SPPL2A is a lysosomal/late endosomal membrane protein which is a member of the signal peptide peptidase-like protease (SPPL) family. Within this family, SPPL2A is unique with its localization in lysosomes/late endosomes. Additional substrates of SPPL2A include TNF-α, Fas ligand, Bri2, and TMEM106B. In mRNA analyses, SPPL2A was found to be expressed in all major human adult tissues, whereas SPPL2B transcripts were primarily detected in the adrenal cortex and the mammary gland. Overexpressed SPPL2A was observed in late endosomal compartments colocalizing with Rab-7.
|Basic Information of SPPL2A|
|Protein Name||Signal peptide peptidase-like 2A|
|Aliases||SPP-like 2A, SPPL2a, Intramembrane protease 3, IMP-3, Presenilin-like protein 2, IMP3, PSL2, PSEC0147|
|Organism||Homo sapiens (Human)|
SPPL2A is a lysosomal/late endosomal membrane protein and is mainly located in membranes of lysosomes and late endosomes. It functions as a protease which cleaves type II transmembrane proteins. CD74, the invariant chain of the MHCII complex, is the substrate of SPPL2A and the intramembrane cleavage of CD74 by SPPL2A is an essential process for development and functionality of B lymphocytes and dendritic cells. In other words, SPPL2A is a regulator for B cell and DC development and survival. Moreover, SPPL2A has been revealed to be involved in the regulation of innate and adaptive immunity by cleaving TNFα in activated dendritic cells. Hence, SPPL2A may represent a useful therapeutic target for autoimmune disorders, especially for B cell dependent.
Fig.1 Proteolysis-dependent post-translational modifications in control of the death factor CD95L. (Lang, 2013)
This research indicates that the elements within the transmembrane segment and the luminal juxtamembrane domain may participate in the regulation of intramembrane proteolysis of CD74 by SPPL2a.
Authors in this research report that CD74 processing mediated by SPPL2a is essential to maintain appropriate levels of tonic BCR signaling to promote B cell maturation.
This investigation shows that the GxGD aspartyl proteases SPPL2a and, to a lesser extent, SPPL2b are responsible for this intramembrane cleavage event.
This article concludes that intramembrane proteolysis by SPPL2A is critical for maintaining cellular homeostasis of ameloblasts.
This study suggests that Sppl2a involves the B cell and DC development and survival, indicating Sppl2a may be a promising target for the treatment of B cell dependent autoimmune disorders.
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