Affinage

DSC1

Desmocollin-1 · UniProt Q08554

Round 2 corrected
Length
894 aa
Mass
100.0 kDa
Annotated
2026-04-28
56 papers in source corpus 9 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DSC1 (desmocollin-1) is a cadherin-family transmembrane glycoprotein that functions as a calcium-dependent cell–cell adhesion molecule within desmosomes of differentiated and keratinizing epithelial layers (PMID:8486729, PMID:8823356). DSC1 is the isoform-specific autoantigen in the subcorneal pustular dermatosis (SPD) subtype of IgA pemphigus, where patient IgA autoantibodies bind DSC1 but not DSC2 or DSC3 (PMID:9242496). During apoptosis, the DSC1 cytoplasmic domain is cleaved by caspases while its extracellular domain is shed by metalloproteinases, contributing to desmosome disassembly and intermediate filament collapse (PMID:11500511). Within the desmosomal plaque, DSC1 physically interacts with plakophilin-3, and its mRNA stability is regulated by METTL3-mediated m6A modification (PMID:12707304, PMID:41453286).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 1993 High

    Molecular cloning of human DSC1 established it as a distinct type 1 desmocollin with differentiation-linked expression, mapping it to chromosome 18 alongside other desmosomal cadherins and defining the gene family framework.

    Evidence cDNA cloning, sequence comparison, and somatic cell hybrid chromosomal mapping; community nomenclature consolidation

    PMID:8288219 PMID:8486729

    Open questions at the time
    • No functional adhesion assay performed at this stage
    • Regulatory elements controlling differentiation-dependent expression undefined
  2. 1996 Medium

    Developmental expression mapping revealed that DSC1 protein appearance is tightly linked to the onset of keratinization rather than to stratification per se, and that DSC1 is regulated independently of desmoglein-1.

    Evidence In situ hybridization and immunofluorescence in mouse embryonic tissues

    PMID:8823356

    Open questions at the time
    • Transcription factors driving DSC1 expression during keratinization not identified
    • Functional consequence of independent DSC1/DSG1 regulation unexplored
  3. 1997 High

    Identification of DSC1 as the specific target of IgA autoantibodies in SPD-type IgA pemphigus revealed that loss of DSC1-mediated adhesion in superficial epidermal layers underlies subcorneal blister formation.

    Evidence COS7 transfection with individual DSC isoforms, immunofluorescence with sera from six SPD patients versus seven IEN patients

    PMID:9242496

    Open questions at the time
    • Precise epitope(s) on DSC1 recognized by pathogenic IgA not mapped
    • No passive-transfer or knockout model to confirm pathogenicity of anti-DSC1 antibodies in vivo
  4. 2001 Medium

    Demonstration that DSC1 is proteolytically processed during apoptosis by both caspases (cytoplasmic domain) and metalloproteinases (extracellular domain) established a mechanism for active desmosome disassembly and intermediate filament collapse during programmed cell death.

    Evidence Western blotting during apoptosis induction with caspase and metalloproteinase inhibitors, immunofluorescence

    PMID:11500511

    Open questions at the time
    • Specific caspase(s) and metalloproteinase(s) responsible not identified
    • Cleavage site(s) on DSC1 not mapped
  5. 2003 Medium

    Yeast two-hybrid and co-immunoprecipitation identified plakophilin-3 as a direct binding partner of DSC1a, placing DSC1 within the desmosomal plaque protein interaction network.

    Evidence Yeast two-hybrid, co-immunoprecipitation, co-localization immunofluorescence

    PMID:12707304

    Open questions at the time
    • Binding interface between PKP3 and DSC1 not structurally resolved
    • Functional consequence of disrupting the DSC1–PKP3 interaction on desmosome integrity not tested
  6. 2021 Low

    A report linking DSC1 to autophagic flux via circRAB11FIP1-facilitated interaction with ATG101 suggested a non-canonical role for DSC1 beyond cell adhesion, though this rests on limited mechanistic evidence.

