CD2AP

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0016477 cell migration	IBA GO_REF:0000033	ACCEPT	Summary: CD2AP promotes actin-linked cell extension and migration as part of its cortical adaptor/scaffold function. Reason: CD2AP/CMS is characterized as an SH3-domain scaffolding adaptor that colocalizes with F-actin at ruffles and leading edges, alters actin organization, forms multimeric partner complexes, and links membrane or junctional proteins to the actin cytoskeleton.
GO:0030674 protein-macromolecule adaptor activity	IBA GO_REF:0000033	ACCEPT	Summary: CD2AP is a membrane- and junction-associated adaptor/scaffold that links partner proteins to actin-rich cortical and endosomal compartments. Reason: CD2AP/CMS is characterized as an SH3-domain scaffolding adaptor that colocalizes with F-actin at ruffles and leading edges, alters actin organization, forms multimeric partner complexes, and links membrane or junctional proteins to the actin cytoskeleton.
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0007015 actin filament organization	IBA GO_REF:0000033	ACCEPT	Summary: CD2AP directly supports actin cytoskeleton organization and acts in actin-rich ruffles, cell extensions, and epithelial junction remodeling. Reason: Retain as core because the original CMS/CD2AP study and later junction work support CD2AP as an actin-associated scaffold that regulates actin arrangement, cell extensions, and junctional actin remodeling.
GO:0031982 vesicle	IBA GO_REF:0000033	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0031252 cell leading edge	IBA GO_REF:0000033	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0001726 ruffle	IEA GO_REF:0000044	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0005856 cytoskeleton	IEA GO_REF:0000044	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0032991 protein-containing complex	IEA GO_REF:0000117	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0070161 anchoring junction	IEA GO_REF:0000044	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0005515 protein binding	IPI PMID:17020880 Atypical polyproline recognition by the CMS N-terminal Src h...	MODIFY	Summary: The cited interaction is compatible with CD2AP scaffold biology, but generic protein binding is too broad for the actual molecular role. Reason: Generic protein binding does not capture CD2AP function; the informative biology is SH3/proline-rich partner recognition, adaptor/scaffold activity, actin association, or specific junction/endosomal complex participation. Proposed replacements: protein-macromolecule adaptor activity
GO:0005515 protein binding	IPI PMID:17474147 Systematic identification of SH3 domain-mediated human prote...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005515 protein binding	IPI PMID:17853893 Human ESCRT and ALIX proteins interact with proteins of the ...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005515 protein binding	IPI PMID:19380743 Charting the molecular network of the drug target Bcr-Abl.	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005515 protein binding	IPI PMID:21706016 Selected reaction monitoring mass spectrometry reveals the d...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005515 protein binding	IPI PMID:21822214 The B-cell antigen receptor signals through a preformed tran...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005515 protein binding	IPI PMID:21988832 Toward an understanding of the protein interaction network o...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005515 protein binding	IPI PMID:22662192 IQGAP1 interacts with components of the slit diaphragm compl...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005515 protein binding	IPI PMID:23663663 Multimeric and differential binding of CIN85/CD2AP with two ...	MODIFY	Summary: The cited interaction is compatible with CD2AP scaffold biology, but generic protein binding is too broad for the actual molecular role. Reason: Generic protein binding does not capture CD2AP function; the informative biology is SH3/proline-rich partner recognition, adaptor/scaffold activity, actin association, or specific junction/endosomal complex participation. Proposed replacements: protein-macromolecule adaptor activity
GO:0005515 protein binding	IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005515 protein binding	IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005515 protein binding	IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005515 protein binding	IPI PMID:32552912 Upregulation of RIN3 induces endosomal dysfunction in Alzhei...	MODIFY	Summary: The cited interaction is compatible with CD2AP scaffold biology, but generic protein binding is too broad for the actual molecular role. Reason: Generic protein binding does not capture CD2AP function; the informative biology is SH3/proline-rich partner recognition, adaptor/scaffold activity, actin association, or specific junction/endosomal complex participation. Proposed replacements: protein-macromolecule adaptor activity
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0042802 identical protein binding	IPI PMID:17020880 Atypical polyproline recognition by the CMS N-terminal Src h...	ACCEPT	Summary: Structural and biochemical evidence supports multimerization of CD2AP/CMS SH3-domain complexes, consistent with homotypic/multimeric scaffold assembly. Reason: CD2AP/CMS is characterized as an SH3-domain scaffolding adaptor that colocalizes with F-actin at ruffles and leading edges, alters actin organization, forms multimeric partner complexes, and links membrane or junctional proteins to the actin cytoskeleton.
GO:0042802 identical protein binding	IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0002102 podosome	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Podosome localization is plausible for an actin-rich adhesion scaffold but is not the central CD2AP function established by the strongest evidence. Reason: Keep as non-core because podosomes are an actin-rich adhesion context related to CD2AP cytoskeletal biology but are less central than ruffles, junctions, slit diaphragm, and endosomal adaptor functions.
GO:0003779 actin binding	IEA GO_REF:0000107	ACCEPT	Summary: CD2AP is an actin-associated scaffold, and actin/actin-filament binding is consistent with the original CMS/CD2AP functional evidence and later CapZ-linked junction work. Reason: Retain as core because the original CMS/CD2AP study and later junction work support CD2AP as an actin-associated scaffold that regulates actin arrangement, cell extensions, and junctional actin remodeling.
GO:0005641 nuclear envelope lumen	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005737 cytoplasm	IEA GO_REF:0000107	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0005770 late endosome	IEA GO_REF:0000107	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0005884 actin filament	IEA GO_REF:0000107	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0005886 plasma membrane	IEA GO_REF:0000107	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0005911 cell-cell junction	IEA GO_REF:0000107	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0030276 clathrin binding	IEA GO_REF:0000107	ACCEPT	Summary: CD2AP/CIN85-family adaptor biology supports vesicle, late-endosome, TGN, and clathrin-linked trafficking annotations, with Alzheimer-context evidence for RIN3/BIN1/CD2AP early-endosome recruitment. Reason: Retain as core or near-core because CD2AP is an endocytic adaptor family member that couples cargo trafficking to the cytoskeleton and participates in early-endosomal/receptor-trafficking contexts.
GO:0030424 axon	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Neuronal projection or synapse context is plausible in Alzheimer/endosomal models but is not the primary defining activity of CD2AP. Reason: Keep as non-core because CD2AP has neuronal/endosomal disease-model evidence, but the strongest conserved function remains SH3-mediated adaptor/scaffold activity at actin-rich membrane, junction, and endosomal structures.
GO:0030425 dendrite	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Neuronal projection or synapse context is plausible in Alzheimer/endosomal models but is not the primary defining activity of CD2AP. Reason: Keep as non-core because CD2AP has neuronal/endosomal disease-model evidence, but the strongest conserved function remains SH3-mediated adaptor/scaffold activity at actin-rich membrane, junction, and endosomal structures.
GO:0030426 growth cone	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Neuronal projection or synapse context is plausible in Alzheimer/endosomal models but is not the primary defining activity of CD2AP. Reason: Keep as non-core because CD2AP has neuronal/endosomal disease-model evidence, but the strongest conserved function remains SH3-mediated adaptor/scaffold activity at actin-rich membrane, junction, and endosomal structures.
GO:0031594 neuromuscular junction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Neuronal projection or synapse context is plausible in Alzheimer/endosomal models but is not the primary defining activity of CD2AP. Reason: Keep as non-core because CD2AP has neuronal/endosomal disease-model evidence, but the strongest conserved function remains SH3-mediated adaptor/scaffold activity at actin-rich membrane, junction, and endosomal structures.
GO:0031982 vesicle	IEA GO_REF:0000107	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0032588 trans-Golgi network membrane	IEA GO_REF:0000107	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0036057 slit diaphragm	IEA GO_REF:0000107	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0036312 phosphatidylinositol 3-kinase regulatory subunit binding	IEA GO_REF:0000107	ACCEPT	Summary: CD2AP proline-rich sequences bind signaling SH3-domain partners including the p85 regulatory subunit of phosphatidylinositol 3-kinase, fitting its adaptor role. Reason: CD2AP/CMS is characterized as an SH3-domain scaffolding adaptor that colocalizes with F-actin at ruffles and leading edges, alters actin organization, forms multimeric partner complexes, and links membrane or junctional proteins to the actin cytoskeleton.
GO:0043005 neuron projection	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Neuronal projection or synapse context is plausible in Alzheimer/endosomal models but is not the primary defining activity of CD2AP. Reason: Keep as non-core because CD2AP has neuronal/endosomal disease-model evidence, but the strongest conserved function remains SH3-mediated adaptor/scaffold activity at actin-rich membrane, junction, and endosomal structures.
GO:0050808 synapse organization	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Neuronal projection or synapse context is plausible in Alzheimer/endosomal models but is not the primary defining activity of CD2AP. Reason: Keep as non-core because CD2AP has neuronal/endosomal disease-model evidence, but the strongest conserved function remains SH3-mediated adaptor/scaffold activity at actin-rich membrane, junction, and endosomal structures.
GO:0051015 actin filament binding	IEA GO_REF:0000107	ACCEPT	Summary: CD2AP is an actin-associated scaffold, and actin/actin-filament binding is consistent with the original CMS/CD2AP functional evidence and later CapZ-linked junction work. Reason: Retain as core because the original CMS/CD2AP study and later junction work support CD2AP as an actin-associated scaffold that regulates actin arrangement, cell extensions, and junctional actin remodeling.
GO:0071944 cell periphery	IEA GO_REF:0000107	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0005886 plasma membrane	IDA GO_REF:0000052	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0070161 anchoring junction	EXP PMID:22891260 Epithelial junction formation requires confinement of Cdc42 ...	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0030424 axon	ISS PMID:32552912 Upregulation of RIN3 induces endosomal dysfunction in Alzhei...	KEEP AS NON CORE	Summary: Neuronal projection or synapse context is plausible in Alzheimer/endosomal models but is not the primary defining activity of CD2AP. Reason: Keep as non-core because CD2AP has neuronal/endosomal disease-model evidence, but the strongest conserved function remains SH3-mediated adaptor/scaffold activity at actin-rich membrane, junction, and endosomal structures.
GO:0030425 dendrite	ISS PMID:32552912 Upregulation of RIN3 induces endosomal dysfunction in Alzhei...	KEEP AS NON CORE	Summary: Neuronal projection or synapse context is plausible in Alzheimer/endosomal models but is not the primary defining activity of CD2AP. Reason: Keep as non-core because CD2AP has neuronal/endosomal disease-model evidence, but the strongest conserved function remains SH3-mediated adaptor/scaffold activity at actin-rich membrane, junction, and endosomal structures.
GO:0050714 positive regulation of protein secretion	IMP PMID:27044754 FRMD4A-cytohesin signaling modulates the cellular release of...	UNDECIDED	Summary: The tau-secretion paper is abstract-only in the cache and the abstract foregrounds FRMD4A rather than CD2AP, so the CD2AP-specific experimental basis cannot be verified here. Reason: Use UNDECIDED rather than REMOVE because this is an experimental annotation and the cached abstract does not expose the CD2AP-specific evidence that curators may have used from the full text.
GO:0045296 cadherin binding	HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005515 protein binding	IPI PMID:22891260 Epithelial junction formation requires confinement of Cdc42 ...	MODIFY	Summary: The cited interaction is compatible with CD2AP scaffold biology, but generic protein binding is too broad for the actual molecular role. Reason: Generic protein binding does not capture CD2AP function; the informative biology is SH3/proline-rich partner recognition, adaptor/scaffold activity, actin association, or specific junction/endosomal complex participation. Proposed replacements: protein-macromolecule adaptor activity
GO:0007015 actin filament organization	IMP PMID:22891260 Epithelial junction formation requires confinement of Cdc42 ...	ACCEPT	Summary: CD2AP directly supports actin cytoskeleton organization and acts in actin-rich ruffles, cell extensions, and epithelial junction remodeling. Reason: Retain as core because the original CMS/CD2AP study and later junction work support CD2AP as an actin-associated scaffold that regulates actin arrangement, cell extensions, and junctional actin remodeling.
GO:0051058 negative regulation of small GTPase mediated signal transduction	IMP PMID:22891260 Epithelial junction formation requires confinement of Cdc42 ...	ACCEPT	Summary: CD2AP is part of a SH3BP1/JACOP/CapZ junctional scaffold required for normal Cdc42 signaling, actin remodeling, and epithelial junction formation. Reason: Retain as core because full-text evidence shows CD2AP in a junctional scaffold with SH3BP1/JACOP and CapZ; CD2AP depletion impaired junctional SH3BP1 targeting, Cdc42 control, and junction formation.
GO:0005515 protein binding	IPI PMID:18641129 Differential requirements for Alix and ESCRT-III in cytokine...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	MARK AS OVER ANNOTATED	Summary: This annotation comes from generic interaction, high-throughput, dataset, or low-specificity localization evidence and does not define CD2AP core molecular function. Reason: Mark as over-annotated because this high-throughput or generic interaction/localization evidence is less informative than CD2AP adaptor, actin-cytoskeleton, endosomal, and junctional terms.
