Function |
Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Stimulates cell-cell adhesion though its association with the E-cadherin/catenin complex. Under conditions of apoptosis or calcium influx, cleaves E-cadherin promoting the disassembly of the E-cadherin/catenin complex and increasing the pool of cytoplasmic beta-catenin, thus negatively regulating Wnt signaling. May also play a role in hematopoiesis. {ECO:0000269PubMed:10206644, ECO:0000269PubMed:10545183, ECO:0000269PubMed:10593990, ECO:0000269PubMed:10811883, ECO:0000269PubMed:10899933, ECO:0000269PubMed:11226248, ECO:0000269PubMed:15341515, ECO:0000269PubMed:16305624}.
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Disease Associations |
Alzheimer disease 3 (AD3) [MIM:607822]: A familial early- onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death. {ECO:0000269PubMed:10025789, ECO:0000269PubMed:10090481, ECO:0000269PubMed:10200054, ECO:0000269PubMed:10208579, ECO:0000269PubMed:10439444, ECO:0000269PubMed:10441572, ECO:0000269PubMed:10447269, ECO:0000269PubMed:10533070, ECO:0000269PubMed:10631141, ECO:0000269PubMed:10644793, ECO:0000269PubMed:11027672, ECO:0000269PubMed:11710891, ECO:0000269PubMed:11920851, ECO:0000269PubMed:12048239, ECO:0000269PubMed:12484344, ECO:0000269PubMed:12493737, ECO:0000269PubMed:22503161, ECO:0000269PubMed:7550356, ECO:0000269PubMed:7596406, ECO:0000269PubMed:7651536, ECO:0000269PubMed:8634711, ECO:0000269PubMed:8634712, ECO:0000269PubMed:8733303, ECO:0000269PubMed:9172170, ECO:0000269PubMed:9225696, ECO:0000269PubMed:9298817, ECO:0000269PubMed:9384602, ECO:0000269PubMed:9507958, ECO:0000269PubMed:9521423, ECO:0000269PubMed:9719376, ECO:0000269PubMed:9831473, ECO:0000269PubMed:9833068, ECO:0000269Ref.77}. Note=The disease is caused by mutations affecting the gene represented in this entry.Frontotemporal dementia (FTD) [MIM:600274]: A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons. {ECO:0000269PubMed:11094121}. Note=The disease is caused by mutations affecting the gene represented in this entry.Cardiomyopathy, dilated 1U (CMD1U) [MIM:613694]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269PubMed:17186461}. Note=The disease is caused by mutations affecting the gene represented in this entry.Acne inversa, familial, 3 (ACNINV3) [MIM:613737]: A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. {ECO:0000269PubMed:20929727}. Note=The disease is caused by mutations affecting the gene represented in this entry.
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