DSG3 (P32926) — curation notes

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Research below is from the cached publications, the UniProt record and PubMed.

Architecture and localization

Desmoglein-3 is a desmosomal cadherin: signal peptide and propeptide, four extracellular
cadherin (EC) domains plus an EC anchor, a single transmembrane helix, and a cytoplasmic
tail with the intracellular anchor and cadherin-like sequences that engage plakoglobin and
plakophilins. The adhesive ectodomain faces the extracellular space, so the protein is
accessible from outside the cell — the basis of pemphigus vulgaris autoantibody binding.

UniProt subcellular location: cell membrane (single-pass type I), cell junction/desmosome,
cell junction/tight junction, and cytoplasm.
[file:human/DSG3/DSG3-uniprot.txt "SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19717567, ECO:0000269|PubMed:30949721, ECO:0000269|PubMed:31835537}; Single-pass type I membrane protein"]

There are two documented pools: the desmosomal pool, and a detergent-soluble,
non-junctional pool at the cell surface that carries much of the signalling activity.
PMID:22294297
PMID:18343367

Conclusion for GO: plasma membrane and desmosome are the core locations, with the
adhesive domain extracellular. Cytoplasm reflects the cytoplasmic tail / soluble pool;
the Reactome cytosol assignment comes from the caspase-released cytoplasmic fragment
(R-HSA-201631, "Caspase-mediated cleavage of Desmoglein 3"). Cornified envelope is a
pathway-level Reactome/ARBA assignment, not a DSG3 localization experiment, and DSG3 is
expressed in the basal and spinous layers with only weak granular-layer expression.

Functions

• Calcium-dependent desmosomal adhesion; knockout mice lose telogen hairs through
  acantholysis around the telogen club.
  PMID:9701552
• Homodimer; trans-interaction measured by AFM/laser tweezers.
  [file:human/DSG3/DSG3-uniprot.txt "SUBUNIT: Homodimer (PubMed:19717567)."]
• Junction assembly under mechanical strain, with a DSG3/PKP1/YAP1/YWHAG complex that
  retains phospho-YAP at the membrane.
  PMID:31835537
• Upstream regulation of Rac1/Cdc42 and cortical actin.
  PMID:22796473
• Suppression of p38MAPK and hence of keratinocyte migration and wound closure.
  PMID:26763450

Protein-binding rows

Per the protein-binding policy, bare GO:0005515 rows are either MODIFYed to an
informative molecular function or REMOVEd as uninformative. Interactors here are PKP2
(PMID:11790773), CTNND1/p120 (PMID:18343367), DSC3 (PMID:19717567), CDH1 (PMID:22294297),
RAC1 (PMID:22796473) and the PKP1/YAP1/YWHAG complex (PMID:31835537).