The reference OMIM entry for this protein is 125647

Desmoplakin; dsp desmoplakin i, included; dspi, included
Desmoplakin ii, included; dspii, included

DESCRIPTION

Desmosomes are the most common type of intercellular junction in vertebrate epithelial cells. They are characterized by 2 forms of interaction with other cellular structures. First, they form membrane anchorage sites for intermediate-size filaments, which are seen as electron-dense plaques evident beneath the plasma membrane. Second, a specific membrane core domain interacts with a corresponding domain of the plasma membrane of an adjacent cell, apparently mediating intercellular adhesion in a stable way. The desmosome intermediate filament complex is thought to impart tensile strength and resilience to the epithelium. Desmosomal proteins can be divided into 2 groups based on whether they fractionate with the urea-insoluble 'core' or the urea-soluble 'plaque' components. Desmoglein (125670) is, for example, a protein of the core. The main proteins of the plaque comprise the desmoplakins and plakoglobin (173325).

CLONING

DSPI and DSPII are related proteins of molecular mass 250 kD and 215 kD, respectively. They are splice variants of the same gene (Green et al., 1990). Virata et al. (1992) identified overlapping cDNA clones predicted to encode a full-length 310-kD polypeptide of 2,677 amino acid residues. Stappenbeck et al. (1993) and Bornslaeger et al. (1996) made use of updated information on the desmoplakin protein sequence indicating that it contains 2,871 amino acids and has a molecular mass of approximately 332 kD. By RT-PCR, Kazerounian et al. (2002) surveyed the tissue distribution of several plakin family members, including periplakin (602871), plectin (601282), desmoplakin, BPAG1 (113810), and envoplakin (601590). Desmoplakin was expressed at high levels in several tissues, but was only weakly expressed in adult brain and was not detected in skeletal muscle or leukocytes.

GENE FUNCTION

Anhalt et al. (1990) discovered an autoimmune disorder, which they called paraneoplastic pemphigus, associated with lymphoid malignancies, thymomas, and poorly differentiated sarcomas. Oursler et al. (1992) demonstrated that autoantibodies against the desmoplakins are an important component of the humeral autoimmune response in paraneoplastic pemphigus.

MAPPING

By the study of somatic cell hybrids, Arnemann et al. (1991) mapped the DSP gene to chromosome 6pter-p21. Olavesen et al. (1997) reported fine mapping of 39 ESTs on 6p25-p23 that had previously been mapped in radiation hybrids. Most of the ESTs (31 of 39) were positioned in the 6p24-p23 interval; of these, 8 were located within a single PAC clone. DSP was the most telomeric of these 8 loci.

MOLECULAR GENETICS

- Keratosis Palmoplantaris Striata II Armstrong et al. (1999) described the first heterozygous mutation in the DSP gene, in a family with a striate form of hereditary palmoplantar keratoderma, designated type II (PPKS2; 612908). The mutation was a C-to-T transition in exon 4, predicted to result in a premature termination codon in the N-terminal region of the peptide (125647.0001). Not only was this the first reported mutation of desmoplakin, but it was also said to be the first inherited skin disease in which haploinsufficiency of the structural element was implicated. Armstrong et al. (1999) concluded that dosage of desmoplakin is critical to the maintenance of epidermal integrity. - Dilated Cardiomyopathy with Woolly Hair and Keratoderma Norgett et al. (2000) described the first recessive human mutation in the DSP g ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 125647 was added.