UniProt ID: F8W381 |
FUNCTION: Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors. {ECO:0000256|RuleBase:RU361148}. SUBUNIT: Homodimer. {ECO:0000256|RuleBase:RU361148}. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000256|RuleBase:RU361148}; Multi-pass membrane protein {ECO:0000256|RuleBase:RU361148}. Golgi apparatus membrane {ECO:0000256|RuleBase:RU361148}; Multi-pass membrane protein {ECO:0000256|RuleBase:RU361148}. Membrane {ECO:0000256|ARBA:ARBA00004141}; Multi-pass membrane protein {ECO:0000256|ARBA:ARBA00004141}. DOMAIN: The PAL motif is required for normal active site conformation. {ECO:0000256|RuleBase:RU361148}. SIMILARITY: Belongs to the peptidase A22A family. {ECO:0000256|ARBA:ARBA00008604, ECO:0000256|RuleBase:RU361148}. |
UniProt ID: Q9W6T7 |
FUNCTION: 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 (amyloid- beta precursor protein) (PubMed:10521267). Requires the presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins (By similarity). {ECO:0000250|UniProtKB:P49768, ECO:0000269|PubMed:10521267}. SUBUNIT: Homodimer. The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity. {ECO:0000250|UniProtKB:P49768}. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P49768}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P49768}. Golgi apparatus membrane {ECO:0000250|UniProtKB:P49768}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P49768}. Cytoplasmic granule {ECO:0000250|UniProtKB:P49768}. Cell membrane {ECO:0000250|UniProtKB:P49768}. Cell projection, axon {ECO:0000250|UniProtKB:Q4JIM4}. Synapse {ECO:0000250|UniProtKB:Q4JIM4}. Cell projection, neuron projection {ECO:0000250|UniProtKB:P49768}. DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. Ubiquitously expressed during embryogenesis. DOMAIN: The PAL motif is required for normal active site conformation. {ECO:0000250|UniProtKB:P49768}. DOMAIN: Substrates, such as NOTCH1 and APP peptides, are bound between PSEN1 transmembrane domains and via the first lumenal loop and the cytoplasmic loop between the sixth and seventh transmembrane domains. Substrate binding causes a conformation change and formation of an intermolecular antiparallel beta-sheet between PSEN1 and its substrates. {ECO:0000250|UniProtKB:P49768}. PTM: Cleaved, probably through autocleavage. {ECO:0000269|PubMed:10521267}. PTM: Heterogeneous proteolytic processing generates N-terminal (NTF) and C-terminal (CTF) fragments of approximately 35 and 20 kDa, respectively. During apoptosis, the C-terminal fragment (CTF) is further cleaved by a caspase. {ECO:0000250|UniProtKB:P49768}. SIMILARITY: Belongs to the peptidase A22A family. {ECO:0000305}. SEQUENCE CAUTION: Sequence=AAH54639.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; |
UniProt ID: F1Q8Y6 |
FUNCTION: Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors. {ECO:0000256|RuleBase:RU361148}. SUBUNIT: Homodimer. {ECO:0000256|RuleBase:RU361148}. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000256|RuleBase:RU361148}; Multi-pass membrane protein {ECO:0000256|RuleBase:RU361148}. Golgi apparatus membrane {ECO:0000256|RuleBase:RU361148}; Multi-pass membrane protein {ECO:0000256|RuleBase:RU361148}. Membrane {ECO:0000256|ARBA:ARBA00004141}; Multi-pass membrane protein {ECO:0000256|ARBA:ARBA00004141}. DOMAIN: The PAL motif is required for normal active site conformation. {ECO:0000256|RuleBase:RU361148}. SIMILARITY: Belongs to the peptidase A22A family. {ECO:0000256|ARBA:ARBA00008604, ECO:0000256|RuleBase:RU361148}. |
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