GO:0005515 protein binding	IPI PMID:10339567 CMS: an adapter molecule involved in cytoskeletal rearrangem...	MODIFY	Summary: The cited interaction is compatible with CD2AP scaffold biology, but generic protein binding is too broad for the actual molecular role. Reason: Generic protein binding does not capture CD2AP function; the informative biology is SH3/proline-rich partner recognition, adaptor/scaffold activity, actin association, or specific junction/endosomal complex participation. Proposed replacements: protein-macromolecule adaptor activity actin filament binding
GO:0017124 SH3 domain binding	IPI PMID:10339567 CMS: an adapter molecule involved in cytoskeletal rearrangem...	ACCEPT	Summary: CD2AP has proline-rich regions that bind SH3-domain-containing partners, supporting its scaffold/adaptor function. Reason: CD2AP/CMS is characterized as an SH3-domain scaffolding adaptor that colocalizes with F-actin at ruffles and leading edges, alters actin organization, forms multimeric partner complexes, and links membrane or junctional proteins to the actin cytoskeleton.
GO:0001726 ruffle	IDA PMID:10339567 CMS: an adapter molecule involved in cytoskeletal rearrangem...	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0031941 filamentous actin	IDA PMID:10339567 CMS: an adapter molecule involved in cytoskeletal rearrangem...	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0007165 signal transduction	NAS PMID:10339567 CMS: an adapter molecule involved in cytoskeletal rearrangem...	MODIFY	Summary: The 1999 paper supports CD2AP as a scaffold/adaptor involved in cytoskeletal rearrangement, but broad signal transduction is not specific enough. Reason: Replace broad signal transduction with the more specific adaptor and actin-organization functions supported by the same study. Proposed replacements: protein-macromolecule adaptor activity actin filament organization
GO:0005200 structural constituent of cytoskeleton	TAS PMID:10339567 CMS: an adapter molecule involved in cytoskeletal rearrangem...	MODIFY	Summary: CD2AP is an actin-associated scaffold, but structural constituent of cytoskeleton overstates the evidence compared with adaptor/actin-binding function. Reason: Replace structural constituent of cytoskeleton with CD2AP adaptor activity and actin filament binding, which better describe the evidence. Proposed replacements: protein-macromolecule adaptor activity actin filament binding
GO:0005737 cytoplasm	TAS PMID:10339567 CMS: an adapter molecule involved in cytoskeletal rearrangem...	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0006930 substrate-dependent cell migration, cell extension	TAS PMID:10339567 CMS: an adapter molecule involved in cytoskeletal rearrangem...	ACCEPT	Summary: CD2AP directly supports actin cytoskeleton organization and acts in actin-rich ruffles, cell extensions, and epithelial junction remodeling. Reason: Retain as core because the original CMS/CD2AP study and later junction work support CD2AP as an actin-associated scaffold that regulates actin arrangement, cell extensions, and junctional actin remodeling.
GO:0015629 actin cytoskeleton	TAS PMID:10339567 CMS: an adapter molecule involved in cytoskeletal rearrangem...	ACCEPT	Summary: This location matches CD2AP localization to cytoplasm, cortical actin structures, ruffles/leading edges, vesicles/endosomal compartments, plasma membrane, and junctional/slit-diaphragm sites. Reason: Retain as core because CD2AP acts at actin-rich membrane and junction compartments, including ruffles, leading edges, cell-cell/anchoring junctions, podocyte slit diaphragm context, and vesicle/endosomal sites.
GO:0065003 protein-containing complex assembly	TAS PMID:10339567 CMS: an adapter molecule involved in cytoskeletal rearrangem...	ACCEPT	Summary: CD2AP directly supports actin cytoskeleton organization and acts in actin-rich ruffles, cell extensions, and epithelial junction remodeling. Reason: Retain as core because the original CMS/CD2AP study and later junction work support CD2AP as an actin-associated scaffold that regulates actin arrangement, cell extensions, and junctional actin remodeling.

Gene Description

Existing Annotations Review

Core Functions

CD2AP functions as a multivalent SH3-domain scaffold/adaptor that links membrane-associated partner proteins and signaling complexes to actin-rich cortical structures, supporting actin organization, cell extension, and partner-complex assembly.

CD2AP associates with F-actin-rich cortical and junctional structures and helps coordinate actin remodeling through scaffolded complexes that include CapZ and SH3BP1/JACOP.

CD2AP also acts in endocytic and receptor-trafficking modules, coupling cargo and signaling complexes to cytoskeletal machinery at vesicles, endosomes, and trans-Golgi network-associated membranes.

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