Affinage

DLGAP5

Disks large-associated protein 5 · UniProt Q15398

Length
846 aa
Mass
95.1 kDa
Annotated
2026-06-09
71 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DLGAP5 (HURP) is a RanGTP-regulated, importin-β-controlled microtubule-associated protein that stabilizes spindle microtubules and is essential for chromosome congression and bipolar spindle assembly during mitosis (PMID:16631580, PMID:16769820). RanGTP releases HURP from an inhibitory importin-β complex and, together with continued importin-β cycling, confines it to the chromosome-proximal, kinetochore-fiber plus-end region of the spindle (PMID:16631580, PMID:34541678). Cryo-EM shows HURP stabilizes the microtubule lattice and preferentially binds the GDP lattice, accumulating on depolymerizing kinetochore fibers while avoiding nascent polymerizing regions (PMID:35948594, PMID:39516491); its tubulin-binding domain engages the vinca site on β-tubulin, allowing it to compete with vinca alkaloids (PMID:39397030). At this location HURP promotes γ-TuRC-mediated and TPX2-synergized branching microtubule nucleation (PMID:39516491), steric-modulates Kif18A motility to control plus-end dynamics (PMID:39516196), and cooperates with TACC3 to drive kinetochore-microtubule assembly and lateral attachment (PMID:30054275). HURP acts within a Ran-dependent complex with TPX2, XMAP215, Eg5 and Aurora A required for spindle formation (PMID:16631581). Its activity is set by layered post-translational control: Aurora A phosphorylation relieves an intramolecular C-terminal autoinhibition of the N-terminal microtubule-binding domain and governs its chromosome-proximal gradient distribution (PMID:18321990, PMID:23610398), while Cdk1–cyclin B phosphorylation targets it for SCF(Fbx7)-mediated proteasomal degradation (PMID:15145941). Outside mitosis, PRMT5-mediated arginine methylation at R122 stabilizes acetyl-tubulin bundling to brake Golgi repositioning and cell migration, an effect reversed by JMJD6 demethylation through an NF-κB–Cdc42 cascade (PMID:34541678, PMID:36250981). HURP is required for female fertility and early development: knockout and patient-variant studies show defective oocyte and embryonic spindle assembly via loss of the DLGAP5–TACC3 interaction, causing oocyte maturation arrest and embryonic arrest (PMID:21173113, PMID:40639803, PMID:40796344). In cancers, DLGAP5 stabilizes E2F1 and MYC through USP11-dependent deubiquitination in self-reinforcing transcriptional feedback loops that promote proliferation, glycolysis and drug resistance (PMID:38182895, PMID:39990228).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2003 Medium

    Establishing that HURP is a cell-cycle-regulated mitotic protein framed it as a candidate spindle factor rather than a generic gene.

    Evidence Cell-cycle synchronization with RT-PCR and immunofluorescence in HeLa cells

    PMID:12527899

    Open questions at the time
    • No molecular function assigned
    • Spindle-pole localization later refined to kinetochore microtubules
  2. 2005 High

    Identifying Aurora A as a HURP kinase showed that HURP function and stability are kinase-controlled, the first layer of its post-translational regulation.

    Evidence In vitro kinase assay, co-IP, phospho-deficient HURP-4P mutant, catalytically inactive Aurora A

    PMID:15987997

    Open questions at the time
    • Mechanism by which phosphorylation enables complex assembly not yet defined
    • Specific phosphosites' structural consequences unresolved at this stage
  3. 2004 High

    Linking Cdk1-cyclin B phosphorylation to SCF(Fbx7)-mediated degradation defined how HURP levels are cleared, complementing its kinase activation.

    Evidence Fbx7 siRNA, ubiquitination assay, co-IP, phosphosite mutagenesis of substrate and adaptor

    PMID:15145941

    Open questions at the time
    • Timing of degradation within mitosis not fully mapped
    • Interplay with Aurora A phosphorylation not directly tested
  4. 2006 High

    Resolving how RanGTP, importin-β and the TPX2/XMAP215/Eg5/Aurora A complex govern HURP localization and microtubule stabilization established its core mitotic mechanism.

    Evidence Importin-β/Ran mutant overexpression, IP-MS complex identification, Xenopus extract antibody injection, siRNA, in vitro MT binding/bundling, FRAP across three independent papers

    PMID:16631580 PMID:16631581 PMID:16769820

    Open questions at the time
    • Structural basis of lattice stabilization not yet known
    • Quantitative localization gradient not yet defined
  5. 2006 High

    Cryo-EM of HURP-decorated microtubules provided the first structural view of how it bundles and reconfigures the lattice.

    Evidence Cryo-EM and surface shadowing of HURP-decorated microtubules in vitro

    PMID:17118403

    Open questions at the time
    • Physiological relevance of the outer tubulin sheet in cells unclear
    • Nucleotide-state preference not yet examined
  6. 2008 High

    Discovering intramolecular autoinhibition relieved by Aurora A phosphorylation explained mechanistically how kinase signaling switches HURP microtubule affinity on.

    Evidence Domain-mapping, in vitro MT binding with N/C fragments, trans-dominant C-terminal expression, Aurora A kinase assay

    PMID:18321990

    Open questions at the time
    • Phosphosite-resolved structural model of the released state lacking
  7. 2008 High

    Knockout phenotyping revealed an estrogen-induced uterine role of HURP in implantation, broadening its biology beyond the spindle.

    Evidence Hurp knockout mice, breeding, uterine histology, estrogen treatment

    PMID:18676373

    Open questions at the time
    • Molecular target of HURP in stromal proliferation unknown
    • Connection to mitotic function not established
  8. 2010 High

    Oocyte and Drosophila ortholog studies showed HURP maintains spindle bipolarity and centrosome-spindle coupling, generalizing its stabilizing role to acentriolar and syncytial systems.

