Affinage

DBNL

Drebrin-like protein · UniProt Q9UJU6

Length
430 aa
Mass
48.2 kDa
Annotated
2026-06-09
32 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DBNL (HIP-55/mAbp1/SH3P7) is a multidomain actin-associated adaptor protein that couples cytoskeletal dynamics to receptor signaling, membrane trafficking, and cell survival across immune, neuronal, and cardiac contexts (PMID:9891087, PMID:10637315). Through an N-terminal actin-binding (ADF-H/SCAD) region and a C-terminal SH3 domain, it binds F-actin with a defined 1:5 stoichiometry and is recruited to cortical actin and the Arp2/3 complex at lamellipodia downstream of Rac1-driven actin polymerization (PMID:10637315). The SH3 domain scaffolds proline-rich partners: DBNL binds and activates HPK1 to drive the JNK cascade downstream of antigen receptors, where it is recruited to lipid rafts and the immunological synapse, phosphorylated by ZAP-70 at Tyr334/344, and is required for TCR-stimulated JNK/HPK1 activation while negatively regulating NFAT (PMID:10567356, PMID:14557276, PMID:14729663, PMID:16055701). In membrane trafficking, DBNL acts downstream of F-actin assembly to link clathrin, actin, and dynamin at clathrin-coated pits, driving late-stage dynamin recruitment and coated-pit scission in receptor-mediated endocytosis and synaptic vesicle recycling (PMID:16601697, PMID:25690657, PMID:38084909). Tyrosine phosphorylation by Src at Tyr337/347 controls its role in podosome rosette formation and ECM degradation, and the same residues, in phospho-mimetic form, govern N-cadherin surface delivery, propeptide maturation, and neuronal migration in the developing cortex (PMID:22303001, PMID:30504273, PMID:33939796). A distinct AKT/RSK1-dependent phosphorylation node at Ser269/Thr291 directs 14-3-3 complex formation, protein stabilization, and liquid-liquid phase separation, suppressing ASK1-mediated apoptosis and MAP4K1/GPX4-driven ferroptosis to protect the heart against myocardial infarction and heart failure (PMID:24912570, PMID:26679646, PMID:36639542, PMID:38328928, PMID:40675322). DBNL is also cleaved by caspase-3 at Asp361 during apoptosis, severing the actin-binding domain from the SH3 domain (PMID:11689006).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1999 Medium

    Established DBNL as an actin-associated adaptor that physically couples antigen-receptor kinase signaling to the cytoskeleton, defining its core molecular identity.

    Evidence In vitro kinase assays with Src/Syk family kinases, actin colocalization, and sequence analysis of the actin-binding SCAD region

    PMID:9891087

    Open questions at the time
    • Functional consequence of tyrosine phosphorylation not defined
    • Specific signaling pathway downstream not yet identified
  2. 1999 High

    Placed DBNL upstream of HPK1 in the JNK cascade, showing its SH3 domain activates a defined kinase module rather than acting as a passive scaffold.

    Evidence In vitro binding, co-IP, kinase activity assays, and dominant-negative HPK1 epistasis

    PMID:10567356

    Open questions at the time
    • Receptor input driving the cascade not yet established
    • Mechanism by which binding stimulates HPK1 activity unresolved
  3. 2000 High

    Quantified DBNL's F-actin binding (1:5 stoichiometry) and linked its recruitment to Rac1-driven actin polymerization at lamellipodia, defining how it senses cytoskeletal remodeling.

    Evidence In vitro F-actin binding stoichiometry, live-cell imaging, dominant-positive Rac1, and actin polymerization inhibition

    PMID:10637315

    Open questions at the time
    • Relationship between two actin-binding domains and signaling unclear
    • Direct Arp2/3 interaction not biochemically reconstituted
  4. 2001 High

    Identified DBNL as a caspase-3 substrate cleaved at Asp361, revealing a regulated mechanism that uncouples its actin-binding and adaptor modules during apoptosis.

    Evidence In vitro caspase cleavage, D361A site-directed mutagenesis, and Western blot during apoptosis

    PMID:11689006

    Open questions at the time
    • Functional consequence of cleavage fragments not characterized
    • Whether cleavage promotes or limits apoptosis unknown
  5. 2003 High

    Defined the receptor-proximal mechanism in T cells: ZAP-70 phosphorylates DBNL at Tyr334/344 upon TCR engagement, making it required for TCR-specific JNK/HPK1 activation.

    Evidence Co-IP, in vitro kinase assay, Y334F/Y344F mutagenesis, RNAi, and sucrose gradient raft fractionation

    PMID:14557276

    Open questions at the time
    • Structural basis of raft recruitment unresolved
    • Distinct roles of Tyr334 vs Tyr344 not separated
  6. 2004 High

    Localized DBNL function to the immunological synapse and showed dual-domain requirement for synapse recruitment, HPK1 activation, NFAT suppression, and TCR endocytosis.

    Evidence GFP live imaging, RNAi, co-IP, NFAT-luciferase reporter, and flow cytometry for TCR surface levels

    PMID:14729663

    Open questions at the time
    • Mechanism linking TCR endocytosis to NFAT regulation not dissected
  7. 2004 Medium

    Showed the DBNL SH3 domain is targeted by a viral proline-rich ligand (ASFV CD2v), implicating it in pathogen exploitation of the host actin/trafficking machinery.

    Evidence Yeast two-hybrid, direct binding, deletion mapping, and colocalization in infected cells

    PMID:14718626

    Open questions at the time
    • Functional consequence for viral replication not established
    • Single-lab interactor not independently confirmed
  8. 2005 High

    Confirmed the in vivo requirement for DBNL in T-cell activation using knockout mice, validating RNAi-based placement in TCR-driven HPK1/JNK signaling.

    Evidence KO mouse, proliferation assays, cytokine ELISA, flow cytometry, signaling Western blots, and co-IP

    PMID:16055701

    Open questions at the time
    • Whether actin-binding or scaffolding drives the phenotype not separated
  9. 2006 High

    Established DBNL as required for clathrin-mediated and synaptic vesicle endocytosis, placing its function downstream of vesicle fission.

    Evidence KO mouse, transferrin uptake, live imaging of synaptic vesicle recycling, and FM dye assays

    PMID:16601697

    Open questions at the time
    • Molecular partners at the fission step not yet identified in this study
  10. 2015 High

    Defined the molecular mechanism of DBNL in endocytosis: it simultaneously binds clathrin, actin, and dynamin, recruiting dynamin to coated pits downstream of F-actin to drive scission.

    Evidence Live-cell imaging, siRNA, binding assays for three partners, and actin disruption epistasis

    PMID:25690657

    Open questions at the time
    • Stoichiometry of the clathrin/actin/dynamin assembly unresolved
  11. 2012 High

    Linked Src phosphorylation at Tyr337/347 to DBNL-driven podosome rosette formation and ECM degradation, distinguishing it from cortactin-dependent podosome dots.

    Evidence siRNA, Y337F/Y347F phospho-mutant rescue, gelatin degradation, and invasion assays

    PMID:22303001

    Open questions at the time
    • Effectors downstream of phospho-DBNL at rosettes not identified
  12. 2018 High

    Showed Tyr337/347 phosphorylation governs DBNL control of surface N-cadherin and neuronal migration in vivo, extending its actin-adaptor role to cortical development.

    Evidence In utero electroporation knockdown, time-lapse imaging, and phospho-mutant/N-cadherin rescue

    PMID:30504273

    Open questions at the time
    • How phospho-DBNL controls N-cadherin trafficking mechanistically not fully resolved
  13. 2021 Medium

    Defined a trafficking mechanism whereby DBNL binds N-cadherin β-catenin-dependently in the Golgi to promote pro-N-cadherin maturation and adherens junction formation.