    Evidence RNA pulldown, co-immunoprecipitation, overexpression/silencing with autophagy flux assays in ovarian cancer cell lines

    PMID:33637694

    Open questions at the time
    • DSC1–ATG101 interaction not validated by reciprocal Co-IP or in non-cancer cells
    • Endogenous relevance of DSC1 in autophagy regulation not established
    • Single-lab finding without independent replication
  7. 2025 Medium

    METTL3-mediated m6A modification was shown to stabilize DSC1 mRNA, establishing an epitranscriptomic layer of DSC1 regulation with functional consequences for cell survival under inflammatory stress.

    Evidence m6A-RIP, qRT-PCR, proliferation/apoptosis assays, siRNA knockdown and overexpression in human periodontal ligament fibroblasts

    PMID:41453286

    Open questions at the time
    • m6A reader protein mediating DSC1 mRNA stabilization not identified
    • Whether m6A regulation of DSC1 operates in epidermal keratinocytes unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of DSC1 homophilic and heterophilic adhesion, the identity of the specific caspase and metalloproteinase cleaving DSC1, whether DSC1 has genuine autophagy-related functions outside cancer cell lines, and the in vivo pathogenic mechanism of anti-DSC1 IgA autoantibodies.
  • No crystal or cryo-EM structure of DSC1 extracellular domain available
  • In vivo loss-of-function phenotype (knockout mouse) not reported in the timeline
  • Pathogenic mechanism of anti-DSC1 IgA in SPD not directly demonstrated in animal models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-1500931 Cell-Cell communication 3 R-HSA-5357801 Programmed Cell Death 1
Partners
ATG101PKP3
Complex memberships
desmosome

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 The human DSC1 gene encodes a type 1 desmocollin (a cadherin-related glycoprotein) expressed in the more differentiated layers of the epidermis, sharing 53% amino acid identity with the previously isolated human type 3 desmocollin (DSC3), with the N- and C-termini being more highly conserved between isoforms. The DSC1 gene was chromosomally assigned to chromosome 18, co-localizing with DSC3 and the three desmoglein genes. cDNA cloning, amino acid sequence comparison, somatic cell hybrid panel chromosomal mapping Genomics Medium 8288219
1993 DSC1 (desmocollin 1) was formally established as part of the desmosomal cadherin nomenclature, defining it as a transmembrane glycoprotein component of desmosomal junctions involved in calcium-dependent cell-cell adhesion in epithelial tissues. Nomenclature review consolidating molecular and biochemical characterization data from multiple labs The Journal of cell biology High 8486729
1996 DSC1 protein expression is closely linked to epithelial keratinization during mouse development. DSC1 protein is first detected in the outermost epithelial cells destined to form keratinized layers (stratum corneum), with DSC1 mRNA upregulation occurring after stratification onset but before keratinization begins, and in tongue coinciding with formation of keratinizing filiform papillae. Desmocollin 1 and desmoglein 1 expression patterns were not tightly coupled during embryonic development, suggesting independent regulatory mechanisms. In situ hybridization of mouse embryonic tissues, immunofluorescence with cross-reactive human DSC1 monoclonal antibodies, full-length mouse Dsc1 cDNA cloning The Journal of investigative dermatology Medium 8823356
