MBTPS2

This gene encodes a intramembrane zinc metalloprotease, which is essential in development. This protease functions in the signal protein activation involved in sterol control of transcription and the ER stress response. Mutations in this gene have been associated with ichthyosis follicularis with atrichia and photophobia (IFAP syndrome); IFAP syndrome has been quantitatively linked to a reduction in cholesterol homeostasis and ER stress response

membrane-bound transcription factor peptidase, site 2

Zinc metalloprotease that mediates intramembrane proteolysis of proteins such as ATF6, ATF6B, SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:11163209, PubMed:10805775).

Catalyzes the second step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2: cleaves SREBPs within the first transmembrane segment, thereby releasing the N-terminal segment with a portion of the transmembrane segment attached (PubMed:10805775, PubMed:27380894, PubMed:9659902).

Mature N-terminal SREBP fragments shuttle to the nucleus and activate gene transcription (PubMed:10805775, PubMed:27380894, PubMed:9659902).

Also mediates the second step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B) (PubMed:11163209).

Involved in intramembrane proteolysis during bone formation (PubMed:27380894).

ATF6-mediated unfolded protein response Source: ParkinsonsUK-UCL
Bone maturation Source: UniProtKB
Cholesterol metabolic process Source: ProtInc
Endoplasmic reticulum unfolded protein response Source: Reactome
Membrane protein intracellular domain proteolysis Source: ParkinsonsUK-UCL
Positive regulation of DNA-binding transcription factor activity Source: ParkinsonsUK-UCL
Positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
Regulation of cholesterol biosynthetic process Source: Reactome
Regulation of response to endoplasmic reticulum stress Source: GO_Central
Response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL

Cytoplasm
Other locations
Membrane

IFAP syndrome 1, with or without Bresheck syndrome (IFAP1):
An X-linked syndrome characterized by a peculiar triad of follicular ichthyosis, total or subtotal atrichia, and photophobia of varying degree. Histopathologically, the epidermal granular layer is generally well-preserved or thickened at the infundibulum. Hair follicles are poorly developed and tend to be surrounded by an inflammatory infiltrate. A subgroup of patients is described with lamellar rather than follicular ichthyosis. Non-consistent features may include growth and psychomotor retardation, aganglionic megacolon, seizures and nail dystrophy.
Olmsted syndrome, X-linked (OLMSX):
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.
Keratosis follicularis spinulosa decalvans X-linked (KFSDX):
A rare disorder affecting the skin and the eye. Affected men show thickening of the skin of the neck, ears, and extremities, especially the palms and soles, loss of eyebrows, eyelashes and beard, thickening of the eyelids with blepharitis and ectropion, and corneal degeneration.
Osteogenesis imperfecta 19 (OI19):
An X-linked form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI19 is characterized by prenatal fractures, short stature, white sclerae, variable scoliosis and pectal deformity, striking tibial anterior angulation and generalized osteopenia.