DSG1

Protein identityUniProt · HPA

UniProt accession

Q02413

Gene

DSG1

Ensembl

ENSG00000134760

Chromosome

18

Canonical length

1049 aa

Protein class

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

OverviewNCBI Gene

This gene encodes a member of the desmoglein protein subfamily. Desmogleins, along with desmocollins, 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 desmoglein family members on chromosome 18. The encoded protein has been identified as a target of auto-antibodies in the autoimmune skin blistering disease pemphigus foliaceus. Disruption of this gene has also been associated with the skin diseases palmoplantar keratoderma and erythroderma. [provided by RefSeq, Feb 2015]

Canonical amino-acid sequenceUniProt

1049 residues, UniProt reviewed canonical sequence.

>Q02413|DSG1
     1  MDWSFFRVVA MLFIFLVVVE VNSEFRIQVR DYNTKNGTIK WHSIRRQKRE WIKFAAACRE
    61  GEDNSKRNPI AKIHSDCAAN QQVTYRISGV GIDQPPYGIF VINQKTGEIN ITSIVDREVT
   121  PFFIIYCRAL NSMGQDLERP LELRVRVLDI NDNPPVFSMA TFAGQIEENS NANTLVMILN
   181  ATDADEPNNL NSKIAFKIIR QEPSDSPMFI INRNTGEIRT MNNFLDREQY GQYALAVRGS
   241  DRDGGADGMS AECECNIKIL DVNDNIPYME QSSYTIEIQE NTLNSNLLEI RVIDLDEEFS
   301  ANWMAVIFFI SGNEGNWFEI EMNERTNVGI LKVVKPLDYE AMQSLQLSIG VRNKAEFHHS
   361  IMSQYKLKAS AISVTVLNVI EGPVFRPGSK TYVVTGNMGS NDKVGDFVAT DLDTGRPSTT
   421  VRYVMGNNPA DLLAVDSRTG KLTLKNKVTK EQYNMLGGKY QGTILSIDDN LQRTCTGTIN
   481  INIQSFGNDD RTNTEPNTKI TTNTGRQEST SSTNYDTSTT STDSSQVYSS EPGNGAKDLL
   541  SDNVHFGPAG IGLLIMGFLV LGLVPFLMIC CDCGGAPRSA AGFEPVPECS DGAIHSWAVE
   601  GPQPEPRDIT TVIPQIPPDN ANIIECIDNS GVYTNEYGGR EMQDLGGGER MTGFELTEGV
   661  KTSGMPEICQ EYSGTLRRNS MRECREGGLN MNFMESYFCQ KAYAYADEDE GRPSNDCLLI
   721  YDIEGVGSPA GSVGCCSFIG EDLDDSFLDT LGPKFKKLAD ISLGKESYPD LDPSWPPQST
   781  EPVCLPQETE PVVSGHPPIS PHFGTTTVIS ESTYPSGPGV LHPKPILDPL GYGNVTVTES
   841  YTTSDTLKPS VHVHDNRPAS NVVVTERVVG PISGADLHGM LEMPDLRDGS NVIVTERVIA
   901  PSSSLPTSLT IHHPRESSNV VVTERVIQPT SGMIGSLSMH PELANAHNVI VTERVVSGAG
   961  VTGISGTTGI SGGIGSSGLV GTSMGAGSGA LSGAGISGGG IGLSSLGGTA SIGHMRSSSD
  1021  HHFNQTIGSA SPSTARSRIT KYSTVQYSK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DSG1 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)

0.47

Highest tissue expression

533 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DSG1.

Disease | AllUniProt

Conditions DSG1 is implicated in, by any mechanism.

• Palmoplantar keratoderma 1, striate, focal, or diffuse (PPKS1) MIM:148700
• Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE (EPKHE) MIM:615508

Disease | GeneticClinVar

45 pathogenic / likely-pathogenic of 964 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Palmoplantar keratoderma i, striate, focal, or diffuse
• Severe dermatitis-multiple allergies-metabolic wasting syndrome
• Hereditary palmoplantar keratoderma
• DSG1-related disorder
• Epidermal disease

Disease | ImmuneIEDB

Conditions an epitope on DSG1 was assayed in.

• pemphigus B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against DSG1 are reported. Each links to that disease's full target list.

• Pemphigus 273
• Blister 12
• Skin Diseases, Vesiculobullous 10
• Pemphigoid, Bullous 6
• Psoriasis 4
• Arthritis, Rheumatoid 3

Showing 6 of 11 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for DSG1 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)

0.33

gnomAD pLI

0.93

gnomAD missense Z

-0.34

DepMap mean gene effect

0.01

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

• calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules
• cell-cell adhesion
• cell-cell junction assembly
• homophilic cell adhesion via plasma membrane adhesion molecules
• maternal process involved in female pregnancy
• protein stabilization
• response to progesterone

Molecular functions

• calcium ion binding
• gamma-catenin binding
• toxic substance binding

Cellular components

• apical plasma membrane
• cornified envelope
• cytoplasm
• cytoplasmic side of plasma membrane
• cytosol
• desmosome
• ficolin-1-rich granule membrane
• lateral plasma membrane
• nucleus
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

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

KeywordsUniProt

• Calcium
• Cell adhesion
• Cell junction
• Cell membrane
• Cleavage on pair of basic residues
• Cytoplasm
• Glycoprotein
• Hypotrichosis
• Membrane
• Metal-binding
• Nucleus
• Palmoplantar keratoderma
• Phosphoprotein
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of DSG1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DSC3
• PKP2
• JUP