| IED ID | IndEnz0002001532 |
| Enzyme Type ID | protease001532 |
| Protein Name |
Signal peptide peptidase-like 2A SPP-like 2A SPPL2a EC 3.4.23.- Intramembrane protease 3 IMP-3 Presenilin-like protein 2 |
| Gene Name | SPPL2A IMP3 PSL2 PSEC0147 |
| 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 | MGPQRRLSPAGAALLWGFLLQLTAAQEAILHASGNGTTKDYCMLYNPYWTALPSTLENATSISLMNLTSTPLCNLSDIPPVGIKSKAVVVPWGSCHFLEKARIAQKGGAEAMLVVNNSVLFPPSGNRSEFPDVKILIAFISYKDFRDMNQTLGDNITVKMYSPSWPNFDYTMVVIFVIAVFTVALGGYWSGLVELENLKAVTTEDREMRKKKEEYLTFSPLTVVIFVVICCVMMVLLYFFYKWLVYVMIAIFCIASAMSLYNCLAALIHKIPYGQCTIACRGKNMEVRLIFLSGLCIAVAVVWAVFRNEDRWAWILQDILGIAFCLNLIKTLKLPNFKSCVILLGLLLLYDVFFVFITPFITKNGESIMVELAAGPFGNNEKLPVVIRVPKLIYFSVMSVCLMPVSILGFGDIIVPGLLIAYCRRFDVQTGSSYIYYVSSTVAYAIGMILTFVVLVLMKKGQPALLYLVPCTLITASVVAWRRKEMKKFWKGNSYQMMDHLDCATNEENPVISGEQIVQQ |
| Enzyme Length | 520 |
| Uniprot Accession Number | Q8TCT8 |
| Absorption | |
| Active Site | ACT_SITE 351; /evidence=ECO:0000250|UniProtKB:P49810; ACT_SITE 412; /evidence=ECO:0000250|UniProtKB:P49810 |
| Activity Regulation | |
| 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 signal peptides in the hydrophobic plane of the membrane. Functions in FASLG, ITM2B and TNF processing (PubMed:16829952, PubMed:16829951, PubMed:17557115, PubMed:17965014). Catalyzes the intramembrane cleavage of the anchored fragment of shed TNF-alpha (TNF), which promotes the release of the intracellular domain (ICD) for signaling to the nucleus (PubMed:16829952). Also responsible for the intramembrane cleavage of Fas antigen ligand FASLG, which promotes the release of the intracellular FasL domain (FasL ICD) (PubMed:17557115). May play a role in the regulation of innate and adaptive immunity (PubMed:16829952). Catalyzes the intramembrane cleavage of the simian foamy virus envelope glycoprotein gp130 independently of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis (PubMed:23132852). {ECO:0000269|PubMed:16829951, ECO:0000269|PubMed:16829952, ECO:0000269|PubMed:17557115, ECO:0000269|PubMed:17965014, ECO:0000269|PubMed:23132852}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Chain (1); Domain (1); Erroneous initiation (2); Glycosylation (7); Motif (2); Mutagenesis (1); Natural variant (1); Sequence conflict (5); Signal peptide (1); Topological domain (10); Transmembrane (9) |
| Keywords | Endosome;Glycoprotein;Hydrolase;Lysosome;Membrane;Protease;Reference proteome;Signal;Transmembrane;Transmembrane helix |
| Interact With | O43765; O76024 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Late endosome membrane {ECO:0000269|PubMed:16829952}; Multi-pass membrane protein {ECO:0000305}. Lysosome membrane {ECO:0000250|UniProtKB:Q9JJF9}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9JJF9}. Membrane {ECO:0000269|PubMed:15385547}; Multi-pass membrane protein {ECO:0000305}; Lumenal side {ECO:0000269|PubMed:15385547}. Note=Colocalizes with palmitoylated and myristoylated proteins at the plasma membrane. |
| Modified Residue | |
| Post Translational Modification | PTM: Glycosylated. {ECO:0000269|PubMed:15385547, ECO:0000269|PubMed:19139490}. |
| Signal Peptide | SIGNAL 1..25; /evidence=ECO:0000269|PubMed:15385547 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 16189514; 21656680; 21896273; 21988832; 23384347; 24872421; 25035924; 25416956; 26987812; 30127434; 30819724; |
| Motif | MOTIF 463..465; /note=PAL; MOTIF 495..498; /note=YXXo lysosomal targeting motif |
| Gene Encoded By | |
| Mass | 58,143 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.23.B24; |