WIPF1 (WAS/WASL-interacting protein family member 1, also known as WIP) encodes a 503-residue proline-rich adapter protein of the verprolin family that plays essential roles in actin cytoskeleton reorganization. WIP functions primarily as a stabilizer and localizer of WASP (Wiskott-Aldrich syndrome protein) and N-WASP (WASL), binding through its C-terminal WASP-binding domain (aa 451-485) to the WH1/EVH1 domain of WASP/N-WASP. This binding protects WASP from calpain-mediated degradation and facilitates WASP localization to sites of actin polymerization, including podosomes, immune synapses, and invadopodia. WIP contains a WH2 domain that directly binds G-actin, multiple proline-rich regions that recruit SH3 domain-containing partners (NCK1/NCK2, GRB2, CrkL, cortactin), and serves as a scaffold for Arp2/3-dependent branched actin nucleation. Loss-of-function mutations cause Wiskott-Aldrich syndrome 2 (WAS2), a severe immunodeficiency characterized by impaired T-cell function, immune synapse defects, and secondary loss of WASP protein. WIP is essential for podosome formation in dendritic cells and macrophages, immune synapse assembly in T cells, and proper lymphocyte chemotaxis and migration.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005884 actin filament | IBA GO_REF:0000033 | ACCEPT | Summary: WIP localizes to actin filaments as part of its core function in regulating actin dynamics. The protein contains a WH2 domain (aa 32-49) that directly binds actin monomers and associates with F-actin in podosomes (PMID:17141616, PMID:9405671). Reason: IBA annotation is well supported. WIP localizes to actin filaments in podosomes and along actin stress fibers as demonstrated in multiple studies. Supporting Evidence: PMID:9405671 WIP binds to WASP at a site distinct from the Cdc42 binding site and has actin as well as profilin binding motifs PMID:17141616 The critical involvement of WIP in DC podosome formation is also supported by the presence of endogenous WIP in the core of podosomes in wild-type cells file:human/WIPF1/WIPF1-deep-research-falcon.md [WIP contains WH2 domain for actin binding] |
| GO:0030048 actin filament-based movement | IBA GO_REF:0000033 | ACCEPT | Summary: WIP participates in actin filament-based movement through its role in regulating WASP/N-WASP-dependent actin dynamics. It is essential for cell polarization, leading edge formation, and directed cell motility in dendritic cells. Reason: WIP-deficient cells fail to polarize and form stable leading edges. IBA annotation captures WIP's role in actin-dependent cell movement processes. Supporting Evidence: PMID:17141616 In contrast, WIP-/- DCs failed to develop a major leading front and instead formed multiple simultaneous and unstable lateral lamellae and ruffles |
| GO:0001726 ruffle | IEA GO_REF:0000044 | ACCEPT | Summary: WIP localizes to membrane ruffles as part of its function in regulating cortical actin dynamics. In WIP-deficient cells, ruffles form aberrantly and lack proper organization (PMID:17141616). Reason: IEA annotation is consistent with experimental evidence. WIP colocalizes with actin at ruffles and is required for proper ruffle formation. Supporting Evidence: PMID:17141616 In contrast, WIP-/- DCs failed to develop a major leading front and instead formed multiple simultaneous and unstable lateral lamellae and ruffles |
| GO:0003779 actin binding | IEA GO_REF:0000120 | ACCEPT | Summary: WIP directly binds actin through its N-terminal WH2 domain (aa 32-49). This interaction is essential for WIP function in actin cytoskeleton regulation. Reason: Direct actin binding is a core function of WIP. The WH2 domain structure has been solved in complex with actin. Supporting Evidence: PMID:9405671 Expression of WIP in human B cells, but not of a WIP truncation mutant that lacks the actin binding motif, increased polymerized actin content |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: WIP localizes to the actin cytoskeleton, particularly at sites of active actin remodeling including podosomes, stress fibers, and cortical actin. Reason: Accurate but general. WIP is associated with the actin cytoskeleton, colocalizing with actin stress fibers and cytoskeletal structures. [2026-08 SL project re-review] Uninformative parent from the UniProt subcellular-location pipeline. The sole source for this annotation is