    Evidence Hurp knockout mouse oocytes, Kinesin-5 inhibition, live imaging; mars mutant Drosophila genetics

    PMID:19174464 PMID:21173113

    Open questions at the time
    • Direct partners mediating MTOC sorting not identified
  9. 2011 Medium

    Identifying Kif18A as a HURP-regulated motor connected HURP to plus-end dynamics control during chromosome congression.

    Evidence Co-IP, BiFC, live imaging, Kif18A rescue of HURP(278) overexpression phenotype

    PMID:21924616

    Open questions at the time
    • Single lab
    • Molecular basis of steric regulation resolved only later [#27]
  10. 2011 Medium

    Transcriptional and oncogenic studies (c-Rel, HBx/SATB1/survivin, gankyrin/p53) positioned HURP as a chemoresistance effector in hepatocellular carcinoma.

    Evidence ChIP, shRNA knockdown, pathway inhibition, ubiquitination assays, xenografts

    PMID:20541537 PMID:21549688 PMID:22230478

    Open questions at the time
    • Single-lab pathway reconstructions
    • Direct vs indirect effects on p53 not fully separated
  11. 2013 Medium

    Chemical-probe imaging showed Aurora A phosphorylation governs HURP's spatial partitioning between centrosomal and kinetochore microtubules, refining the regulatory logic of its localization gradient.

    Evidence Multiple Aurora A inhibitors, phospho-specific antibodies, immunofluorescence

    PMID:23516487 PMID:23610398

    Open questions at the time
    • No direct mutagenesis of sites controlling the gradient
    • Single lab
  12. 2018 Medium

    Defining the HURP–TACC3 interaction established a partner-based mechanism for kinetochore-microtubule assembly and lateral attachment.

    Evidence Co-IP, BiFC, siRNA, immunofluorescence

    PMID:30054275

    Open questions at the time
    • Structural basis of the interaction unknown
    • Single lab
  13. 2019 High

    Single-centrosome experiments showed HURP accumulation scales inversely with half-spindle length, defining a length-dependent feedback that sets k-fiber stability and spindle symmetry.

    Evidence Centrinone/laser-ablation single-centrosome cells, siRNA, live imaging in 3 cell lines

    PMID:31668617

    Open questions at the time
    • Molecular sensor of length not identified
  14. 2020 High

    Acute Ran degradation dissected importin-β/Ran control as specifically required for HURP and HSET chromosome-proximal localization, distinguishing it from NuMA/TPX2 activation.

    Evidence Auxin-inducible degron Ran depletion, FRAP, immunofluorescence

    PMID:33186548

    Open questions at the time
    • How the binding–dissociation cycle is biochemically tuned not fully resolved
  15. 2021 Medium

    PRMT5 methylation of HURP at R122 revealed a non-mitotic role stabilizing Golgi tubulin bundling and braking cell migration.

    Evidence PRMT5 methyltransferase assay, R122F mutant, acetyl-tubulin co-IP, nocodazole sensitivity, wound healing

    PMID:34541678

    Open questions at the time
    • Single lab
    • Endogenous methylation stoichiometry not measured
  16. 2022 Medium

    JMJD6 demethylation of R122 and the NF-κB–centrosome–Cdc42 cascade defined the reversible methylation switch controlling Golgi repositioning and migration.

    Evidence JMJD6 demethylase assay, R122F/R122K mutants, NF-κB reporter, Cdc42 knockdown, Golgi repositioning assay

    PMID:36250981

    Open questions at the time
    • Single lab
    • Crosstalk with mitotic phosphorylation not addressed here
  17. 2022 High

    Demonstrating HURP's preference for the GDP lattice explained the chromosome-proximal 'HURP-gap' and how it discriminates depolymerizing from polymerizing k-fibers.

    Evidence In vitro GDP vs GTP microtubule binding, endogenously labeled HURP imaging, FRAP, quantitative modeling

    PMID:35948594

    Open questions at the time
    • Structural basis of nucleotide discrimination defined only by later cryo-EM
  18. 2023 Medium

    Identifying Ser627 phosphorylation and at least two distinct metaphase complexes refined the multilayered control of HURP localization and partner binding.

    Evidence Photoactivation, FRAP, phospho-Ser627 mutant IP of multiple partners

    PMID:37484914

    Open questions at the time
    • Composition and function of the two complexes not fully resolved
    • Single lab
  19. 2023 Medium

    The Ajuba/PRMT5/Aurora-A complex coupling sequential methylation then p725 phosphorylation showed how a PTM cascade directs HURP to shape Golgi morphology by stabilizing GA assembly factors.

    Evidence Scaffold complex co-IP, p725A mutagenesis, knockdown-rescue, GA marker colocalization, GST-pulldown of TRIP11/GRASP65/GM130

    PMID:37370099

    Open questions at the time
    • Single lab
    • Direct vs scaffold-mediated GAF stabilization not fully separated
  20. 2024 High

    Cryo-EM resolved HURP binding the vinca site on β-tubulin, giving a structural mechanism for its lattice stabilization and for vinca-alkaloid drug resistance.

    Evidence Cryo-EM HURP–tubulin structure, in vitro vinorelbine competition, cell-based MT growth assay

    PMID:39397030

    Open questions at the time
    • Clinical relevance of HURP-mediated vinca resistance not tested in patients
  21. 2024 High

    Reconstitution showed HURP promotes γ-TuRC-mediated and TPX2-synergized branching nucleation and steric-modulates Kif18A motility, integrating its stabilizing role into nucleation and length control.

