Protein: Signal peptide peptidase-like 2A (SPP-like 2A) (SPPL2a) (EC 3.4.23.-) (Intramembrane protease 3) (IMP-3) (Presenilin-like protein 2) (Q8TCT8)
Organism: Homo sapiens (Human)
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. 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. Also responsible for the intramembrane cleavage of Fas antigen ligand FASLG, which promotes the release of the intracellular FasL domain (FasL ICD). Essential for degradation of the invariant chain CD74 that plays a central role in the function of antigen-presenting cells in the immune system (By similarity). Plays a role in the regulation of innate and adaptive immunity. 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.
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.
Sequence: MGPQRRLSPAGAALLWGFLLQLTAAQEAILHASGNGTTKDYCMLYNPYWTALPSTLENATSISLMNLTSTPLCNLSDIPPVGIKSKAVVVPWGSCHFLEKARIAQKGGAEAMLVVNNSVLFPPSGNRSEFPDVKILIAFISYKDFRDMNQTLGDNITVKMYSPSWPNFDYTMVVIFVIAVFTVALGGYWSGLVELENLKAVTTEDREMRKKKEEYLTFSPLTVVIFVVICCVMMVLLYFFYKWLVYVMIAIFCIASAMSLYNCLAALIHKIPYGQCTIACRGKNMEVRLIFLSGLCIAVAVVWAVFRNEDRWAWILQDILGIAFCLNLIKTLKLPNFKSCVILLGLLLLYDVFFVFITPFITKNGESIMVELAAGPFGNNEKLPVVIRVPKLIYFSVMSVCLMPVSILGFGDIIVPGLLIAYCRRFDVQTGSSYIYYVSSTVAYAIGMILTFVVLVLMKKGQPALLYLVPCTLITASVVAWRRKEMKKFWKGNSYQMMDHLDCATNEENPVISGEQIVQQ
InterPro domains: - IPR006639: Presenilin/signal peptide peptidase (family) [214-483]
- IPR003137: PA domain (domain) [70-145]
- IPR007369: Peptidase A22B, signal peptide peptidase (family) [51-503]
- IPR046450: PA domain superfamily (homologous_superfamily) [77-157]
Interaction partners: - Tumor necrosis factor
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0140096 (catalytic activity, acting on a protein), GO:0016787 (hydrolase activity), GO:0005515 (protein binding), GO:0042802 (identical protein binding), GO:0008233 (peptidase activity), GO:0046983 (protein dimerization activity), GO:0042803 (protein homodimerization activity), GO:0004175 (endopeptidase activity), GO:0070001 (aspartic-type peptidase activity), GO:0004190 (aspartic-type endopeptidase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0048583 (regulation of response to stimulus), GO:0002682 (regulation of immune system process), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0050776 (regulation of immune response), GO:1901564 (organonitrogen compound metabolic process), GO:0019538 (protein metabolic process), GO:0043170 (macromolecule metabolic process), GO:0006508 (proteolysis), GO:0033619 (membrane protein proteolysis)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0031974 (membrane-enclosed lumen), GO:0071944 (cell periphery), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005654 (nucleoplasm), GO:0031090 (organelle membrane), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0005773 (vacuole), GO:0043233 (organelle lumen), GO:0005783 (endoplasmic reticulum), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0000323 (lytic vacuole), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0012506 (vesicle membrane), GO:0005770 (late endosome), GO:0005774 (vacuolar membrane), GO:0010008 (endosome membrane), GO:0031982 (vesicle), GO:0070013 (intracellular organelle lumen), GO:0030659 (cytoplasmic vesicle membrane), GO:0005764 (lysosome), GO:0097708 (intracellular vesicle), GO:0005634 (nucleus), GO:0031981 (nuclear lumen), GO:0031902 (late endosome membrane), GO:0098852 (lytic vacuole membrane), GO:0005765 (lysosomal membrane)