Affinage

HASPIN

Serine/threonine-protein kinase haspin · UniProt Q8TF76

Length
798 aa
Mass
88.5 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Haspin is an atypical Ser/Thr kinase that governs the spatial organization of mitotic chromatin signaling, principally by phosphorylating histone H3 at Thr3 (H3T3ph) during mitosis (PMID:15681610). Crystal structures show that Haspin is constitutively active: haspin-specific helical inserts and an unprecedented activation-segment conformation hold the αC helix and catalytic apparatus in an active state without canonical activation-loop phosphorylation, with His651 directly mediating ATP recognition (PMID:19918057, PMID:19918049). Substrate engagement is highly selective—co-crystal and peptide studies reveal a bent H3-tail binding mode that positions Arg2 and Lys4 in acidic pockets, so that H3K4 methylation and H3R2 dimethylation sterically and electrostatically suppress phosphorylation (PMID:24732914, PMID:21397507)—and a cryo-EM nucleosome complex shows Haspin contacts only nucleosomal DNA by inserting into a supergroove between two DNA gyres, a mode required for phosphorylation of chromatin-embedded H3 (PMID:39979508). The H3T3ph mark is read directly by the chromosomal passenger complex (CPC) subunit Survivin, concentrating Aurora B at inner centromeres to control MCAK localization, kinetochore-microtubule attachments, and the spindle checkpoint (PMID:20705812, PMID:23071152, PMID:23071153). Haspin activity is cell-cycle gated: an autoinhibitory N-terminal basic segment is relieved when Cdk1 phosphorylation recruits Plk1 for multi-site activating phosphorylation at mitotic entry, while Aurora-A primes the pathway in late G2 and Aurora B feeds back positively onto Haspin (PMID:21658950, PMID:24184212, PMID:24413556, PMID:28101375). In parallel with Aurora B positioning, Haspin protects centromeric cohesion both by binding the cohesin regulator Pds5B through a conserved YGA/R motif and by directly phosphorylating the Wapl YSR motif to block Wapl-mediated cohesin release (PMID:17084365, PMID:28343965, PMID:29138236). Haspin centromere recruitment depends on SUMOylated topoisomerase IIα, linking Topo II catalytic state to H3T3ph-based checkpoint responses (PMID:27325792, PMID:31712254). Beyond mitosis, Haspin functions in meiosis to recruit Aurora kinase C in oocytes (PMID:27562071, PMID:25315835), in primary cilia length and resorption (PMID:34299370), and in spindle orientation through an ARHGAP11A-Rho-ROCK-LIMK1 axis (PMID:37841592).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 Medium

    Establishing that Haspin was a genuine nuclear Ser/Thr kinase whose own autophosphorylation modulated DNA binding set the foundation for treating it as a chromatin-associated enzyme rather than an orphan sequence.

    Evidence In vitro kinase assay, nuclear immunostaining, DNA-cellulose binding, and kinase-dead transfection in mouse cells

    PMID:10358056

    Open questions at the time
    • No physiological substrate identified at this stage
    • Mechanism linking autophosphorylation to DNA binding not structurally resolved
    • Cell-cycle regulation of activity unaddressed
  2. 2005 High

    Identifying H3 Thr3 as Haspin's mitotic substrate answered what the kinase does on chromatin and tied it to chromosome alignment.

    Evidence In vitro kinase assay, RNAi depletion, and phospho-specific immunostaining in mitotic cells

    PMID:15681610

    Open questions at the time
    • Downstream reader of H3T3ph unknown
    • Structural basis of substrate specificity unresolved
    • How misalignment arises mechanistically not defined
  3. 2006 High

    Demonstrating that Haspin maintains centromeric cohesin and sister chromatid cohesion revealed a second, distinct mitotic role beyond histone marking.

    Evidence RNAi depletion, cohesin immunostaining, overexpression, and live-cell imaging

    PMID:17084365

    Open questions at the time
    • Molecular link between Haspin and cohesin retention not defined
    • Whether this required kinase activity or H3T3ph unresolved
  4. 2009 High

    Crystal structures explained how Haspin is constitutively active without activation-loop phosphorylation, answering why an atypical kinase still adopts a productive conformation.

    Evidence X-ray crystallography of the kinase domain plus His651Ala mutagenesis and enzyme kinetics, with an independent confirmatory structure

    PMID:19918049 PMID:19918057

    Open questions at the time
    • How cell-cycle regulation overrides constitutive activity unexplained
    • Nucleosomal substrate engagement not captured
  5. 2010 High

    Identifying Survivin as a direct reader of H3T3ph closed the loop between Haspin's mark and CPC/Aurora B centromere recruitment.

    Evidence Survivin pulldown with H3T3ph peptide, non-binding D70A/D71A mutant rescue, antibody microinjection, and RNAi

    PMID:20705812

    Open questions at the time
    • Quantitative contribution relative to other CPC targeting pathways unresolved
    • Spatial dynamics of recruitment not addressed
  6. 2011 High

    Showing Aurora B phosphorylates Haspin and that H3K4/H3R2 methylation blocks H3T3ph defined both a positive feedback loop and combinatorial histone control of substrate recognition.

    Evidence Kinase assays, RNAi, Aurora B inhibition, and in vitro assays with modified H3 peptides

    PMID:21397507 PMID:21658950

    Open questions at the time
    • Sites on Haspin phosphorylated by Aurora B not fully mapped
    • In vivo relevance of methylation crosstalk not quantified
  7. 2012 High

    Inhibitor and Aurora B retargeting experiments established the epistatic Haspin→H3T3ph→CPC pathway as causal for centromeric Aurora B function and checkpoint signaling.

    Evidence Small-molecule Haspin inhibitors, anti-H3T3ph antibody injection, Aurora B retargeting bypass, and substrate immunostaining across two simultaneous papers

    PMID:23071152 PMID:23071153

    Open questions at the time
    • Relative weighting versus Bub1 pathway not yet tested
    • Off-target inhibitor effects not fully excluded
  8. 2013 High

    Defining N-terminal autoinhibition and its relief by Cdk1-primed Plk1 phosphorylation answered how a constitutively active kinase is restricted to M phase.

    Evidence In vitro kinase assays, Xenopus egg extracts, and mutagenesis of the autoinhibitory segment and phospho-sites

    PMID:24184212

    Open questions at the time
    • Precise phospho-sites controlling autoinhibition relief partially defined
    • Structural basis of autoinhibition not visualized
  9. 2014 High

    Plk1 binding in a Cdk1-dependent manner and the H3-tail co-crystal structure together explained activation timing and the structural basis of methylation-sensitive substrate selection, while phosphoproteomics extended substrates to macroH2A Ser137.

    Evidence Co-IP and Plk1 inhibition in cells; X-ray co-crystallography with H3 peptide, mass spectrometry, and in vitro kinase assays

    PMID:24413556 PMID:24732914

    Open questions at the time
    • Functional consequence of macroH2A S137 phosphorylation inferred, not proven
    • macroH2A finding from single lab
  10. 2016 High

    SUMOylated Topo IIα CTD was identified as the recruiter of Haspin to centromeres, linking chromosome topology to where H3T3ph and the CPC are deposited.

    Evidence Xenopus egg extract biochemistry, SUMO-site mutagenesis, and co-immunoprecipitation

    PMID:27325792

    Open questions at the time
    • Stoichiometry and dynamics of the interaction unresolved
    • Conservation in somatic human cells not directly shown here
  11. 2017 High

    Discovery of the Pds5B-binding YGA/R motif and direct phosphorylation of the Wapl YSR motif provided two parallel kinase-dependent and -independent mechanisms by which Haspin protects centromeric cohesion, while Aurora-A was shown to prime activation before spindle assembly.

    Evidence Co-IP, CRISPR knockout, motif and phospho-mimetic mutant rescue, in vitro kinase assays, and Aurora-A knockout/inhibition with site mapping

    PMID:28101375 PMID:28343965 PMID:29138236

    Open questions at the time
    • Relative contribution of Pds5B-binding versus Wapl phosphorylation not quantified
    • Aurora-A pathway evidence from single lab with limited reconstitution
  12. 2016 Medium

    Meiotic studies in mouse oocytes showed Haspin recruits Aurora kinase C to chromosomes and acentriolar MTOCs and is needed for spindle bipolarity and accurate kinetochore-microtubule attachments, extending the pathway to a meiosis-specific Aurora.

    Evidence Haspin and AURKC inhibitors, AURKC overexpression rescue, and live imaging in oocytes

    PMID:25315835 PMID:27562071

    Open questions at the time
    • Mechanistic basis of MTOC clustering control unresolved
    • Findings from single lab in mouse oocytes
  13. 2020 High

    Dual Haspin/Bub1 inhibition showed that abolishing centromeric Aurora B does not block the checkpoint or kinetochore substrate phosphorylation, refining the spatial model of how Aurora B corrects attachments, and SUMO-Topo II coupling was extended to an ectopic-site checkpoint response.

    Evidence Selective Haspin and Bub1 inhibitors, Aurora B substrate phosphorylation and segregation analysis; Topo II catalytic inhibition with SUMO-site mutants

    PMID:31712254 PMID:32027339

    Open questions at the time
    • How kinetochore Aurora B activity is sustained without centromeric pool unresolved
    • Single-lab dual-inhibitor design
  14. 2021 Medium

    Interphase and non-mitotic functions emerged, with Haspin controlling primary cilia length and resorption via Dido3-HDAC6 relocalization to the basal body, broadening its role beyond chromosome segregation.

    Evidence Haspin inhibition in quiescent cells, cilia length measurement, Dido3 overexpression rescue, and zebrafish validation

    PMID:34299370

    Open questions at the time
    • Direct substrate at the basal body not defined
    • Connection to H3T3ph unclear
  15. 2022 High

    A cryo-EM nucleosome complex revealed the supergroove DNA-insertion binding mode, confirmation that Haspin alone supplies mitotic H3T3ph, and identification of testis interactors/substrates expanded the structural and tissue-specific picture.

    Evidence Cryo-EM with DNA-binding mutagenesis and nucleosomal phosphorylation assays; KiPIK/CRISPR exclusion of VRK1/2; yeast two-hybrid and in vitro kinase assays from testis

    PMID:35778595 PMID:36012324 PMID:39979508

    Open questions at the time
    • Functional role of C1QBP, CENPJ, KPNA6 interactions largely uncharacterized (Low confidence)
    • How DNA-only contacts achieve centromere targeting in vivo not fully linked
  16. 2023 Medium

    Linking Haspin to ARHGAP11A-Rho-ROCK-LIMK1 signaling established a cytoskeletal role controlling spindle orientation and tissue morphology, distinct from chromatin marking.

    Evidence Haspin inhibition/KO, ARHGAP11A interaction, ROCK/LIMK1 activation assays, and 3D culture morphology

    PMID:37841592

    Open questions at the time
    • Whether Haspin acts catalytically in this axis not reconstituted
    • Direct substrate in the Rho pathway unidentified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Haspin's many spatially and temporally distinct activities—centromeric H3T3ph, cohesion protection, ciliary control, and cytoskeletal/spindle-orientation signaling—are coordinated and prioritized within a single cell remains unresolved.
  • No integrated model reconciling kinase-dependent and kinase-independent functions
  • Physiological substrate spectrum beyond H3T3 incompletely defined
  • Disease relevance not established in the available corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016740 transferase activity 3 GO:0003677 DNA binding 2 GO:0042393 histone binding 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0000228 nuclear chromosome 2 GO:0005694 chromosome 2 GO:0005634 nucleus 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-4839726 Chromatin organization 3 R-HSA-1474165 Reproduction 2
Partners
ARHGAP11AAURAAURBPDS5BPLK1SURVIVINTOP2AWAPL

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Haspin phosphorylates histone H3 at Thr3 in vitro and is required for H3T3 phosphorylation in mitotic cells; depletion by RNAi causes metaphase chromosome misalignment and Haspin associates with chromosomes, centrosomes, and spindle during mitosis. In vitro kinase assay, RNAi depletion, immunostaining with phospho-specific antibodies Genes & development High 15681610
2006 Haspin depletion disrupts centromeric cohesin binding and sister chromatid cohesion in mitosis, causing chromosome misalignment and spindle assembly checkpoint activation; overexpression stabilizes arm cohesion, indicating Haspin is required to maintain centromeric cohesion. RNAi depletion, immunostaining for cohesin and H3T3ph, live-cell imaging Developmental cell High 17084365
2009 Crystal structure of the human Haspin kinase domain reveals a constitutively active conformation stabilized by haspin-specific inserts, an atypical activation segment without phosphorylatable residues, and that His651 in the catalytic loop plays a direct role in ATP recognition (His651Ala mutant is inactive). Increasing H3K4 methylation strongly decreases substrate recognition. X-ray crystallography, active-site mutagenesis (His651Ala), enzyme kinetic assays Proceedings of the National Academy of Sciences of the United States of America High 19918049 19918057
2009 Crystal structure of human Haspin kinase domain (2.15 Å) shows the αC helix adopts its active conformation stabilized by a helical insertion and an unprecedented activation segment conformation, explaining constitutive activity without external activation loop phosphorylation. X-ray crystallography (2.15 Å resolution) Proceedings of the National Academy of Sciences of the United States of America High 19918049
2010 Haspin-generated H3T3 phosphorylation provides a direct chromatin docking site for the CPC subunit Survivin at centromeres; Survivin binds directly to H3T3ph (pulldown), and a non-binding Survivin-D70A/D71A mutant fails to support centromeric CPC concentration, diminishing Aurora B centromere functions including MCAK localization and spindle checkpoint response. Direct binding assay (Survivin pulldown with H3T3ph peptide), Survivin point mutant rescue, antibody microinjection, RNAi Science High 20705812
2011 Aurora B phosphorylates Haspin to promote H3T3ph generation, establishing a positive CPC–Haspin–H3T3ph feedback loop at centromeres; Aurora B kinase activity is required for normal chromosomal CPC localization. The Bub1–shugoshin–CPC pathway provides a centromere-specific boost to this feedback loop. Kinase assays, RNAi, Aurora B inhibitor treatment, live-cell imaging Current biology : CB High 21658950
2013 A conserved basic segment in Haspin's N-terminus autoinhibits kinase activity during interphase; Cdk1 phosphorylation of the N-terminus recruits Plk1/Plx1, which further phosphorylates multiple N-terminal sites to neutralize autoinhibition and activate Haspin in M phase. In vitro kinase assays, Xenopus egg extract experiments, mutagenesis of autoinhibitory segment and phosphorylation sites Molecular cell High 24184212
2014 Plk1 binds to Haspin in a Cdk1-phosphorylation-dependent manner and is required for initial Haspin phosphorylation and H3T3ph in prophase, positively regulating CPC recruitment at mitotic entry. Co-immunoprecipitation, Plk1 inhibitor treatment, phospho-Haspin immunostaining EMBO reports High 24413556
2014 Co-crystal structure of Haspin with the histone H3 tail reveals a unique bent substrate binding mode positioning H3 residues Arg2 and Lys4 into acidic binding pockets adjacent to the phosphorylated Thr3, explaining how H3K4 methylation reduces Haspin activity by steric/charge interference. X-ray co-crystallography, mass spectrometry-based phosphoproteomics, in vitro kinase assays Molecular & cellular proteomics : MCP High 24732914
2014 Haspin phosphorylates macroH2A at Ser137 in addition to H3T3; the Ser137 site is in a basic stretch required to stabilize extranucleosomal DNA, suggesting phosphorylation regulates macroH2A–DNA interactions. Mass spectrometry-based phosphoproteomics, in vitro kinase assays, consensus motif analysis Molecular & cellular proteomics : MCP Medium 24732914
2016 SUMOylation of DNA topoisomerase IIα CTD is required for Haspin localization at centromeres and H3T3ph; SUMOylated TOP2A CTD directly interacts with Haspin through SUMO-interaction motifs to regulate CPC recruitment in mitosis, established using Xenopus egg extracts. Xenopus egg extract biochemistry, SUMO site mutagenesis, co-immunoprecipitation The Journal of cell biology High 27325792
2017 Haspin binds the cohesin regulatory subunit Pds5B through a conserved YGA/R motif in its non-catalytic N-terminus (similar to Wapl's YSR motif); disruption of this interaction causes weakened centromeric cohesion and premature chromatid separation, rescued by prevention of Wapl-mediated cohesin removal. Co-immunoprecipitation, CRISPR knockout, domain mutant rescue experiments Current biology : CB High 28343965
2017 The Haspin kinase domain directly binds and phosphorylates the YSR motif of Wapl, inhibiting Wapl–Pds5B interaction and preventing Wapl-dependent cohesin release from centromeres; phospho-mimetic mutation in Wapl-YSR prevents Wapl from releasing cohesin. In vitro kinase assay, co-immunoprecipitation, phospho-mimetic mutagenesis, centromere targeting assays EMBO reports High 29138236
2017 Aurora-A phosphorylates Haspin at multiple N-terminal sites in late G2/nuclear phase to promote H3T3ph and CPC centromere recruitment before spindle assembly, independently of Plk1; Aurora-A also facilitates association of Aurora-B with Haspin and Plk1. Aurora-A knockout/inhibition/nuclear-import blockade, phosphorylation site mapping, centromere localization assays in cells Cell discovery Medium 28101375
2009 RNAi depletion of Haspin (along with Sgo1 and Scc1) causes generation of multiple acentriolar centrosome-like foci and spindle disruption only when chromatid cohesion is lost; these effects require kinesin-5 activity and microtubule dynamics, indicating spindle-pole integrity depends indirectly on chromosome cohesion. RNAi, live-cell imaging, topoisomerase II inhibition rescue, kinesin-5 inhibitor Journal of cell science Medium 19910498