    Evidence Xenopus extract branching assays, cryo-EM of HURP on lattice, γ-TuRC nucleation, single-molecule Kif18A imaging

    PMID:39516196 PMID:39516491

    Open questions at the time
    • How TPX2 condensates switch HURP function in cells not fully defined
  22. 2024 Medium

    Oncogenic E2F1/MYC feedback loops via USP11-dependent deubiquitination established DLGAP5 as a stabilizer of proliferative transcription factors driving cancer and drug resistance.

    Evidence Co-IP, ubiquitination/deubiquitination assays, ChIP, glycolysis assays, xenograft and spontaneous tumor models

    PMID:38182895 PMID:39990228

    Open questions at the time
    • Direct binding interfaces with USP11 not structurally defined
    • Relationship to its mitotic microtubule function unclear
  23. 2025 High

    Patient variants, Trim-Away knockdown, and mouse models tied DLGAP5 loss to oocyte and early-embryo spindle failure via the DLGAP5–TACC3 interaction, defining a human reproductive disease link.

    Evidence Whole-exome sequencing, Trim-Away/siRNA in human oocytes, IP-MS interactome, knock-in/mutant mouse models, mRNA injection rescue, PI3K-AKT activator rescue

    PMID:40639803 PMID:40796344 PMID:42121242

    Open questions at the time
    • Mechanistic link between spindle defects and PI3K-AKT signaling not fully resolved
  24. 2025 Medium

    Co-translational centrosomal mRNA targeting via nascent MBD1 microtubule binding revealed a spatial control layer for where HURP is produced during mitosis.

    Evidence APEX2 proximity labeling, drug perturbation, mRNA truncation/mutagenesis, imaging

    PMID:40248433

    Open questions at the time
    • Functional consequence of localized translation for spindle assembly not directly tested
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the mitotic microtubule-stabilizing function, the Golgi/migration methylation switch, and the oncogenic transcription-factor-stabilizing roles are integrated into a single regulatory framework remains unresolved.
  • No unified model connecting spindle, Golgi, and deubiquitinase-scaffolding functions
  • Structural basis of E2F1/MYC/USP11 scaffolding undefined
  • In vivo relevance of HURP-mediated drug resistance untested clinically

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005794 Golgi apparatus 3 GO:0005815 microtubule organizing center 3 GO:0005856 cytoskeleton 3 GO:0005634 nucleus 1
Pathway
R-HSA-1474165 Reproduction 4 R-HSA-1640170 Cell Cycle 4 R-HSA-1643685 Disease 4
Partners
AURKAFBXO7KIF18AKPNB1PRMT5TACC3TPX2USP11
Complex memberships
Ajuba/PRMT5/Aurora-A complexRan-dependent TPX2/XMAP215/Eg5/Aurora A spindle complexSCF(Fbx7) ubiquitin ligase complex (as substrate)