GO_REF:0000044 (UniProtKB-SubCell), and the gene already carries strictly more specific term(s) from independent evidence, namely GO:0005884 actin filament (IBA) and GO:0015629 actin cytoskeleton. The term is not false; it is an under-specified location that adds no information over what is already annotated, which is the dominant failure mode of the SL pipeline (see projects/SL.md). Marked over-annotated rather than MODIFY because the more precise term is already present, so there is nothing to replace it with. Supporting Evidence: PMID:9405671 WIP binds to WASP at a site distinct from the Cdc42 binding site and has actin as well as profilin binding motifs |
| GO:0006457 protein folding | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: This annotation is inferred from WIP's chaperone-like function (GO:0044183). WIP stabilizes WASP protein, preventing its degradation, but this is more accurately described as a chaperone/stabilization function rather than classical protein folding. Reason: While WIP does have chaperone activity toward WASP, this is better captured by GO:0044183 (protein folding chaperone). The protein folding annotation is an inference from the chaperone annotation and represents a secondary aspect of WIP function, not its core role. |
| GO:0030029 actin filament-based process | IEA GO_REF:0000117 | ACCEPT | Summary: WIP is involved in multiple actin filament-based processes including polymerization, podosome assembly, and cell migration. Reason: This is a broad parent term that accurately captures WIP's involvement in actin dynamics. More specific child terms are also annotated. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000120 | ACCEPT | Summary: WIP localizes to cytoplasmic vesicle surfaces, particularly in the context of the intracellular motility of vaccinia virus and PIP5K-induced vesicles (UniProt annotation). Reason: UniProt notes that WIP is recruited to vesicle surfaces and along actin tails. This localization relates to its role in actin-based vesicle motility. Supporting Evidence: PMID:10878810 A complex of N-WASP and WIP integrates signalling cascades that lead to actin polymerization |
| GO:0005515 protein binding | IPI PMID:10202051 Mutations that cause the Wiskott-Aldrich syndrome impair the... | MARK AS OVER ANNOTATED | Summary: Demonstrates WIP-WASP interaction. However, more specific terms should be used to describe this functional interaction. Reason: While the interaction is valid, GO:0005515 (protein binding) is uninformative. The interaction with WASP is better captured by GO:0008093 (cytoskeletal anchor activity) which specifically describes WIP's function of anchoring WASP. Supporting Evidence: PMID:10202051 Mutations that cause the Wiskott-Aldrich syndrome impair the interaction of Wiskott-Aldrich syndrome protein (WASP) with WASP interacting protein |
| GO:0005515 protein binding | IPI PMID:11331876 WIP regulates N-WASP-mediated actin polymerization and filop... | MARK AS OVER ANNOTATED | Summary: Demonstrates WIP-N-WASP interaction in context of filopodium formation. Reason: The interaction is real but GO:0005515 is uninformative. WIP's binding to N-WASP/WASL is functionally significant for activating actin polymerization. Supporting Evidence: PMID:11331876 WIP regulates N-WASP-mediated actin polymerization and filopodium formation. |
| GO:0005515 protein binding | IPI PMID:12029088 Identification of novel SH3 domain ligands for the Src famil... | MARK AS OVER ANNOTATED | Summary: Demonstrates WIP interaction with Hck (Src family kinase). Reason: While the interaction is valid, protein binding is too general. More informative would be GO:0017124 (SH3 domain binding). Supporting Evidence: PMID:12029088 2002 May 23. Identification of novel SH3 domain ligands for the Src family kinase Hck. |
| GO:0005515 protein binding | IPI PMID:12437929 Structure of the N-WASP EVH1 domain-WIP complex: insight int... | MARK AS OVER ANNOTATED | Summary: Structural study of N-WASP EVH1 domain-WIP complex providing molecular basis for the interaction. Reason: Important structural insight but protein binding is uninformative. Supporting Evidence: PMID:12437929 Structure of the N-WASP EVH1 domain-WIP complex: insight into the molecular basis of Wiskott-Aldrich Syndrome. |