    Evidence Co-IP, knockdown, pro- versus mature N-cadherin Western blot, and AJ marker immunofluorescence

    PMID:33939796

    Open questions at the time
    • Identity of the protease excising the propeptide not established
  14. 2014 High

    Discovered the Ser269/Thr291 14-3-3 binding node and linked it to DBNL protein stability and a pro-oncogenic role antagonizing HPK1.

    Evidence Affinity chromatography, S269A/T291A mutagenesis, BiFC, puromycin pulse-chase, and xenograft tumor models

    PMID:24912570 PMID:26679646

    Open questions at the time
    • Kinase generating the phospho-sites not identified at this stage
  15. 2014 Medium

    Identified DBNL as a negative regulator of β-adrenergic ERK1/2 signaling and contractility in cardiac cells, opening its cardiovascular role.

    Evidence Proteomics, gain/loss-of-function in cardiac fibroblasts and cardiomyocytes, ERK1/2 phosphorylation, proliferation, and traction force microscopy

    PMID:24802081 PMID:24880669

    Open questions at the time
    • Molecular link between DBNL and the β-AR/ERK pathway not defined
    • Single-lab findings
  16. 2016 Medium

    Linked the DBNL ADF-H domain to FHL2-dependent suppression of Rho-driven invasion, defining a domain-specific tumor-suppressive axis distinct from its scaffolding functions.

    Evidence Yeast two-hybrid, co-IP, siRNA, ADFH domain overexpression, Rho activity, and invasion assays

    PMID:27129278

    Open questions at the time
    • Reconciliation of pro-oncogenic (14-3-3) versus anti-invasive (FHL2) roles unresolved
  17. 2021 Medium

    Showed DBNL couples Smad7 to TβRI degradation by competing with the Smad7/Axin complex, identifying a mechanism restraining TGF-β signaling and ECM accumulation.

    Evidence Co-IP, gain/loss-of-function, and Western blot for pathway components and ECM genes

    PMID:34331017

    Open questions at the time
    • Single-lab finding; receptor-degradation route (lysosomal vs proteasomal) not defined
  18. 2023 High

    Identified AKT as a kinase for the S269/T291 node, channeling AKT signaling against MAP4K1/GPX4 ferroptosis to protect against myocardial infarction.

    Evidence In vitro AKT kinase assay, S269A/T291A mutagenesis, cardiac-specific overexpression mouse, co-IP, GPX4 assay, and MI model

    PMID:36639542

    Open questions at the time
    • Direct biochemical link between phospho-DBNL and MAP4K1 inhibition not detailed
  19. 2024 High

    Established that AKT phosphorylation of S269/T291 governs DBNL liquid-liquid phase separation, with aberrant aggregation suppressing protective β-AR/P38 signaling in failing hearts.

    Evidence FRAP, DIC microscopy, pull-down, phospho-mutant knock-in mice, cardiac KO/OE models, and P38/MAPK assays

    PMID:38328928

    Open questions at the time
    • Composition of phase-separated condensates not defined
    • Relationship between condensates and 14-3-3 binding unresolved
  20. 2024 Medium

    Linked DBNL to macrophage M1 polarization via AP-1 activation through ERK1/2 and JNK, extending its adaptor role to inflammatory signaling.

    Evidence Overexpression/genetic deletion in macrophages, AP-1 reporter/inhibitor epistasis, MAPK Western blots, and M1 marker assays

    PMID:38417633

    Open questions at the time
    • Direct molecular partners upstream of MAPK in macrophages not identified
  21. 2025 High

    Identified RSK1 as a second kinase phosphorylating S269/T291 to drive 14-3-3 complex formation and ASK1-apoptosis suppression, cementing the cardioprotective phospho-node.