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 HURP is a direct cargo of importin beta; RanGTP controls HURP localization to the mitotic spindle by releasing it from the importin beta inhibitory complex. HURP localizes predominantly to kinetochore microtubules near chromosomes during mitosis, and depletion of HURP impairs K-fiber stabilization and delays chromosome congression. Overexpression of importin beta / RanT24N / RanQ69L mutants in cells, tsBN2 mutant cell analysis, in vitro microtubule bundling assay, siRNA depletion with live-cell imaging Current biology : CB High 16631580
2006 HURP is a component of a Ran-dependent multiprotein complex containing TPX2, XMAP215, Eg5, and Aurora A that is required for conversion of aster-like to spindle-like structures. Aurora A activity is required for complex formation and function. HURP binds microtubules and affects their organization in vitro and in vivo. Immunoprecipitation/mass spectrometry identification of complex, anti-HURP antibody injection in Xenopus egg extract, siRNA depletion in HeLa cells, in vitro microtubule binding assay Current biology : CB High 16631581
2006 HURP binds directly to microtubules in vitro via its N-terminal region, enhances microtubule polymerization, stabilizes mitotic microtubules in vivo, and decreases spindle turnover rate. Depletion results in unaligned chromosomes, reduced interkinetochore tension, and spindle checkpoint activation. Functional genomic siRNA screen, in vitro microtubule binding assay, live-cell imaging, FRAP, immunofluorescence in HeLa cells The Journal of cell biology High 16769820
2003 HURP mRNA expression is cell-cycle regulated, peaking at G2/M in synchronized HeLa cells; HURP protein localizes to spindle poles during mitosis by immunofluorescence. Cell cycle synchronization with RT-PCR, immunofluorescence in mitotic cells Oncogene Medium 12527899
2005 Aurora A phosphorylates HURP in vitro and in vivo; phosphorylation by Aurora A is required for HURP stability and its assembly into complexes. A phosphorylation-deficient HURP-4P mutant (Aurora A sites mutated to Ala) showed reduced stability and poor complex assembly. In vitro kinase assay, co-immunoprecipitation, site-directed mutagenesis, stable transfection of Aurora A catalytically inactive form Molecular and cellular biology High 15987997
2004 Fbx7, an F-box protein of the SCF ubiquitin-ligase complex, recruits HURP through its C-terminal proline-rich region in a Cdk1-cyclin B phosphorylation-dependent manner, leading to proteasome-mediated HURP proteolysis. Mutation of Cdk1-cyclin B phosphorylation sites on HURP or the proline-rich region of Fbx7 abolishes their association. siRNA depletion of Fbx7, ubiquitination assay, co-immunoprecipitation, site-directed mutagenesis of phosphorylation sites The Journal of biological chemistry High 15145941
2006 HURP wraps microtubule ends with an additional tubulin sheet forming two concentric tubes; the outer sheet consists of anti-parallel protofilaments with a novel 42.5° inclination. HURP stabilizes and bundles microtubules and also polymerizes free tubulin into a new configuration. Cryo-electron microscopy, unidirectional surface shadowing of HURP-decorated microtubules in vitro Journal of molecular biology High 17118403
2008 HURP binds microtubules through its N-terminal domain; in the hypophosphorylated state, the C-terminal region of HURP intramolecularly binds the N-terminal microtubule-binding domain and abrogates microtubule affinity. Aurora A phosphorylation of the C-terminal domain releases this autoinhibition, enabling microtubule binding and stabilization. Biochemical domain-mapping, in vitro microtubule binding assay with N- and C-terminal fragments, ectopic expression of C-terminal domain in HeLa cells, Aurora A kinase assay Molecular biology of the cell High 18321990
2010 In mouse oocytes (acentriolar meiotic spindle), HURP accumulates on interpolar MTs near chromosomes via Kinesin-5 activity. HURP promotes MT stability in the spindle central domain to allow efficient MTOC sorting into distinct poles, establishing and maintaining bipolarity. Hurp knockout females are viable but sterile due to defective oocyte divisions. Hurp knockout mouse generation, immunofluorescence, live-cell imaging of oocytes, Kinesin-5 inhibitor treatment The Journal of cell biology High 21173113
2008 Hurp knockout female mice are infertile due to an implantation defect caused by a failure in endometrial stromal proliferation and the decidual reaction, not in ovulation, fertilization, or pre-implantation development. HURP expression in the uterus is induced by estrogen. Hurp knockout mouse generation, breeding experiments, histological analysis of uterus, estrogen treatment The Journal of biological chemistry High 18676373
2011 HURP regulates chromosome congression by interacting with kinesin Kif18A and controlling Kif18A localization and dynamics at the plus ends of kinetochore MTs. The N-terminal microtubule-binding domain of HURP (aa 1-278) mimics Kif18A depletion phenotypes; overexpression of Kif18A partially rescues misaligned chromosomes in HURP(278)-overexpressing cells. Co-immunoprecipitation, bimolecular fluorescence complementation (BiFC), live-cell imaging, rescue experiments Current biology : CB Medium 21924616
2011 HURP overexpression promotes ubiquitination and proteasomal degradation of p53 via upregulation of gankyrin, a positive regulator of MDM2 E3 ubiquitin ligase. Knockdown of HURP leads to p53 accumulation, reduced proliferation, and sensitization to cisplatin in p53-positive cells. Ubiquitination assay, shRNA knockdown, gankyrin siRNA, exogenous p53 expression, tumor xenograft in nude mice Biochemical pharmacology Medium 22230478
2011 HBx viral protein upregulates HURP expression via p38/MAPK pathway through SATB1, and HURP mediates HBx-induced upregulation of survivin, contributing to cisplatin resistance in HCC cells. HBx expression in Hep3B cells, HURP shRNA knockdown, p38/MAPK pathway inhibition, survivin western blotting Biochemical pharmacology Medium 20541537
2011 Sorafenib inhibits HURP expression primarily at the transcriptional level by reducing translation and nuclear translocation of NF-κB family member c-Rel, which directly activates HURP gene transcription. c-Rel knockdown reduces HURP protein level and enhances taxol-induced cell death. Real-time PCR, chromatin immunoprecipitation (ChIP) assay, c-Rel shRNA knockdown, sorafenib treatment Biochemical pharmacology Medium 21549688
