CDB25:0003121 ANXA2 — TLR4

Experimentally validated in Mixed species; Orthology-inferred in Human, Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

Annexin A2 tetramer activates human and murine macrophages through TLR4.

Blood, 2010; PubMed, Bos taurus ANXA2 — Homo sapiens TLR4

ABSTRACT: Annexins are a large family of intracellular phospholipid-binding proteins, yet several extracellular roles have been identified. Specifically, annexin A2, found in a heterotetrameric complex with S100A10, not only serves as a key extracellular binding partner for pathogens and host proteins alike, but also can be shed or secreted. We reported previously that soluble annexin A2 tetramer (A2t) activates human monocyte-derived macrophages (MDM), resulting in secretion of inflammatory mediators and enhanced phagocytosis. Although a receptor for A2t has been cloned from bone marrow stromal cells, data contained in this study demonstrate that it is dispensable for A2t-dependent activation of MDM. Furthermore, A2t activates wild-type murine bone marrow-derived macrophages, whereas macrophages from myeloid differentiation factor 88-deficient mice display a blunted response, suggesting a role for Toll-like receptor (TLR) signaling. Small interfering RNA knockdown of TLR4 in human MDM reduced the response to A2t, blocking antibodies against TLR4 (but not TLR2) blocked activation altogether, and bone marrow-derived macrophages from TLR4(-/-) mice were refractory to A2t. These data demonstrate that the modulation of macrophage function by A2t is mediated through TLR4, suggesting a previously unknown, but important role for this stress-sensitive protein in the detection of danger to the host, whether from injury or invasion.

Basic Information on ANXA2

Ligand Name: annexin A2

Other Symbols: ANX2, ANX2L4, CAL1H, LPC2D, LIP2

Ligand Location: secreted based on hpa, perplexity, uniprot, cell membrane based on hpa, perplexity

HGNC Gene Symbol Report: ANXA2

GeneCards: ANXA2

HGNC Gene Group: Annexins

Functional Annotations for ANXA2

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for ANXA2

ANXA2 — ROBO4 ・ ANXA2 — TLR2

Basic Information on TLR4

Receptor Name: toll like receptor 4

Other Symbols: hToll, CD284, TLR-4, ARMD10

Receptor Location: cell membrane based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: TLR4

GeneCards: TLR4

HGNC Gene Group: TIR domain containing, CD molecules

Functional Annotations for TLR4

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for TLR4

BGN — TLR4 ・ DEFB4A — TLR4 ・ HSP90B1 — TLR4 ・ HSPA1A — TLR4 ・ S100A8 — TLR4 ・ S100A9 — TLR4 ・ SFTPD — TLR4 ・ ZG16B — TLR4 ・ DCN — TLR4 ・ FGA — TLR4 ・ FGB — TLR4 ・ FGG — TLR4 ・ PRG4 — TLR4 ・ AHSG — TLR4 ・ CCN1 — TLR4 ・ CIRBP — TLR4 ・ CXCL10 — TLR4 ・ FCN2 — TLR4 ・ HMGB1 — TLR4 ・ HP — TLR4 ・ HSPA4 — TLR4 ・ LGALS9 — TLR4 ・ MMP9 — TLR4 ・ NAMPT — TLR4 ・ RBP4 — TLR4 ・ RETN — TLR4 ・ S100A1 — TLR4 ・ S100A12 — TLR4 ・ S100A4 — TLR4 ・ SAA1 — TLR4 ・ SFTPA1 — TLR4 ・ TNC — TLR4 ・ WNT5A — TLR4