    Evidence In vitro RSK1 kinase assay, S269A/T291A mutagenesis, co-IP, phospho-resistant knock-in MI model, and apoptosis assays

    PMID:40675322

    Open questions at the time
    • Coordination between AKT and RSK1 inputs at the same sites not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DBNL's competing actin-cytoskeletal, endocytic, and S269/T291 phase-separation/14-3-3 functions are coordinated within a single cell, and how phospho-state integrates these roles, remains unresolved.
  • No unified structural model integrating ADF-H, SH3, and disordered phospho-region
  • Tissue-specific partitioning of functions not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005794 Golgi apparatus 2 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1266738 Developmental Biology 2
Partners
14-3-3CLATHRINDYNAMINFHL2HPK1N-CADHERINSMAD7ZAP-70
Complex memberships
HIP-55/14-3-3 complexHIP-55/HPK1 complexclathrin–actin–dynamin coat assembly

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 SH3P7/HIP-55 is a substrate for Src and Syk family kinases (tyrosine phosphorylation at YXXP motifs), contains an SCAD region homologous to actin-binding proteins that mediates actin binding, and colocalizes with actin filaments of the cytoskeleton, implicating it as an adaptor linking antigen receptor signaling to the cytoskeleton. In vitro kinase assay, colocalization immunofluorescence, sequence analysis, SDS-PAGE migration analysis Molecular and cellular biology Medium 9891087
1999 HIP-55 binds HPK1 (hematopoietic progenitor kinase 1) both in vitro and in vivo via its SH3 domain interacting with HPK1 proline-rich domains. Co-expression of HIP-55 increases HPK1 kinase activity and JNK1 kinase activity. A dominant-negative HPK1 mutant blocked HIP-55-mediated JNK1 activation, placing HIP-55 upstream of HPK1 in the JNK signaling cascade. In vitro binding assay, co-immunoprecipitation, kinase activity assay, dominant-negative epistasis The Journal of biological chemistry High 10567356
2000 Mouse Abp1 (mAbp1/SH3P7/DBNL) binds actin filaments using two independent actin-binding domains with a 1:5 saturation stoichiometry. In cells, mAbp1 colocalizes with cortical F-actin and the Arp2/3 complex at lamellipodia; dominant-positive Rac1 expression mimics growth factor-induced mAbp1 recruitment, and this recruitment depends on de novo actin polymerization. In vitro F-actin binding assay (stoichiometry), live-cell fluorescence imaging, dominant-positive Rac1 expression, actin polymerization inhibition Molecular biology of the cell High 10637315
2001 HIP-55 is a direct substrate of caspase-3 during apoptosis; it is cleaved at EHID(361), and the D361A mutant is resistant to caspase cleavage. Caspase cleavage dissociates the actin-binding domain from the SH3 domain of HIP-55. In vitro caspase cleavage assay, site-directed mutagenesis (D361A), Western blot during apoptosis Biochemical and biophysical research communications High 11689006
2001 SH3P7 localizes primarily to dendrites of neurons in rat brain and to peripheral protrusive structures of astrocytes, as determined by immunohistochemistry with isoform-specific antibodies, with immunoreactivity absent from presynaptic terminals. Immunohistochemistry, immunofluorescence double-labeling, RT-PCR for isoforms The European journal of neuroscience Medium 11595038
2003 HIP-55 is recruited to glycolipid-enriched microdomains (lipid rafts) upon TCR stimulation. ZAP-70 interacts with HIP-55 in a TCR-stimulation-dependent manner and phosphorylates HIP-55 at Tyr-334 and Tyr-344 in vitro and in vivo; the Y334F/Y344F mutant is not phosphorylated in stimulated T cells. RNAi-mediated depletion of HIP-55 in Jurkat cells decreased TCR-stimulated (but not UV-stimulated) JNK activation and HPK1 activation. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis (Y334F/Y344F), RNA interference, sucrose density gradient fractionation The Journal of biological chemistry High 14557276