2012 Haspin inhibitors (and anti-H3T3ph antibody microinjection) decrease centromeric Aurora B and its substrates (CENP-A, Hec1), compromise metaphase chromosome alignment and spindle checkpoint signaling; retargeting Aurora B to centromeres bypasses the Haspin requirement, confirming the Haspin→H3T3ph→CPC centromere recruitment pathway. Small-molecule Haspin inhibitors, antibody microinjection, Aurora B retargeting, phosphosubstrate immunostaining The Journal of cell biology High 23071152 23071153
2011 Methylation at H3K4 abolishes Haspin-mediated H3T3 phosphorylation; dimethylation at H3R2 also substantially reduces Haspin activity on H3T3, establishing combinatorial histone modification control of Haspin substrate recognition. In vitro kinase assays with variously modified H3 peptides Bioorganic & medicinal chemistry Medium 21397507
1999 Haspin (mouse) has intrinsic Ser/Thr kinase activity; it localizes exclusively to nuclei; autophosphorylation regulates its DNA-binding activity (deletion mutant lacking autophosphorylation binds DNA-cellulose constitutively); ectopic expression without kinase activity causes G1 cell cycle arrest. In vitro kinase assay, nuclear localization by immunostaining, DNA-cellulose binding assay, transfection with kinase-dead mutant The Journal of biological chemistry Medium 10358056
2016 In mouse oocytes, Haspin is required for Aurora kinase C (AURKC) localization at both chromosomes and acentriolar MTOCs; Haspin inhibition perturbs MTOC clustering into two poles and spindle bipolarity, and AURKC overexpression rescues these defects. Haspin inhibitor treatment, overexpression rescue, live imaging of AURKC and MTOC markers in mouse oocytes Journal of cell science Medium 27562071
2014 In mouse oocytes, Haspin-mediated H3T3ph recruits the CPC along chromosome arms (rather than kinetochores), and Haspin inhibition causes improper kinetochore-microtubule attachments and aneuploidy at metaphase II; AURKC rather than AURKB mediates correction of microtubule attachments during meiosis I. Haspin inhibitor and AURKC inhibitor treatment, chromosome alignment and aneuploidy assays in mouse oocytes Journal of cell science Medium 25315835
2020 Either Haspin or Bub1 activity alone is sufficient to recruit Aurora B to a centromeric locus; combined inhibition of both Haspin and Bub1 fully abolishes Aurora B centromere accumulation and impairs correction of erroneous KT-MT attachments but does not compromise the mitotic checkpoint or kinetochore Aurora B substrate phosphorylation, arguing against a purely centromere-based spatial model. Selective kinase inhibitors (Haspin + Bub1), Aurora B substrate phosphorylation assays, chromosome segregation analysis The Journal of cell biology High 32027339
2020 Catalytic inhibition of Topo II leads to its SUMOylation, which triggers H3T3ph via Haspin and recruitment of Aurora B to ectopic chromosomal sites; both Haspin and Aurora B are required for this metaphase checkpoint response. Topo II catalytic inhibitor, SUMOylation site mutants, Haspin and Aurora B inhibitors, centromere localization assays The Journal of cell biology Medium 31712254
2017 In Drosophila, Haspin phosphorylates H3T3 both in mitosis and interphase; H3T3ph in interphase localizes to heterochromatin and lamin-enriched euchromatin; Haspin loss compromises insulator activity, reduces nuclear size, and is required for Polycomb-dependent homeotic gene silencing; Haspin associates with the cohesin complex in interphase and mediates Pds5 binding to chromatin. Haspin mutant Drosophila, ChIP, enhancer-blocking assays, live imaging, co-immunoprecipitation PLoS genetics Medium 32750047
2021 Haspin phosphorylates H3T3 in quiescent cells and its activity is required for primary cilia length regulation and timely cilia resorption; Haspin activity promotes relocalization of Dido3-HDAC6 to the basal body, and this pathway was confirmed in zebrafish. Haspin inhibitor in quiescent cells, cilia length measurement, Dido3 overexpression rescue, zebrafish model International journal of molecular sciences Medium 34299370
2022 Cryo-EM structure of human Haspin kinase domain bound to a nucleosome shows Haspin contacts only nucleosomal DNA, inserting into a supergroove formed by apposing major grooves of two DNA gyres; key basic residues essential for this DNA binding are required for phosphorylation of nucleosomal H3 and binding to mitotic chromatin. Cryo-EM structure determination, mutagenesis of DNA-binding residues, nucleosomal H3 phosphorylation assay, mitotic chromatin binding assay Nature structural & molecular biology High 39979508
2022 In vitro kinase assays and CRISPR/Cas9 approaches show VRK1 and VRK2 do not phosphorylate H3T3 or H3S10 in mitosis; Haspin is the kinase specifically required for H3T3ph during mitosis. In vitro kinase assays, KiPIK screening, RNAi, CRISPR/Cas9 Scientific reports Medium 35778595
2017 Haspin phosphorylates TH2A (germ cell-specific H2A variant) at Thr127 at meiotic centromeres; identified by candidate kinase approach and confirmed in vivo using Haspin inhibitor. Haspin inhibitor in oocytes and spermatocytes, phospho-specific antibody, comparison with TH2A-T127A knock-in mice Chromosoma Medium 28803373
2022 Two-hybrid screening from mouse testis identified CENPJ/CPAP, KPNA6/importin alpha 6, and C1QBP/HABP1 as Haspin-interacting proteins; Haspin phosphorylates C1QBP in vitro, suggesting a role in spermatogenesis through C1QBP phosphorylation and potentially centrosome formation. Yeast two-hybrid, co-immunoprecipitation, in vitro kinase assay International journal of molecular sciences Low 36012324
2023 During mitosis, Haspin regulates Rho-ROCK activity through the GAP protein ARHGAP11A, and ROCK in turn activates LIMK1 and stabilizes the actin cytoskeleton to support spindle orientation; this pathway is required for correct tissue morphology in 3D cultures. Haspin inhibition/KO, ARHGAP11A interaction studies, ROCK/LIMK1 activation assays, 3D cell culture morphology iScience Medium 37841592

