SPPL2A Membrane Protein Introduction

Introduction of SPPL2A

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
Gene Name SPPL2A
Aliases SPP-like 2A, SPPL2a, Intramembrane protease 3, IMP-3, Presenilin-like protein 2, IMP3, PSL2, PSEC0147
Organism Homo sapiens (Human)
UniProt ID Q8TCT8
Transmembrane Times 9
Length (aa) 520

Function of SPPL2A Membrane Protein

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.

SPPL2A Membrane Protein IntroductionFig.1 Proteolysis-dependent post-translational modifications in control of the death factor CD95L. (Lang, 2013)

Application of SPPL2A Membrane Protein in Literature

  1. Hüttl S., et al. Substrate determinants of signal peptide peptidase-like 2a (SPPL2a)-mediated intramembrane proteolysis of the invariant chain CD74. Biochem J. 2016, 473(10): 1405-1422. PubMed ID: 26987812

    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.

  2. Hüttl S., et al. Processing of CD74 by the intramembrane protease SPPL2a is critical for B cell receptor signaling in transitional B cells. J Immunol. 2015, 195(4): 1548-1563. PubMed ID: 26157172

    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.

  3. Brady O.A., et al. Regulated intramembrane proteolysis of the frontotemporal lobar degeneration risk factor, TMEM106B, by signal peptide peptidase-like 2a (SPPL2a). J Biol Chem. 2014, 289(28): 19670-19680. PubMed ID: 24872421

    This investigation shows that the GxGD aspartyl proteases SPPL2a and, to a lesser extent, SPPL2b are responsible for this intramembrane cleavage event.

  4. Bronckers A.L., et al. The intramembrane protease SPPL2A is critical for tooth enamel formation. J Bone Miner Res. 2013, 28(7): 1622-1630. PubMed ID: 23426979

    This article concludes that intramembrane proteolysis by SPPL2A is critical for maintaining cellular homeostasis of ameloblasts.

  5. Beisner D.R., et al. The intramembrane protease Sppl2a is required for B cell and DC development and survival via cleavage of the invariant chain. J Exp Med. 2013, 210(1): 23-30. PubMed ID: 23267013

    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.

SPPL2A Preparation Options

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