2004 HIP-55 localizes to the T cell–APC immunological synapse in an antigen-dependent manner, requiring both its SH3 and actin-binding domains for recruitment. HIP-55 binds and activates HPK1 at the synapse, forming a complex that negatively regulates NFAT activation downstream of TCR. HIP-55 also promotes basal and ligand-dependent TCR down-modulation/endocytosis, requiring both ADF-H and SH3 domains. GFP fusion live imaging, RNA interference, overexpression, co-immunoprecipitation, NFAT-luciferase reporter assay, flow cytometry for TCR surface expression The Journal of biological chemistry High 14729663
2004 The cytoplasmic tail of ASFV CD2v protein binds to the SH3 domain of SH3P7/HIP-55 via proline-rich PPPKPC repeats, as shown by yeast two-hybrid and direct binding studies. CD2v and SH3P7 co-localize in Golgi-derived membranes surrounding perinuclear virus factories in ASFV-infected cells. Yeast two-hybrid, direct binding assay, deletion mutagenesis, co-localization immunofluorescence in infected cells The Journal of general virology Medium 14718626
2005 HIP-55 knockout mice show defective T-cell proliferation, decreased cytokine production, reduced activation marker upregulation, and partially defective TCR signaling (LAT/PLCγ1 phosphorylation, HPK1/JNK activation) upon TCR stimulation. HIP-55 interacts with and is phosphorylated by ZAP-70, and is required for JNK and HPK1 activation in TCR signaling. Gene knockout mouse model, T-cell proliferation assay, cytokine ELISA, flow cytometry, Western blot signaling assays, co-immunoprecipitation Molecular and cellular biology High 16055701
2006 SH3P7/mAbp1-deficient mice show reduced receptor-mediated endocytosis in embryonic fibroblasts and reduced synaptic vesicle endocytosis in hippocampal neurons; recycling of synaptic vesicles is severely delayed ~4-fold. These results place mAbp1 function downstream of vesicle fission in clathrin-mediated endocytosis (CME). Targeted gene disruption (KO mouse), transferrin uptake assay (CME), live imaging of synaptic vesicle recycling in hippocampal boutons, FM dye loading/unloading The EMBO journal High 16601697
2007 The adapter protein 3BP2 directly interacts with the SH3 domain of HIP-55 via a proline-rich domain of 3BP2. 3BP2 co-localizes with HIP-55 in T cell lipid rafts and at the T cell/APC synapse. Direct binding assay, co-localization immunofluorescence, deletion mapping FEBS letters Medium 17306257
2009 Upon platelet activation by thrombin, HIP-55 becomes increasingly associated with both Syk kinase and integrin β3. HIP-55-deficient platelets show reduced fibrinogen binding upon thrombin stimulation, demonstrating a role for HIP-55 in integrin activation and platelet function. Proteomics/mass spectrometry, NeutrAvidin affinity chromatography, co-immunoprecipitation, fibrinogen binding assay on HIP-55-deficient platelets Proteomics Medium 19725075
2012 mAbp1/DBNL localizes to podosomes in Src-transformed fibroblasts and is required for formation of podosome rosettes but not individual podosome dots (which require cortactin). Src phosphorylates mAbp1 at Tyr337 and Tyr347, and these phosphorylation events are required for podosome rosette formation and ECM degradation. Depletion of mAbp1 increased invasive cell migration. Interaction with WIP was not required for podosome rosette formation. siRNA knockdown, overexpression of phospho-mutants (Y337F/Y347F), immunofluorescence, gelatin degradation assay, Boyden chamber invasion assay Journal of cell science High 22303001
2014 HIP-55 forms a complex with 14-3-3 proteins via phospho-Ser269/Thr291 sites, identified by affinity chromatography. S269A/T291A mutant HIP-55 (HIP-55AA) abolishes 14-3-3 binding. Tumors expressing HIP-55AA show significantly reduced growth in xenograft models compared to wild-type HIP-55, supporting a pro-oncogenic role mediated by the HIP-55/14-3-3 interaction node that antagonizes HPK1 tumor suppressor function. Affinity chromatography (14-3-3 pull-down), site-directed mutagenesis (S269A/T291A), xenograft tumor model, colony formation and invasion assays Oncotarget High 24912570
2014 HIP-55 negatively regulates β-adrenergic receptor-activated ERK1/2 signaling and cardiac fibroblast proliferation; both HIP-55 overexpression and knockdown studies confirmed this regulatory role. Proteomics, HIP-55 overexpression and knockdown in cardiac fibroblasts, ERK1/2 phosphorylation assay, proliferation assay Molecular bioSystems Medium 24802081
2014 14-3-3 interacts with HIP-55 through S269/T291 sites (confirmed by BiFC and co-IP); the 14-3-3/HIP-55 complex increases HIP-55 protein stability, as the S269A/T291A mutant (defective in 14-3-3 binding) shows reduced stability after puromycin block of new protein synthesis. Bimolecular fluorescence complementation (BiFC), co-immunoprecipitation, pulse-chase with puromycin, site-directed mutagenesis Journal of Peking University. Health sciences Medium 26679646
2014 HIP-55 negatively regulates myocardial contractility; knockdown increased and overexpression decreased contractile traction forces in single cardiomyocytes. HIP-55 co-localizes with F-actin in cardiomyocytes, suggesting the mechanism involves HIP-55–F-actin interaction. Adenoviral overexpression and knockdown, traction force microscopy, immunofluorescence co-localization Journal of biomechanics Medium 24880669
2015 mAbp1/HIP-55 binds clathrin, actin, and dynamin simultaneously, acting as an adaptor that links dynamin to actin at clathrin-coated pits (CCPs). Live-cell imaging shows mAbp1 is recruited specifically at a late stage to long-lived CCPs. mAbp1 knockdown reduced dynamin recruitment at the plasma membrane and impaired CCP scission. Actin disruption eliminated both mAbp1 and dynamin recruitment, indicating mAbp1 acts downstream of F-actin assembly to recruit dynamin. Live-cell imaging, siRNA knockdown, co-immunoprecipitation/binding assays with clathrin/actin/dynamin, actin disruption experiments FASEB journal High 25690657
2016 mAbp1/HIP-55 interacts with FHL2 through its N-terminal ADF homology (ADFH) domain, identified by yeast two-hybrid. Depletion of mAbp1 or ectopic expression of its ADFH domain increased Rho GTPase signaling and breast cancer cell invasion; ADFH-domain-induced invasion required FHL2 expression, placing FHL2 downstream of mAbp1 in the Rho/invasion axis. Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, domain overexpression, Rho GTPase activity assay, Boyden chamber invasion assay The Journal of biological chemistry Medium 27129278
2018 Dbnl (DBNL) is required for neuronal migration, multipolar morphology, and polarity in the developing cerebral cortex. Dbnl knockdown decreased plasma membrane-localized N-cadherin in cortical neurons. Neuronal migration defects were rescued by N-cadherin/αN-catenin overexpression or by a phospho-mimetic Dbnl (Y337E/Y347E) but not by phospho-resistant Dbnl (Y337F/Y347F), placing Tyr337/347 phosphorylation upstream of N-cadherin regulation. In utero electroporation knockdown, time-lapse imaging, rescue with N-cadherin/αN-catenin and phospho-mutants, surface N-cadherin quantification The Journal of neuroscience High 30504273
