Desmoglein-1 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''DSG1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. Desmoglein-1 is expressed everywhere in the skin epidermis, but mainly it is expressed in the superficial upper layers of the skin epidermis.

Function

Desmosomes are cell-cell junctions between

epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

myocardial Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of ...

and certain other cell types. Desmoglein-1 is a calcium-binding

transmembrane A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...

glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...

component of

desmosomes A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for ''adhering spot''), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like ad ...

vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

epithelial cells. Currently, four desmoglein subfamily members have been identified and all are members of the

cadherin Cadherins (named for "calcium-dependent adhesion") are cell adhesion molecules important in forming adherens junctions that let cells adhere to each other. Cadherins are a class of type-1 transmembrane proteins, and they depend on calcium (Ca2+) ...

cell adhesion molecule superfamily. These desmoglein

gene family A gene family is a set of several similar genes, formed by duplication of a single original gene, and generally with similar biochemical functions. One such family are the genes for human hemoglobin subunits; the ten genes are in two clusters on ...

members are located in a

cluster may refer to: Science and technology Astronomy * Cluster (spacecraft), constellation of four European Space Agency spacecraft * Cluster II (spacecraft), a European Space Agency mission to study the magnetosphere * Asteroid cluster, a small ...

chromosome 18 Chromosome 18 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 18 spans about 80 million base pairs (the building material of DNA) and represents about 2.5 percent of the total DNA in ...

. The protein encoded by this gene has been identified as the

autoantigen In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...

of the

autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an " autoimmune disease" ...

skin blistering disease

pemphigus foliaceus Pemphigus foliaceus is an autoimmune blistering disease of the skin. Pemphigus foliaceus causes a characteristic inflammatory attack at the subcorneal layer of epidermis, which results in skin lesions that are scaly or crusted erosions with an ...

. It has been found that desmoglein-1 is the target antigen in majority of the cases linked to IgG/IgA pemphigus, which is an autoimmune

IgG Immunoglobulin G (IgG) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ant ...

IgA IGA or IgA may refer to: Businesses and organizations * IGA (supermarkets) (initially Independent Grocers Alliance), a name used by many independent supermarkets throughout the world ** IGA (Australian supermarket group), the local Australian v ...

antibody mediated response. Desmoglein-1 is also a target of ''

Staphylococcus ''Staphylococcus'', from Ancient Greek σταφυλή (''staphulḗ''), meaning "bunch of grapes", and (''kókkos''), meaning "kernel" or " Kermes", is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillale ...

exotoxin An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, sim ...

s (

exfoliatin Exfoliatin is a ''Staphylococcus aureus'' exotoxin that causes a blistering of the skin known as staphylococcal scalded skin syndrome, usually in infants. Exfoliatins are glutamate-specific serine proteases highly specific to desmoglein I, a cadhe ...

s) A and B which contribute to the pathoaetiology of

staphylococcal scalded skin syndrome Staphylococcal scalded skin syndrome (SSSS) is a dermatology, dermatological condition caused by ''Staphylococcus aureus''. Signs and symptoms The disease presents with the widespread formation of fluid-filled blisters that are thin walled and ea ...

(SSSS). Deficiency of the desmoglein-1 protein has been found to be associated with increased expression of multiple genes encoding

allergy Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...

-related

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

s. Desmoglein-1 is haploinsufficient and a mutation in the gene can cause the

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

mutation

striate palmoplantar keratoderma Palmoplantar keratodermas are a heterogeneous group of skin disorders characterized by abnormal thickening (scleroderma) of the stratum corneum of the palms and soles. Autosomal recessive, dominant, X-linked, and acquired forms have all been de ...

. In 2013, cases have arisen where the homozygous loss of the desmoglein-1 gene has resulted in a rare syndrome known as SAM syndrome – severe dermatitis, multiple allergies, and metabolic wasting.

Interactions

Desmoglein-1 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with

PKP3 Plakophilin-3 is a protein that in humans is encoded by the ''PKP3'' gene. Function This gene encodes a member of the arm-repeat (armadillo) and plakophilin gene families. Plakophilin proteins contain numerous armadillo repeats, localize to ce ...

PKP2 Plakophilin-2 is a protein that in humans is encoded by the ''PKP2'' gene. Plakophilin 2 is expressed in skin and cardiac muscle, where it functions to link cadherins to intermediate filaments in the cytoskeleton. In cardiac muscle, plakophilin- ...

, and

PTPRT Receptor-type tyrosine-protein phosphatase T is an enzyme that in humans is encoded by the ''PTPRT'' gene. PTPRT is also known as PTPrho, PTPρ and human accelerated region 9. The human accelerated regions are 49 regions of the human genome tha ...

(PTPrho)

Function

Interactions

See also

References

Further reading