GO:1990665 AnxA2-p11 complex: Components, Assembly and Research Methods

The AnxA2-p11 complex (GO:1990665) is a heterotetrameric protein assembly composed of two Annexin A2 (ANXA2) monomers and two copies of the S100 family protein p11 (S100A10). This complex is a defined cellular_component that serves as a molecular hub at the interface between the plasma membrane, the actin cytoskeleton, and the extracellular protease network. Because it coordinates calcium-dependent membrane binding with plasminogen activation, the AnxA2-p11 complex is a focal point for studies of cell migration, tissue remodeling, and immune regulation. Researchers value GO:1990665 as a discrete entity for annotating proteomic and imaging data, enabling reproducible comparisons across cell types and disease states. The complex has also emerged as a candidate link between autoimmunity and neuropsychiatric phenotypes, including anxiety and depression. Understanding its assembly, regulation, and downstream effectors is therefore essential for both basic cell biology and translational medicine.

GO:1990665 defines the AnxA2-p11 complex as a heterotetrameric protein complex comprising two Annexin A2 (AnxA2) monomers and two copies of its binding partner, S100 protein p11 (S100A10). In practical terms, it is a stable, non-covalent assembly in which the two S100A10 subunits bridge the two ANXA2 molecules, forming a (AnxA2)2(p11)2 tetramer. This complex is annotated as a cellular_component because it localizes to specific subcellular sites, including the plasma membrane and cytoskeletal structures, where it performs scaffolding and signaling functions.

The AnxA2-p11 complex is important because it integrates calcium-dependent membrane binding with proteolytic and signaling outputs that control cell migration, extracellular matrix remodeling, and immune cell behavior. Its dysfunction has been linked to autoimmune pathology and to anxiety and depression, making it a rare example of a molecular complex that bridges peripheral inflammation and central nervous system phenotypes. For researchers, GO:1990665 provides a precise annotation target for proteomics, imaging, and functional genomics, enabling reproducible interrogation of ANXA2 and S100A10 in health and disease.

The AnxA2-p11 complex is defined by two core genes, ANXA2 and S100A10, with additional interacting partners that modulate its function and disease relevance.

The AnxA2-p11 complex is regulated at multiple levels, including calcium availability, phosphorylation of ANXA2, and expression levels of S100A10. Calcium binding to ANXA2 promotes membrane association and complex assembly, while phosphorylation by SRC and PKC family kinases modulates its interactions and subcellular localization. S100A10 expression is controlled by inflammatory and growth factor signaling, and changes in its abundance can shift the balance between free ANXA2 and the heterotetramer. In neuropsychiatric contexts, the complex is influenced by immune and stress-related pathways, linking peripheral inflammation to anxiety and depression phenotypes.

The AnxA2-p11 complex has been implicated in autoimmune pathology, where it may contribute to autoantibody generation and immune dysregulation. ANXA2 and S100A10 are expressed in immune cells and can influence inflammatory signaling and cell migration. Autoantibodies against ANXA2 have been reported in autoimmune conditions, suggesting the complex as a candidate biomarker and therapeutic target.

The AnxA2-p11 complex has been associated with anxiety and depression, potentially through its role in neuroinflammation and synaptic regulation. S100A10 (p11) is a known modulator of serotonin receptor trafficking and mood-related behaviors. Dysregulation of the complex may therefore contribute to neuropsychiatric phenotypes, making it a target for further mechanistic studies.

The AnxA2-p11 complex promotes plasminogen activation and extracellular matrix degradation, processes that support tumor cell invasion and metastasis. Elevated ANXA2 and S100A10 expression has been observed in several cancers and correlates with poor prognosis. Targeting the complex may therefore offer a strategy to limit cancer cell dissemination.

By promoting plasmin generation, the AnxA2-p11 complex influences fibrinolysis and vascular homeostasis. Dysregulation of this activity may contribute to thrombotic or hemorrhagic tendencies, although direct clinical evidence remains an active area of research. The complex is thus a candidate for studies of vascular biology and hemostasis.

Co-immunoprecipitation coupled with mass spectrometry can identify the AnxA2-p11 complex and its associated proteins in different cell states. This approach helps define the complex composition and dynamic interactions under physiological and pathological conditions.

Fluorescence microscopy and live-cell imaging using tagged ANXA2 or S100A10 can reveal the subcellular localization and trafficking of the AnxA2-p11 complex. These methods are essential for linking complex assembly to membrane and cytoskeletal dynamics.

Chromogenic and fluorogenic plasminogen activation assays measure the ability of the AnxA2-p11 complex to generate plasmin on cell surfaces. These assays are used to test the impact of CRISPR-mediated knockout or point mutations on complex function.

RNA-seq and CRISPR library screening can identify genes that regulate ANXA2 and S100A10 expression or that synthetic-lethal with the complex. These approaches enable unbiased discovery of pathways that depend on the AnxA2-p11 complex.

Researchers studying AnxA2-p11 complex-related genes often need to determine whether a candidate gene is causally involved in complex assembly, plasminogen activation, or disease phenotypes. EDITGENE provides publication-ready CRISPR models and bioinformatics support to accelerate this discovery process.

The AnxA2-p11 complex (GO:1990665) is a defined heterotetrameric cellular_component that integrates calcium signaling, membrane dynamics, and pericellular proteolysis. Its core subunits, ANXA2 and S100A10, are implicated in autoimmune disease, anxiety, depression, cancer, and thrombosis, making the complex a high-value target for mechanistic and translational research. CRISPR-based knockout, point mutation, knock-in, and overexpression models provide the tools needed to dissect its assembly, regulation, and disease contributions. EDITGENE offers end-to-end services to accelerate these studies and support publication-ready discoveries.