SPPL2A

This gene is a member of the signal peptide peptidase-like protease (SPPL) family and encodes an endosomal membrane protein with a protease associated (PA) domain. This protein plays a role in innate and adaptive immunity. A pseudogene of this gene also lies on chromosome 15. [provided by RefSeq]

Full Name

signal peptide peptidase-like 2A

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).
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).

Biological Process

Biological Process membrane protein ectodomain proteolysisManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process membrane protein intracellular domain proteolysisManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process membrane protein proteolysisManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of immune responseManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of tumor necrosis factor-mediated signaling pathwayTAS:Reactome

Cellular Location

Late endosome membrane
Lysosome membrane
Membrane
Colocalizes with palmitoylated and myristoylated proteins at the plasma membrane.

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.

Topology

Lumenal: 26-172
Helical: 173-193
Cytoplasmic: 194-220
Helical: 221-241
Lumenal: 242-247
Helical: 248-268
Cytoplasmic: 269-285
Helical: 286-306
Lumenal: 307-311
Helical: 312-332
Cytoplasmic: 333-340
Helical: 341-361
Lumenal: 362-399
Helical: 400-420
Cytoplasmic: 421-437
Helical: 438-458
Lumenal: 459-460
Helical: 461-481
Cytoplasmic: 482-520

PTM

Glycosylated.