2021 Dbnl interacts with N-cadherin in a β-catenin-dependent manner during anterograde Golgi trafficking and promotes pro-N-cadherin propeptide excision and maturation. Dbnl knockdown causes pro-N-cadherin accumulation and limits adherens junction formation, disrupting apico-basal polarity in the neural tube. Co-immunoprecipitation, Dbnl knockdown, Western blot for pro-N-cadherin vs mature N-cadherin, immunofluorescence for AJ markers The Journal of cell biology Medium 33939796
2021 HIP-55 interacts with Smad7 and competes with Smad7/Axin complex formation, thereby inhibiting Axin-mediated Smad7 degradation. HIP-55 couples Smad7 to TβRI (but not TβRII) to drive TβRI degradation; loss of HIP-55 causes TGF-β signaling overactivation and abnormal ECM gene accumulation. Co-immunoprecipitation, overexpression and knockdown, Western blot for signaling pathway components and ECM genes Acta pharmacologica Sinica Medium 34331017
2023 HIP-55 is a new AKT substrate phosphorylated at S269 and T291. AKT-phosphorylated HIP-55 directs AKT signaling to negatively regulate the MAP4K1 pathway, protecting against MI-induced ferroptosis. S269A/T291A-mutated HIP-55 fails to inhibit the MAP4K1/GPX4 ferroptosis pathway and fails to protect against MI injury in vivo. In vitro kinase assay (AKT phosphorylation), site-directed mutagenesis (S269A/T291A), cardiac-specific overexpression mouse model, co-immunoprecipitation, GPX4 assay, MI model Cell death and differentiation High 36639542
2023 HIP-55 interacts with clathrin and F-actin to promote clathrin-mediated endocytosis of nanoparticles (quantum dots). A HIP-55 ΔADF mutant defective in F-actin binding fails to promote nanoparticle endocytosis. HIP-55 knockout inhibits QD endocytosis in vivo. Co-immunoprecipitation (HIP-55–clathrin interaction), ΔADF domain mutant overexpression, pharmacological clathrin inhibition, HIP-55 KO mouse, live imaging Nano letters Medium 38084909
2024 AKT phosphorylates HIP-55 at S269 and T291, which is required for normal liquid-liquid phase separation of HIP-55. Failure of AKT-mediated phosphorylation leads to abnormal HIP-55 aggregation. HIP-55 phase separation inhibits β-adrenergic receptor-mediated P38/MAPK signaling. Phospho-deficient HIP-55 (S269A/T291A) undergoes massive aberrant phase separation, loses protective activity against heart failure, and phospho-resistant knock-in mice show aggravated HF. FRAP assay, DIC microscopy, pull-down, immunofluorescence, phospho-mutant knock-in mice, cardiac-specific KO and OE mouse models, P38/MAPK signaling assays Circulation High 38328928
2024 HIP-55 facilitates AP-1 complex activation in macrophages by promoting ERK1/2 and JNK phosphorylation in response to Ang II; blocking AP-1 attenuates HIP-55-mediated macrophage M1 polarization. HIP-55 expression is upregulated in M1 macrophages, and its genetic deletion inhibits Ang II-induced M1 polarization. HIP-55 overexpression and genetic deletion in macrophages, AP-1 reporter/inhibitor assay, ERK1/2 and JNK phosphorylation Western blot, M1 polarization marker assay Cellular signalling Medium 38417633
2025 RSK1 phosphorylates HIP-55 at S269/T291 to promote 14-3-3/HIP-55 complex formation, which suppresses the ASK1 apoptotic pathway. S269A/T291A HIP-55 (RSK1-phosphorylation-deficient) fails to form the 14-3-3/HIP-55 complex and fails to protect cardiomyocytes against MI-induced apoptosis in vivo and in vitro. In vitro kinase assay (RSK1), site-directed mutagenesis (S269A/T291A), co-immunoprecipitation, in vivo MI model with phospho-resistant knock-in, apoptosis assays Journal of molecular and cellular cardiology High 40675322

