Q9JJF9 · SPP2A_MOUSE
- ProteinSignal peptide peptidase-like 2A
- GeneSppl2a
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids523 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 355 | |||||
Sequence: D | ||||||
Active site | 416 | |||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasmic side of endoplasmic reticulum membrane | |
Cellular Component | Golgi-associated vesicle membrane | |
Cellular Component | late endosome membrane | |
Cellular Component | lumenal side of endoplasmic reticulum membrane | |
Cellular Component | lysosomal membrane | |
Cellular Component | plasma membrane | |
Molecular Function | aspartic endopeptidase activity, intramembrane cleaving | |
Molecular Function | protein homodimerization activity | |
Biological Process | membrane protein ectodomain proteolysis | |
Biological Process | membrane protein intracellular domain proteolysis | |
Biological Process | membrane protein proteolysis | |
Biological Process | regulation of immune response |
Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSignal peptide peptidase-like 2A
- EC number
- Short namesSPP-like 2A ; SPPL2a
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9JJF9
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 26-175 | Lumenal | ||||
Sequence: QEAILHASTNGVSSLSKDYCMYYNNNWTRLPSSLENATSLSLMNLTGTALCHLSDIPPDGIRNKAVVVHWGPCHFLEKARIAQEGGAAALLIANNSVLIPSSRNKSTFQNVTVLIAVITQKDFKDMKETLGDDITVKMYSPSWPNFDYTL | ||||||
Transmembrane | 176-196 | Helical | ||||
Sequence: VVIFVIAVFTVALGGYWSGLI | ||||||
Topological domain | 197-224 | Cytoplasmic | ||||
Sequence: ELENMKSVEDAEDRETRKKKDDYLTFSP | ||||||
Transmembrane | 225-245 | Helical | ||||
Sequence: LTVVVFVVICCIMIVLLYFFY | ||||||
Topological domain | 246-247 | Lumenal | ||||
Sequence: RW | ||||||
Transmembrane | 248-268 | Helical | ||||
Sequence: LVYVMIAIFCIASSMSLYNCL | ||||||
Topological domain | 269-288 | Cytoplasmic | ||||
Sequence: SALIHRMPCGQCTILCCGKN | ||||||
Transmembrane | 289-309 | Helical | ||||
Sequence: IKVSLIFLSGLCISVAVVWAV | ||||||
Topological domain | 310-315 | Lumenal | ||||
Sequence: FRNEDR | ||||||
Transmembrane | 316-336 | Helical | ||||
Sequence: WAWILQDILGIAFCLNLIKTM | ||||||
Topological domain | 337-344 | Cytoplasmic | ||||
Sequence: KLPNFMSC | ||||||
Transmembrane | 345-365 | Helical | ||||
Sequence: VILLGLLLIYDVFFVFITPFI | ||||||
Topological domain | 366-403 | Lumenal | ||||
Sequence: TKNGESIMVELAAGPFENAEKLPVVIRVPKLMGYSVMS | ||||||
Transmembrane | 404-424 | Helical | ||||
Sequence: VCSVPVSVLGFGDIIVPGLLI | ||||||
Topological domain | 425-440 | Cytoplasmic | ||||
Sequence: AYCRRFDVQTGSSIYY | ||||||
Transmembrane | 441-461 | Helical | ||||
Sequence: ISSTIAYAVGMIITFVVLMVM | ||||||
Topological domain | 462-463 | Lumenal | ||||
Sequence: KT | ||||||
Transmembrane | 464-484 | Helical | ||||
Sequence: GQPALLYLVPCTLITVSVVAW | ||||||
Topological domain | 485-523 | Cytoplasmic | ||||
Sequence: SRKEMKKFWKGSSYQVMDHLDYSTNEENPVTTDEQIVQQ |
Keywords
- Cellular component
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 498 | Inhibits lysosomal/late endosomal targeting. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 506 | Does not inhibit lysosomal/late endosomal targeting. | ||||
Sequence: Y → A |
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.
Chemistry
PTM/Processing
Features
Showing features for signal, chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-25 | |||||
Sequence: MGLLHSLHAPAAALLWSCLLGLAAA | ||||||
Chain | PRO_0000073911 | 26-523 | Signal peptide peptidase-like 2A | |||
Sequence: QEAILHASTNGVSSLSKDYCMYYNNNWTRLPSSLENATSLSLMNLTGTALCHLSDIPPDGIRNKAVVVHWGPCHFLEKARIAQEGGAAALLIANNSVLIPSSRNKSTFQNVTVLIAVITQKDFKDMKETLGDDITVKMYSPSWPNFDYTLVVIFVIAVFTVALGGYWSGLIELENMKSVEDAEDRETRKKKDDYLTFSPLTVVVFVVICCIMIVLLYFFYRWLVYVMIAIFCIASSMSLYNCLSALIHRMPCGQCTILCCGKNIKVSLIFLSGLCISVAVVWAVFRNEDRWAWILQDILGIAFCLNLIKTMKLPNFMSCVILLGLLLIYDVFFVFITPFITKNGESIMVELAAGPFENAEKLPVVIRVPKLMGYSVMSVCSVPVSVLGFGDIIVPGLLIAYCRRFDVQTGSSIYYISSTIAYAVGMIITFVVLMVMKTGQPALLYLVPCTLITVSVVAWSRKEMKKFWKGSSYQVMDHLDYSTNEENPVTTDEQIVQQ | ||||||
Glycosylation | 51 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 61 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 69 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 119 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 129 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 135 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Glycosylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Structure
Family & Domains
Features
Showing features for domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 70-155 | PA | ||||
Sequence: LTGTALCHLSDIPPDGIRNKAVVVHWGPCHFLEKARIAQEGGAAALLIANNSVLIPSSRNKSTFQNVTVLIAVITQKDFKDMKETL | ||||||
Motif | 466-468 | PAL | ||||
Sequence: PAL | ||||||
Motif | 498-501 | YXXo lysosomal targeting motif | ||||
Sequence: YQVM |
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).
The C-terminal tail is necessary for lysosomal transport (PubMed:21896273).
Sequence similarities
Belongs to the peptidase A22B family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length523
- Mass (Da)58,129
- Last updated2011-07-27 v2
- ChecksumA15109A71FCF25C4
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F6RJQ8 | F6RJQ8_MOUSE | Sppl2a | 253 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 74 | in Ref. 2; AAH26578 | ||||
Sequence: A → P | ||||||
Sequence conflict | 331-333 | in Ref. 2; AAH26578 | ||||
Sequence: NLI → PKV | ||||||
Sequence conflict | 502 | in Ref. 1; BAA95032 | ||||
Sequence: D → G |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |