Protein / target

Signal transducer and activator of transcription 1-alpha/beta

Encoded bySTAT1P42224Homo sapiensSwiss-Prot

UniProt: P42224 Ensembl: ENSG00000115415 HGNC: HGNC:11362 NCBI Gene: 6772

Small-molecule tractable

Druggability

High-Quality Ligand

Research papers

Protein at a glance

Biological role

RNA polymerase II core promoter sequence-specific DNA binding

Strongest disease association

Severe Combined Immunodeficiency

Via encoding gene STAT1 · Genetic literature evidence · score 0.76

Research activity

Emerging research

3 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors.

View complete UniProt function annotation

Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:12764129, PubMed:12855578, PubMed:15322115, PubMed:23940278, PubMed:34508746, PubMed:35568036, PubMed:9724754, PubMed:32814877). Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus (PubMed:28753426, PubMed:35568036). ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of IFN-stimulated genes (ISG), which drive the cell in an antiviral state (PubMed:28753426, PubMed:35568036). In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated (PubMed:26479788). It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state (PubMed:8156998). Becomes activated in response to KITLG/SCF and KIT signaling (PubMed:15526160). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:19088846). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylated at Thr-749 by IKBKB which promotes binding of STAT1 to the 5'-TTTGAGGC-3' sequence in the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (PubMed:32209697). Phosphorylation at Thr-749 also promotes binding of STAT1 to the 5'-TTTGAGTC-3' sequence in the IL12B promoter and activation of IL12B transcription (PubMed:32209697). Involved in food tolerance in small intestine: associates with the Gasdermin-D, p13 cleavage product (13 kDa GSDMD) and promotes transcription of CIITA, inducing type 1 regulatory T (Tr1) cells in upper small intestine (By similarity)

Subcellular location

CytoplasmNucleus

Domains and Gene Ontology detail (61)

Domains & features

SH2

Gene Ontology

Cchromatin
Ccytoplasm
Ccytosol
CISGF3 complex
Cnucleoplasm
Cnucleus
Cperinuclear region of cytoplasm
Cprotein-containing complex
Fcadherin binding
FDNA-binding transcription factor activity
FDNA-binding transcription factor activity, RNA polymerase II-specific
Fdouble-stranded DNA binding

750 aa · 87 kDa · 2 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell proliferation & survivalGOImmune signallingUniProt · GOTranscriptional regulationUniProt · GO

View supporting evidence

Cell proliferation & survival

·regulation of cell population proliferation

Immune signalling

·Signal transducer and transcription activator that mediates cellular responses to interf…
·interleukin-27-mediated signaling pathway
·interleukin-7-mediated signaling pathway
·interleukin-9-mediated signaling pathway

Transcriptional regulation

·Signal transducer and transcription activator that mediates cellular responses to interf…
·DNA-binding transcription factor activity
·DNA-binding transcription factor activity, RNA polymerase II-specific
·RNA polymerase II cis-regulatory region sequence-specific DNA binding

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene STAT1

Gene-level evidence surfaced through the gene STAT1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Severe Combined Immunodeficiency

0.61Moderately supported

Genetic literature evidence dominant · Open Targets 0.47

Neoplasms

0.44Preliminary

Pathway evidence dominant · Open Targets 0.55 · no direct causal or clinical evidence

View evidence synthesis (2)

Severe Combined ImmunodeficiencyModerately supported

0.61

agreement 0.46–0.77

Genetic literature97%Literature3%

Open Targets aggregate 0.47 · 2 independent evidence families

NeoplasmsPreliminary

0.44

agreement 0.26–0.61

Pathway72%Literature28%

Open Targets aggregate 0.55 · 2 independent evidence families · no direct causal or clinical evidence

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 per-type scores above show the calculation.

Show all associations

Neoplasms0.55

Severe Combined Immunodeficiency0.47

Tractability

Small molecules — Emerging

Feasibility evidence (high-quality ligand and druggable family) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (6)

SM · High-Quality LigandSM · Druggable FamilyPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.