Plakoglobin
Encyclopedia
Junction plakoglobin, also known as gamma-catenin or JUP, is a protein
that in humans is encoded by the JUP gene
.
Plakoglobin (gamma-catenin) was originally identified as a component of desmosome
s, where it can bind to the cadherin
family member desmoglein I
. Plakoglobin also associates with classical cadherins such as E-cadherin; in that context, it was called gamma-catenin
. Plakoglobin is O-glycosylated
near its N-terminal destruction box.
known as arrhythmogenic right ventricular dysplasia
(ARVD). The form of ARVD in which a mutated form of plakoglobin is present was first identified in a small cluster of families on the Greek island of Naxos. This form of the disorder is autosomal recessive. The phenotype of the Naxos variant of ARVD is unique in that it involves the hair and skin as well as the right ventricle. Affected individuals have wooly, kinky hair; there is also palmar and plantar erythema
at birth that progresses to keratosis
as the palms and soles of the feet are used in crawling and walking. These findings co-segregate 100% with the development of ARVD by early adolescence.
It is also implicated in Pemphigus vulgaris
along with genes encoding for Desmoglein
1 and 3.
with Beta-catenin
, MUC1
, CDH1
, CDH2
, CDH3
, Catenin (cadherin-associated protein), alpha 1, VE-cadherin
, Desmoglein 2
, Desmoplakin
, APC
, PTPRK
and PKP2
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the JUP gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
This gene encodes a major cytoplasmic protein that is the only known constituent common to submembranous plaques of both desmosomes and intermediate junctions. This protein forms distinct complexes with cadherins and desmosomal cadherins and is a member of the catenin family, since it contains a distinct repeating amino acid motif called the armadillo repeat.Plakoglobin (gamma-catenin) was originally identified as a component of desmosome
Desmosome
A desmosome , also known as macula adherens , is a cell structure specialized for cell-to-cell adhesion...
s, where it can bind to the cadherin
Cadherin
Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...
family member desmoglein I
Desmoglein
The desmogleins are a family of cadherins consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes that join cells to one another....
. Plakoglobin also associates with classical cadherins such as E-cadherin; in that context, it was called gamma-catenin
Catenin
Catenins are proteins found in complexes with cadherin cell adhesion molecules of animal cells. The first two catenins that were identified became known as alpha-catenin and beta-catenin. Alpha-catenin can bind to beta-catenin and can also bind actin. Beta-catenin binds the cytoplasmic domain of...
. Plakoglobin is O-glycosylated
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
near its N-terminal destruction box.
Clinical significance
Mutation of the gene encoding plakoglobin has been implicated as one of the causes of the cardiomyopathyCardiomyopathy
Cardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both. Cardiomyopathy can often go undetected, making it especially dangerous to...
known as arrhythmogenic right ventricular dysplasia
Arrhythmogenic right ventricular dysplasia
Arrhythmogenic right ventricular dysplasia , also called arrhythmogenic right ventricular cardiomyopathy or arrhythmogenic right ventricular dysplasia/cardiomyopathy , is an inherited heart disease....
(ARVD). The form of ARVD in which a mutated form of plakoglobin is present was first identified in a small cluster of families on the Greek island of Naxos. This form of the disorder is autosomal recessive. The phenotype of the Naxos variant of ARVD is unique in that it involves the hair and skin as well as the right ventricle. Affected individuals have wooly, kinky hair; there is also palmar and plantar erythema
Erythema
Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...
at birth that progresses to keratosis
Keratosis
Keratosis is a growth of keratin on the skin. More specifically, it can refer to:* actinic keratosis * hydrocarbon keratosis* keratosis pilaris , also known as * seborrheic keratosis-See also:...
as the palms and soles of the feet are used in crawling and walking. These findings co-segregate 100% with the development of ARVD by early adolescence.
It is also implicated in Pemphigus vulgaris
Pemphigus vulgaris
Pemphigus vulgaris is a chronic blistering skin disease with skin lesions that are rarely pruritic, but which are often painful.-Pathophysiology:...
along with genes encoding for Desmoglein
Desmoglein
The desmogleins are a family of cadherins consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes that join cells to one another....
1 and 3.
Interactions
Plakoglobin has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Beta-catenin
Beta-catenin
Beta-catenin is a protein that in humans is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo...
, MUC1
MUC1
Mucin 1, cell surface associated or polymorphic epithelial mucin is a mucin encoded by the MUC1 gene in humans. MUC1 is a proteoglycan with extensive O-linked glycosylation of its extracellular domain. Mucins line the apical surface of epithelial cells in the lungs, stomach, intestines, eyes and...
, CDH1
CDH1 (gene)
Cadherin-1 also known as CAM 120/80 or epithelial cadherin or uvomorulin is a protein that in humans is encoded by the CDH1 gene. CDH1 has also been designated as CD324 . It is a tumor suppressor gene.- Function :Cadherin-1 is a classical member of the cadherin superfamily...
, CDH2
CDH2
Cadherin-2 , also known as neural cadherin is a protein that in humans is encoded by the CDH2 gene. CDH2 has also been designated as CD325 .- Function :...
, CDH3
CDH3 (gene)
Cadherin-3 is a protein that in humans is encoded by the CDH3 gene.-Interactions:CDH3 has been shown to interact with CDH1, Beta-catenin, Plakoglobin, Nephrin and Catenin , alpha 1.-Further reading:...
, Catenin (cadherin-associated protein), alpha 1, VE-cadherin
VE-cadherin
Cadherin 5, type 2 or VE-cadherin also known as CD144 , is a type of cadherin...
, Desmoglein 2
Desmoglein 2
Desmoglein-2 is a protein that in humans is encoded by the DSG2 gene.-Interactions:Desmoglein 2 has been shown to interact with DSC1, Plakoglobin and PKP3.-External links:* *...
, Desmoplakin
Desmoplakin
Desmoplakin is a protein associated with desmosomes.Desmoplakin is a protein that in humans is encoded by the DSP gene. The C-terminus of desmoplakin binds with intermediate filaments. These are further sub divided to three homologous Plakin repeat domains . In the mid-region of desmoplakin, a...
, APC
APC (gene)
Adenomatous polyposis coli also known as deleted in polyposis 2.5 is a protein that in humans is encoded by the APC gene. Mutations in the APC gene may result in colorectal cancer....
, PTPRK
PTPRK
Receptor-type tyrosine-protein phosphatase kappa is an enzyme that in humans is encoded by the PTPRK gene.-Interactions:PTPRK has been shown to interact with Beta-catenin and Plakoglobin.-Further reading:...
and PKP2
PKP2
Plakophilin-2 is a protein that in humans is encoded by the PKP2 gene.-Interactions:PKP2 has been shown to interact with Desmoplakin, Plakoglobin and Desmoglein 1.-External links:* *...
.
External links
- GeneReviews/NCBI/NIH/UW entry on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant
- http://www.ncbi.nlm.nih.gov/omim/604772,605676,601214,107970,125645,125647,125671,173325,180902,190230,600996,602086,602087,602861,604400,604401,607450,609040,609160,610193,610476,611528,612048,107970,125645,125647,125671,173325,180902,190230,600996,602086,602087,602861,604400,604401,607450,609040,609160,610193,610476,611528,612048 OMIM entries on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant]