CD47

UniProt ID: Q08722
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

CD47 (also known as integrin-associated protein, IAP) is a ubiquitously expressed cell surface receptor that functions as an innate immune checkpoint - the "don't eat me" signal. The core function of CD47 is to bind SIRPalpha on myeloid cells (macrophages, dendritic cells) in trans, which recruits SHP-1/SHP-2 phosphatases to inhibit phagocytosis. This CD47-SIRPalpha axis is critical for self-recognition and prevents inappropriate phagocytic clearance of healthy cells. CD47 also binds thrombospondin-1 (TSP1) to modulate vascular signaling, including inhibition of nitric oxide signaling. Additionally, CD47 associates with multiple integrins (alphaVbeta3, alphaIIbbeta3, etc.) to modulate integrin-mediated signaling and cell adhesion. The protein contains an extracellular Ig-like V-type domain and five transmembrane helices.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005886 plasma membrane
IBA
GO_REF:0000033
ACCEPT
Summary: CD47 is a multi-pass transmembrane protein localized to the plasma membrane. This is well-established from early characterization studies and confirmed by multiple structural and functional studies (PMID:7691831, PMID:7998989).
Reason: Plasma membrane localization is a core property of CD47 function. The protein must be at the cell surface to engage SIRPalpha on opposing cells and to interact with thrombospondin-1. UniProt confirms "Cell membrane; Multi-pass membrane protein".
Supporting Evidence:
PMID:7691831
Integrin Associated Protein (IAP) is a 50-kD membrane protein which copurifies with the integrin alpha v beta 3 from placenta
file:human/CD47/CD47-deep-research-falcon.md
model: Edison Scientific Literature
GO:0022409 positive regulation of cell-cell adhesion
IBA
GO_REF:0000033
ACCEPT
Summary: CD47 mediates cell-cell adhesion through its interactions with SIRPalpha and SIRPgamma on opposing cells (PMID:11509594, PMID:15383453). The CD47-SIRPbeta2 interaction promotes T cell adhesion to antigen-presenting cells.
Reason: Cell-cell adhesion mediation is experimentally validated. The CD47-SIRP interactions physically bridge cells and this is a core function of the protein.
Supporting Evidence:
PMID:15383453
SIRPbeta2 is expressed on T cells and activated natural killer (NK) cells and, like SIRPalpha, binds CD47, mediating cell-cell adhesion
PMID:11509594
CD47/integrin-associated protein, a ubiquitous multispan transmembrane protein highly expressed on T cells, interacts with signal-regulator protein (SIRP)-alpha
GO:0050729 positive regulation of inflammatory response
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: CD47 signaling is involved in modulating inflammatory responses, particularly through its effects on cytokine production and dendritic cell function (PMID:11509594). The deep research notes that CD47-SIRPalpha and TSP1-CD47 axes can modulate inflammatory tone.
Reason: While CD47 can modulate inflammatory responses, this is a downstream consequence of its core phagocytosis checkpoint function, not the primary function. The annotation is valid but represents a non-core pleiotropic effect.
Supporting Evidence:
PMID:11509594
Proinflammatory molecules, including IFN-gamma and IL-12, play a crucial role in the elimination of causative agents
GO:0050766 positive regulation of phagocytosis
IBA
GO_REF:0000033
MODIFY
Summary: This annotation is MISLEADING. CD47 is fundamentally a NEGATIVE regulator of phagocytosis - the "don't eat me" signal. When CD47 engages SIRPalpha on macrophages, it INHIBITS phagocytosis. Blocking CD47 or the CD47-SIRPalpha axis PROMOTES phagocytosis (PMID:11509594, deep research).
Reason: CD47's core function is as an inhibitory checkpoint that prevents phagocytosis. The annotation to "positive regulation of phagocytosis" appears to be an error or over-annotation. The ISS annotation (GO:0050765, negative regulation) is correct. The positive regulation may have been inferred incorrectly from studies where CD47 blockade increases phagocytosis.
Supporting Evidence:
PMID:11509594
CD47 on T cells and its cognate receptor SIRP-alpha on DC define a novel regulatory pathway that may be involved in the maintenance of homeostasis by preventing the escalation of the inflammatory immune response
GO:0070053 thrombospondin receptor activity
IBA
GO_REF:0000033
ACCEPT
