Q9JJF9 · SPP2A_MOUSE

  • Protein
    Signal peptide peptidase-like 2A
  • Gene
    Sppl2a
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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. 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. Also responsible for the intramembrane cleavage of Fas antigen ligand FASLG, which promotes the release of the intracellular FasL domain (FasL ICD). Essential for degradation of the invariant chain CD74 that plays a central role in the function of antigen-presenting cells in the immune system. Plays a role in the regulation of innate and adaptive immunity.

Features

Showing features for active site.

152350100150200250300350400450500
TypeIDPosition(s)Description
Active site355
Active site416

GO annotations

AspectTerm
Cellular Componentcytoplasmic side of endoplasmic reticulum membrane
Cellular ComponentGolgi-associated vesicle membrane
Cellular Componentlate endosome membrane
Cellular Componentlumenal side of endoplasmic reticulum membrane
Cellular Componentlysosomal membrane
Cellular Componentplasma membrane
Molecular Functionaspartic endopeptidase activity, intramembrane cleaving
Molecular Functionprotein homodimerization activity
Biological Processmembrane protein ectodomain proteolysis
Biological Processmembrane protein intracellular domain proteolysis
Biological Processmembrane protein proteolysis
Biological Processregulation of immune response

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Signal peptide peptidase-like 2A
  • EC number
  • Short names
    SPP-like 2A
    ; SPPL2a
  • Alternative names
    • Intramembrane protease 3
      (IMP-3
      )
    • Presenilin-like protein 2

Gene names

    • Name
      Sppl2a
    • Synonyms
      Imp3
      , Psl2
    • ORF names
      MNCb-3763

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9JJF9
  • Secondary accessions
    • A2AI51
    • Q8R354

Proteomes

Organism-specific databases

Subcellular Location

Late endosome membrane
; Multi-pass membrane protein
Lysosome membrane
; Multi-pass membrane protein
Membrane
; Multi-pass membrane protein
Note: Colocalizes with palmitoylated and myristoylated proteins at the plasma membrane.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain26-175Lumenal
Transmembrane176-196Helical
Topological domain197-224Cytoplasmic
Transmembrane225-245Helical
Topological domain246-247Lumenal
Transmembrane248-268Helical
Topological domain269-288Cytoplasmic
Transmembrane289-309Helical
Topological domain310-315Lumenal
Transmembrane316-336Helical
Topological domain337-344Cytoplasmic
Transmembrane345-365Helical
Topological domain366-403Lumenal
Transmembrane404-424Helical
Topological domain425-440Cytoplasmic
Transmembrane441-461Helical
Topological domain462-463Lumenal
Transmembrane464-484Helical
Topological domain485-523Cytoplasmic

Keywords

Phenotypes & Variants

Disruption phenotype

Knockout mice increase susceptibility to mycobacterial infection after BCG administration compared to wild-type mice. Mutant animals have decreased numbers of DC2 dendritic cells (cDC2), a smaller sized IFNG+ CD4+ and CD8+ T cell fraction, and decreased production of IFNG by splenocytes compared to wild-type animals. They also have profound B cell deficiency due to CD74 NTF accumulation. The protein is required for optimal IFNG production by T cells after mycobacterial infection (PubMed:30127434).
Mutant mice confirm depletion of conventional cDC2 cells in lymphatic tissues of null mice. Detailed studies of bone marrow-derived dendritic cells exposed to mycobacteria show enhanced secretion of Il1b, where production of Il10 and Ifnb1 is reduced. There are also some alterations in stimulation of pattern recognition receptors (PubMed:33239420).

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis498Inhibits lysosomal/late endosomal targeting.
Mutagenesis506Does not inhibit lysosomal/late endosomal targeting.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 18 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for signal, chain, glycosylation.

TypeIDPosition(s)Description
Signal1-25
ChainPRO_000007391126-523Signal peptide peptidase-like 2A
Glycosylation51N-linked (GlcNAc...) asparagine
Glycosylation61N-linked (GlcNAc...) asparagine
Glycosylation69N-linked (GlcNAc...) asparagine
Glycosylation119N-linked (GlcNAc...) asparagine
Glycosylation129N-linked (GlcNAc...) asparagine
Glycosylation135N-linked (GlcNAc...) asparagine

Post-translational modification

Glycosylated.

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

Interacts with ITM2B.

Protein-protein interaction databases

Chemistry

Miscellaneous

Structure

Family & Domains

Features

Showing features for domain, motif.

TypeIDPosition(s)Description
Domain70-155PA
Motif466-468PAL
Motif498-501YXXo lysosomal targeting motif

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 (By similarity).
The C-terminal tail is necessary for lysosomal transport (PubMed:21896273).

Sequence similarities

Belongs to the peptidase A22B family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    523
  • Mass (Da)
    58,129
  • Last updated
    2011-07-27 v2
  • Checksum
    A15109A71FCF25C4
MGLLHSLHAPAAALLWSCLLGLAAAQEAILHASTNGVSSLSKDYCMYYNNNWTRLPSSLENATSLSLMNLTGTALCHLSDIPPDGIRNKAVVVHWGPCHFLEKARIAQEGGAAALLIANNSVLIPSSRNKSTFQNVTVLIAVITQKDFKDMKETLGDDITVKMYSPSWPNFDYTLVVIFVIAVFTVALGGYWSGLIELENMKSVEDAEDRETRKKKDDYLTFSPLTVVVFVVICCIMIVLLYFFYRWLVYVMIAIFCIASSMSLYNCLSALIHRMPCGQCTILCCGKNIKVSLIFLSGLCISVAVVWAVFRNEDRWAWILQDILGIAFCLNLIKTMKLPNFMSCVILLGLLLIYDVFFVFITPFITKNGESIMVELAAGPFENAEKLPVVIRVPKLMGYSVMSVCSVPVSVLGFGDIIVPGLLIAYCRRFDVQTGSSIYYISSTIAYAVGMIITFVVLMVMKTGQPALLYLVPCTLITVSVVAWSRKEMKKFWKGSSYQVMDHLDYSTNEENPVTTDEQIVQQ

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
F6RJQ8F6RJQ8_MOUSESppl2a253

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict74in Ref. 2; AAH26578
Sequence conflict331-333in Ref. 2; AAH26578
Sequence conflict502in Ref. 1; BAA95032

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AB041547
EMBL· GenBank· DDBJ
BAA95032.1
EMBL· GenBank· DDBJ
mRNA
AL732330
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AL928836
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH466519
EMBL· GenBank· DDBJ
EDL28169.1
EMBL· GenBank· DDBJ
Genomic DNA
BC026578
EMBL· GenBank· DDBJ
AAH26578.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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