2013 Aurora A phosphorylation of HURP regulates its spatial distribution on the mitotic spindle: unphosphorylated HURP associates with centrosomal microtubules while phosphorylated HURP associates with kinetochore microtubules. HURP cycles continuously between these two forms in mitotic cells. Aurora A inhibitors (IBPR001, IBPR002, MLN8237) as chemical probes, immunofluorescence, phospho-specific antibodies in live cells Proceedings of the National Academy of Sciences of the United States of America Medium 23610398
2013 Tripolin A, a non-ATP competitive Aurora A inhibitor, reduces HURP's chromosome-proximal gradient distribution without affecting its microtubule binding, revealing Aurora A phosphorylation controls the gradient localization of HURP but not its general MT association. In vitro Aurora A kinase assay, immunofluorescence in human cells, comparison with MLN8054/MLN8237, in silico docking PloS one Medium 23516487
2009 Mars, the Drosophila ortholog of HURP, is required for the attachment of centrosomes to the mitotic spindle during syncytial nuclear divisions; loss of Mars causes centrosome detachment from spindles and ectopic microtubule nucleation. Mars localizes to nuclei in interphase and to spindle poles during mitosis. mars mutant Drosophila genetics, live-cell and fixed immunofluorescence imaging of early embryos Journal of cell science Medium 19174464
2018 HURP directly interacts with centrosomal protein TACC3 (via HURP residues 1-625) by co-immunoprecipitation and BiFC; HURP is required for TACC3 function during kinetochore microtubule assembly at chromosomes in prometaphase, and HURP regulates lateral kinetochore attachment and chromosome congression through modulation of TACC3. Co-immunoprecipitation, bimolecular fluorescence complementation, siRNA depletion, immunofluorescence The Journal of biological chemistry Medium 30054275
2019 HURP accumulates on k-fiber plus ends inversely proportionally to half-spindle length; centrosomes regulate k-fiber plus-end dynamics indirectly via length-dependent HURP accumulation. HURP depletion in cells with only one centrosome rebalances k-fiber stability and plus-end dynamics and improves spindle symmetry. Generation of human cells with one centrosome by centrinone treatment/laser ablation, HURP siRNA depletion, live-cell imaging in 3 cell lines, immunofluorescence Current biology : CB High 31668617
2020 Ran-GTP and importin-β coordinately promote HURP's dynamic microtubule binding-dissociation cycle to maintain HURP near chromosomes during metaphase. Acute mitotic depletion of Ran reveals it is specifically required for HURP and HSET localization to chromosome-proximal spindle regions to set proper spindle length during prometaphase, but not for NuMA or TPX2 activation. Auxin-inducible degron (AID) technology for acute mitotic Ran depletion in human cells, FRAP, immunofluorescence Current biology : CB High 33186548
2021 PRMT5 methylates HURP at R122; methylated HURP (m122) interacts with acetyl-tubulin and stabilizes its bundling pattern, rigidifying the Golgi apparatus and retarding Golgi repositioning and cell migration. This acts as a brake on cell migration. PRMT5 is downregulated early in wound-healing, decreasing HURP m122. PRMT5 methyltransferase assay, HURP methylation-mimicking mutant (R122F) expression, acetyl-tubulin co-immunoprecipitation, nocodazole sensitivity assay, wound healing assay Journal of cellular physiology Medium 34541678
2022 JMJD6 demethylates HURP at R122, promoting Golgi repositioning and cell migration via NF-κB-induced centrosome repositioning and subsequently Cdc42-dependent Golgi repositioning. The HURP methylation-deficiency mutant (R122K) promotes Golgi repositioning through this NF-κB-CR-Cdc42 cascade. JMJD6 demethylase assay, HURP methylation mutants (122F vs 122K), NF-κB reporter, Cdc42 knockdown, Golgi repositioning assay Journal of cellular physiology Medium 36250981
2022 HURP preferentially binds the GDP microtubule lattice rather than GTP-tubulin in vitro and in vivo, accumulating on the kinetochore-proximal region of depolymerising kinetochore-fibres while avoiding nascent polymerising K-fibres, creating a 'HURP-gap' that corresponds to a mixed-nucleotide zone. In vitro HURP binding to GDP vs GTP microtubules, endogenously-labelled HURP live-cell imaging, FRAP, quantitative modeling Nature communications High 35948594
2023 HURP phosphorylation at Ser627 regulates its localization to kinetochore fibers and its interactions with partner proteins (TPX2, Aurora A, Eg5, Dynein, Kif5B, importin β) in mammalian mitotic cells. HURP participates in at least two distinct complexes during metaphase. Microtubule flux affects HURP dynamics. Photoactivation and FRAP experiments, immunoprecipitation with phospho-Ser627 mutant HURP, co-IP of interaction partners in mitotic cells Frontiers in cell and developmental biology Medium 37484914
2023 The Ajuba/PRMT5/Aurora-A complex coordinates sequential methylation and phosphorylation of HURP; mutual activation of PRMT5 and Aurora-A in this complex leads to HURP methylation (PRMT5) followed by phosphorylation (Aurora-A) to generate HURP p725. HURP p725 localizes near the Golgi apparatus and its crescent distribution shapes GA morphology by stabilizing Golgi assembly factors TRIP11, GRASP65, and GM130. HURP knockdown fragments GA; rescue requires phosphorylation-competent HURP. Scaffold protein complex co-IP, site-directed mutagenesis (p725A), knockdown-rescue, co-localization with GA markers, GST-pulldown of GAFs Cell communication and signaling : CCS Medium 37370099
2024 HURP contains a tubulin-binding domain that binds the vinca domain on β-tubulin (the site targeted by vinca alkaloid drugs). Cryo-EM reveals HURP's tubulin-binding domain interacts directly at the vinca binding site. HURP competes directly with vinorelbine and counters vinorelbine-induced microtubule growth defects in vitro and in vivo, providing a mechanism for drug resistance. Cryo-EM structure of HURP–tubulin complex, in vitro competition assay with vinorelbine, cell-based microtubule growth assay Nature communications High 39397030
2024 HURP stabilizes the microtubule lattice to promote γ-TuRC-mediated microtubule formation; in the presence of TPX2 condensates, HURP localization to microtubules is enhanced, shifting its function toward promoting branching microtubule nucleation. Cryo-EM structure reveals the molecular basis of HURP-mediated microtubule lattice stabilization. HURP is necessary for RanGTP-induced branching microtubule nucleation in Xenopus egg extract. Xenopus egg extract branching nucleation assay, HURP depletion, cryo-EM structure of HURP on microtubule lattice, γ-TuRC nucleation assay, TPX2 condensate co-localization Nature communications High 39516491