| GO:0005515 protein binding | IPI PMID:12591280 X-linked thrombocytopenia caused by a mutation in the Wiskot... | MARK AS OVER ANNOTATED | Summary: Demonstrates that X-linked thrombocytopenia mutations in WASP disrupt WIP binding. Reason: Confirms WIP-WASP interaction importance but protein binding is too general. Supporting Evidence: PMID:12591280 X-linked thrombocytopenia caused by a mutation in the Wiskott-Aldrich syndrome (WAS) gene that disrupts interaction with the WAS protein (WASP)-interacting protein (WIP). |
| GO:0005515 protein binding | IPI PMID:12620186 Cortactin interacts with WIP in regulating Arp2/3 activation... | MARK AS OVER ANNOTATED | Summary: Demonstrates WIP interaction with cortactin and NCK1 in regulating Arp2/3 activation and membrane protrusion. Reason: Important functional interaction but better captured by SH3 domain binding or cytoskeletal protein binding terms. Supporting Evidence: PMID:12620186 Cortactin interacts with WIP in regulating Arp2/3 activation and membrane protrusion |
| GO:0005515 protein binding | IPI PMID:16488394 WASP suppresses the growth defect of Saccharomyces cerevisia... | MARK AS OVER ANNOTATED | Summary: Functional study of WASP-WIP interaction in yeast model. Reason: Protein binding is uninformative. Cross-species complementation study. Supporting Evidence: PMID:16488394 WASP suppresses the growth defect of Saccharomyces cerevisiae las17Delta strain in the presence of WIP. |
| GO:0005515 protein binding | IPI PMID:16582881 Wiskott-Aldrich syndrome protein is involved in alphaIIb bet... | MARK AS OVER ANNOTATED | Summary: Demonstrates WIP-WASL interaction in alphaIIb beta3-mediated cell adhesion. Reason: Protein binding too general for this specific functional context. Supporting Evidence: PMID:16582881 Wiskott-Aldrich syndrome protein is involved in alphaIIb beta3-mediated cell adhesion. |
| GO:0005515 protein binding | IPI PMID:17213309 WIP is a chaperone for Wiskott-Aldrich syndrome protein (WAS... | MARK AS OVER ANNOTATED | Summary: Key study demonstrating WIP is a chaperone for WASP, stabilizing and protecting it from degradation. Reason: Important mechanistic study but protein binding is uninformative. Better captured by GO:0044183 (protein folding chaperone) which is already annotated. Supporting Evidence: PMID:17213309 WIP is a chaperone for Wiskott-Aldrich syndrome protein (WASP) |
| GO:0005515 protein binding | IPI PMID:17606906 Src phosphorylation of cortactin enhances actin assembly. | MARK AS OVER ANNOTATED | Summary: Demonstrates WIP-cortactin interaction in actin assembly. Reason: Protein binding too general. Supporting Evidence: PMID:17606906 Src phosphorylation of cortactin enhances actin assembly. |
| GO:0005515 protein binding | IPI PMID:19805221 Phosphorylation of WASp is a key regulator of activity and s... | MARK AS OVER ANNOTATED | Summary: Study of WASP phosphorylation regulation and WIP interaction. Reason: Protein binding uninformative. Supporting Evidence: PMID:19805221 Phosphorylation of WASp is a key regulator of activity and stability in vivo. |
| GO:0005515 protein binding | IPI PMID:19817875 Characterization of Wiskott-Aldrich syndrome (WAS) mutants u... | MARK AS OVER ANNOTATED | Summary: WAS mutant characterization study using yeast model. Reason: Protein binding too general. Supporting Evidence: PMID:19817875 Epub 2009 Sep 7. Characterization of Wiskott-Aldrich syndrome (WAS) mutants using Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:20936779 A human MAP kinase interactome. | MARK AS OVER ANNOTATED | Summary: High-throughput interactome study identifying GRB2 as WIP interactor. Reason: From high-throughput screen. GRB2 interaction confirmed but protein binding is uninformative. Supporting Evidence: PMID:20936779 A human MAP kinase interactome. |
| GO:0005515 protein binding | IPI PMID:21398607 Hematopoietic lineage cell-specific protein 1 functions in c... | MARK AS OVER ANNOTATED | Summary: Demonstrates WIP interaction with HCLS1 in podosome organization. Reason: Protein binding too general for this specific functional context. Supporting Evidence: PMID:21398607 Hematopoietic lineage cell-specific protein 1 functions in concert with the Wiskott-Aldrich syndrome protein to promote podosome array organization |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | MARK AS OVER ANNOTATED | Summary: High-throughput interactome study. Reason: From high-throughput screen. Protein binding uninformative. Supporting Evidence: PMID:21516116 Next-generation sequencing to generate interactome datasets. |
| GO:0005515 protein binding | IPI PMID:21706016 Selected reaction monitoring mass spectrometry reveals the d... | MARK AS OVER ANNOTATED | Summary: Study of GRB2 signaling dynamics showing WIP interaction. Reason: Protein binding too general. Supporting Evidence: PMID:21706016 Selected reaction monitoring mass spectrometry reveals the dynamics of signaling through the GRB2 adaptor. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MARK AS OVER ANNOTATED | Summary: High-throughput liver interactome study. Reason: From high-throughput study. Protein binding uninformative. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver. |
| GO:0005515 protein binding | IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv... | MARK AS OVER ANNOTATED | Summary: Skeletal muscle interactome study showing WIP-WASL interaction. Reason: From interactome study. Protein binding too general. Supporting Evidence: PMID:23414517 A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD interactome. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Large-scale proteome map identifying multiple WIP interactors. Reason: High-throughput study. Protein binding uninformative. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Human interactome architecture study. Reason: High-throughput study. Protein binding too general. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | MARK AS OVER ANNOTATED | Summary: Interactome perturbation study. Reason: High-throughput study. Protein binding uninformative. Supporting Evidence: PMID:29892012 Jun 11. An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Dual proteome-scale network study. Reason: High-throughput study. Protein binding too general. 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:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: OpenCell endogenous tagging study. Reason: High-throughput study. Protein binding uninformative. Supporting Evidence: PMID:35271311 2022 Mar 11. OpenCell: Endogenous tagging for the cartography of human cellular organization. |
| GO:0005515 protein binding | IPI PMID:36935496 CLDN6 inhibits breast cancer metastasis through WIP-dependen... | MARK AS OVER ANNOTATED | Summary: Study on CLDN6 inhibiting breast cancer metastasis through WIP-dependent actin cytoskeleton-mediated autophagy. Reason: Protein binding too general. Study demonstrates WIP role in cancer metastasis context. Supporting Evidence: PMID:36935496 CLDN6 inhibits breast cancer metastasis through WIP-dependent actin cytoskeleton-mediated autophagy. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: Multimodal cell maps study. Reason: High-throughput study. Protein binding uninformative. Supporting Evidence: PMID:40205054 Apr 9. Multimodal cell maps as a foundation for structural and functional genomics. |
| GO:0005515 protein binding | IPI PMID:9405671 WIP, a protein associated with wiskott-aldrich syndrome prot... | MARK AS OVER ANNOTATED | Summary: Original discovery paper showing WIP binds WASP, profilin, and actin. Reason: Foundational paper but protein binding is uninformative. The specific interactions (actin binding, profilin binding) are captured by more specific terms. Supporting Evidence: PMID:9405671 WIP binds to WASP at a site distinct from the Cdc42 binding site and has actin as well as profilin binding motifs |
| GO:0005884 actin filament | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl orthology-based transfer from mouse. Reason: Consistent with IBA annotation and experimental evidence. WIP localizes to actin filaments. |
| GO:0015629 actin cytoskeleton | IEA GO_REF:0000120 | ACCEPT | Summary: WIP is a component of the actin cytoskeleton machinery. Reason: Accurate localization. WIP associates with actin cytoskeleton at multiple sites including stress fibers, podosomes, and cortical actin. Supporting Evidence: PMID:9405671 WIP binds to WASP at a site distinct from the Cdc42 binding site and has actin as well as profilin binding motifs |
