Back to discover

Protein / target

Metalloproteinase inhibitor 3

Encoded byTIMP3P35625Homo sapiensSwiss-Prot
UniProt: P35625Ensembl: ENSG00000100234HGNC: HGNC:11822NCBI Gene: 7078
Antibody-tractable
Druggability
GO CC high conf
1
Research papers

Protein at a glance

Biological role

Metalloendopeptidase inhibitor

Strongest disease association

Venous Thromboembolism

Via encoding gene TIMP3 · Genetic evidence · score 0.71

Research activity

Emerging research

1 papers · latest 2020

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

Mediates a variety of processes including matrix regulation and turnover, inflammation, and angiogenesis, through reversible inhibition of zinc protease superfamily enzymes, primarily matrix metalloproteinases (MMPs).

View complete UniProt function annotation

Mediates a variety of processes including matrix regulation and turnover, inflammation, and angiogenesis, through reversible inhibition of zinc protease superfamily enzymes, primarily matrix metalloproteinases (MMPs). Regulates extracellular matrix (ECM) remodeling through inhibition of matrix metalloproteinases (MMP) including MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MMP-14 and MMP-15. Additionally, modulates the processing of amyloid precursor protein (APP) and apolipoprotein E receptor ApoER2 by inhibiting two alpha-secretases ADAM10 and ADAM17 (PubMed:17913923). Functions as a tumor suppressor and a potent inhibitor of angiogenesis. Exerts its anti-angiogenic effect by directly interacting with vascular endothelial growth factor (VEGF) receptor-2/KDR, preventing its binding to the VEGFA ligand (PubMed:12652295). Selectively induces apoptosis in angiogenic endothelial cells through a caspase-independent cell death pathway (PubMed:25558000). Mechanistically, inhibits matrix-induced focal adhesion kinase PTK2 tyrosine phosphorylation and association with paxillin/PXN and disrupts the incorporation of ITGB3, PTK2 and PXN into focal adhesion contacts on the matrix (PubMed:25558000)

Subcellular location

Secreted, extracellular space, extracellular matrix
Domains and Gene Ontology detail (14)

Domains & features

NTR

Gene Ontology

  • Cbasement membrane
  • Cextracellular matrix
  • Cextracellular region
  • Cextracellular space
  • Cnucleus
  • Cplatelet dense granule lumen
  • Fmetal ion binding
  • Fmetalloendopeptidase inhibitor activity
  • Pnegative regulation of extracellular matrix disassembly
  • Pnegative regulation of membrane protein ectodomain proteolysis
  • Presponse to cytokine
  • Presponse to hormone

211 aa · 24 kDa

Biological roles

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

Tumour suppressionUniProtLipid & lipoprotein metabolismUniProtCell adhesionUniProt · GOImmune signallingUniProt · GOProteolysisUniProt · GO
View supporting evidence

Tumour suppression

  • ·Mediates a variety of processes including matrix regulation and turnover, inflammation,…

Lipid & lipoprotein metabolism

  • ·Mediates a variety of processes including matrix regulation and turnover, inflammation,…

Cell adhesion

  • ·Mediates a variety of processes including matrix regulation and turnover, inflammation,…
  • ·Secreted, extracellular space, extracellular matrix
  • ·extracellular matrix
  • ·negative regulation of extracellular matrix disassembly

Immune signalling

  • ·Mediates a variety of processes including matrix regulation and turnover, inflammation,…
  • ·response to cytokine

Proteolysis

  • ·Mediates a variety of processes including matrix regulation and turnover, inflammation,…
  • ·negative regulation of membrane protein ectodomain proteolysis

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 TIMP3

Gene-level evidence surfaced through the gene TIMP3that 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.

Venous Thromboembolism
0.71Moderately supported

Genetic evidence dominant · Open Targets 0.43

Glaucoma, Open-Angle
0.69Moderately supported

Genetic evidence dominant · Open Targets 0.42

Glaucoma
0.68Moderately supported

Genetic evidence dominant · Open Targets 0.42

Retinal Diseases
0.68Moderately supported

Genetic evidence dominant · Open Targets 0.41

Acne Vulgaris
0.67Moderately supported

Genetic evidence dominant · Open Targets 0.41

View evidence synthesis (5)
Venous ThromboembolismModerately supported
0.71
agreement 0.57–0.85
Genetic98%Literature2%

Open Targets aggregate 0.43 · 2 independent evidence families

Glaucoma, Open-AngleModerately supported
0.69
agreement 0.55–0.83
Genetic96%Literature4%

Open Targets aggregate 0.42 · 2 independent evidence families

GlaucomaModerately supported
0.68
agreement 0.54–0.82
Genetic97%Literature3%

Open Targets aggregate 0.42 · 2 independent evidence families

Retinal DiseasesModerately supported
0.68
agreement 0.54–0.81
Genetic97%Literature3%

Open Targets aggregate 0.41 · 2 independent evidence families

Acne VulgarisModerately supported
0.67
agreement 0.53–0.81
Genetic100%Literature0%

Open Targets aggregate 0.41 · 2 independent evidence families

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
Venous Thromboembolism0.43
Glaucoma, Open-Angle0.42
Glaucoma0.42
Retinal Diseases0.41
Acne Vulgaris0.41
Eye Diseases0.37
Cutaneous lupus erythematosus0.29

Tractability

Antibodies — Emerging

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

Protein degraders — Emerging

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

View underlying tractability evidence (4)
AB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2020

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

Most cited

The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases.1,154 cites

Cabral-Pacheco GA · International journal of molecular sciences · 2020

Recent

The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases.

Cabral-Pacheco GA · International journal of molecular sciences · 2020

Europe PMC papers linked directly to this protein.