DSC2

Protein identityUniProt · HPA

UniProt accession

Q02487

Gene

DSC2

Ensembl

ENSG00000134755

Chromosome

18

Canonical length

901 aa

Protein class

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

Subcellular location

Endoplasmic reticulum,Plasma membrane

OverviewNCBI Gene

This gene encodes a member of the desmocollin protein subfamily. Desmocollins, along with desmogleins, are cadherin-like transmembrane glycoproteins that are major components of the desmosome. Desmosomes are cell-cell junctions that help resist shearing forces and are found in high concentrations in cells subject to mechanical stress. This gene is found in a cluster with other desmocollin family members on chromosome 18. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia-11, and reduced protein expression has been described in several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

Canonical amino-acid sequenceUniProt

901 residues, UniProt reviewed canonical sequence.

>Q02487|DSC2
     1  MEAARPSGSW NGALCRLLLL TLAILIFASD ACKNVTLHVP SKLDAEKLVG RVNLKECFTA
    61  ANLIHSSDPD FQILEDGSVY TTNTILLSSE KRSFTILLSN TENQEKKKIF VFLEHQTKVL
   121  KKRHTKEKVL RRAKRRWAPI PCSMLENSLG PFPLFLQQVQ SDTAQNYTIY YSIRGPGVDQ
   181  EPRNLFYVER DTGNLYCTRP VDREQYESFE IIAFATTPDG YTPELPLPLI IKIEDENDNY
   241  PIFTEETYTF TIFENCRVGT TVGQVCATDK DEPDTMHTRL KYSIIGQVPP SPTLFSMHPT
   301  TGVITTTSSQ LDRELIDKYQ LKIKVQDMDG QYFGLQTTST CIINIDDVND HLPTFTRTSY
   361  VTSVEENTVD VEILRVTVED KDLVNTANWR ANYTILKGNE NGNFKIVTDA KTNEGVLCVV
   421  KPLNYEEKQQ MILQIGVVNE APFSREASPR SAMSTATVTV NVEDQDEGPE CNPPIQTVRM
   481  KENAEVGTTS NGYKAYDPET RSSSGIRYKK LTDPTGWVTI DENTGSIKVF RSLDREAETI
   541  KNGIYNITVL ASDQGGRTCT GTLGIILQDV NDNSPFIPKK TVIICKPTMS SAEIVAVDPD
   601  EPIHGPPFDF SLESSTSEVQ RMWRLKAIND TAARLSYQND PPFGSYVVPI TVRDRLGMSS
   661  VTSLDVTLCD CITENDCTHR VDPRIGGGGV QLGKWAILAI LLGIALLFCI LFTLVCGASG
   721  TSKQPKVIPD DLAQQNLIVS NTEAPGDDKV YSANGFTTQT VGASAQGVCG TVGSGIKNGG
   781  QETIEMVKGG HQTSESCRGA GHHHTLDSCR GGHTEVDNCR YTYSEWHSFT QPRLGEKVYL
   841  CNQDENHKHA QDYVLTYNYE GRGSVAGSVG CCSERQEEDG LEFLDNLEPK FRTLAEACMK
   901  R

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DSC2 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)

0.4

Highest tissue expression

161 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DSC2.

Disease | AllUniProt

Conditions DSC2 is implicated in, by any mechanism.

• Arrhythmogenic right ventricular dysplasia, familial, 11 (ARVD11) MIM:610476

Disease | GeneticClinVar

104 pathogenic / likely-pathogenic of 2,094 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Arrhythmogenic right ventricular dysplasia 11
• Cardiovascular phenotype
• Arrhythmogenic right ventricular cardiomyopathy
• Arrhythmogenic right ventricular dysplasia, familial, 11, with mild palmoplantar keratoderma and woolly hair
• ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 11, WITH OR WITHOUT MILD PALMOPLANTAR KERATODERMA

Disease | ImmuneIEDB

Conditions an epitope on DSC2 was assayed in.

• pemphigus B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against DSC2 are reported. Each links to that disease's full target list.

• Pemphigus 11

ReferencesPubMed · IEDB

Publications for DSC2 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)

0.69

gnomAD pLI

0

gnomAD missense Z

0.37

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
• cellular response to starvation
• homophilic cell adhesion via plasma membrane adhesion molecules
• positive regulation of p38MAPK cascade
• regulation of heart rate by cardiac conduction
• regulation of ventricular cardiac muscle cell action potential
• cardiac muscle cell-cardiac muscle cell adhesion

Molecular functions

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

Cellular components

• adherens junction
• cornified envelope
• cytoplasmic vesicle
• desmosome
• endoplasmic reticulum
• extracellular exosome
• intercalated disc
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Cadherin, Y-type LIR-motif
• Cadherin-like
• Desmosomal cadherin
• Cadherin prodomain
• Cadherin-like superfamily
• Cadherin conserved site
• Catenin binding domain superfamily
• Cadherin domain-containing protein
• Cadherin domain
• Cadherin, Y-type LIR-motif
• Cadherin prodomain like

KeywordsUniProt

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

InteractionsUniProt · HPA

Protein binding partners of DSC2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DSG3
• DSP
• JUP
• PKP2