| GO:0008093 cytoskeletal anchor activity | IDA PMID:17141616 WIP regulates the stability and localization of WASP to podo... | ACCEPT | Summary: WIP anchors WASP at sites of actin polymerization, particularly in podosomes. This is a core molecular function of WIP - it not only stabilizes WASP but localizes it to appropriate cellular sites for actin nucleation. Reason: Excellent annotation capturing a core function. WIP anchors WASP to podosomes and other actin-rich structures. The study shows that even when WASP levels are restored in WIP-deficient cells, WASP cannot localize properly to podosomes without WIP. Supporting Evidence: PMID:17141616 These results indicate that WIP not only protects WASP from calpain cleavage but also facilitates the localization of WASP to sites of actin polymerization PMID:17141616 WIP is essential for podosome formation and cell polarity by preventing the extensive degradation of WASP by calpain and by facilitating the recruitment of WASP to discrete foci to form the core of podosomes |
| GO:0044183 protein folding chaperone | EXP PMID:23870269 NMR determines transient structure and dynamics in the disor... | ACCEPT | Summary: NMR study characterizing the intrinsically disordered C-terminal domain of WIP that contains the WASP-binding site. The study reveals transient structure in the WIP C-terminus, consistent with its chaperone-like function toward WASP. Reason: WIP functions as a chaperone for WASP, stabilizing it and preventing degradation (PMID:17213309, PMID:17141616). This EXP annotation from DisProt is appropriate for WIP's role in maintaining WASP stability. Supporting Evidence: PMID:23870269 The WIP C-terminal domain binds to Wiskott-Aldrich syndrome protein (WASp) and regulates its activation and degradation PMID:17141616 WIP prevents WASP cleavage by calpain in DCs since inhibition of this protease in WIP-/- DCs resulted in major recovery of WASP expression |
| GO:0017124 SH3 domain binding | IPI PMID:19798448 Requirements for F-BAR proteins TOCA-1 and TOCA-2 in actin d... | ACCEPT | Summary: WIP binds SH3 domains of multiple proteins including TOCA-1/FNBP1L, NCK1/NCK2, GRB2, and CrkL through its proline-rich regions. This is a core molecular function enabling WIP's scaffold role. Reason: The proline-rich regions of WIP mediate SH3 domain interactions that are essential for WIP's scaffold function. This is more informative than generic protein binding. Supporting Evidence: PMID:19798448 Next, we tested whether the SH3 domain of CeTOCA-1 is also functional and able to associate with one of the known mammalian ligands, N-WASP or C. elegans WSP-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2029466 | ACCEPT | Summary: WIP is present in cytosol as part of WASP/WAVE-ARP2/3 complexes that bind F-actin. Reason: WIP is a cytosolic protein that associates with actin regulatory complexes. Reactome pathway evidence is consistent with biochemical evidence. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2197690 | ACCEPT | Summary: Reactome pathway for WASP/WAVE detachment. Reason: Cytosolic localization consistent with WIP function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2197691 | ACCEPT | Summary: Reactome pathway for WIP binding and activating WASP/N-WASP. Reason: Core function of WIP in cytosol - activating WASP/N-WASP. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2197698 | ACCEPT | Summary: Reactome pathway for Src phosphorylation of WASP/N-WASP. Reason: WIP in cytosol participates in WASP regulation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013157 | ACCEPT | Summary: CDC42 GTPase cycle pathway involving WIP-WASP complex. Reason: WIP cytosolic localization for CDC42-WASP signaling. |
| GO:0003779 actin binding | TAS PMID:9405671 WIP, a protein associated with wiskott-aldrich syndrome prot... | ACCEPT | Summary: Original paper demonstrating WIP binds actin through actin-binding motifs. Reason: Core molecular function. The WH2 domain directly binds G-actin. Expression of WIP increases polymerized actin content. Supporting Evidence: PMID:9405671 Expression of WIP in human B cells, but not of a WIP truncation mutant that lacks the actin binding motif, increased polymerized actin content |
| GO:0005522 profilin binding | TAS PMID:9405671 WIP, a protein associated with wiskott-aldrich syndrome prot... | ACCEPT | Summary: WIP binds profilin, an actin monomer-binding protein that promotes actin polymerization. Reason: Core molecular function enabling WIP's role in actin dynamics. Profilin binding links WIP to actin polymerization machinery. Supporting Evidence: PMID:9405671 WIP binds to WASP at a site distinct from the Cdc42 binding site and has actin as well as profilin binding motifs |
| GO:0008154 actin polymerization or depolymerization | TAS PMID:9405671 WIP, a protein associated with wiskott-aldrich syndrome prot... | ACCEPT | Summary: WIP induces actin polymerization in lymphoid cells. Expression of WIP increases polymerized actin content and induces cerebriform projections. Reason: Core biological process. WIP promotes actin polymerization through direct actin binding and WASP/N-WASP activation. Supporting Evidence: PMID:9405671 Expression of WIP in human B cells, but not of a WIP truncation mutant that lacks the actin binding motif, increased polymerized actin content and induced the appearance of actin-containing cerebriform projections on the cell surface |
| GO:0015629 actin cytoskeleton | TAS PMID:9405671 WIP, a protein associated with wiskott-aldrich syndrome prot... | ACCEPT | Summary: WIP localizes to the actin cytoskeleton. Reason: Accurate localization. WIP colocalizes with actin stress fibers. Supporting Evidence: PMID:9405671 WIP binds to WASP at a site distinct from the Cdc42 binding site and has actin as well as profilin binding motifs |
| GO:0065003 protein-containing complex assembly | TAS PMID:9405671 WIP, a protein associated with wiskott-aldrich syndrome prot... | KEEP AS NON CORE | Summary: WIP assembles protein complexes containing WASP, profilin, and actin. Reason: While WIP does function as a scaffold to assemble multi-protein complexes, this term is very broad. The core function is better captured by more specific annotations. Supporting Evidence: PMID:9405671 WIP, a protein associated with wiskott-aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells. |
| GO:0002102 podosome | IDA PMID:17141616 WIP regulates the stability and localization of WASP to podo... | NEW | Summary: WIP localizes to the core of podosomes and is essential for podosome formation in dendritic cells. WIP-deficient DCs fail to form podosomes and instead form aberrant focal contacts. Reason: Strong experimental evidence for podosome localization and function. This is a core localization for WIP's immune cell function. Supporting Evidence: PMID:17141616 The critical involvement of WIP in DC podosome formation is also supported by the presence of endogenous WIP in the core of podosomes in wild-type cells PMID:17141616 WIP is essential for podosome formation and cell polarity by preventing the extensive degradation of WASP by calpain |
| GO:0071800 podosome assembly | IMP PMID:17141616 WIP regulates the stability and localization of WASP to podo... | NEW | Summary: WIP is essential for podosome assembly. In WIP-deficient cells, podosomes fail to form and are replaced by large focal contacts. Reason: WIP is required for organizing F-actin and clustering integrins into podosome complexes. This is a core biological process. Supporting Evidence: PMID:17141616 Our data suggest that the key role of WIP in podosome formation is in the organization of F-actin and the clustering of integrins and associated proteins |
| GO:0001772 immunological synapse | IDA PMID:17141616 WIP regulates the stability and localization of WASP to podo... | NEW | Summary: WIP is essential for immune synapse formation in T cells and NK cells. WIP-deficient lymphocytes show severe defects in immune synapse assembly, polarity, and function. Reason: Immune synapse localization and function is a core role of WIP in lymphocytes, directly relevant to Wiskott-Aldrich syndrome pathology. Supporting Evidence: file:human/WIPF1/WIPF1-deep-research-falcon.md [WIP is critical for immune synapse formation in T cells] PMID:17141616 WIP regulates the stability and localization of WASP to podosomes in migrating dendritic cells. |
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Q: What is the role of WIP phosphorylation (Ser488) in regulating WIP-WASP interaction?
Experiment: Determine the structure of full-length WIP or WIP-WASP complex. Only the WH2 domain and C-terminal WASP-binding region structures are known. Full structure would reveal how WIP coordinates its multiple functions.
Experiment: Investigate WIP function in cancer cell invasion and metastasis. WIP is overexpressed in some cancers and promotes invadopodia formation. Detailed mechanistic studies could reveal therapeutic targets.
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