Protein / target
Tyrosine-protein kinase JAK1
Protein at a glance
Biological role
Non-membrane spanning protein tyrosine kinase activity
Primary system
Immune system
Strongest disease association
hypothyroidism
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
14 approved · 11 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
Non-membrane spanning protein tyrosine kinase that phosphorylates signal-transducing subunits of cytokine receptor complexes like IL2RB, IL10RA, IFNAR2, IL6ST, LIFR, OSMR and IL31RA (PubMed:11909529, PubMed:12133952, PubMed:15194700, PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552, PubMed:9188471). Functionnally, is involved in the IFN-alpha/beta/gamma signal pathway (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552). Mechanistically, in response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins (PubMed:7759950). Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors (PubMed:16239216, PubMed:32750333, PubMed:8232552). Involved in the MT-RNR2/humanin-mediated signaling pathway leading to STAT3 phosphorylation (PubMed:27384491). Binding of CNTF or the CLCF1/CLF heterodimer to CNTFR leads to IL6ST/gp130-LIFR dimerization followed by activation of JAK1 and JAK2 which in turns phosphorylate IL6ST/gp130 and LIFR (PubMed:11294841). The tyrosine phosphorylated signaling receptors serve in turn as docking proteins for STAT3 (PubMed:11294841). Involved in the oncostatin-M-mediated signaling pathway through both type I OSM receptor complex (heterodimers composed of LIFR and IL6ST) and type II OSM receptor complex (heterodimers composed of OSMR and IL6ST) (PubMed:9188471). Involved in the oncostatin-M-mediated signaling pathway through both type I OSM receptor complex (heterodimers composed of LIFR and IL6ST) and type II OSM receptor complex (heterodimers composed of OSMR and IL6ST) (PubMed:9188471). Involved in the Interleukin-31-mediated signaling pathway through the IL31 receptor complex (heterodimers composed of OSMR and IL31RA) (PubMed:15194700)
Subcellular location
Domains and Gene Ontology detail (44)Hide
Domains & features
Gene Ontology
- Ccytoplasm
- Ccytoplasmic side of plasma membrane
- Ccytosol
- Cendoplasmic reticulum lumen
- Cendosome
- Cextrinsic component of cytoplasmic side of plasma membrane
- Cfocal adhesion
- Cnucleus
- Cplasma membrane
- FATP binding
- FCCR5 chemokine receptor binding
- Fgrowth hormone receptor binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Immune signalling
- ·Non-membrane spanning protein tyrosine kinase that phosphorylates signal-transducing sub…
- ·cytokine-mediated signaling pathway
- ·interleukin-10-mediated signaling pathway
- ·interleukin-11-mediated signaling pathway
Kinase signalling
- ·Non-membrane spanning protein tyrosine kinase that phosphorylates signal-transducing sub…
- ·non-membrane spanning protein tyrosine kinase activity
- ·protein tyrosine kinase activity
- ·protein phosphorylation
Cell adhesion
- ·positive regulation of homotypic cell-cell adhesion
- ·protein localization to cell-cell junction
View underlying pathways (25)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.
Tyrosine-protein kinase JAK1 inhibitor
Appears in clinical studies involving atopic eczema, Eczematoid dermatitis, atopic eczema, systemic lupus erythematosus
Tyrosine-protein kinase JAK1 inhibitor
Appears in clinical studies involving juvenile idiopathic arthritis, atopic eczema, rheumatoid arthritis, juvenile dermatomyositis
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 1,660 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 · 25 total
graft versus host disease · vitiligo · myelofibrosis
myelofibrosis · Splenomegaly · myeloproliferative disorder
COVID-19 · acute lung injury · COVID-19
alopecia areata
dermatomyositis · lichen planopilaris · asthma
graft versus host disease · chronic graft versus host disease · cancer
psoriasis vulgaris · rheumatoid arthritis · psoriasis vulgaris
systemic lupus erythematosus · psoriasis vulgaris · Arthritis
ulcerative colitis · Crohn disease · Crohn disease
psoriatic arthritis · rheumatoid arthritis · Alopecia universalis
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 “Janus Kinase 1” — 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.
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 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Label change
Label change: BARICITINIB (NDA207924)
- Label change
Label change: ABROCITINIB (NDA213871)
- Indication expanded
Indication expansion: ABROCITINIB (NDA213871)
- Indication expanded
Indication expansion: ABROCITINIB (NDA213871)
- Indication expanded
Indication expansion: BARICITINIB (NDA207924)
- Indication expanded
Indication expansion: BARICITINIB (NDA207924)
- Regulatory approval
Approval: ABROCITINIB (NDA213871)
- Regulatory approval
Approval: Cibinqo (EMA)
- Label change
Label change: BARICITINIB (NDA207924)
- New publicationImmunopathogenesis and treatment of cytokine storm in COVID-19.
- Safety communication
Drug Safety Update: Baricitinib (Olumiant▼): increased risk of diverticulitis, particularly in patients with risk factors
- Label change
Label change: BARICITINIB (NDA207924)
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.