2024 Kif18A motility on microtubules is regulated by HURP concentration: sparse HURP decoration activates Kif18A motor activity while higher HURP concentrations inhibit processive motility by steric exclusion (HURP partially overlaps the Kif18A motor-domain microtubule-binding site). HURP and Kif18A together suppress microtubule plus-end dynamics, providing a mechanism for spindle/microtubule length control. Single-molecule imaging in vitro, cryo-EM structure of HURP on microtubule, microtubule dynamics assay with HURP+Kif18A Nature communications High 39516196
2024 DLGAP5 directly binds E2F1 and stabilizes E2F1 by preventing its ubiquitination via USP11 (a deubiquitinase). E2F1 in turn transcriptionally activates DLGAP5, forming a positive feedback loop that drives bladder cancer progression. Co-immunoprecipitation to show DLGAP5-E2F1 direct binding, ubiquitination assay, ChIP/transcription reporter for E2F1 → DLGAP5, in vitro and in vivo tumor assays Oncogene Medium 38182895
2025 DLGAP5 stabilizes MYC protein via deubiquitination mediated by USP11; DLGAP5 facilitates the interaction between USP11 and MYC, and MYC in turn transcriptionally drives DLGAP5 expression, forming a positive feedback loop that increases glycolytic activity and gemcitabine resistance in bladder cancer. Co-immunoprecipitation of DLGAP5-USP11-MYC complex, ubiquitination/deubiquitination assay, ChIP for MYC on DLGAP5 promoter, glycolysis assay, xenograft and spontaneous BLCA mouse models Theranostics Medium 39990228
2025 DLGAP5 mRNA is co-translationally targeted to the centrosome during mitosis; centrosomal transport requires microtubule binding of nascent HURP MBD1 polypeptides. mRNA targeting efficiency is linked to coding sequence length. APEX2-mediated proximity labeling to map centrosome-proximal transcriptome, drug perturbation, truncation/deletion/mutagenesis of DLGAP5 mRNA, imaging of centrosomal mRNA localization RSC chemical biology Medium 40248433
2025 DLGAP5 variants causing protein degradation or reduced expression impair spindle assembly in human oocytes (shown by DLGAP5 Trim-Away knockdown causing abnormal spindle morphology and oocyte maturation arrest). Homozygous Dlgap5 knock-in mice show embryonic arrest at the 4-cell stage with disrupted cell cycle regulation. Whole-exome sequencing of infertility patients, Trim-Away knockdown in human oocytes, knock-in mouse model (CRISPR-Cas9), IVF, immunofluorescence, RNA-seq of 4-cell embryos Human reproduction (Oxford, England) High 40639803
2025 DLGAP5 deficiency disrupts spindle assembly in oocytes and early embryos through its interaction with TACC3; mutant DLGAP5 variants alter protein localization and cause spindle abnormalities in HeLa cells and mouse zygotes. Loss of DLGAP5-TACC3 interaction is the underlying mechanism of embryonic arrest. Whole-exome sequencing, transfection of mutants in HeLa cells, immunoprecipitation-mass spectrometry for interactome, mRNA microinjection in mouse zygotes, site-directed mutant mouse model Human reproduction (Oxford, England) High 40796344
2025 DLGAP5 knockdown in oocytes disrupts PI3K-AKT signaling pathway; PI3K-AKT activators can rescue oocyte maturation defects in Dlgap5-deficient mice. DLGAP5 depletion in human oocytes by siRNA causes abnormal spindle morphology and reduced germinal vesicle breakdown and polar body extrusion. siRNA microinjection in human oocytes, Dlgap5 knockout mouse oocyte analysis, single-cell RNA-seq, PI3K-AKT activator rescue experiment, immunofluorescence Journal of ovarian research Medium 42121242
2025 METTL3-mediated m6A modification of DLGAP5 mRNA promotes DLGAP5 expression in an IGF2BP2-dependent manner during acute liver injury; METTL3 can bind DLGAP5 protein, and DLGAP5 promotes hepatocyte pyroptosis via NF-κB-dependent NLRP3 inflammasome activation and direct potentiation of inflammasome assembly. MeRIP-seq, Mettl3 mutant and Nlrp3 knockout mouse models, primary cell isolation, co-immunoprecipitation (METTL3-DLGAP5), inflammasome assembly assay International journal of biological sciences Medium 40959279
2024 AR (androgen receptor) directly binds the DLGAP5 promoter, enhancing its transcriptional activity; DLGAP5 acts downstream of AR to suppress p53 signaling pathway activation, reducing CD8+ T cell infiltration in triple-negative breast cancer. ChIP assay for AR on DLGAP5 promoter, DLGAP5 siRNA knockdown, p53 pathway reporter/western blot, in vivo xenograft with T cell analysis Translational oncology Medium 39182361
2024 DLGAP5 promotes lung adenocarcinoma cell proliferation via upregulation of PLK1; PLK1 overexpression rescues DLGAP5 knockdown-induced proliferation inhibition, and DLGAP5 overexpression reverses PLK1 suppression by AT9283, establishing DLGAP5 as an upstream regulator of PLK1. siRNA/overexpression of DLGAP5, PLK1 western blot, PLK1 rescue overexpression, in vitro and in vivo tumor assays Journal of translational medicine Medium 38414025
2023 DLGAP5 promotes gallbladder cancer cell proliferation and migration and macrophage M2 polarization by directly activating the cAMP pathway; GST-pulldown demonstrated direct interaction between DLGAP5 and cAMP. GST-pulldown for DLGAP5-cAMP interaction, DLGAP5 overexpression/knockdown, macrophage polarization assay, in vivo xenograft Cancer immunology, immunotherapy : CII Medium 37421434
2023 DLGAP5 silencing inactivates the Wnt/β-catenin signaling pathway in endometrial cancer cells; β-catenin overexpression abolishes the effects of DLGAP5 knockdown on malignant phenotypes, placing DLGAP5 upstream of Wnt/β-catenin in this context. siRNA knockdown of DLGAP5, β-catenin overexpression rescue, western blot for Wnt3/c-Myc/Ki67, apoptosis assays Environmental toxicology Low 36454672
2018 DLGAP5 knockdown has a strong synergistic effect with docetaxel specifically in androgen-sensitive LNCaP prostate cancer cells; siRNA knockdown of the androgen receptor attenuates this synergy, and androgen receptor knockdown enables cells to progress through metaphase arrest induced by DLGAP5 KD + docetaxel. This places androgen receptor signaling in an epistatic relationship with DLGAP5 function in spindle stabilization. siRNA screen, cell viability assays, androgen receptor siRNA knockdown, immunofluorescence for mitotic stage, LNCaP-AI androgen-desensitized cells Cell death & disease Medium 30341281

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 HURP is a Ran-importin beta-regulated protein that stabilizes kinetochore microtubules in the vicinity of chromosomes. Current biology : CB 229 16631580
2006 HURP is part of a Ran-dependent complex involved in spindle formation. Current biology : CB 223 16631581
2006 HURP controls spindle dynamics to promote proper interkinetochore tension and efficient kinetochore capture. The Journal of cell biology 160 16769820
2003 Identification of a novel cell cycle regulated gene, HURP, overexpressed in human hepatocellular carcinoma. Oncogene 134 12527899
2005 Phosphorylation and stabilization of HURP by Aurora-A: implication of HURP as a transforming target of Aurora-A. Molecular and cellular biology 104 15987997
2010 HURP permits MTOC sorting for robust meiotic spindle bipolarity, similar to extra centrosome clustering in cancer cells. The Journal of cell biology 100 21173113
2004 Fbx7 functions in the SCF complex regulating Cdk1-cyclin B-phosphorylated hepatoma up-regulated protein (HURP) proteolysis by a proline-rich region. The Journal of biological chemistry 98 15145941
2013 Silencing of DLGAP5 by siRNA significantly inhibits the proliferation and invasion of hepatocellular carcinoma cells. PloS one 75 24324629
2011 Combined expression of BUB1B, DLGAP5, and PINK1 as predictors of poor outcome in adrenocortical tumors: validation in a Brazilian cohort of adult and pediatric patients. European journal of endocrinology 73 22048964
2008 Aurora A regulates the activity of HURP by controlling the accessibility of its microtubule-binding domain. Molecular biology of the cell 69 18321990
2010 Hepatitis B virus X protein prevents apoptosis of hepatocellular carcinoma cells by upregulating SATB1 and HURP expression. Biochemical pharmacology 55 20541537
2018 Nucleolar and Spindle Associated Protein 1 (NUSAP1) Inhibits Cell Proliferation and Enhances Susceptibility to Epirubicin In Invasive Breast Cancer Cells by Regulating Cyclin D Kinase (CDK1) and DLGAP5 Expression. Medical science monitor : international medical journal of experimental and clinical research 53 30476929
2021 Pan-cancer analysis and experiments with cell lines reveal that the slightly elevated expression of DLGAP5 is involved in clear cell renal cell carcinoma progression. Life sciences 46 34687756
2013 Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules. Proceedings of the National Academy of Sciences of the United States of America 43 23610398
2011 Knockdown of HURP inhibits the proliferation of hepacellular carcinoma cells via downregulation of gankyrin and accumulation of p53. Biochemical pharmacology 41 22230478
2006 HURP wraps microtubule ends with an additional tubulin sheet that has a novel conformation of tubulin. Journal of molecular biology 40 17118403
2011 HURP regulates chromosome congression by modulating kinesin Kif18A function. Current biology : CB 39 21924616
2021 Pan-cancer analysis of the oncogenic role of discs large homolog associated protein 5 (DLGAP5) in human tumors. Cancer cell international 34 34454476
2024 DLGAP5 promotes lung adenocarcinoma growth via upregulating PLK1 and serves as a therapeutic target. Journal of translational medicine 31 38414025
2023 DLGAP5 Regulates the Proliferation, Migration, Invasion, and Cell Cycle of Breast Cancer Cells via the JAK2/STAT3 Signaling Axis. International journal of molecular sciences 30 37958803
2019 Spindle-Length-Dependent HURP Localization Allows Centrosomes to Control Kinetochore-Fiber Plus-End Dynamics. Current biology : CB 29 31668617
2011 The tyrosine kinase inhibitor sorafenib sensitizes hepatocellular carcinoma cells to taxol by suppressing the HURP protein. Biochemical pharmacology 26 21549688
2008 Hurp deficiency in mice leads to female infertility caused by an implantation defect. The Journal of biological chemistry 25 18676373
2021 Knockdown of DLGAP5 suppresses cell proliferation, induces G2/M phase arrest and apoptosis in ovarian cancer. Experimental and therapeutic medicine 24 34539841
2013 Evaluation of urinary HURP mRNA as a marker for detection of bladder cancer: relation to bilharziasis. Medical oncology (Northwood, London, England) 23 24375315
2022 Bisphenol A interacts with DLGAP5 and regulates IL-6/JAK2/STAT3 signaling pathway to promote tumorigenesis and progression of osteosarcoma. Chemosphere 22 36155021
2020 Ran-GTP Is Non-essential to Activate NuMA for Mitotic Spindle-Pole Focusing but Dynamically Polarizes HURP Near Chromosomes. Current biology : CB 22 33186548
2024 DLGAP5 triggers proliferation and metastasis of bladder cancer by stabilizing E2F1 via USP11. Oncogene 20 38182895
2018 A functional genomics screen reveals a strong synergistic effect between docetaxel and the mitotic gene DLGAP5 that is mediated by the androgen receptor. Cell death & disease 20 30341281
2025 DLGAP5 enhances bladder cancer chemoresistance by regulating glycolysis through MYC stabilization. Theranostics 19 39990228
2007 Expression of hurP, a gene encoding a prospective site 2 protease, is essential for heme-dependent induction of bhuR in Bordetella bronchiseptica. Journal of bacteriology 18 17586630
2021 Screening and identification of LMNB1 and DLGAP5, two key biomarkers in gliomas. Bioscience reports 17 33956061
2013 Tripolin A, a novel small-molecule inhibitor of aurora A kinase, reveals new regulation of HURP's distribution on microtubules. PloS one 16 23516487
2009 Mars, a Drosophila protein related to vertebrate HURP, is required for the attachment of centrosomes to the mitotic spindle during syncytial nuclear divisions. Journal of cell science 16 19174464
2024 HURP facilitates spindle assembly by stabilizing microtubules and working synergistically with TPX2. Nature communications 13 39516491
2022 Whole Genome Transcriptomic Analysis of Ovary Granulosa Cells Revealed an Anti-Apoptosis Regulatory Gene DLGAP5 in Polycystic Ovary Syndrome. Frontiers in endocrinology 13 35370991
2022 Evidence for a HURP/EB free mixed-nucleotide zone in kinetochore-microtubules. Nature communications 13 35948594
2022 DLGAP5 knockdown inactivates the Wnt/β-catenin signal to repress endometrial cancer cell malignant activities. Environmental toxicology 13 36454672
2018 The microtubule-associated protein HURP recruits the centrosomal protein TACC3 to regulate K-fiber formation and support chromosome congression. The Journal of biological chemistry 13 30054275
2004 KIAA0008 gene is associated with invasive phenotype of human hepatocellular carcinoma--a functional analysis. Journal of cancer research and clinical oncology 13 15340842
2023 DLGAP5 promotes gallbladder cancer migration and tumor-associated macrophage M2 polarization by activating cAMP. Cancer immunology, immunotherapy : CII 12 37421434
2022 Serum-derived extracellular vesicles promote the growth and metastasis of non-small cell lung cancer by delivering the m6A methylation regulator HNRNPC through the regulation of DLGAP5. Journal of cancer research and clinical oncology 12 36175801
2022 MicroRNA-409-5p inhibits cell proliferation, and induces G2/M phase arrest and apoptosis by targeting DLGAP5 in ovarian cancer cells. Oncology letters 11 35765271
2020 Overexpression of HURP mRNA in head and neck carcinoma and association with in vitro response to vinorelbine. Oncology letters 11 32194751
2024 circ_0058063 promotes breast cancer progression by upregulating DLGAP5 via sponging miR-557. Cancer biomarkers : section A of Disease markers 7 37334578
2024 Transcriptional regulation of DLGAP5 by AR suppresses p53 signaling and inhibits CD8+T cell infiltration in triple-negative breast cancer. Translational oncology 6 39182361
2021 The PRMT5/HURP axis retards Golgi repositioning by stabilizing acetyl-tubulin and Golgi apparatus during cell migration. Journal of cellular physiology 5 34541678
2025 DLGAP5 Promotes Acute Liver Injury via Hepatocyte Pyroptosis-Driven Macrophage Metabolic Reprogramming and M1 Polarization. International journal of biological sciences 4 40959279
2024 HURP binding to the vinca domain of β-tubulin accounts for cancer drug resistance. Nature communications 4 39397030
2023 HURP localization in metaphase is the result of a multi-step process requiring its phosphorylation at Ser627 residue. Frontiers in cell and developmental biology 4 37484914
2023 HURP facilitates spindle assembly by stabilizing microtubules and working synergistically with TPX2. bioRxiv : the preprint server for biology 4 38187686
2022 The JMJD6/HURP axis promotes cell migration via NF-κB-dependent centrosome repositioning and Cdc42-mediated Golgi repositioning. Journal of cellular physiology 4 36250981
2025 DLGAP5 upregulates E2F1 to promote prostate adenocarcinoma neuroendocrine differentiation. Life sciences 3 39923838
2025 Enzyme-mediated proximity labeling reveals the co-translational targeting of DLGAP5 mRNA to the centrosome during mitosis. RSC chemical biology 3 40248433
2025 Pathogenic variants in DLGAP5 cause female infertility characterized by oocyte maturation arrest and embryonic arrest. Human reproduction (Oxford, England) 3 40639803
2024 HURP regulates Kif18A recruitment and activity to synergistically control microtubule dynamics. Nature communications 3 39516196
2023 The crescent-like Golgi ribbon is shaped by the Ajuba/PRMT5/Aurora-A complex-modified HURP. Cell communication and signaling : CCS 3 37370099
2024 Molecular interplay between HURP and Kif18A in mitotic spindle regulation. bioRxiv : the preprint server for biology 2 38645125
2025 Biallelic variants in DLGAP5 cause spindle assembly defects and human early embryonic arrest. Human reproduction (Oxford, England) 1 40796344
2026 DLGAP5 regulates malignancy and lenvatinib sensitivity of hepatocellular carcinoma through AKT/mTOR/NF-κB pathway. European journal of medical research 0 41664119
2026 DLGAP5 promotes salivary adenoid cystic carcinoma proliferation and metastasis through PI3K/AKT pathway. American journal of cancer research 0 41868655
2026 Machine learning-based multi-omic analysis identifies CEP55, DLGAP5, and EZH2 as regulated cell death biomarkers linked to immunotherapy resistance in hepatocellular carcinoma. Naunyn-Schmiedeberg's archives of pharmacology 0 41984188
2026 DLGAP5 protects glioblastoma cells against DNA damage through E2F1-transcripted RAD51AP1. Biochimica et biophysica acta. Molecular basis of disease 0 42002087
2026 Knockdown of DLGAP5 inhibits microglia activation in spinal cord injury rats through limiting NF-κB activation. International immunopharmacology 0 42105706
2026 Loss of DLGAP5 impairs human and mouse oocyte maturation via disrupting the PI3K-AKT signaling axis. Journal of ovarian research 0 42121242
2026 YY1-induced upregulation of DLGAP5 promotes tumor progression in lung adenocarcinoma via Wnt/β-catenin/EMT pathway. Journal of translational medicine 0 42210256
2026 DLGAP5 Drives Lung Adenocarcinoma Cell Growth by Promoting Autophagy Activity. Canadian respiratory journal 0 42257272
2025 DLGAP5 facilitates glioblastoma growth and tumor-associated macrophage M2 polarization. Journal of molecular histology 0 40944860
2025 TFAP4/DLGAP5 promotes tumor progression and macrophage M2 polarization in prostate cancer by activating the JAK2/STAT3 signaling. Experimental cell research 0 40962169
2024 Molecular interplay between HURP and Kif18A in mitotic spindle regulation. Research square 0 38854046
2021 Retracted article: MicroRNA-4521 targets hepatoma up-regulated protein (HURP) to inhibit the malignant progression of breast cancer. Bioengineered 0 34699315

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