Summary: CD47 is a well-established receptor for the C-terminal cell-binding domain of thrombospondin-1 (TSP1). This was demonstrated by affinity labeling, antibody blocking, and functional assays (PMID:8550562, PMID:19004835).
Reason: Thrombospondin receptor activity is a core molecular function of CD47. The interaction with TSP1 modulates important signaling pathways including nitric oxide signaling and integrin function.
Supporting Evidence:
PMID:8550562
IAP (CD47) as a receptor for the CBD of TS1 and suggest a mechanism for the well established effects of the CBD on cell motility
PMID:8550562
Cell-binding peptides based on the sequence RFYVVM from the CBD of TS1 affinity label a 52-kDa cell surface glycoprotein, which we show is integrin-associated protein (IAP or CD47)
GO:0070062 extracellular exosome
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: CD47 has been detected in extracellular exosomes. This may reflect the ubiquitous expression of CD47 on cell membranes that become incorporated into exosomes.
Reason: While CD47 may be present in exosomes, this is not a core localization for its primary phagocytosis checkpoint function. The plasma membrane localization is the functionally critical one.
GO:0034113 heterotypic cell-cell adhesion
IEA
GO_REF:0000108
ACCEPT
Summary: CD47 mediates heterotypic cell-cell adhesion through trans interactions with SIRP family members on different cell types (e.g., T cells expressing CD47 binding to SIRPalpha on dendritic cells or macrophages).
Reason: This is an accurate annotation. The CD47-SIRPalpha/SIRPgamma interactions mediate adhesion between different cell types, which is central to its immune checkpoint function.
Supporting Evidence:
PMID:11509594
CD47/integrin-associated protein... interacts with signal-regulator protein (SIRP)-alpha, an immunoreceptor tyrosine-based inhibition motif-containing molecule selectively expressed on myelomonocytic cells
GO:0001525 angiogenesis
IEA
GO_REF:0000043
KEEP AS NON CORE
Summary: CD47-TSP1 signaling has anti-angiogenic effects through inhibition of VEGF and nitric oxide signaling. CD47 plays a role in suppressing angiogenesis (PMID:32679764, deep research).
Reason: While CD47 does modulate angiogenesis through TSP1 signaling, this is a downstream consequence of TSP1-CD47 interaction rather than the core phagocytosis checkpoint function. The annotation is valid but represents a pleiotropic effect of the TSP1 signaling axis.
GO:0002684 positive regulation of immune system process
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: CD47 modulates immune responses through multiple mechanisms including the SIRPalpha checkpoint and T cell costimulation via SIRPbeta2/gamma.
Reason: This is a very general term. CD47 has complex effects on immune processes - it can both inhibit (via SIRPalpha checkpoint) and promote (via T cell costimulation) immune responses depending on context. The annotation is too general to be informative about core function.
GO:0005886 plasma membrane
IEA
GO_REF:0000120
ACCEPT
Summary: Duplicate of IBA annotation. CD47 is a plasma membrane protein - this is well established.
Reason: Plasma membrane localization is correct and represents core localization for CD47 function.
GO:0006915 apoptotic process
IEA
GO_REF:0000043
MARK AS OVER ANNOTATED
Summary: This annotation is an OVER-ANNOTATION and MISLEADING. CD47's core function is as a phagocytosis checkpoint. When CD47 is lost or blocked, cells are cleared by phagocytes - this appears as "cell death" but is NOT apoptosis. The cells are engulfed by macrophages, not dying by apoptotic program. While CD47 can augment FAS-mediated apoptosis (PMID:15917238), this is a secondary/modulatory effect, not its core function.
Reason: CD47 is fundamentally a "don't eat me" signal that prevents phagocytosis. Loss of CD47 leads to phagocytic clearance, not apoptosis. The annotation to "apoptotic process" is fundamentally misleading about the protein's function. The keyword-based mapping from Swiss-Prot "Apoptosis" is inappropriate because CD47's relationship to cell death is indirect - it modulates whether cells get cleared by phagocytes, not whether they undergo intrinsic apoptotic cell death.
Supporting Evidence:
PMID:15917238
CD47 associates with Fas upon its activation and augments Fas-mediated apoptosis
GO:0006954 inflammatory response
IEA
GO_REF:0000043
KEEP AS NON CORE
Summary: CD47 modulates inflammatory responses through its effects on cytokine production and immune cell activation (PMID:11509594).
Reason: CD47 does participate in inflammatory response modulation, but this is downstream of its core checkpoint function, not the primary function.
GO:0007155 cell adhesion
IEA
GO_REF:0000043
ACCEPT
Summary: CD47 mediates cell adhesion through SIRP interactions and integrin associations. This is supported by multiple studies.
Reason: Cell adhesion is a core function of CD47, enabling the physical interaction between cells required for the phagocytosis checkpoint.
Supporting Evidence:
PMID:15383453
SIRPbeta2 is expressed on T cells... and, like SIRPalpha, binds CD47, mediating cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
IEA
GO_REF:0000002
ACCEPT
Summary: Duplicate of IBA annotation. CD47 promotes cell-cell adhesion through SIRP interactions.
Reason: Cell-cell adhesion is a validated function of CD47.
GO:0050729 positive regulation of inflammatory response
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: Duplicate of IBA annotation. CD47 modulates inflammatory responses.
Reason: This is a pleiotropic effect, not the core function.
GO:0050766 positive regulation of phagocytosis
IEA
GO_REF:0000002
MODIFY
Summary: This is INCORRECT. CD47 is a NEGATIVE regulator of phagocytosis, not a positive regulator.
Reason: CD47's core function is inhibiting phagocytosis via the SIRPalpha checkpoint. This annotation is fundamentally wrong.
GO:0070053 thrombospondin receptor activity
IEA
GO_REF:0000002
ACCEPT
Summary: Duplicate of IBA annotation. CD47 is a TSP1 receptor.
Reason: Thrombospondin receptor activity is a core function.
GO:0098609 cell-cell adhesion
IEA
GO_REF:0000117
ACCEPT
Summary: CD47 mediates cell-cell adhesion through SIRP interactions.
Reason: Cell-cell adhesion is a core function of CD47.
GO:0005515 protein binding
IPI
PMID:15383453
Adhesion of human T cells to antigen-presenting cells throug...
MODIFY
Summary: This study demonstrates CD47 binding to SIRPbeta2 (SIRPgamma), which mediates T cell adhesion to antigen-presenting cells and costimulates T-cell proliferation. A more specific term should be used.
Reason: "Protein binding" is uninformative. The actual binding partner (SIRPgamma/SIRPbeta2) is characterized. Should use a more specific molecular function term such as "signaling receptor binding" or the specific cell-cell adhesion mediator function.
Proposed replacements: signaling receptor binding
Supporting Evidence:
PMID:15383453
SIRPbeta2 is expressed on T cells and activated natural killer (NK) cells and, like SIRPalpha, binds CD47, mediating cell-cell adhesion
GO:0005515 protein binding
IPI
PMID:17070842
Functional elements on SIRPalpha IgV domain mediate cell sur...
MODIFY
Summary: This study characterizes the SIRPalpha-CD47 binding interaction at the molecular level, identifying key residues on SIRPalpha required for CD47 binding.
Reason: "Protein binding" is uninformative. The interaction with SIRPalpha is well-characterized and more specific terms should be used.
Proposed replacements: signaling receptor binding
Supporting Evidence:
PMID:17070842
binding of SIRPalpha with CD47... through the extracellular IgV domain regulates important leukocyte functions including macrophage recognition, leukocyte adhesion and transmigration
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: High-throughput interactome study. Generic protein binding.
Reason: "Protein binding" from high-throughput studies provides no functional information. Should be removed in favor of more specific annotations.
Supporting Evidence:
PMID:25416956
A proteome-scale map of the human interactome network.
GO:0005515 protein binding
IPI
PMID:32822567
A Human IgSF Cell-Surface Interactome Reveals a Complex Netw...
REMOVE
Summary: IgSF cell-surface interactome study. Generic protein binding.
Reason: High-throughput generic binding annotations are uninformative.
Supporting Evidence:
PMID:32822567
A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
REMOVE
Summary: Proteome-scale interactome study. Generic protein binding.
Reason: High-throughput generic binding annotations are uninformative.
Supporting Evidence:
PMID:33961781
2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding
IPI
PMID:35922511
A physical wiring diagram for the human immune system.
REMOVE
Summary: Physical wiring diagram study. Generic protein binding.
Reason: High-throughput generic binding annotations are uninformative.
Supporting Evidence:
PMID:35922511
Aug 3. A physical wiring diagram for the human immune system.
GO:0005886 plasma membrane
IDA
GO_REF:0000052
ACCEPT
Summary: Plasma membrane localization based on immunofluorescence data.
Reason: Core localization confirmed by direct experimental evidence.
GO:0005515 protein binding
IPI
PMID:15917238
CD47 augments Fas/CD95-mediated apoptosis
MODIFY
Summary: This study shows CD47 interacts with FAS/CD95 upon Fas activation, augmenting Fas-mediated apoptosis.
Reason: The binding partner (FAS) is specific and characterized. A more informative term should be used. However, this is a secondary function of CD47.
Proposed replacements: signaling receptor binding
Supporting Evidence:
PMID:15917238
CH11 induces association of Fas and CD47
GO:0070051 fibrinogen binding
IDA
PMID:22079249
Integrin-associated protein (CD47) is a putative mediator fo...
KEEP AS NON CORE
Summary: CD47 was identified as a putative mediator for soluble fibrinogen interaction with human red blood cells (PMID:22079249).
Reason: Fibrinogen binding has been demonstrated but this is not a core function of CD47. It may relate to the integrin-associated functions.
Supporting Evidence:
PMID:22079249
Integrin-associated protein (CD47) is a putative mediator for soluble fibrinogen interaction with human red blood cells membrane
GO:0005515 protein binding
IPI
PMID:19004835
Differential interactions of thrombospondin-1, -2, and -4 wi...
MODIFY
Summary: This study characterizes differential interactions of thrombospondin-1, -2, and -4 with CD47. CD47 binds TSP1 most strongly.
Reason: The binding to thrombospondin is well-characterized. The thrombospondin receptor activity annotation (GO:0070053) is more appropriate.
Proposed replacements: thrombospondin receptor activity
Supporting Evidence:
PMID:19004835
Differential interactions of thrombospondin-1, -2, and -4 with CD47 and effects on cGMP signaling and ischemic injury responses
GO:0005515 protein binding
IPI
PMID:8550562
Integrin-associated protein is a receptor for the C-terminal...
MODIFY
Summary: Original identification of CD47 as the thrombospondin receptor.
Reason: The specific thrombospondin receptor activity term is more appropriate.
Proposed replacements: thrombospondin receptor activity
Supporting Evidence:
PMID:8550562
Integrin-associated protein is a receptor for the C-terminal domain of thrombospondin
GO:0070053 thrombospondin receptor activity
IDA
PMID:8550562
Integrin-associated protein is a receptor for the C-terminal...
ACCEPT
Summary: Direct experimental demonstration that CD47/IAP is the receptor for thrombospondin C-terminal cell-binding domain (PMID:8550562).
Reason: Core molecular function of CD47 with strong experimental support.
Supporting Evidence:
PMID:8550562
IAP (CD47) as a receptor for the CBD of TS1
GO:0050765 negative regulation of phagocytosis
ISS
GO_REF:0000024
ACCEPT
Summary: CD47 engagement of SIRPalpha delivers a "don't eat me" signal that inhibits phagocytosis. This is the CORE function of CD47.
Reason: This is the primary, core function of CD47 as an innate immune checkpoint. The CD47-SIRPalpha axis is the central "don't eat me" signal.
Supporting Evidence:
PMID:11509594
CD47 on T cells and its cognate receptor SIRP-alpha on DC define a novel regulatory pathway that may be involved in the maintenance of homeostasis
GO:0060368 regulation of Fc receptor mediated stimulatory signaling pathway
ISS
PMID:21401967
Myelin down-regulates myelin phagocytosis by microglia and m...
ACCEPT
Summary: CD47-SIRPalpha interaction down-regulates Fc receptor signaling in phagocytes, contributing to the "don't eat me" signal.
Reason: This is related to the core phagocytosis checkpoint function. The CD47-SIRPalpha axis inhibits Fc receptor-mediated phagocytosis.
Supporting Evidence:
PMID:21401967
Myelin down-regulates myelin phagocytosis by microglia and macrophages through interactions between CD47 on myelin and SIRPΞ± (signal regulatory protein-Ξ±) on phagocytes.
GO:2000439 positive regulation of monocyte extravasation
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: CD47 has been implicated in monocyte extravasation through its interactions with SIRPalpha and effects on cell migration.
Reason: This is a secondary effect related to cell adhesion functions, not the core phagocytosis checkpoint function.
GO:1904669 ATP export
IDA
PMID:24022490
CR1-mediated ATP release by human red blood cells promotes C...
KEEP AS NON CORE
Summary: CD47 has been implicated in CR1-mediated ATP release by human red blood cells.
Reason: ATP export is a specialized function in red blood cells, not the core immune checkpoint function of CD47.
Supporting Evidence:
PMID:24022490
2013 Sep 10. CR1-mediated ATP release by human red blood cells promotes CR1 clustering and modulates the immune transfer process.
GO:0009986 cell surface
IDA
PMID:11509594
Bidirectional negative regulation of human T and dendritic c...
ACCEPT
Summary: CD47 is expressed on the cell surface where it engages SIRPalpha in trans. Confirmed by this study on T and dendritic cells.
Reason: Cell surface localization is essential for CD47's checkpoint function.
Supporting Evidence:
PMID:11509594
CD47/integrin-associated protein, a ubiquitous multispan transmembrane protein highly expressed on T cells
GO:0032649 regulation of type II interferon production
IMP
PMID:11509594
Bidirectional negative regulation of human T and dendritic c...
KEEP AS NON CORE
Summary: CD47-SIRPalpha engagement modulates IFN-gamma production. CD47-Fc decreases IFN-gamma production in allogeneic MLR (PMID:11509594).
Reason: Cytokine regulation is a downstream consequence of the CD47-SIRPalpha checkpoint, not the core function.
Supporting Evidence:
PMID:11509594
CD47-Fc decreases IFN-gamma production after priming and impairs the development of a Th1 response
GO:0032653 regulation of interleukin-10 production
IMP
PMID:11509594
Bidirectional negative regulation of human T and dendritic c...
KEEP AS NON CORE
Summary: CD47-SIRPalpha engagement modulates IL-10 production.
Reason: Cytokine regulation is a downstream effect, not core function.
Supporting Evidence:
PMID:11509594
Bidirectional negative regulation of human T and dendritic cells by CD47 and its cognate receptor signal-regulator protein-alpha: down-regulation of IL-12 responsiveness and inhibition of dendritic cell activation.
GO:0032655 regulation of interleukin-12 production
IMP
PMID:11509594
Bidirectional negative regulation of human T and dendritic c...
KEEP AS NON CORE
Summary: CD47 ligation down-regulates IL-12 responsiveness of T cells (PMID:11509594).
Reason: Cytokine regulation is a downstream effect, not core function.
Supporting Evidence:
PMID:11509594
CD47 ligation by CD47 mAb or L-SIRP-alpha transfectants inhibits IL-12R expression and down-regulates IL-12 responsiveness of activated CD4(+) and CD8(+) adult T cells
GO:0032675 regulation of interleukin-6 production
IMP
PMID:11509594
Bidirectional negative regulation of human T and dendritic c...
KEEP AS NON CORE
Summary: CD47-SIRPalpha engagement modulates IL-6 production.
Reason: Cytokine regulation is a downstream effect, not core function.
Supporting Evidence:
PMID:11509594
Bidirectional negative regulation of human T and dendritic cells by CD47 and its cognate receptor signal-regulator protein-alpha: down-regulation of IL-12 responsiveness and inhibition of dendritic cell activation.
GO:0032680 regulation of tumor necrosis factor production
IMP
PMID:11509594
Bidirectional negative regulation of human T and dendritic c...
KEEP AS NON CORE
Summary: CD47-SIRPalpha engagement modulates TNF production.
Reason: Cytokine regulation is a downstream effect, not core function.
Supporting Evidence:
PMID:11509594
Bidirectional negative regulation of human T and dendritic cells by CD47 and its cognate receptor signal-regulator protein-alpha: down-regulation of IL-12 responsiveness and inhibition of dendritic cell activation.
GO:0071349 cellular response to interleukin-12
IMP
PMID:11509594
Bidirectional negative regulation of human T and dendritic c...
KEEP AS NON CORE
Summary: CD47 ligation down-regulates IL-12 responsiveness of T cells (PMID:11509594).
Reason: This is downstream signaling modulation, not core function.
Supporting Evidence:
PMID:11509594
CD47 ligation by CD47 mAb or L-SIRP-alpha transfectants inhibits IL-12R expression and down-regulates IL-12 responsiveness
GO:0098632 cell-cell adhesion mediator activity
IPI
PMID:11509594
Bidirectional negative regulation of human T and dendritic c...
ACCEPT
Summary: CD47 mediates cell-cell adhesion through its interactions with SIRPalpha and other SIRP family members.
Reason: Cell-cell adhesion mediator activity is a well-supported core molecular function of CD47.
Supporting Evidence:
PMID:11509594
CD47/integrin-associated protein... interacts with signal-regulator protein (SIRP)-alpha
GO:0045428 regulation of nitric oxide biosynthetic process
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: TSP1-CD47 signaling inhibits NO signaling, which has effects on vascular function (UniProt, deep research).
Reason: This is mediated by TSP1-CD47 signaling, which is a secondary axis distinct from the core phagocytosis checkpoint function.
GO:0086080 protein binding involved in heterotypic cell-cell adhesion
ISS
GO_REF:0000024
ACCEPT
Summary: CD47 binds SIRP family members on opposing cells to mediate heterotypic cell-cell adhesion.
Reason: This is a well-supported molecular function of CD47 that is central to its immune checkpoint activity.
GO:0009986 cell surface
ISS
GO_REF:0000024
ACCEPT
Summary: Duplicate localization annotation. CD47 is on the cell surface.
Reason: Core localization is well-established.
GO:0016477 cell migration
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: CD47 is involved in cell migration, likely through its integrin associations and TSP1 signaling.
Reason: Cell migration is a downstream effect of CD47's adhesion and signaling functions, not its core checkpoint function.
GO:0051496 positive regulation of stress fiber assembly
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: CD47 signaling can affect cytoskeletal organization.
Reason: This is a downstream effect of CD47 signaling, not core function.
GO:0071346 cellular response to type II interferon
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: CD47 expression is induced by IFN-gamma signaling.
Reason: This describes regulation of CD47, not its core function.
GO:0071347 cellular response to interleukin-1
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: CD47 may respond to IL-1 signaling.
Reason: This describes regulation of CD47, not its core function.
GO:0009986 cell surface
NAS
PMID:25795378
SIRP/CD47 signaling in neurological disorders
ACCEPT
Summary: Review of SIRP/CD47 signaling confirms cell surface localization.
Reason: Core localization confirmed by review.
Supporting Evidence:
PMID:25795378
2015 Mar 17. SIRP/CD47 signaling in neurological disorders.
GO:0005515 protein binding
IPI
PMID:24026300
Inflammation-induced proteolytic processing of the SIRPΞ± cyt...
MODIFY
Summary: Study on SIRPalpha proteolytic processing and CD47 interaction.
Reason: More specific binding terms should be used.
Proposed replacements: signaling receptor binding
Supporting Evidence:
PMID:24026300
Inflammation-induced proteolytic processing of the SIRPΞ± cytoplasmic ITIM in neutrophils propagates a proinflammatory state.
GO:0035579 specific granule membrane
TAS
Reactome:R-HSA-6799350
KEEP AS NON CORE
Summary: CD47 is present on specific granule membranes in neutrophils, where it can be mobilized to the cell surface.
Reason: This is a cell-type specific localization in neutrophils, not the core localization for CD47's checkpoint function.
GO:0070821 tertiary granule membrane
TAS
Reactome:R-HSA-6798747
KEEP AS NON CORE
Summary: CD47 is present on tertiary granule membranes in neutrophils.
Reason: Cell-type specific localization in neutrophils.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-202703
ACCEPT
Summary: Reactome annotation for CD47 binding SIRP. Confirms plasma membrane localization.
Reason: Core localization.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-2426259
ACCEPT
Summary: Reactome annotation for COMP binding to CD47. Confirms plasma membrane localization.
Reason: Core localization.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-391151
ACCEPT
Summary: Reactome pathway annotation for SIRPalpha-CD47 signaling.
Reason: Core localization.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-391152
ACCEPT
Summary: Reactome pathway annotation.
Reason: Core localization.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-391153
ACCEPT
Summary: Reactome pathway annotation.
Reason: Core localization.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-391157
ACCEPT
Summary: Reactome pathway annotation.
Reason: Core localization.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-391158
ACCEPT
Summary: Reactome annotation for SIRPalpha binding CD47.
Reason: Core localization.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-391168
ACCEPT
Summary: Reactome annotation for SIRPgamma binding CD47.
Reason: Core localization.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-6798747
ACCEPT
Summary: Reactome pathway annotation.
Reason: Core localization.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-6799350
ACCEPT
Summary: Reactome pathway annotation.
Reason: Core localization.
GO:0070053 thrombospondin receptor activity
IPI
PMID:15700281
Insulin-like growth factor binding protein-5 (IGFBP-5) inter...
ACCEPT
Summary: Study showing IGFBP-5 interacts with TSP1 to modulate IGF-I actions through CD47.
Reason: Supports CD47's role as thrombospondin receptor.
Supporting Evidence:
PMID:15700281
Insulin-like growth factor binding protein-5 (IGFBP-5) interacts with thrombospondin-1 to induce negative regulatory effects on IGF-I actions.
GO:0008284 positive regulation of cell population proliferation
IDA
PMID:15383453
Adhesion of human T cells to antigen-presenting cells throug...
KEEP AS NON CORE
Summary: CD47 engagement by SIRPbeta2 costimulates T-cell proliferation (PMID:15383453).
Reason: T cell costimulation is a secondary function of CD47 through SIRP interactions, not the core phagocytosis checkpoint function.
Supporting Evidence:
PMID:15383453
engagement of SIRPbeta2 on T cells by CD47 on antigen-presenting cells results in enhanced antigen-specific T-cell proliferation
GO:0022409 positive regulation of cell-cell adhesion
IDA
PMID:15383453
Adhesion of human T cells to antigen-presenting cells throug...
ACCEPT
Summary: CD47-SIRPbeta2 interaction promotes cell-cell adhesion (PMID:15383453).
Reason: Cell-cell adhesion promotion is a well-supported function.
Supporting Evidence:
PMID:15383453
Here, we show that SIRPbeta2 is expressed on T cells and activated natural killer (NK) cells and, like SIRPalpha, binds CD47, mediating cell-cell adhesion
GO:0050870 positive regulation of T cell activation
IDA
PMID:15383453
Adhesion of human T cells to antigen-presenting cells throug...
KEEP AS NON CORE
Summary: CD47-SIRPbeta2 interaction costimulates T cell activation (PMID:15383453).
Reason: T cell costimulation is a secondary function, not the core phagocytosis checkpoint function.
Supporting Evidence:
PMID:15383453
engagement of SIRPbeta2 on T cells by CD47 on antigen-presenting cells results in enhanced antigen-specific T-cell proliferation
GO:0005886 plasma membrane
TAS
PMID:7998989
Isolation and characterization of CD47 glycoprotein: a multi...
ACCEPT
Summary: Original characterization of CD47 confirms plasma membrane localization.
Reason: Core localization.
Supporting Evidence:
PMID:7998989
Isolation and characterization of CD47 glycoprotein: a multispanning membrane protein which is the same as integrin-associated protein (IAP) and the ovarian tumour marker OA3.
GO:0005886 plasma membrane
TAS
PMID:10429193
A CD9, alphaIIbbeta3, integrin-associated protein, and GPIb/...
ACCEPT
Summary: Study on platelet surface complexes confirms CD47 at plasma membrane.
Reason: Core localization.
Supporting Evidence:
PMID:10429193
A CD9, alphaIIbbeta3, integrin-associated protein, and GPIb/V/IX complex on the surface of human platelets is influenced by alphaIIbbeta3 conformational states.
GO:0007229 integrin-mediated signaling pathway
TAS
PMID:8294396
Rh-related antigen CD47 is the signal-transducer integrin-as...
KEEP AS NON CORE
Summary: CD47 was originally identified as integrin-associated protein (IAP) and participates in integrin-mediated signaling.
Reason: Integrin association is a secondary function of CD47, though historically important. The primary function is the SIRPalpha phagocytosis checkpoint.
Supporting Evidence:
PMID:8294396
Rh-related antigen CD47 is the signal-transducer integrin-associated protein.

Core Functions

CD47 on target cells binds SIRPalpha on macrophages/phagocytes, recruiting SHP-1/SHP-2 phosphatases to inhibit phagocytosis. This is the primary innate immune checkpoint function of CD47 - the "don't eat me" signal.

Cellular Locations:

CD47 is the receptor for the C-terminal cell-binding domain of TSP1, modulating integrin function and vascular signaling (including NO signaling).

Cellular Locations:

References

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Deep Research

Falcon

(CD47-deep-research-falcon.md)

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πŸ“„ View Raw YAML

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