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Protein / target

Platelet factor 4

Encoded byPF4P02776Homo sapiensSwiss-Prot
UniProt: P02776Ensembl: ENSG00000163737HGNC: HGNC:8861NCBI Gene: 5196
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

CXCR3 chemokine receptor binding

Strongest disease association

Scleroderma, Systemic

Via encoding gene PF4 · Literature evidence · score 0.12

Research activity

Emerging research

1 papers · latest 2023

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

Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation.

View complete UniProt function annotation

Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation (PubMed:29930254, PubMed:9531587). Acts via different functional receptors including CCR1, CXCR3A or CXCR3B (PubMed:18174362, PubMed:29930254). Upon interaction with CXCR3A receptor, induces activated T-lymphocytes migration mediated via downstream Ras/extracellular signal-regulated kinase (ERK) signaling (PubMed:18174362, PubMed:24469069). Neutralizes the anticoagulant effect of heparin by binding more strongly to heparin than to the chondroitin-4-sulfate chains of the carrier molecule. Plays a role in the inhibition of hematopoiesis and in the maintenance of hematopoietic stem cell (HSC) quiescence (PubMed:9531587). Chemotactic for neutrophils and monocytes via CCR1 (PubMed:29930254). Inhibits endothelial cell proliferation. In cooperation with toll-like receptor 8/TLR8, induces chromatin remodeling and activates inflammatory gene expression via the TBK1-IRF5 axis (PubMed:35701499). In addition, induces myofibroblast differentiation and collagen synthesis in different precursor cells, including endothelial cells, by stimulating endothelial-to-mesenchymal transition (PubMed:34986347). Interacts with thrombomodulin/THBD to enhance the activation of protein C and thus potentiates its anticoagulant activity (PubMed:9395524)

Subcellular location

Secreted
Domains and Gene Ontology detail (32)

Gene Ontology

  • Ccytoplasm
  • Cextracellular matrix
  • Cextracellular region
  • Cextracellular space
  • Cplatelet alpha granule lumen
  • Fchemokine activity
  • FCXCR chemokine receptor binding
  • FCXCR3 chemokine receptor binding
  • Fheparin binding
  • Freceptor ligand activity
  • Padenylate cyclase-activating G protein-coupled receptor signaling pathway
  • Pantimicrobial humoral immune response mediated by antimicrobial peptide

101 aa · 11 kDa

Biological roles

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

Cell migrationGOCell proliferation & survivalGOHaemostasisUniProt · GOTranscriptional regulationUniProt · GOImmune signallingGO
View supporting evidence

Cell migration

  • ·leukocyte chemotaxis
  • ·monocyte chemotaxis
  • ·neutrophil chemotaxis

Cell proliferation & survival

  • ·regulation of cell population proliferation

Haemostasis

  • ·Chemokine released during platelet aggregation that plays a role in different biological…
  • ·platelet alpha granule lumen
  • ·negative regulation of blood coagulation
  • ·platelet activation

Transcriptional regulation

  • ·Chemokine released during platelet aggregation that plays a role in different biological…
  • ·positive regulation of gene expression
  • ·positive regulation of transcription by RNA polymerase II

Immune signalling

  • ·antimicrobial humoral immune response mediated by antimicrobial peptide
  • ·cytokine-mediated signaling pathway
  • ·inflammatory response
  • ·killing by host of symbiont cells

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 PF4

Gene-level evidence surfaced through the gene PF4that 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.

Acquired polycythemia vera
0.24Preliminary

Animal model evidence dominant · Open Targets 0.10 · no direct causal or clinical evidence

Scleroderma, Systemic
0.14Preliminary

Literature evidence dominant · Open Targets 0.12 · no direct causal or clinical evidence

Neoplasms
0.14Preliminary

Literature evidence dominant · Open Targets 0.11 · no direct causal or clinical evidence

COVID-19
0.13Preliminary

Literature evidence dominant · Open Targets 0.11 · no direct causal or clinical evidence

Carcinoma, Hepatocellular
0.12Preliminary

Literature evidence dominant · Open Targets 0.10 · no direct causal or clinical evidence

View evidence synthesis (5)
Acquired polycythemia veraPreliminary
0.24
agreement 0.07–0.42
Animal model59%Literature41%

Open Targets aggregate 0.10 · 2 independent evidence families · no direct causal or clinical evidence

Scleroderma, SystemicPreliminary
0.14
agreement 0.00–0.42
Literature100%

Open Targets aggregate 0.12 · 1 independent evidence family · no direct causal or clinical evidence

NeoplasmsPreliminary
0.14
agreement 0.00–0.41
Literature100%

Open Targets aggregate 0.11 · 1 independent evidence family · no direct causal or clinical evidence

COVID-19Preliminary
0.13
agreement 0.00–0.40
Literature100%

Open Targets aggregate 0.11 · 1 independent evidence family · no direct causal or clinical evidence

Carcinoma, HepatocellularPreliminary
0.12
agreement 0.00–0.31
Literature96%RNA expression4%

Open Targets aggregate 0.10 · 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
Scleroderma, Systemic0.12
Neoplasms0.11
COVID-190.11
Acquired polycythemia vera0.10
Colorectal Neoplasms0.10
Arthritis, Rheumatoid0.10
Carcinoma, Hepatocellular0.10
Dengue0.10

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality pocket) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (half-life data and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (7)
SM · Structure with LigandSM · High-Quality PocketAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2023

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Platelet factors attenuate inflammation and rescue cognition in ageing.187 cites

Schroer AB · Nature · 2023

Recent

Platelet factors attenuate inflammation and rescue cognition in ageing.

Schroer AB · Nature · 2023

Europe PMC papers linked directly to this protein.