SPPL2A

Signal peptide peptidase-like 2A, also known as SPPL2A, is a human gene.[5]

SPPL2A
Identifiers
Aliases	SPPL2A, IMP3, PSL2, signal peptide peptidase like 2A
External IDs	OMIM: 608238 MGI: 1913802 HomoloGene: 36411 GeneCards: SPPL2A
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q21.2 Start 50,702,266 bp[1] End 50,765,709 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 F1 Start 126,890,391 bp[2] End 126,933,235 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • protein homodimerization activity • aspartic-type endopeptidase activity • peptidase activity • GO:0001948 protein binding • hydrolase activity • aspartic endopeptidase activity, intramembrane cleaving Cellular component • integral component of membrane • endosome • late endosome • membrane • late endosome membrane • intracellular membrane-bounded organelle • integral component of cytoplasmic side of endoplasmic reticulum membrane • lysosomal membrane • Golgi-associated vesicle membrane • lysosome • integral component of lumenal side of endoplasmic reticulum membrane • extracellular exosome • cell membrane Biological process • membrane protein proteolysis • proteolysis • membrane protein ectodomain proteolysis • membrane protein intracellular domain proteolysis • regulation of immune response • regulation of tumor necrosis factor-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	84888	66552
Ensembl	ENSG00000138600	ENSMUSG00000027366
UniProt	Q8TCT8	Q9JJF9
RefSeq (mRNA)	NM_032802	NM_023220
RefSeq (protein)	NP_116191	NP_075709
Location (UCSC)	Chr 15: 50.7 – 50.77 Mb	Chr 2: 126.89 – 126.93 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene is a member of the signal peptide peptidase-like protease (SPPL) family and encodes a lysosomal/late endosomal membrane protein[6] with the conserved active site motifs 'YD' and 'GxGD' in adjacent transmembrane domains (TMDs). This protein plays a role in innate and adaptive immunity by cleaving TNFα in activated dendritic cells.[7][8] A pseudogene of this gene also lies on chromosome 15.[5]

References

1. GRCh38: Ensembl release 89: ENSG00000138600 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027366 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: SPPL2A signal peptide peptidase-like 2A".
6. Behnke J, Schneppenheim J, Koch-Nolte F, Haag F, Saftig P, Schröder B (2011). "Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes by a tyrosine motif in its C-terminal tail". FEBS Letters. 585 (19): 2951–7. doi:10.1016/j.febslet.2011.08.043. PMID 21896273.
7. Friedmann E, Hauben E, Maylandt K, et al. (2006). "SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production". Nat. Cell Biol. 8 (8): 843–8. doi:10.1038/ncb1440. PMID 16829952.
8. Fluhrer R, Grammer G, Israel L, et al. (2006). "A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2b" (PDF). Nat. Cell Biol. 8 (8): 894–6. doi:10.1038/ncb1450. PMID 16829951.

Further reading

• Weihofen A, Binns K, Lemberg MK, et al. (2002). "Identification of signal peptide peptidase, a presenilin-type aspartic protease". Science. 296 (5576): 2215–8. doi:10.1126/science.1070925. PMID 12077416.
• Grigorenko AP, Moliaka YK, Korovaitseva GI, Rogaev EI (2002). "Novel class of polytopic proteins with domains associated with putative protease activity". Biochemistry Mosc. 67 (7): 826–35. doi:10.1023/A:1016365227942. PMID 12139484.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Granneman S, Gallagher JE, Vogelzangs J, et al. (2003). "The human Imp3 and Imp4 proteins form a ternary complex with hMpp10, which only interacts with the U3 snoRNA in 60–80S ribonucleoprotein complexes". Nucleic Acids Res. 31 (7): 1877–87. doi:10.1093/nar/gkg300. PMC 152815. PMID 12655004.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Friedmann E, Lemberg MK, Weihofen A, et al. (2005). "Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins". J. Biol. Chem. 279 (49): 50790–8. doi:10.1074/jbc.M407898200. PMID 15385547.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
• Otsuki T, Ota T, Nishikawa T, et al. (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Res. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Kirkin V, Cahuzac N, Guardiola-Serrano F, et al. (2007). "The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells". Cell Death Differ. 14 (9): 1678–87. doi:10.1038/sj.cdd.4402175. PMID 17557115.