Source papers

Stage 0 corpus · 32 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Association of mouse actin-binding protein 1 (mAbp1/SH3P7), an Src kinase target, with dynamic regions of the cortical actin cytoskeleton in response to Rac1 activation. Molecular biology of the cell 130 10637315
1999 SH3P7 is a cytoskeleton adapter protein and is coupled to signal transduction from lymphocyte antigen receptors. Molecular and cellular biology 77 9891087
2004 Recruitment of the actin-binding protein HIP-55 to the immunological synapse regulates T cell receptor signaling and endocytosis. The Journal of biological chemistry 74 14729663
1999 A novel src homology 3 domain-containing adaptor protein, HIP-55, that interacts with hematopoietic progenitor kinase 1. The Journal of biological chemistry 56 10567356
2005 HIP-55 is important for T-cell proliferation, cytokine production, and immune responses. Molecular and cellular biology 49 16055701
2004 The CD2v protein of African swine fever virus interacts with the actin-binding adaptor protein SH3P7. The Journal of general virology 48 14718626
2003 The SH3 domain-containing adaptor HIP-55 mediates c-Jun N-terminal kinase activation in T cell receptor signaling. The Journal of biological chemistry 39 14557276
2023 Adaptor protein HIP-55-mediated signalosome protects against ferroptosis in myocardial infarction. Cell death and differentiation 36 36639542
2001 Caspase-mediated cleavage of actin-binding and SH3-domain-containing proteins cortactin, HS1, and HIP-55 during apoptosis. Biochemical and biophysical research communications 35 11689006
2006 SH3P7/mAbp1 deficiency leads to tissue and behavioral abnormalities and impaired vesicle transport. The EMBO journal 29 16601697
2012 Src-mediated phosphorylation of mammalian Abp1 (DBNL) regulates podosome rosette formation in transformed fibroblasts. Journal of cell science 26 22303001
2009 Proteomic analysis of resting and thrombin-stimulated platelets reveals the translocation and functional relevance of HIP-55 in platelets. Proteomics 25 19725075
2018 Drebrin-like (Dbnl) Controls Neuronal Migration via Regulating N-Cadherin Expression in the Developing Cerebral Cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 30504273
2024 Phosphorylation-Regulated Dynamic Phase Separation of HIP-55 Protects Against Heart Failure. Circulation 19 38328928
2023 Nanoparticles Internalization through HIP-55-Dependent Clathrin Endocytosis Pathway. Nano letters 18 38084909
2014 HIP-55/DBNL-dependent regulation of adrenergic receptor mediates the ERK1/2 proliferative pathway. Molecular bioSystems 17 24802081
2007 Abl-SH3 binding protein 2, 3BP2, interacts with CIN85 and HIP-55. FEBS letters 17 17306257
2014 Pro-oncogenic function of HIP-55/Drebrin-like (DBNL) through Ser269/Thr291-phospho-sensor motifs. Oncotarget 15 24912570
2016 Mammalian Actin-binding Protein-1/Hip-55 Interacts with FHL2 and Negatively Regulates Cell Invasion. The Journal of biological chemistry 12 27129278
2001 Molecular cloning and dendritic localization of rat SH3P7. The European journal of neuroscience 12 11595038
2021 Dbnl and β-catenin promote pro-N-cadherin processing to maintain apico-basal polarity. The Journal of cell biology 9 33939796
2014 Regulation of cell survival by the HIP-55 signaling network. Molecular bioSystems 8 24668193
2015 Mammalian actin-binding protein 1/HIP-55 is essential for the scission of clathrin-coated pits by regulating dynamin-actin interaction. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 7 25690657
2024 Adaptor protein HIP-55 promotes macrophage M1 polarization through promoting AP-1 complex activation. Cellular signalling 4 38417633
2021 The multifunctional adaptor protein HIP-55 couples Smad7 to accelerate TGF-β type I receptor degradation. Acta pharmacologica Sinica 2 34331017
2020 Multi-omic analysis reveals HIP-55-dependent regulation of cytokines release. Bioscience reports 2 32134471
2019 Identification of a new type of haematopoietic progenitor kinase-interacting protein (HIP-55) in Aedes aegypti mosquito haemocytes and its involvement in immunity-like functions in mosquito: a molecular study. Parasitology research 2 31377908
2014 Phosphosite mapping of HIP-55 protein in mammalian cells. International journal of molecular sciences 2 24651461
2014 HIP-55 negatively regulates myocardial contractility at the single-cell level. Journal of biomechanics 2 24880669
2025 14-3-3/HIP-55 complex attenuates cardiomyocyte apoptosis. Journal of molecular and cellular cardiology 1 40675322
2026 Molecular Mechanisms of DBNL in Heart Failure: From Macrophage Immunometabolism to Therapeutic Implications. Journal of visualized experiments : JoVE 0 41553874
2015 [14-3-3/HIP-55 complex increases the stability of HIP-55]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 0 26679646

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