DSC3

Protein identityUniProt · HPA

UniProt accession

Q14574

Gene

DSC3

Ensembl

ENSG00000134762

Chromosome

18

Canonical length

896 aa

Protein class

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

Subcellular location

Plasma membrane,Cell Junctions

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is a calcium-dependent glycoprotein that is a member of the desmocollin subfamily of the cadherin superfamily. These desmosomal family members, along with the desmogleins, are found primarily in epithelial cells where they constitute the adhesive proteins of the desmosome cell-cell junction and are required for cell adhesion and desmosome formation. The desmosomal family members are arranged in two clusters on chromosome 18, occupying less than 650 kb combined. Mutations in this gene are a cause of hypotrichosis and recurrent skin vesicles disorder. The protein can act as an autoantigen in pemphigus diseases, and it is also considered to be a biomarker for some cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2014]

Canonical amino-acid sequenceUniProt

896 residues, UniProt reviewed canonical sequence.

>Q14574|DSC3
     1  MAAAGPRRSV RGAVCLHLLL TLVIFSRAGE ACKKVILNVP SKLEADKIIG RVNLEECFRS
    61  ADLIRSSDPD FRVLNDGSVY TARAVALSDK KRSFTIWLSD KRKQTQKEVT VLLEHQKKVS
   121  KTRHTRETVL RRAKRRWAPI PCSMQENSLG PFPLFLQQVE SDAAQNYTVF YSISGRGVDK
   181  EPLNLFYIER DTGNLFCTRP VDREEYDVFD LIAYASTADG YSADLPLPLP IRVEDENDNH
   241  PVFTEAIYNF EVLESSRPGT TVGVVCATDR DEPDTMHTRL KYSILQQTPR SPGLFSVHPS
   301  TGVITTVSHY LDREVVDKYS LIMKVQDMDG QFFGLIGTST CIITVTDSND NAPTFRQNAY
   361  EAFVEENAFN VEILRIPIED KDLINTANWR VNFTILKGNE NGHFKISTDK ETNEGVLSVV
   421  KPLNYEENRQ VNLEIGVNNE APFARDIPRV TALNRALVTV HVRDLDEGPE CTPAAQYVRI
   481  KENLAVGSKI NGYKAYDPEN RNGNGLRYKK LHDPKGWITI DEISGSIITS KILDREVETP
   541  KNELYNITVL AIDKDDRSCT GTLAVNIEDV NDNPPEILQE YVVICKPKMG YTDILAVDPD
   601  EPVHGAPFYF SLPNTSPEIS RLWSLTKVND TAARLSYQKN AGFQEYTIPI TVKDRAGQAA
   661  TKLLRVNLCE CTHPTQCRAT SRSTGVILGK WAILAILLGI ALLFSVLLTL VCGVFGATKG
   721  KRFPEDLAQQ NLIISNTEAP GDDRVCSANG FMTQTTNNSS QGFCGTMGSG MKNGGQETIE
   781  MMKGGNQTLE SCRGAGHHHT LDSCRGGHTE VDNCRYTYSE WHSFTQPRLG EKLHRCNQNE
   841  DRMPSQDYVL TYNYEGRGSP AGSVGCCSEK QEEDGLDFLN NLEPKFITLA EACTKR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DSC3 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)

0.41

Highest tissue expression

352 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DSC3.

Disease | AllUniProt

Conditions DSC3 is implicated in, by any mechanism.

• Hypotrichosis and recurrent skin vesicles (HRSV) MIM:613102

Disease | GeneticClinVar

9 pathogenic / likely-pathogenic of 211 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary hypotrichosis with recurrent skin vesicles
• Sarcoma

Disease | AutoantibodyPubMed

Conditions in which antibodies against DSC3 are reported. Each links to that disease's full target list.

• Pemphigus 26

ReferencesPubMed · IEDB

Publications for DSC3 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. 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)

1.2

gnomAD pLI

0

gnomAD missense Z

-0.65

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell adhesion
• cell-cell adhesion
• homophilic cell adhesion via plasma membrane adhesion molecules
• in utero embryonic development
• protein stabilization

Molecular functions

• calcium ion binding
• gamma-catenin binding

Cellular components

• cell junction
• cell-cell junction
• cornified envelope
• cytoplasm
• desmosome
• extracellular region
• membrane
• 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
• Cell adhesion
• Cell junction
• Cell membrane
• Cleavage on pair of basic residues
• Cytoplasm
• Glycoprotein
• Hypotrichosis
• Membrane
• Metal-binding
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of DSC3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DSG1
• DSG3