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis. Science (New York, N.Y.) 400 20705812
2005 The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment. Genes & development 306 15681610
2006 Regulation of mitotic chromosome cohesion by Haspin and Aurora B. Developmental cell 190 17084365
2011 A positive feedback loop involving Haspin and Aurora B promotes CPC accumulation at centromeres in mitosis. Current biology : CB 142 21658950
2009 Structure and functional characterization of the atypical human kinase haspin. Proceedings of the National Academy of Sciences of the United States of America 137 19918057
2011 Antitumor activity of a small-molecule inhibitor of the histone kinase Haspin. Oncogene 105 21804608
1999 Identification and characterization of a haploid germ cell-specific nuclear protein kinase (Haspin) in spermatid nuclei and its effects on somatic cells. The Journal of biological chemistry 99 10358056
2012 Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation. The Journal of cell biology 98 23071152
2012 A small-molecule inhibitor of Haspin alters the kinetochore functions of Aurora B. The Journal of cell biology 96 23071153
2013 Autoinhibition and Polo-dependent multisite phosphorylation restrict activity of the histone H3 kinase Haspin to mitosis. Molecular cell 75 24184212
2020 Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis. The Journal of cell biology 72 32027339
2014 Polo-like kinase-1 triggers histone phosphorylation by Haspin in mitosis. EMBO reports 66 24413556
2017 The N-Terminal Non-Kinase-Domain-Mediated Binding of Haspin to Pds5B Protects Centromeric Cohesion in Mitosis. Current biology : CB 62 28343965
2005 Haspin: a mitotic histone kinase required for metaphase chromosome alignment. Cell cycle (Georgetown, Tex.) 61 15846065
2009 Crystal structure of the catalytic domain of Haspin, an atypical kinase implicated in chromatin organization. Proceedings of the National Academy of Sciences of the United States of America 59 19918049
2012 Structure-activity relationship study of beta-carboline derivatives as haspin kinase inhibitors. Bioorganic & medicinal chemistry letters 57 22335895
2009 Haspin: a newly discovered regulator of mitotic chromosome behavior. Chromosoma 56 19997740
2001 Haspin-like proteins: a new family of evolutionarily conserved putative eukaryotic protein kinases. Protein science : a publication of the Protein Society 54 11468364
2016 Haspin kinase regulates microtubule-organizing center clustering and stability through Aurora kinase C in mouse oocytes. Journal of cell science 51 27562071
2009 Studies of haspin-depleted cells reveal that spindle-pole integrity in mitosis requires chromosome cohesion. Journal of cell science 51 19910498
2014 Phosphorylation of threonine 3 on histone H3 by haspin kinase is required for meiosis I in mouse oocytes. Journal of cell science 49 25315835
2017 A kinase-dependent role for Haspin in antagonizing Wapl and protecting mitotic centromere cohesion. EMBO reports 47 29138236
2017 Haspin: a promising target for the design of inhibitors as potent anticancer drugs. Drug discovery today 44 29031622
2003 Structure, function and evolution of haspin and haspin-related proteins, a distinctive group of eukaryotic protein kinases. Cellular and molecular life sciences : CMLS 43 12737306
2016 SUMOylation of DNA topoisomerase IIα regulates histone H3 kinase Haspin and H3 phosphorylation in mitosis. The Journal of cell biology 41 27325792
2014 Modulation of the chromatin phosphoproteome by the Haspin protein kinase. Molecular & cellular proteomics : MCP 41 24732914
2010 Structure-activity relationship study of acridine analogs as haspin and DYRK2 kinase inhibitors. Bioorganic & medicinal chemistry letters 38 20836251
2001 The Haspin gene: location in an intron of the integrin alphaE gene, associated transcription of an integrin alphaE-derived RNA and expression in diploid as well as haploid cells. Gene 36 11311556
2018 3H-pyrazolo[4,3-f]quinoline haspin kinase inhibitors and anticancer properties. Bioorganic chemistry 35 29698892
2008 Identification of small molecule inhibitors of the mitotic kinase haspin by high-throughput screening using a homogeneous time-resolved fluorescence resonance energy transfer assay. Journal of biomolecular screening 35 18978305
2017 Coumestrol Epigenetically Suppresses Cancer Cell Proliferation: Coumestrol Is a Natural Haspin Kinase Inhibitor. International journal of molecular sciences 33 29064398
2001 Cloning and characterization of human haspin gene encoding haploid germ cell-specific nuclear protein kinase. Molecular human reproduction 32 11228240
2011 Identification and characterization of plant Haspin kinase as a histone H3 threonine kinase. BMC plant biology 31 21527018
2017 Aurora-A promotes the establishment of spindle assembly checkpoint by priming the Haspin-Aurora-B feedback loop in late G2 phase. Cell discovery 28 28101375
