PERP
Function
Component of intercellular desmosome junctions (By similarity). Plays a role in stratified epithelial integrity and cell-cell adhesion by promoting desmosome assembly (By similarity). Thereby plays a role in barrier function of the skin against infection (By similarity). Plays a role in mammary epithelial tissue homeostasis and remodeling during and after pregnancy, potentially via its involvement in desmosome cell-cell junctions (By similarity). Required for tooth enamel development via facilitating desmosome-mediated ameloblast adhesion to the stratum intermedium during the transitional stage of amelogenesis (By similarity). May also play a role in downstream transcriptional regulation of other genes involved in amelogenesis such as AMBN, ENAM, MMP20 and KLK4 (By similarity). Plays a role as an effector in the TP53-dependent apoptotic pathway (By similarity). Positively regulates apoptosis in T-helper 17 (Th17) cell populations via caspase-dependent signaling (By similarity). Promotes neutrophil transepithelial migration in response to chemoattractants such as hepoxilin A3 (HXA3), N-Formylmethionyl-leucyl-phenylalanine (fMLP) and CXCL8/IL-8 (PubMed:25486861). Required for neutrophil transepithelial migration in response to S.typhimurium infection (PubMed:25486861). May act as a positive regulator of endothelial cell apoptosis in response to blood flow-derived sheer stress (By similarity).
Involvement in disease
Erythrokeratodermia variabilis et progressiva 7
EKVP7
A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases. EKVP7 is an autosomal recessive form characterized by palmoplantar keratoderma that extends to the dorsal surface of the hands and feet, as well as erythematous annular skin lesions. Pruritus, woolly hair, and dystrophic nails may also be present.
None
The disease is caused by variants affecting the gene represented in this entry.
Olmsted syndrome 2
OLMS2
A form of Olmsted syndrome, a rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma and periorificial keratotic plaques with severe itching at all lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas. The digital constriction may progress to autoamputation of fingers and toes. OLMS2 is an autosomal dominant form with onset in the first months of life or in early childhood.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the TMEM47 family.
Tissue Specificity
Expressed in skin, heart, placental, liver, pancreas, keratinocytes and dermal fibroblasts. May translocate to the intestinal apical epithelial cell surface via sipA and sctB1/sipC-promoted exocytic translocation following infection by S. Typhimurium (PubMed:25486861, PubMed:27078059).
Cellular localization
- Cell junction
- Desmosome
- Cell membrane
- Multi-pass membrane protein
- Cytoplasm
- Associated with desmosomes (By similarity). Colocalizes with KRT14 in the cell membrane (PubMed:31898316). Clusters in a punctate pattern throughout the epithelial cytoplasm, in response to S.typhimurium infection (PubMed:25486861).
Alternative names
KCP1, KRTCAP1, PIGPC1, THW, PERP, p53 apoptosis effector related to PMP-22, Keratinocyte-associated protein 1, P53-induced protein PIGPC1, Transmembrane protein THW, KCP-1