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FLASH GENE
Symbol SPPL2A contributors: npt/mct - updated : 17-09-2014
HGNC name signal peptide peptidase like 2A
HGNC id 30227
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
Homologene
FAMILY
  • presenilin-like protein 2 family (I-Clip family)
  • peptidase A22B family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    basic FUNCTION
  • may be involved in proteolysis and peptidolysis
  • with SPPL2B mediate the intramembrane cleavage, whereas neither SPP nor SPPL3 is capable of processing the ITM2B N-terminal fragment
  • important role for the final step in the CD74-MHC II pathway and a new target for protease inhibitor treatment of B cell diseases
  • enzyme controlling turnover and functions of the invariant chain (CD74) of the MHCII complex, with critical importance of this process for B cell development
  • presenilin-homologue residing in lysosomes/late endosomes, cleaving type II-oriented transmembrane proteins
  • is critical for formation of dental enamel, and intramembrane proteolysis by SPPL2A is essential for maintaining cellular homeostasis of ameloblasts
  • distinct functions of SPPL2A and SPPL2B and, high abundance of SPPL2B in brain suggests a physiological role of this protease in the central nervous system
  • SPPL2A and SPPL2B have been implicated in regulated intramembrane proteolysis (RIP) of type II transmembrane proteins
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with ADAM10
  • SPPL2A and SPPL2B mediate the intramembrane cleavage, whereas neither SPP nor SPPL3 is capable of processing the ITM2B N-terminal fragment (pMID: 17965014)
  • aspartyl intramembrane protease, implicated in the proteolysis of TNF, FASLG and ITM2B
  • regulation of CD74-NTF levels by SPPL2A is indispensable for B cell development and function by maintaining trafficking and integrity of MHCII-containing endosomes, highlighting SPPL2a as a promising pharmacological target for depleting and/or modulating B cells
  • SPPL2A, and mainly SPPL2B are responsible for the intramembrane proteolysis of TFRC-N-terminal fragment
  • TMEM106B undergoes regulated intramembrane proteolysis through SPPL2A
  • SPPL2A-mediated processing of CD74 N-terminal fragment (NTF) is indispensable to maintain appropriate levels of tonic BCR signaling to promote B cell maturation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS