CD47
Description
The CD47 (CD47 molecule) is a protein-coding gene located on chromosome 3.
CD47 (Cluster of Differentiation 47), also known as integrin associated protein (IAP), is a transmembrane protein encoded by the CD47 gene. It belongs to the immunoglobulin superfamily and partners with membrane integrins, binding to ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha (SIRPα). CD47 acts as a 'don't eat me' signal to macrophages of the immune system, making it a potential therapeutic target in some cancers and for treating pulmonary fibrosis. CD47 is involved in various cellular processes including apoptosis, proliferation, adhesion, migration, insulin secretion, and immune and angiogenic responses. It is ubiquitously expressed in human cells and has been found to be overexpressed in many different tumor cells. Expression in equine cutaneous tumors has been reported as well.
CD47 is a 50 kDa membrane receptor with an extracellular N-terminal IgV domain, five transmembrane domains, and a short C-terminal intracellular tail. There are four alternatively spliced isoforms of CD47, differing only in the length of their cytoplasmic tail. Form 2, the most widely expressed form, is found in all circulating and immune cells.
CD47 is an adhesive protein that mediates cell-to-cell interactions. It acts as a receptor for thrombospondin (THBS1) and modulates integrin signaling through the activation of heterotrimeric G proteins. CD47 is involved in signal transduction, cardiovascular homeostasis, inflammation, apoptosis, angiogenesis, cellular self-renewal, and immunoregulation. It plays a role in modulating pulmonary endothelin (EDN1) signaling and modulates nitrous oxide (NO) signaling in response to THBS1, supporting blood pressure. CD47 is important for memory formation and synaptic plasticity in the hippocampus. As a receptor for SIRPA, it prevents the maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. Interaction with SIRPG mediates cell-cell adhesion, enhances superantigen-dependent T-cell-mediated proliferation and costimulates T-cell activation. CD47 positively modulates FAS-dependent apoptosis in T-cells, potentially by enhancing FAS clustering. It plays a role in suppressing angiogenesis and may be involved in metabolic dysregulation during normal aging. In response to THBS1, CD47 negatively modulates wound healing and inhibits stem cell self-renewal, likely by regulating the stem cell transcription factors POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4. CD47 may play a role in membrane transport and/or integrin-dependent signal transduction and may prevent premature elimination of red blood cells.
CD47 is also known as IAP, MER6, OA3.
