DSG2

Protein identityUniProt · HPA

UniProt accession

Q14126

Gene

DSG2

Ensembl

ENSG00000046604

Chromosome

18

Canonical length

1118 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Cell Junctions

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of the desmoglein family and cadherin cell adhesion molecule superfamily of proteins. Desmogleins are calcium-binding transmembrane glycoprotein components of desmosomes, cell-cell junctions between epithelial, myocardial, and other cell types. The encoded preproprotein is proteolytically processed to generate the mature glycoprotein. This gene is present in a gene cluster with other desmoglein gene family members on chromosome 18. Mutations in this gene have been associated with arrhythmogenic right ventricular dysplasia, familial, 10. [provided by RefSeq, Jan 2016]

Canonical amino-acid sequenceUniProt

1118 residues, UniProt reviewed canonical sequence.

>Q14126|DSG2
     1  MARSPGRAYA LLLLLICFNV GSGLHLQVLS TRNENKLLPK HPHLVRQKRA WITAPVALRE
    61  GEDLSKKNPI AKIHSDLAEE RGLKITYKYT GKGITEPPFG IFVFNKDTGE LNVTSILDRE
   121  ETPFFLLTGY ALDARGNNVE KPLELRIKVL DINDNEPVFT QDVFVGSVEE LSAAHTLVMK
   181  INATDADEPN TLNSKISYRI VSLEPAYPPV FYLNKDTGEI YTTSVTLDRE EHSSYTLTVE
   241  ARDGNGEVTD KPVKQAQVQI RILDVNDNIP VVENKVLEGM VEENQVNVEV TRIKVFDADE
   301  IGSDNWLANF TFASGNEGGY FHIETDAQTN EGIVTLIKEV DYEEMKNLDF SVIVANKAAF
   361  HKSIRSKYKP TPIPIKVKVK NVKEGIHFKS SVISIYVSES MDRSSKGQII GNFQAFDEDT
   421  GLPAHARYVK LEDRDNWISV DSVTSEIKLA KLPDFESRYV QNGTYTVKIV AISEDYPRKT
   481  ITGTVLINVE DINDNCPTLI EPVQTICHDA EYVNVTAEDL DGHPNSGPFS FSVIDKPPGM
   541  AEKWKIARQE STSVLLQQSE KKLGRSEIQF LISDNQGFSC PEKQVLTLTV CECLHGSGCR
   601  EAQHDSYVGL GPAAIALMIL AFLLLLLVPL LLLMCHCGKG AKGFTPIPGT IEMLHPWNNE
   661  GAPPEDKVVP SFLPVDQGGS LVGRNGVGGM AKEATMKGSS SASIVKGQHE MSEMDGRWEE
   721  HRSLLSGRAT QFTGATGAIM TTETTKTARA TGASRDMAGA QAAAVALNEE FLRNYFTDKA
   781  ASYTEEDENH TAKDCLLVYS QEETESLNAS IGCCSFIEGE LDDRFLDDLG LKFKTLAEVC
   841  LGQKIDINKE IEQRQKPATE TSMNTASHSL CEQTMVNSEN TYSSGSSFPV PKSLQEANAE
   901  KVTQEIVTER SVSSRQAQKV ATPLPDPMAS RNVIATETSY VTGSTMPPTT VILGPSQPQS
   961  LIVTERVYAP ASTLVDQPYA NEGTVVVTER VIQPHGGGSN PLEGTQHLQD VPYVMVRERE
  1021  SFLAPSSGVQ PTLAMPNIAV GQNVTVTERV LAPASTLQSS YQIPTENSMT ARNTTVSGAG
  1081  VPGPLPDFGL EESGHSNSTI TTSSTRVTKH STVQHSYS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DSG2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.51

Highest tissue expression

149 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DSG2.

Disease | AllUniProt

Conditions DSG2 is implicated in, by any mechanism.

• Arrhythmogenic right ventricular dysplasia, familial, 10 (ARVD10) MIM:610193
• Cardiomyopathy, dilated, 1BB (CMD1BB) MIM:612877

Disease | GeneticClinVar

133 pathogenic / likely-pathogenic of 2,294 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Arrhythmogenic right ventricular dysplasia 10
• Cardiovascular phenotype
• Dilated cardiomyopathy 1BB
• Arrhythmogenic right ventricular cardiomyopathy
• Cardiomyopathy

ReferencesPubMed · IEDB

Publications for DSG2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.79

gnomAD pLI

0

gnomAD missense Z

0.3

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• bundle of His cell-Purkinje myocyte adhesion involved in cell communication
• cell adhesion
• cell-cell adhesion
• desmosome organization
• homophilic cell adhesion via plasma membrane adhesion molecules
• maternal process involved in female pregnancy
• mesenchymal to epithelial transition
• negative regulation of apoptotic process
• negative regulation of endothelial cell differentiation
• negative regulation of epithelial to mesenchymal transition
• negative regulation of inflammatory response to wounding
• positive regulation of cell adhesion
• positive regulation of protein localization to cell-cell junction
• positive regulation of sprouting angiogenesis
• positive regulation of stem cell population maintenance
• Purkinje myocyte development
• regulation of heart rate by cardiac conduction
• regulation of ventricular cardiac muscle cell action potential
• response to progesterone
• stem cell proliferation

Molecular functions

• calcium ion binding
• cell adhesion molecule binding
• cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication

Cellular components

• apical plasma membrane
• cell junction
• cell surface
• cell-cell junction
• cornified envelope
• cytoplasm
• desmosome
• extracellular exosome
• intercalated disc
• lateral plasma membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Cadherin-like
• Desmosomal cadherin
• Cadherin-like superfamily
• Cadherin conserved site
• Catenin binding domain superfamily
• Cadherin domain-containing protein
• Cadherin domain

KeywordsUniProt

• Calcium
• Cardiomyopathy
• Cell adhesion
• Cell junction
• Cell membrane
• Cleavage on pair of basic residues
• Cytoplasm
• Glycoprotein
• Lipoprotein
• Membrane
• Metal-binding
• Palmitate
• Phosphoprotein
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of DSG2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CTNNB1
• PKP2