Protein / target
ALK tyrosine kinase receptor
Protein at a glance
Biological role
Receptor signaling protein tyrosine kinase activator activity
Primary system
Nervous system
Strongest disease association
neuroblastoma
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
7 approved · 5 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
Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150). May function as regulator of gastric epithelial differentiation (By similarity)
Subcellular location
Domains and Gene Ontology detail (26)Hide
Domains & features
Gene Ontology
- Cextracellular exosome
- Cplasma membrane
- Cprotein-containing complex
- Creceptor complex
- FATP binding
- Fheparin binding
- Fidentical protein binding
- Fprotein tyrosine kinase activity
- Freceptor signaling protein tyrosine kinase activator activity
- Ftransmembrane receptor protein tyrosine kinase activity
- Pcell surface receptor protein tyrosine kinase signaling pathway
- Penergy homeostasis
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Kinase signalling
- ·Neuronal receptor tyrosine kinase that is essentially and transiently expressed in speci…
- ·protein tyrosine kinase activity
- ·transmembrane receptor protein tyrosine kinase activity
- ·peptidyl-tyrosine autophosphorylation
Apoptosis & cell death
- ·regulation of apoptotic process
View underlying pathways (11)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.
ALK tyrosine kinase receptor inhibitor
Appears in clinical studies involving lymphoma, non-small cell lung carcinoma, non-small cell lung carcinoma, non-small cell lung carcinoma
ALK tyrosine kinase receptor inhibitor
Appears in clinical studies involving non-small cell lung carcinoma, anaplastic large cell lymphoma, non-small cell lung carcinoma, non-small cell lung carcinoma
ALK tyrosine kinase receptor inhibitor
Appears in clinical studies involving non-small cell lung carcinoma, non-small cell lung carcinoma, non-small cell lung carcinoma, neoplasm
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 1,443 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 · 12 total
lymphoma · 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
non-small cell lung carcinoma · anaplastic large cell lymphoma · 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 · non-small cell lung carcinoma · non-Hodgkin lymphoma
diffuse large B-cell lymphoma · non-small cell lung carcinoma · neuroblastoma
malignant pancreatic neoplasm · non-small cell lung carcinoma
non-small cell lung carcinoma · non-small cell lung carcinoma · neoplasm
neoplasm
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.
Related literature
Papers indexed under “Anaplastic Lymphoma Kinase” — a subject heading that covers this protein without being specific to it. Shown as context; not counted as this protein's own research activity.
Europe PMC literature, reached through a MeSH descriptor linked to this protein.
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 3 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- 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 publicationBrigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial.
- Regulatory approval
Approval: Lorviqua (EMA)
- Regulatory approval
Approval: Alunbrig (EMA)
- 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.