2006 Alk1 and Alk2 are two new cell cycle-regulated haspin-like proteins in budding yeast. Cell cycle (Georgetown, Tex.) 28 16855400
2019 Inhibition of Haspin Kinase Promotes Cell-Intrinsic and Extrinsic Antitumor Activity. Cancer research 27 31882401
2019 Haspin knockdown can inhibit progression and development of pancreatic cancer in vitro and vivo. Experimental cell research 23 31493385
2022 Roles and regulation of Haspin kinase and its impact on carcinogenesis. Cellular signalling 21 35278668
2020 Genome-wide CRISPR screen uncovers a synergistic effect of combining Haspin and Aurora kinase B inhibition. Oncogene 21 32300176
2019 Sangivamycin and its derivatives inhibit Haspin-Histone H3-survivin signaling and induce pancreatic cancer cell death. Scientific reports 21 31719634
2013 Yeast haspin kinase regulates polarity cues necessary for mitotic spindle positioning and is required to tolerate mitotic arrest. Developmental cell 21 23973165
2001 Nested genomic structure of haploid germ cell specific haspin gene. Gene 21 11311555
2020 Topoisomerase II SUMOylation activates a metaphase checkpoint via Haspin and Aurora B kinases. The Journal of cell biology 20 31712254
2020 GSG2 (Haspin) promotes development and progression of bladder cancer through targeting KIF15 (Kinase-12). Aging 20 32439830
2019 Haspin inhibition delays cell cycle progression through interphase in cancer cells. Journal of cellular physiology 20 31625162
2017 Anti-Melanoma Activities of Haspin Inhibitor CHR-6494 Deployed as a Single Agent or in a Synergistic Combination with MEK Inhibitor. Journal of Cancer 20 28928884
2020 Haspin kinase modulates nuclear architecture and Polycomb-dependent gene silencing. PLoS genetics 18 32750047
2015 Bisubstrate inhibitor approach for targeting mitotic kinase Haspin. Bioconjugate chemistry 18 25595038
2020 Knockdown of GSG2 inhibits prostate cancer progression in vitro and in vivo. International journal of oncology 17 32319597
2020 Design of new disubstituted imidazo[1,2-b]pyridazine derivatives as selective Haspin inhibitors. Synthesis, binding mode and anticancer biological evaluation. Journal of enzyme inhibition and medicinal chemistry 15 33040634
2017 Structure, Roles and Inhibitors of a Mitotic Protein Kinase Haspin. Current medicinal chemistry 15 28413956
2016 Haspin has Multiple Functions in the Plant Cell Division Regulatory Network. Plant & cell physiology 15 26872832
2021 GSG2 knockdown suppresses cholangiocarcinoma progression by regulating cell proliferation, apoptosis and migration. Oncology reports 14 33846801
2021 Distinct roles of haspin in stem cell division and male gametogenesis. Scientific reports 14 34615946
2020 Haspin regulates Ras localization to promote Cdc24-driven mitotic depolarization. Cell discovery 14 32595981
2021 Loss of haspin suppresses cancer cell proliferation by interfering with cell cycle progression at multiple stages. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 13 34551143
2020 HASPIN kinase inhibitor CHR-6494 suppresses intestinal polyp development, cachexia, and hypogonadism in Apcmin/+ mice. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 13 31833958
2011 Methylation-mediated control of aurora kinase B and Haspin with epigenetically modified histone H3 N-terminal peptides. Bioorganic & medicinal chemistry 13 21397507
2020 HASPIN is involved in the progression of gallbladder carcinoma. Experimental cell research 12 31987787
2017 Slowly on, Slowly off: Bisubstrate-Analogue Conjugates of 5-Iodotubercidin and Histone H3 Peptide Targeting Protein Kinase Haspin. Chembiochem : a European journal of chemical biology 12 28181383
2017 TH2A is phosphorylated at meiotic centromere by Haspin. Chromosoma 12 28803373
2022 Haspin participates in AURKB recruitment to centromeres and contributes to chromosome congression in male mouse meiosis. Journal of cell science 11 35694956
2022 Co-inhibition of Aurora A and Haspin kinases enhances survivin blockage and p53 induction for mitotic catastrophe and apoptosis in human colorectal cancer. Biochemical pharmacology 11 36241092
2021 Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation. International journal of molecular sciences 11 34299370
2020 Haspin-dependent and independent effects of the kinase inhibitor 5-Iodotubercidin on self-renewal and differentiation. Scientific reports 11 31937797
2017 Haspin inhibition reveals functional differences of interchromatid axis-localized AURKB and AURKC. Molecular biology of the cell 11 28659416
2006 The 193-base pair Gsg2 (haspin) promoter region regulates germ cell-specific expression bidirectionally and synchronously. Biology of reproduction 11 17123944
2023 In Silico Discovery of 5'-Modified 7-Deoxy-7-ethynyl-4'-thioadenosine as a HASPIN Inhibitor and Its Synergistic Anticancer Effect with the PLK1 Inhibitor. ACS central science 10 37396870
