles; no effect on localization of DSG2 to intercalated disks or at intercellular junctions; abnormally localized within intra-cytoplasmic vesicles in an EGFR-dependent manner; reduction in incorporation into desmosomes during mechanical stress; no effect on cleavage of propeptide or ability to form homodimers; no effect on expression or localization of PKP2, JUP or CTNNB1; dbSNP:rs752522753","featureCrossReferences":[{"database":"dbSNP","id":"rs752522753"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31845994"}],"featureId":"VAR_090716","alternativeSequence":{"originalSequence":"R","alternativeSequences":["W"]}},{"type":"Natural variant","location":{"start":{"value":49,"modifier":"EXACT"},"end":{"value":49,"modifier":"EXACT"}},"description":"in ARVD10; uncertain significance; propeptide present at intercellular junctions of cardiomyocytes; no effect on DSG2 expression at intercalated disks or at intercellular junctions; no effect on expression or localization of PKP2, JUP or CTNNB1; dbSNP:rs121913006","featureCrossReferences":[{"database":"dbSNP","id":"rs121913006"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16773573"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19863551"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20031617"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21062920"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31845994"}],"featureId":"VAR_029366","alternativeSequence":{"originalSequence":"R","alternativeSequences":["H"]}},{"type":"Natural variant","location":{"start":{"value":56,"modifier":"EXACT"},"end":{"value":56,"modifier":"EXACT"}},"description":"probable risk factor for CMD1BB and ARVD10; dbSNP:rs121913013","featureCrossReferences":[{"database":"dbSNP","id":"rs121913013"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18678517"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20031617"}],"featureId":"VAR_062387","alternativeSequence":{"originalSequence":"V","alternativeSequences":["M"]}},{"type":"Natural variant","location":{"start":{"value":87,"modifier":"EXACT"},"end":{"value":87,"modifier":"EXACT"}},"description":"in ARVD10; uncertain significance; dbSNP:rs1192343050","featureCrossReferences":[{"database":"dbSNP","id":"rs1192343050"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16505173"}],"featureId":"VAR_090717","alternativeSequence":{"originalSequence":"Y","alternativeSequences":["C"]}},{"type":"Natural variant","location":{"start":{"value":89,"modifier":"EXACT"},"end":{"value":89,"modifier":"EXACT"}},"description":"in dbSNP:rs2230232","featureCrossReferences":[{"database":"dbSNP","id":"rs2230232"}],"featureId":"VAR_048508","alternativeSequence":{"originalSequence":"Y","alternativeSequences":["C"]}},{"type":"Natural variant","location":{"start":{"value":100,"modifier":"EXACT"},"end":{"value":100,"modifier":"EXACT"}},"description":"in ARVD10; uncertain significance; evidence of residual myocardium, fibrous tissue, fatty tissue, dysmetric and dysmorphic nuclei and prominent cytoplasmic vacuolization; decreases the number of desmosomes at intercalated disks also increases desmosome gap; 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