protein
Annexin A2
Gene
ANXA2
Organism
Homo sapiens(9606)
Length
339 aa
Mass
38,604 Da
Annexin A2 (ANXA2) is a calcium-regulated membrane-binding protein that binds two calcium ions with high affinity in the presence of anionic phospholipids (UniProt: P07355). The protein participates in multiple cellular processes including endosomal membrane stabilization, lipid metabolism regulation through PCSK9 inhibition, and endothelial fibrinolytic function. It also serves as a receptor for pathogenic toxins from microbial infection.
ANXA2 is broadly expressed and functions across multiple tissue and cellular compartments, particularly in membrane trafficking and lipid-dependent signaling pathways. UniProt records no specific disease associations in its curated data; however, the protein has been detected in inflammatory and metabolic contexts relevant to endothelial and innate immune function.
Annexin A2 shows increased abundance in Alzheimer's Disease brain tissue. In post-mortem AD brain compared to age-matched controls across multiple subcellular fractions, ANXA2 was significantly upregulated with a mean log2 fold-change of 1.36 (Chaparral AD proteomics). This elevation across multiple fractions suggests a consistent AD-associated increase, potentially reflecting altered calcium signaling, membrane dynamics, or inflammatory responses in the diseased brain.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
+1.365
P2
+1.515
S2
+0.811
S3
+1.748
Mean log₂FC across detected fractions: +1.3599 (4 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
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Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
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)
(Microbial infection) Binds M.pneumoniae CARDS toxin, probably serves as one receptor for this pathogen. When ANXA2 is down-regulated by siRNA, less toxin binds to human cells and less vacuolization (a symptom of M.pneumoniae infection) is seen
Sources
Last updated 5/8/2026, 6:33:06 AM
