Target intelligence / Profile preview

Annexin A5 (ANXA5)

Target
ANXA5
Molecular classification
Phospholipid-binding protein, Calcium-binding protein, Member of the annexin family, Other
01

Overview

Annexin A5 (ANXA5) is a member of the annexin family of calcium-dependent phospholipid-binding proteins. Its canonical function is to bind with high affinity to phosphatidylserine (PS) on the plasma membrane—especially when exposed during apoptosis—making it a key marker for apoptotic cell detection. In the coagulation cascade, annexin A5 acts as an indirect anticoagulant by forming a shield on PS-rich membranes, thereby inhibiting access of coagulation factors and downregulating thrombin generation. It participates in diverse physiological and pathological processes including signal transduction, vesicle trafficking, membrane repair, bone and cartilage mineralization, anti-inflammatory, antithrombotic, and neuroprotective roles. Autoantibodies against annexin A5 are implicated in antiphospholipid syndrome—a thrombophilic disorder associated with recurrent pregnancy loss and vascular thrombosis. Recombinant annexin A5 is widely used in laboratory diagnostics, especially as a probe for apoptosis. Although prominent as a biomarker/reagent, there are no approved direct drugs targeting ANXA5; its high affinity and specific biochemical actions, however, have been explored experimentally for drug delivery and imaging applications[1][2][3][4][5][6].

Other names
Annexin VAnnexin-5ANX5ENX2PP4CPB-IPAP-IVAC-alphaendonexin IIcalphobindin Iplacental anticoagulant protein Iplacental anticoagulant protein 4thromboplastin inhibitorvascular anticoagulant-alphaanchorin CIIlipocortin Vepididymis secretory protein Li 7RPRGL3HEL-S-7
02

Mechanism of action

Binds to exposed phosphatidylserine on cell surfaces in a calcium-dependent manner, shielding negatively charged phospholipids and inhibiting coagulation cascade (by blocking access to coagulation factors such as prothrombin)[5][3][2]. Inhibits apoptosis or signals apoptosis detection (by binding to PS externalized on apoptotic cells)[3][6]. Indirect antithrombotic activity (prevents formation of procoagulant complexes)[2][3][5]. Inhibits phospholipase A1 (protects membrane integrity)[3]. Modulates mineralization in bone and cartilage by enhancing calcium influx and hydroxyapatite deposition[2].

03

Biological functions

Apoptosis detection and regulationAnticoagulation/antithrombotic activityPhospholipid binding, especially to phosphatidylserine (PS)Signal transduction processesVesicle transportMineralization (bone and cartilage)Inhibition of tumor growthAngiogenesis and vascular protectionAnti-inflammatory functionsNeuroprotective effectsCell growth and differentiation
04

Disease associations

Cardiovascular disease (thrombosis, antiphospholipid syndrome)Cancer (thyroid, hepatocellular carcinoma, prostate)Inflammation (anti-inflammatory and immune-modulating roles)Pregnancy disorders (e.g., used as marker in preeclampsia, APS)Neurodegenerative disease (Alzheimer’s, neurotoxicity)Bone and cartilage disorders (osteoporosis, mineralization defects)
05

Safety considerations

Not typically targeted as a drug, so systemic safety concerns from drug targeting are minimal.Possible concern: autoimmunity (antibodies against annexin A5 can cause or exacerbate thrombotic phenomena in antiphospholipid syndrome)[3].Therapeutic challenges: Short plasma half-life and issues with delivery for experimental therapeutic/diagnostic agents based on annexin A5[1][2].
06

Interacting drugs

No classical direct-acting small molecule drugs; however, annexin A5 is used as a reagent/biomarker, not targeted pharmacologically in clinical practice[2][5][3].

1 more in the full profile.

07

Biomarkers

Widely used as a marker for detecting apoptosis (annexin V-binding assay in flow cytometry)[2][3].Biomarker for antiphospholipid syndrome and related autoimmune coagulation disorders[3].Marker in preeclampsia and some pregnancy disorders[2].Investigated as a biomarker in some cancers (e.g., thyroid carcinoma)[3].Marker for bone and cartilage mineralization and osteogenesis research[2].

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