| IED ID | IndEnz0002008477 |
| Enzyme Type ID | protease008477 |
| Protein Name |
Signal peptide peptidase-like 3 SPP-like 3 EC 3.4.23.- Intramembrane protease 2 IMP-2 Presenilin homologous protein 1 PSH1 Presenilin-like protein 4 |
| Gene Name | SPPL3 IMP2 PSL4 |
| 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 | MAEQTYSWAYSLVDSSQVSTFLISILLIVYGSFRSLNMDFENQDKEKDSNSSSGSFNGNSTNNSIQTIDSTQALFLPIGASVSLLVMFFFFDSVQVVFTICTAVLATIAFAFLLLPMCQYLTRPCSPQNKISFGCCGRFTAAELLSFSLSVMLVLIWVLTGHWLLMDALAMGLCVAMIAFVRLPSLKVSCLLLSGLLIYDVFWVFFSAYIFNSNVMVKVATQPADNPLDVLSRKLHLGPNVGRDVPRLSLPGKLVFPSSTGSHFSMLGIGDIVMPGLLLCFVLRYDNYKKQASGDSCGAPGPANISGRMQKVSYFHCTLIGYFVGLLTATVASRIHRAAQPALLYLVPFTLLPLLTMAYLKGDLRRMWSEPFHSKSSSSRFLEV |
| Enzyme Length | 384 |
| Uniprot Accession Number | Q8TCT6 |
| Absorption | |
| Active Site | ACT_SITE 200; /evidence=ECO:0000250|UniProtKB:P49810; ACT_SITE 271; /evidence=ECO:0000250|UniProtKB:P49810 |
| Activity Regulation | ACTIVITY REGULATION: Its proteolytic activity is blocked by a signal peptide peptidase (SPP) inhibitor, (ZLL)2-ketone (ZLL) or a gamma-secretase inhibitor, LY411,575 (PubMed:16873890). However, is not inhibited by ZLL and LY411,575 for activity on simian foamy virus envelope glycoprotein gp130 (PubMed:23132852). {ECO:0000269|PubMed:16873890, ECO:0000269|PubMed:23132852}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.23.- |
| Enzyme Function | FUNCTION: Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane protein substrates in or close to their luminal transmembrane domain boundaries (PubMed:16873890, PubMed:25354954, PubMed:25827571). Acts like a sheddase by mediating the proteolytic release and secretion of active site-containing ectodomains of glycan-modifiying glycosidase and glycosyltransferase enzymes such as MGAT5, B4GAT1 and B4GALT1 (PubMed:25354954, PubMed:25827571). Catalyzes the intramembrane cleavage of the envelope glycoprotein gp130 and/or the leader peptide gp18LP of the simian foamy virus independent of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis (PubMed:23132852). May also have the ability to serve as a shedding protease for subsequent intramembrane proteolysis by SPPL2A and SPPL2B of the envelope glycoprotein gp130 (PubMed:23132852). Plays a role in the regulation of cellular glycosylation processes (PubMed:25354954). Required to link T-cell antigen receptor (TCR) and calcineurin-NFAT signaling cascades in lymphocytes by promoting the association of STIM1 and ORAI1 during store-operated calcium entry (SOCE) in a protease-independent manner (PubMed:25384971). {ECO:0000269|PubMed:16873890, ECO:0000269|PubMed:23132852, ECO:0000269|PubMed:25354954, ECO:0000269|PubMed:25384971, ECO:0000269|PubMed:25827571}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (1); Chain (1); Erroneous initiation (1); Motif (1); Mutagenesis (2); Sequence conflict (2); Topological domain (10); Transmembrane (9) |
| Keywords | Alternative splicing;Endoplasmic reticulum;Golgi apparatus;Hydrolase;Membrane;Protease;Reference proteome;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:15998642}; Multi-pass membrane protein {ECO:0000305}. Golgi apparatus {ECO:0000269|PubMed:16829952}. Membrane {ECO:0000269|PubMed:15385547}; Multi-pass membrane protein {ECO:0000305}; Lumenal side {ECO:0000269|PubMed:15385547}. |
| Modified Residue | |
| Post Translational Modification | PTM: Not glycosylated (PubMed:15385547, PubMed:15998642). {ECO:0000269|PubMed:15385547, ECO:0000269|PubMed:15998642}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 28292959; 33271119; 34303967; |
| Motif | MOTIF 341..343; /note=PAL |
| Gene Encoded By | |
| Mass | 42,261 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |