Protein / target

Annexin A2

Encoded byANXA2P07355Homo sapiensSwiss-Prot

UniProt: P07355 Ensembl: ENSG00000182718 HGNC: HGNC:537 NCBI Gene: 302

Small-molecule tractable

Druggability

Structure with Ligand

Research papers

Protein at a glance

Biological role

Cadherin binding involved in cell-cell adhesion

Strongest disease association

Urologic Neoplasms

Via encoding gene ANXA2 · Genetic evidence · score 0.49

Research activity

Emerging research

1 papers · latest 1999

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

Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids.

View complete UniProt function annotation

Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. Inhibits PCSK9-enhanced LDLR degradation, probably reduces PCSK9 protein levels via a translational mechanism but also competes with LDLR for binding with PCSK9 (PubMed:18799458, PubMed:22848640, PubMed:24808179). Binds to endosomes damaged by phagocytosis of particulate wear debris and participates in endosomal membrane stabilization, thereby limiting NLRP3 inflammasome activation (By similarity). Required for endothelial cell surface plasmin generation and may support fibrinolytic surveillance and neoangiogenesis (By similarity)

Subcellular location

Secreted, extracellular space, extracellular matrix, basement membraneMelanosome

Domains and Gene Ontology detail (61)

Gene Ontology

Cadherens junction
CAnxA2-p11 complex
Cazurophil granule lumen
Cbasement membrane
Cbasolateral plasma membrane
Ccell surface
Ccornified envelope
Ccytoplasm
Ccytosol
Cearly endosome
Cendosome
Cextracellular exosome

339 aa · 39 kDa · 2 isoforms

Biological roles

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

Lipid & lipoprotein metabolismUniProt · GOCell adhesionUniProt · GOTranscriptional regulationGO

View supporting evidence

Lipid & lipoprotein metabolism

·Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhance…
·calcium-dependent phospholipid binding
·negative regulation of low-density lipoprotein particle receptor catabolic process
·positive regulation of low-density lipoprotein particle clearance

Cell adhesion

·Secreted, extracellular space, extracellular matrix, basement membrane
·extracellular matrix
·cadherin binding involved in cell-cell adhesion
·cell adhesion

Transcriptional regulation

·mRNA transcription by RNA polymerase II
·positive regulation of transcription by RNA polymerase II

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 ANXA2

Gene-level evidence surfaced through the gene ANXA2that 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.

Urologic Neoplasms

0.49Limited support

Genetic evidence dominant · Open Targets 0.30

Ovarian neoplasm

0.45Limited support

Genetic evidence dominant · Open Targets 0.27

Myasthenia Gravis

0.38Limited support

Genetic evidence dominant · Open Targets 0.23

Neurodegenerative Diseases

0.29Preliminary

Pathway evidence dominant · Open Targets 0.44 · no direct causal or clinical evidence

Alzheimer's Disease

0.29Preliminary

Pathway evidence dominant · Open Targets 0.31 · no direct causal or clinical evidence

View evidence synthesis (5)

Urologic NeoplasmsLimited support

0.49

agreement 0.37–0.61

Genetic100%

Open Targets aggregate 0.30 · 1 independent evidence family

Ovarian neoplasmLimited support

0.45

agreement 0.31–0.59

Genetic99%Literature1%

Open Targets aggregate 0.27 · 2 independent evidence families

Myasthenia GravisLimited support

0.38

agreement 0.26–0.50

Genetic100%

Open Targets aggregate 0.23 · 1 independent evidence family

Neurodegenerative DiseasesPreliminary

0.29

agreement 0.12–0.47

Pathway98%Literature2%

Open Targets aggregate 0.44 · 2 independent evidence families · no direct causal or clinical evidence

Alzheimer's DiseasePreliminary

0.29

agreement 0.11–0.46

Pathway62%Literature38%

Open Targets aggregate 0.31 · 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

Neurodegenerative Diseases0.44

Alzheimer's Disease0.31

Parkinson's Disease0.30

Urologic Neoplasms0.30

Multiple Sclerosis0.29

Lysosomal Storage Diseases0.29

Ovarian neoplasm0.27

Myasthenia Gravis0.23

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

View underlying tractability evidence (9)

SM · Structure with LigandSM · High-Quality PocketAB · UniProt loc high confAB · GO CC high confAB · Human Protein Atlas locPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 1999

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

Most cited

Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73.822 cites

Théry C · The Journal of cell biology · 1999

Recent

Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73.

Théry C · The Journal of cell biology · 1999

Europe PMC papers linked directly to this protein.