SPPL2A explained

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

Function

This gene is a member of the signal peptide peptidase-like protease (SPPL) family and encodes a lysosomal/late endosomal membrane protein^[1] 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.^{[2] [3]} A pseudogene of this gene also lies on chromosome 15.^[4]

Further reading

• Weihofen A, Binns K, Lemberg MK, etal . Identification of signal peptide peptidase, a presenilin-type aspartic protease. . Science . 296 . 5576 . 2215–8 . 2002 . 12077416 . 10.1126/science.1070925 . 2002Sci...296.2215W . 45633906 .
• Grigorenko AP, Moliaka YK, Korovaitseva GI, Rogaev EI . Novel class of polytopic proteins with domains associated with putative protease activity. . Biochemistry Mosc. . 67 . 7 . 826–35 . 2002 . 12139484 . 10.1023/A:1016365227942 . 11785597 .
• Strausberg RL, Feingold EA, Grouse LH, etal . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Granneman S, Gallagher JE, Vogelzangs J, etal . 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 . 2003 . 12655004 . 10.1093/nar/gkg300 . 152815 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Friedmann E, Lemberg MK, Weihofen A, etal . 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 . 2005 . 15385547 . 10.1074/jbc.M407898200 . free . 2262/89311 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Rual JF, Venkatesan K, Hao T, etal . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Otsuki T, Ota T, Nishikawa T, etal . 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 . 2007 . 16303743 . 10.1093/dnares/12.2.117 . free .
• Kimura K, Wakamatsu A, Suzuki Y, etal . Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes . Genome Res. . 16 . 1 . 55–65 . 2006 . 16344560 . 10.1101/gr.4039406 . 1356129 .
• Kirkin V, Cahuzac N, Guardiola-Serrano F, etal . The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells . Cell Death Differ. . 14 . 9 . 1678–87 . 2007 . 17557115 . 10.1038/sj.cdd.4402175 . free .

Notes and References

1. Behnke J, Schneppenheim J, Koch-Nolte F, Haag F, Saftig P, Schröder B . 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 . 2011 . 21896273 . 10.1016/j.febslet.2011.08.043 . free .
2. Friedmann E, Hauben E, Maylandt K, etal . SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production . Nat. Cell Biol. . 8 . 8 . 843–8 . 2006 . 16829952 . 10.1038/ncb1440. 129089 .
3. Fluhrer R, Grammer G, Israel L, etal . A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2b . Nat. Cell Biol. . 8 . 8 . 894–6 . 2006 . 16829951 . 10.1038/ncb1450. 23712486 .
4. Web site: Entrez Gene: SPPL2A signal peptide peptidase-like 2A.