| IED ID | IndEnz0002001862 |
| Enzyme Type ID | protease001862 |
| Protein Name |
Presenilin-2 PS-2 EC 3.4.23.- AD3LP AD5 E5-1 STM-2 Cleaved into: Presenilin-2 NTF subunit; Presenilin-2 CTF subunit |
| Gene Name | PSEN2 AD4 PS2 PSNL2 STM2 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MLTFMASDSEEEVCDERTSLMSAESPTPRSCQEGRQGPEDGENTAQWRSQENEEDGEEDPDRYVCSGVPGRPPGLEEELTLKYGAKHVIMLFVPVTLCMIVVVATIKSVRFYTEKNGQLIYTPFTEDTPSVGQRLLNSVLNTLIMISVIVVMTIFLVVLYKYRCYKFIHGWLIMSSLMLLFLFTYIYLGEVLKTYNVAMDYPTLLLTVWNFGAVGMVCIHWKGPLVLQQAYLIMISALMALVFIKYLPEWSAWVILGAISVYDLVAVLCPKGPLRMLVETAQERNEPIFPALIYSSAMVWTVGMAKLDPSSQGALQLPYDPEMEEDSYDSFGEPSYPEVFEPPLTGYPGEELEEEEERGVKLGLGDFIFYSVLVGKAAATGSGDWNTTLACFVAILIGLCLTLLLLAVFKKALPALPISITFGLIFYFSTDNLVRPFMDTLASHQLYI |
| Enzyme Length | 448 |
| Uniprot Accession Number | P49810 |
| Absorption | |
| Active Site | ACT_SITE 263; /evidence="ECO:0000305|PubMed:10652302"; ACT_SITE 366; /evidence="ECO:0000305|PubMed:10497236, ECO:0000305|PubMed:10652302" |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.23.- |
| Enzyme Function | 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 (amyloid-beta 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. May function in the cytoplasmic partitioning of proteins. The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is involved in calcium homeostasis (PubMed:16959576). Is a regulator of mitochondrion-endoplasmic reticulum membrane tethering and modulates calcium ions shuttling between ER and mitochondria (PubMed:21285369). {ECO:0000269|PubMed:10497236, ECO:0000269|PubMed:10652302, ECO:0000269|PubMed:16959576, ECO:0000269|PubMed:21285369}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (2); Chain (2); Compositional bias (1); Intramembrane (1); Modified residue (3); Motif (1); Mutagenesis (2); Natural variant (11); Region (1); Sequence conflict (6); Topological domain (10); Transmembrane (8) |
| Keywords | Alternative splicing;Alzheimer disease;Amyloidosis;Cardiomyopathy;Disease variant;Endoplasmic reticulum;Golgi apparatus;Hydrolase;Membrane;Neurodegeneration;Notch signaling pathway;Phosphoprotein;Protease;Reference proteome;Transmembrane;Transmembrane helix |
| Interact With | P54819; P05067; Q0P5N6; Q16611; P29466-3; Q86WV2; Q14204; Q9BQ95; O00472; Q3SYB3; P02792; P68431; Q8WVV9-3; Q8TDB4; O94851; A4FUJ8; P41218; Q96HT8; O76041; Q53EL6; Q13113; P27986-2; Q99496; Q8N488; Q2NKQ1-4; Q9NSD5-3; O95416; Q3SY56; Q9BSL1; Q9GZS3; Q96NC0; Q8N895; Q8NBB4-2; Q2QGD7 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:8574969}; Multi-pass membrane protein {ECO:0000269|PubMed:8574969}. Golgi apparatus membrane {ECO:0000269|PubMed:8574969}; Multi-pass membrane protein {ECO:0000269|PubMed:8574969}. |
| Modified Residue | MOD_RES 22; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 25; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 30; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q61144" |
| Post Translational Modification | PTM: Heterogeneous proteolytic processing generates N-terminal and C-terminal fragments.; PTM: Phosphorylated on serine residues. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10206645; 10366599; 10369872; 10393846; 10446169; 10748169; 10822446; 10879540; 11001931; 11076969; 11436125; 11518718; 11568920; 11679632; 11723295; 11803125; 11847232; 11876645; 11891288; 11904448; 11987239; 12048259; 12058025; 12173418; 12198112; 12209127; 12210343; 12232783; 12403846; 12471034; 12556443; 12605888; 12770698; 12817569; 12843241; 12846562; 12885769; 12925374; 14567914; 14577603; 14623725; 14741365; 14769392; 15004330; 15123653; 15130954; 15258222; 15537629; 15591316; 15629423; 15663477; 15755689; 15776278; 15951428; 15965470; 15975068; 16014629; 16135086; 16233903; 16258850; 16331303; 16375654; 16423463; 16474849; 16511561; 16620965; 16630834; 17268504; 17268505; 17345043; 17401156; 17401676; 17412506; 17428795; 17560791; 17614368; 17727891; 17903177; 17914065; 18087668; 18283638; 18293935; 18350357; 18427071; 18591429; 18608129; 18667258; 18713744; 18727676; 18842294; 18846634; 19036728; 19073399; 19151708; 19276543; 19376115; 19382908; 19560505; 19573580; 19632874; 19640841; 19768372; 19834068; 19889971; 19913121; 20008660; 20009122; 20164579; 20333730; 20375137; 20457965; 20594621; 20628086; 20677014; 20701429; 20850903; 21163940; 21234330; 21409510; 21545304; 21914807; 21959359; 22027014; 22045484; 22074918; 22221884; 22249458; 22302987; 22312439; 22410445; 22475797; 22580083; 22753229; 22755192; 22872014; 23546527; 23589300; 23990795; 24145027; 24594196; 24650794; 24704512; 24842903; 24858037; 24885952; 24927704; 25104557; 25323700; 25333068; 25429133; 25614624; 25814654; 25937274; 25998117; 26159191; 26166204; 26203236; 26312828; 26337232; 26422362; 26496610; 26522186; 27059953; 27128372; 27135718; 27293189; 27608597; 27799753; 28106563; 28502043; 28527213; 28987665; 28994238; 29078389; 29109765; 30104866; 30119059; 30560948; 30822634; 30892128; 31020001; 31167792; 31914229; 31991578; 32087291; 32420742; 32556937; 32917274; 32957903; 32992716; 33413468; 33720885; 33769986; 33973882; 34002480; 34067945; 34102969; 8972483; 9196071; 9223340; 9558331; 9620803; 9813158; |
| Motif | MOTIF 414..416; /note=PAL |
| Gene Encoded By | |
| Mass | 50,140 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |