Signal peptide peptidase-like 2A (SPPL2A)
The protein contains 520 amino acids for an estimated molecular weight of 58143 Da.
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 (PubMed:16829952, PubMed:16829951, PubMed:17557115, PubMed:17965014). 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 (PubMed:16829952). Also responsible for the intramembrane cleavage of Fas antigen ligand FASLG, which promotes the release of the intracellular FasL domain (FasL ICD) (PubMed:17557115). May play a role in the regulation of innate and adaptive immunity (PubMed:16829952). Catalyzes the intramembrane cleavage of the simian foamy virus envelope glycoprotein gp130 independently of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis (PubMed:23132852). (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| dbSNP:rs8034443 |
No binding partner found
Biological Process
Membrane protein ectodomain proteolysis
Membrane protein intracellular domain proteolysis
Membrane protein proteolysis
Regulation of immune response
Regulation of tumor necrosis factor-mediated signaling pathway
Cellular Component
Extracellular exosome
Golgi-associated vesicle membrane
Integral component of cytoplasmic side of endoplasmic reticulum membrane
Integral component of lumenal side of endoplasmic reticulum membrane
Intracellular membrane-bounded organelle
Late endosome
Late endosome membrane
Lysosomal membrane
Membrane
Plasma membrane
The reference OMIM entry for this protein is 608238
Signal peptide peptidase-like 2a
Spp-like 2a; sppl2a
Intramembrane protease 3; imp3
CLONING
By searching sequence databases for homologs of Dictyostelium discoideum Impas, which shares homology with presenilin (104311), followed by PCR of lymphocyte and hippocampus cDNA libraries, Grigorenko et al. (2002) cloned IMP3. The deduced protein contains 520 amino acids. Like other IMP proteins, IMP3 contains an N-terminal protease-associated (PA) domain, several transmembrane regions, a hydrophilic loop, conservative sequences around the first and second aspartate residues, and an invariant PAL motif near the C terminus.MAPPING
By genomic sequence analysis, Grigorenko et al. (2002) mapped the IMP3 gene to chromosome 15. ... More on the omim web site
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 608238 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).