ArticleMolecular and cellular biology2015
A protease-independent function for SPPL3 in NFAT activation.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Common variants on 6q16.2, 12q24.31 and 16p13.3 are associated with major depressive disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Pooled it
- Potentiation of noncanonical NF-κB signaling and marginal zone B cell expansion by CARD11-mediated regulation of p100 processing.Cell reports · 2025Article
- QRICH1 mediates an intracellular checkpoint for CD8Science immunology · 2025Article
- C11orf94/Frey is a key regulator for male fertility by controlling Izumo1 complex assembly.Science advances · 2022Article
- S1P defects cause a new entity of cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome.EMBO molecular medicine · 2022Article
- N-terminome analyses underscore the prevalence of SPPL3-mediated intramembrane proteolysis among Golgi-resident enzymes and its role in Golgi enzyme secretion.Cellular and molecular life sciences : CMLS · 2022Article
- Methylation of Immune-Related Genes in Peripheral Blood Leukocytes and Breast Cancer.Frontiers in oncology · 2022Article
- Downregulation of Three Novel miRNAs in the Lymph Nodes of Sheep Immunized With theFrontiers in veterinary science · 2022Article
- More Than Just Simple Interaction between STIM and Orai Proteins: CRAC Channel Function Enabled by a Network of Interactions with Regulatory Proteins.International journal of molecular sciences · 2021Review
- Physiological functions of SPP/SPPL intramembrane proteases.Cellular and molecular life sciences : CMLS · 2020Review
- Signaling Functions of Intramembrane Aspartyl-Proteases.Frontiers in cardiovascular medicine · 2020Review
- Article
- Molecular physiology and pathophysiology of stromal interaction molecules.Experimental biology and medicine (Maywood, N.J.) · 2018Review
- NK Cell Maturation and Cytotoxicity Are Controlled by the Intramembrane Aspartyl Protease SPPL3.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Negative Regulation of CARD11 Signaling and Lymphoma Cell Survival by the E3 Ubiquitin Ligase RNF181.Molecular and cellular biology · 2015Article
- Secretome analysis identifies novel signal Peptide peptidase-like 3 (Sppl3) substrates and reveals a role of Sppl3 in multiple Golgi glycosylation pathways.Molecular & cellular proteomics : MCP · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The signal peptide peptidase (SPP)-related intramembrane aspartyl proteases are a homologous group of polytopic membrane proteins, some of which function in innate or adaptive immunity by cleaving proteins involved in antigen presentation or intracellular signaling. Signal peptide peptidase-like 3 (SPPL3) is a poorly characterized endoplasmic reticulum (ER)-localized member of this family, with no validated cellular substrates. We report here the isolation of SPPL3 in a screen for activators of NFAT, a transcription factor that controls lymphocyte development and function. We find that SPPL3 is required downstream of T cell receptor engagement for maximal Ca(2+) influx and NFAT activation. Surprisingly, the proteolytic activity of SPPL3 is not required for its role in this pathway. SPPL3 enhances the signal-induced association of stromal interaction molecule 1 (STIM1) and Orai1 and is even required for the full activity of constitutively active STIM1 variants that bind Orai1 independently of ER Ca(2+) release. SPPL3 associates with STIM1 through at least two independent domains, the transmembrane region and the CRAC activation domain (CAD), and can promote the association of the STIM1 CAD with Orai1. Our results assign a function in lymphocyte signaling to SPPL3 and highlight the emerging importance of nonproteolytic functions for members of the intramembrane aspartyl protease family.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.