1997 Human DSC1 is the specific autoantigen for the subcorneal pustular dermatosis (SPD) subtype of IgA pemphigus. IgA autoantibodies from all six SPD-type IgA pemphigus patients reacted with the surface of COS7 cells transfected with human DSC1, but not with cells expressing DSC2 or DSC3, demonstrating isoform-specific targeting of DSC1 by pathogenic autoantibodies and implicating DSC1 in SPD pathogenesis. Transient transfection of COS7 cells with mammalian expression vectors encoding individual human Dsc isoforms, immunofluorescence with patient IgA sera The Journal of investigative dermatology High 9242496
2000 The human DSC1 gene has a defined intron-exon structure comprising 17 exons spanning approximately 33 kb on chromosome 18q12.1, providing the genomic framework for its regulated expression and enabling mutation screening strategies. PCR-based genomic amplification, sequencing, and intron-exon boundary mapping Biochemical and biophysical research communications Medium 11027496
2001 Desmocollins (including DSC1) are specifically cleaved during apoptosis by a dual mechanism: the cytoplasmic domain is cleaved by caspases, while the extracellular domain is shed from the cell surface by metalloproteinase activity. Both cleavage reactions are inhibited by caspase and metalloproteinase inhibitors, respectively, and their cleavage contributes to disruption of desmosome structure, cell rounding, and disintegration of the intermediate filament system. Western blotting with desmosomal antibodies during apoptosis induction, caspase and metalloproteinase inhibitor experiments, immunofluorescence The Journal of biological chemistry Medium 11500511
2003 Plakophilin-3 (PKP3) physically binds desmocollin 1a (Dsc1a) as well as Dsc2a and all three desmogleins, placing DSC1 within the desmosomal plaque protein interaction network. This interaction was established by yeast two-hybrid assay and confirmed by co-immunoprecipitation and co-localization experiments. Yeast two-hybrid, co-immunoprecipitation, co-localization immunofluorescence The Journal of cell biology Medium 12707304
2021 CircRAB11FIP1 directly binds to DSC1 (desmocollin 1) protein and facilitates its interaction with ATG101, a component of the autophagy initiation complex, thereby promoting autophagic flux in ovarian cancer cells. This places DSC1 at a functional interface between desmosomal adhesion and autophagy regulation. RNA pulldown, co-immunoprecipitation, overexpression and silencing experiments with autophagic flux assays in ovarian cancer cell lines Cell death & disease Low 33637694
2025 METTL3-mediated N6-methyladenosine (m6A) modification of DSC1 mRNA positively regulates DSC1 expression and stability. METTL3 overexpression increases DSC1 levels, and DSC1 overexpression alleviates LPS-induced apoptosis and inflammation in human periodontal ligament fibroblasts. Silencing METTL3 partially reverses the protective effect of DSC1 upregulation, establishing METTL3 as a writer for m6A modification of DSC1. m6A RNA immunoprecipitation (m6A-RIP), quantitative RT-PCR, CCK-8/EdU proliferation assays, flow cytometry (apoptosis), ELISA (inflammation markers), siRNA knockdown and overexpression experiments International dental journal Medium 41453286
2024 Ephrin-A3 (EFNA3) regulates DSC1 (desmocollin-1) expression in vaginal epithelium. Topical administration of recombinant EFNA3 promotes vaginal DSC1 expression in a biphasic dose-dependent manner and partially reverses the loss of vaginal epithelial barrier function induced by progestin (DMPA) treatment, which reduces DSC1 levels. This identifies EFNA3 signaling as an upstream regulator of DSC1-dependent desmosomal function. In vivo mouse model with DMPA and recombinant EFNA3 treatment, measurement of vaginal DSG1 and DSC1 protein levels, epithelial barrier function assays, HSV-2 infection model bioRxivpreprint Low