2022 Synthesis and biological evaluation of Haspin inhibitors: Kinase inhibitory potency and cellular activity. European journal of medicinal chemistry 10 35447555
2022 Dissecting the roles of Haspin and VRK1 in histone H3 phosphorylation during mitosis. Scientific reports 10 35778595
2023 Function and inhibition of Haspin kinase: targeting multiple cancer therapies by antimitosis. The Journal of pharmacy and pharmacology 9 36334086
2021 Phosphorylation of histone H3 by Haspin regulates chromosome alignment and segregation during mitosis in maize. Journal of experimental botany 9 33130883
2021 Evaluation of the antiproliferative effects of the HASPIN inhibitor CHR-6494 in breast cancer cell lines. PloS one 9 33852630
2016 Co-crystal structures of the protein kinase haspin with bisubstrate inhibitors. Acta crystallographica. Section F, Structural biology communications 9 27139824
2023 Ingestion of Soybean Sprouts Containing a HASPIN Inhibitor Improves Condition in a Mouse Model of Alzheimer's Disease. Biology 8 36829593
2019 HASPIN kinase mediates histone deacetylation to regulate oocyte meiotic maturation in pigs. Reproduction (Cambridge, England) 8 30870811
2014 Plk1 puts a (Has)pin on the mitotic histone code. EMBO reports 8 24531719
2022 GSG2 promotes tumor growth through regulating cell proliferation in hepatocellular carcinoma. Biochemical and biophysical research communications 7 35952607
2021 Role of Aurora B and Haspin kinases in the metaphase Topoisomerase II checkpoint. Cell cycle (Georgetown, Tex.) 7 33459116
2022 Halogen Bonding in Haspin-Halogenated Tubercidin Complexes: Molecular Dynamics and Quantum Chemical Calculations. Molecules (Basel, Switzerland) 6 35163974
2024 Synthesis and evaluation of novel N1-acylated 5-(4-pyridinyl)indazole derivatives as potent and selective haspin inhibitors. Bioorganic chemistry 5 38447464
2024 A Comprehensive In Vitro Characterization of a New Class of Indole-Based Compounds Developed as Selective Haspin Inhibitors. Journal of medicinal chemistry 5 39038808
2022 Knockdown of GSG2 Suppresses the Progression of Colorectal Cancer Cells. Genetic testing and molecular biomarkers 5 35089075
2022 Design and biological evaluation of substituted 5,7-dihydro-6H-indolo[2,3-c]quinolin-6-one as novel selective Haspin inhibitors. Journal of enzyme inhibition and medicinal chemistry 5 35670091
2021 Haspin Modulates the G2/M Transition Delay in Response to Polarization Failures in Budding Yeast. Frontiers in cell and developmental biology 5 33585466
2024 N1-Benzoylated 5-(4-pyridinyl)indazole-based kinase inhibitors: Attaining haspin and Clk4 selectivity via modulation of the benzoyl substituents. Archiv der Pharmazie 4 38478964
2023 Haspin balances the ratio of asymmetric cell division through Wnt5a and regulates cell fate decisions in mouse embryonic stem cells. Cell death discovery 4 37612272
2023 A Haspin-ARHGAP11A axis regulates epithelial morphogenesis through Rho-ROCK dependent modulation of LIMK1-Cofilin. iScience 4 37841592
2022 Analysis of Ser/Thr Kinase HASPIN-Interacting Proteins in the Spermatids. International journal of molecular sciences 4 36012324
2021 Exploring the thermodynamic, kinetic and inhibitory mechanisms of 5-iTU targeting mitotic kinase haspin by integrated molecular dynamics. Physical chemistry chemical physics : PCCP 4 34612381
2024 GSG2 promotes thyroid cancer via stabilizing AURKB and activating AKT pathway. Aging 3 38441546
2024 The Natural HASPIN Inhibitor Coumestrol Suppresses Intestinal Polyp Development, Cachexia, and Hypogonadism in a Mouse Model of Familial Adenomatous Polyposis (Apc). Biology 3 39336163
2023 GSG2 facilitates the progression of human breast cancer through MDM2-mediated ubiquitination of E2F1. Journal of translational medicine 3 37537694
2023 Dual FLT3/haspin kinase inhibitor based on 3H-pyrazolo[4,3-f]quinoline scaffold with activities against acute myeloid leukemia. RSC medicinal chemistry 3 37731695
2022 Combined HASPIN and mTOR inhibition is synergistic against KRAS-driven carcinomas. Translational oncology 3 36115073
2021 Synthesis and biological evaluation of selected 7H-pyrrolo[2,3-d]pyrimidine derivatives as novel CDK9/CyclinT and Haspin inhibitors. Chemico-biological interactions 3 34508710
2025 Haspin kinase binds to a nucleosomal DNA supergroove. Nature structural & molecular biology 2 39979508
2025 Haspin kinase inhibition dampens pseudorabies virus infection in vitro. Frontiers in veterinary science 2 40336815
2024 GSG2 promotes progression of human endometrial cancer by regulating PD-1/PD-L1 expression via PI3K-AKT pathway. International immunopharmacology 2 38759367
2022 Knockdown of GSG2 inhibits the development and progression of non-small cell lung cancer in vitro and in vivo. Cell cycle (Georgetown, Tex.) 2 35972887

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