Protein / target
Sphingosine 1-phosphate receptor 4
Protein at a glance
Biological role
Sphingosine-1-phosphate receptor activity
Primary system
Immune system
Strongest disease association
hypothyroidism
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
5 approved · 2 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
G protein-coupled receptor highly expressed in immune cells, where it regulates immune response and cytokine production. Functions as a receptor for the lysosphingolipid sphingosine-1-phosphate (S1P). Upon S1P binding, promotes regulatory T-cell differentiation and enhances fatty acid oxidation, through activation of the NRF2/PPARA signaling pathway (By similarity). Modulates also M1 macrophage activation through interaction with FPR2 and the JNK signaling, contributing to the inflammatory response (By similarity). In addition, facilitates early neutrophil mobilization and vascular activation during inflammation, promoting lymphocyte recruitment to draining lymph nodes and supporting the development of germinal centers for an effective adaptive immune response (By similarity)
Subcellular location
Domains and Gene Ontology detail (10)Hide
Gene Ontology
- Ccytoplasm
- Cmitochondrion
- Cplasma membrane
- Cpresynapse
- FG protein-coupled receptor activity
- Flipid binding
- Fsphingosine-1-phosphate receptor activity
- Padenylate cyclase-activating G protein-coupled receptor signaling pathway
- PG protein-coupled receptor signaling pathway
- Psphingosine-1-phosphate receptor signaling pathway
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
G protein-coupled signalling
- ·G protein-coupled receptor highly expressed in immune cells, where it regulates immune r…
- ·G protein-coupled receptor activity
- ·adenylate cyclase-activating G protein-coupled receptor signaling pathway
- ·G protein-coupled receptor signaling pathway
Synaptic signalling
- ·presynapse
Immune signalling
- ·G protein-coupled receptor highly expressed in immune cells, where it regulates immune r…
View underlying pathways (2)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Sphingosine 1-phosphate receptor agonist
Appears in clinical studies involving multiple sclerosis, relapsing-remitting multiple sclerosis, kidney transplant
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Show all associationsHide all associations
Open Targets ranks 170 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 7 total
ulcerative colitis · multiple sclerosis · systemic lupus erythematosus
ulcerative colitis · Crohn disease · atopic eczema
primary progressive multiple sclerosis · multiple sclerosis · relapsing-remitting multiple sclerosis
multiple sclerosis · relapsing-remitting multiple sclerosis · kidney transplant
Crohn disease · multiple sclerosis · psoriasis
ulcerative colitis
multiple sclerosis
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- New publicationGlial Sphingosine-Mediated Epigenetic Regulation Stabilizes Synaptic Function in <i>Drosophila</i> Models of Alzheimer's Disease.
- Regulatory approval
Approval: Fingolimod Accord (EMA)
- Regulatory approval
Approval: Gilenya (EMA)
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.