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2005 Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules. Molecular & cellular proteomics : MCP 434 15951569
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2008 A genome-wide association study identifies protein quantitative trait loci (pQTLs). PLoS genetics 390 18464913
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. PloS one 312 23251661
1993 Nomenclature of the desmosomal cadherins. The Journal of cell biology 268 8486729
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2014 Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes. Molecular cell 173 25544563
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
1997 Human desmocollin 1 (Dsc1) is an autoantigen for the subcorneal pustular dermatosis type of IgA pemphigus. The Journal of investigative dermatology 163 9242496
2014 E-cadherin interactome complexity and robustness resolved by quantitative proteomics. Science signaling 162 25468996
2003 Defining desmosomal plakophilin-3 interactions. The Journal of cell biology 138 12707304
2019 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature cell biology 137 31871319
2016 SPATA2 Links CYLD to LUBAC, Activates CYLD, and Controls LUBAC Signaling. Molecular cell 134 27591049
2014 The central role of EED in the orchestration of polycomb group complexes. Nature communications 131 24457600
2019 The Functional Proximal Proteome of Oncogenic Ras Includes mTORC2. Molecular cell 124 30639242
2001 The fate of desmosomal proteins in apoptotic cells. The Journal of biological chemistry 109 11500511
2010 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Molecular medicine (Cambridge, Mass.) 108 20379614
2023 ESCRT-dependent STING degradation inhibits steady-state and cGAMP-induced signalling. Nature communications 104 36739287
2009 Desmocollin 3-mediated binding is crucial for keratinocyte cohesion and is impaired in pemphigus. The Journal of biological chemistry 96 19717567
2013 A genome-wide association study (GWAS) for bronchopulmonary dysplasia. Pediatrics 93 23897914
2005 Epigenetic silencing of DSC3 is a common event in human breast cancer. Breast cancer research : BCR 93 16168112
2018 Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function. EMBO reports 92 29467282
1995 A yeast transcription factor bypassing the requirement for SBF and DSC1/MBF in budding yeast has homology to bacterial signal transduction proteins. The EMBO journal 92 8521825
2020 Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. Molecular cell 88 32707033
2021 CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. Cell death & disease 73 33637694
1993 Cloning of the cDNA (DSC1) coding for human type 1 desmocollin and its assignment to chromosome 18. Genomics 49 8288219
2002 The DSC1 channel, encoded by the smi60E locus, contributes to odor-guided behavior in Drosophila melanogaster. Genetics 45 12196396
1996 Expression of the "skin-type" desmosomal cadherin DSC1 is closely linked to the keratinization of epithelial tissues during mouse development. The Journal of investigative dermatology 36 8823356
2011 Molecular characterization and functional expression of the DSC1 channel. Insect biochemistry and molecular biology 31 21571069
2020 The TIR-NB-LRR pair DSC1 and WRKY19 contributes to basal immunity of Arabidopsis to the root-knot nematode Meloidogyne incognita. BMC plant biology 24 32054439
2013 Role of the DSC1 channel in regulating neuronal excitability in Drosophila melanogaster: extending nervous system stability under stress. PLoS genetics 24 23505382
2003 The Schizosaccharomyces pombe cdt2(+) gene, a target of G1-S phase-specific transcription factor complex DSC1, is required for mitotic and premeiotic DNA replication. Genetics 24 12871901
2015 Distinct roles of the DmNav and DSC1 channels in the action of DDT and pyrethroids. Neurotoxicology 18 25687544
2001 The role of DSC1 components cdc10+, rep1+ and rep2+ in MCB gene transcription at the mitotic G1-S boundary in fission yeast. Current genetics 18 11795845
2012 Molecular characterization of DSC1 orthologs in invertebrate species. Insect biochemistry and molecular biology 17 22321571
2003 DSC1-MCB regulation of meiotic transcription in Schizosaccharomyces pombe. Molecular genetics and genomics : MGG 17 14648198
2001 DSC1 channels are expressed in both the central and the peripheral nervous system of adult Drosophila melanogaster. Invertebrate neuroscience : IN 17 12488978
2016 Biophysical characterization of the honeybee DSC1 orthologue reveals a novel voltage-dependent Ca2+ channel subfamily: CaV4. The Journal of general physiology 16 27432995
2014 The Drosophila Sodium Channel 1 (DSC1): The founding member of a new family of voltage-gated cation channels. Pesticide biochemistry and physiology 11 25987218
1998 Phenotypic analysis and molecular cloning of discolored-1 (dsc1), a maize gene required for early kernel development. Plant molecular biology 11 9617815
1993 Domains of p85cdc10 required for function of the fission yeast DSC-1 factor. Nucleic acids research 11 8367276
2012 Discolored1 (DSC1) is an ADP-Ribosylation Factor-GTPase Activating Protein Required to Maintain Differentiation of Maize Kernel Structures. Frontiers in plant science 9 22666226
2018 DSC1 channel-dependent developmental regulation of pyrethroid susceptibility in Drosophila melanogaster. Pesticide biochemistry and physiology 8 29891372
2000 Genomic organization and amplification of the human desmosomal cadherin genes DSC1 and DSC3, encoding desmocollin types 1 and 3. Biochemical and biophysical research communications 8 11027496
2006 Association of DSC1, a gene modulated by adrenergic stimulation, with Alzheimer's disease. Neuroscience letters 6 17014956
2013 Molecular characterization and alternative splicing of a sodium channel and DSC1 ortholog genes in Liposcelis bostrychophila Badonnel (Psocoptera: Liposcelididae). International journal of biological sciences 4 24155671
2025 METTL3-Mediated m6A Modification of DSC1 Alleviates Inflammation and Cellular Dysfunction in Periodontitis. International dental journal 0 41453286
2006 Transcription of the Schizosaccharomyces pombe gene cdc18+: roles of MCB elements and the DSC1 complex. Gene 0 16460890