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FLASH GENE
Symbol HASPIN contributors: mct - updated : 04-12-2017
HGNC name histone H3 associated protein kinase
HGNC id 19682
Location 17p13.2      Physical location : -
Synonym name
  • haspin
  • haploid germ cell-specific nuclear protein kinase
  • serine/threonine-protein kinase haspin
  • germ cell associated 2 (haspin)
  • Synonym symbol(s) GSG2
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    SPECIAL FEATURE gene in gene, antisens
    text within an intron of ITGAE; in an intron of the integrin alpha E gene
    STRUCTURE 2.80 kb     1 Exon(s)
    text structure features of retroposons
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 2797 88.4 798 - 2017 28413956
    EXPRESSION
    Rna function abundant in testis, somatic cells
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   lowly
    Reproductivemale systemtestis  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivegerm cell Homo sapiens
    cell lineage
    cell lines proliferating cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    cell cycle     cell cycle, interphase, M
    Text liver and other tissues
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-domain having the potential to modulate haspin activity in cells by influencing the conformation of the kinase domain and perhaps making direct interactions with the H3 substrate , and conserved YGA/R motif in its non-catalytic N terminus
  • leucine zipper domain
  • potential phosphorylation sites
  • HASPIN kinase domain (from Lys-470 to the C-terminal end
  • Lys-798), atypical kinase domain with an unprecedented mechanism of activation , and C-terminal kinase domain of HASPIN (Haspin-KD) binds and phosphorylates the YSR motif of WAPAL
    HOMOLOGY
    interspecies homolog to murine Gsg2
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • Haspin subfamily
  • CATEGORY receptor membrane serine/threonine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleoplasm
    text ectopically expressed haspin localizes to the nucleus in interphase and to the chromosomes in mitosis
    basic FUNCTION
  • regulating diploid as well as haploid cell differentiation in a variety of tissues (haploid spermatids)
  • plays an important role in mitosis, where it specifically phosphorylates Thr-3 in histone H3 (H3T3)
  • plays an important role during mitosis and appears to be vital for maintaining chromosome cohesion
  • required for recruitment of the chromosomal passenger complex to metaphase chromosomes
  • controls chromatin-induced Aurora B (AURKB)activation to promote spindle assembly
  • cell cycle control of its activity restricts chromosomal Aurora B localization and activation to M phase through histone modification
  • AURKB kinase activity is required for normal chromosomal localization of the CPC, indicating an intimate linkage between AURKB and HASPIN functions in mitosis
  • HASPIN activity affects likely the phosphorylation state of proteins involved in gene expression regulation and splicing
  • HASPIN kinase plays a key role in maintaining the slowly exchanging centromere CDCA8 pool, while AURKB play minimal role in maintaining chromosomal passenger complex (CPC) localization once cells are in mitosis
  • role for HASPIN as a regulator of bipolar spindle assembly by regulating AURKC function at acentriolar microtubule-organizing centers (MTOCs) in oocytes
  • atypical serine/threonine-protein kinase that was for a long time considered an inactive pseudokinase due to low degree of structural homology of HASPIN with the 'classical' protein kinases, but, the discovery of HASPIN-catalyzed phosphorylation of histone H3 at Thr3 residue unveiled importance of HASPIN in mitosis
  • haspin kinase regulates resumption of meiosis from prophase arrest, chromosome condensation, and kinetochore-microtubule attachments during early prometaphase of meiosis I (MI)
  • atypical eukaryotic protein kinase that lacks sequence similarity with other eukaryotic protein kinases
  • kinase-dependent role for HASPIN in antagonizing WAPAL and protecting centromeric cohesion in mitosis
  • CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to nucleosomes with high-affinity
  • HASPIN inhibitors are implicated in loss of centromeric AURKB and reduced phosphorylation of centromere and kinetochore AURKB substrates
  • target of HASPIN inhibitor possibly HASPIN itself, may further contribute to spindle assembly checkpoint (SAC) signaling downstream of AURKB
  • by phosphorylating Thr3 of histone H3, promotes centromeric recruitment of the chromosome passenger complex (CPC) during mitosis
  • nuclear-accumulated AURKA phosphorylates HASPIN at multiple sites at its N-terminus and that this promotes H3T3-ph and the rapid recruitment to the centromere of the chromosomal passenger complex
  • AURKA promotes the establishment of spindle assembly checkpoint by priming the HASPIN-AURKB feedback loop in late G2 phase
  • HASPIN binds to the cohesin regulatory subunit PDS5B through a conserved YGA/R motif in its non-catalytic N terminus
  • HASPIN-PDS5B interaction is required to ensure proper sister-chromatid cohesion, most likely through antagonizing WAPAL-mediated cohesin release from mitotic centromeres
  • is a serine/threonine kinase that associates with chromosome and phosphorylates threonine 3 of histone 3 during mitosis
  • strong centromere cohesion requires centromeric localization of the mitotic histone kinase HASPIN, which is dependent on the interaction of its non-catalytic N-terminus with PDS5B
  • cell & other
    REGULATION
    Phosphorylated by AURKA
    Other regulated by H3K4 methylation (key role of H3K4 methylation in the regulation of haspin activity)
    is under epigenetic control
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    depletion leads to premature chromatid separation, failure of chromosome alignment, and a block in mitosis in a prometaphase-like state
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    HASPIN inhibitors have potent anti-tumoral effects
    ANIMAL & CELL MODELS