Protein / target
Proto-oncogene tyrosine-protein kinase ROS
Protein at a glance
Biological role
Transmembrane receptor protein tyrosine kinase activity
Strongest disease association
lung carcinoma
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
3 approved · 1 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
Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. NELL2 is an endogenous ligand for ROS1. Upon endogenous stimulation by NELL2, ROS1 activates the intracellular signaling pathway and triggers epididymal epithelial differentiation and subsequent sperm maturation (By similarity). May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and PLCG2
Subcellular location
Domains and Gene Ontology detail (25)Hide
Domains & features
Gene Ontology
- Cmembrane
- Cplasma membrane
- Creceptor complex
- FATP binding
- Fprotein phosphatase binding
- Fprotein tyrosine kinase activity
- Ftransmembrane receptor protein tyrosine kinase activity
- Pcell differentiation
- Pcell surface receptor protein tyrosine kinase signaling pathway
- Pcolumnar/cuboidal epithelial cell development
- Pprotein phosphorylation
- Pregulation of cell growth
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Kinase signalling
- ·Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and…
- ·protein tyrosine kinase activity
- ·transmembrane receptor protein tyrosine kinase activity
- ·protein phosphorylation
Immune signalling
- ·Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and…
Transcriptional regulation
- ·Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and…
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.
Proto-oncogene tyrosine-protein kinase ROS inhibitor
Appears in clinical studies involving non-small cell lung carcinoma, non-small cell lung carcinoma, non-small cell lung carcinoma, neoplasm
Proto-oncogene tyrosine-protein kinase ROS inhibitor
Appears in clinical studies involving non-small cell lung carcinoma, non-small cell lung carcinoma, non-small cell lung carcinoma, cancer
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.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 667 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 · 4 total
non-small cell lung carcinoma · non-small cell lung carcinoma · non-small cell lung carcinoma
non-small cell lung carcinoma · non-small cell lung carcinoma · neoplasm
non-small cell lung carcinoma · non-small cell lung carcinoma · neoplasm
non-small cell lung carcinoma · non-small cell lung carcinoma · non-small cell lung carcinoma
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.
Show remaining trials (24)Hide
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.
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 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Regulatory approval
Approval: Augtyro (EMA)
- New publicationLorlatinib Versus Crizotinib in Patients With Advanced <i>ALK</i>-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study.
- New publicationRepotrectinib in <i>ROS1</i> Fusion-Positive Non-Small-Cell Lung Cancer.
- New publicationBrigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial.
- Safety communication
Drug Safety Update: Crizotinib (Xalkori▼): risk of cardiac failure
- New publicationFirst-line crizotinib versus chemotherapy in ALK-positive lung cancer.
- Regulatory approval
Approval: Xalkori (EMA)
- New publicationROS1 rearrangements define a unique molecular class of lung cancers.
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.