SPPL2A
Domain
The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family; therefore, it is predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP. The C-terminal tail is necessary for lysosomal transport.
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:16829951, PubMed:16829952, 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). 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 (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).
Involvement in disease
Immunodeficiency 86
IMD86
An autosomal recessive disorder characterized by susceptibility to mycobacterial disease after exposure to BCG vaccine. Affected individuals usually develop localized mycobacterial lymphadenopathy.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Glycosylated.
Sequence Similarities
Belongs to the peptidase A22B family.
Tissue Specificity
Ubiquitous.
Cellular localization
- Late endosome membrane
- Multi-pass membrane protein
- Lysosome membrane
- Multi-pass membrane protein
- Membrane
- Multi-pass membrane protein
- Lumenal side
- Colocalizes with palmitoylated and myristoylated proteins at the plasma membrane.
Alternative names
IMP3, PSL2, PSEC0147, SPPL2A, Signal peptide peptidase-like 2A, SPP-like 2A, SPPL2a, Intramembrane protease 3, Presenilin-like protein 2, IMP-3