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FLASH GENE
Symbol WAPL contributors: mct - updated : 05-12-2017
HGNC name wings apart-like homolog (Drosophila)
HGNC id 23293
Location 10q23.2      Physical location : -
Synonym name
  • friend of EBNA2 (Epstein-Barr virus nuclear protein 2)
  • KIAA0261
  • wings apart-like protein
  • Synonym symbol(s) FOE, WAPAL, KIAA0261
    DNA
    TYPE functioning gene
    STRUCTURE 86.56 kb     19 Exon(s)
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    text a large number of additional alternatively spliced WAPL variants consisting of a variable 5'-terminal region and the conserved remainder, from various cervical epithelia (Oikawa 2008)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 splicing 6317 132.8 1190 - 2017 28475897
    19 - 6299 - 1184 - 2017 28475897
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Endocrineneuroendocrinepituitary  highly
    Lymphoid/Immunelymph node   highly
    Reproductivemale systemtestis  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectiveadipose  highly
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a functional bipartite nuclear localization signal
  • an N-terminal arginine-rich motif, and a flexible, variable N-terminal region (Wapl-N)
  • four predicted coiled-coil domain
  • a C-terminal nuclear export signal as well as with three highly acidic regions, a conserved C-terminal domain (Wapl-C) consisting of eight HEAT (Huntingtin, Elongation factor 3, A subunit, and target of rapamycin) repeats
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Wapal (93.6 pc)
    Homologene
    FAMILY
    CATEGORY regulatory , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,centromere
    text localized in the synaptonemal complex of testicular chromosomes
    basic FUNCTION
  • involved in spermatogenesis and may be a target gene mediating the reproductive toxicity induced by TCDD
  • may be associating with transcriptionally active nuclear subregions in interphase cells and concentrating at the ends of formed chromosomes during mitosis
  • is required to unlock cohesin from a particular state in which it is stably bound to chromatin
  • promoting sister-chromatid resolution in mitotic prophase
  • playing an important role in tumorigenesis and cell cycle progression
  • contributing to tumor progression by induction of chromosomal instability (CIN)
  • essential for the prophase removal of sister chromatid arm cohesins
  • WAPL protein regulates binding of the cohesin complex to chromosomes during interphase and helps remove cohesin from chromosomes at mitosis
  • is a key negative regulator of cohesin and forms a complex with precocious dissociation of sisters protein 5 (PDS5A, PDS5B) to promote cohesin release from chromatin
  • in mitosis, WAPL-mediated release of cohesin from DNA is essential for proper chromosome segregation and protects cohesin from cleavage by the protease separase
  • WAPL-dependent prophase pathway is essential for proper chromosome segregation and is crucial to maintain genomic integrity
  • cohesin dynamics are controlled by the releasing factors PDS5B and WAPL and the cohesin stabilizer CDCA5
  • plays a critical role in silencing of Polycomb group (PcG) target genes through the interaction of distal cis-regulatory element (CRE) with promoters
  • cohesin regulator WAPL promotes the release of cohesin from chromosomes during both interphase and mitosis
  • NEK1 phosphorylates PPP1CC, leading to the dephosphorylation of WAPL, which, in turn, results in its retention on chromosome cores to promote loss of cohesion at the end of prophase I in mammals
  • balanced activity of NIPBL/MAU2 and WAPL enables cohesin to correctly structure chromosomes
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • cohesin-binding protein
  • interacting with Epstein-Barr virus EBNA2
  • RAD21 sumoylation by NSMCE2 promotes sister chromatid homologous recombination (SCR) by antagonizing WAPL at a step after cohesin loading at DSBs and in a way not solely dependent on SMC3 acetylation
  • stepwise loss of cohesion between chromosome arms and centromeres is caused by local regulation of WAPL activity, which is controlled by the phosphorylation state of CDCA5
  • AURKB and CDK1 mediate WAPL activation and release of acetylated cohesin from chromosomes by phosphorylating CDC5A
  • in addition to recruiting PPP2CA to dephosphorylate cohesin and CDCA5, SGO1 physically shields cohesin from WAPL
  • SMC3 acetylation leads to recruitment of CDCA5, inhibition of WAPL, and stabilization of cohesin on DNA
  • role for NEK1 in the regulation of WAPL loading during meiotic prophase I, via an interaction between NEK1 and PDS5B
  • HASPIN-PDS5B interaction is required to ensure proper sister-chromatid cohesion, most likely through antagonizing WAPAL-mediated cohesin release from mitotic centromeres
  • through binding the cohesin subunit PDS5A, WAPAL releases the bulk of cohesin from chromosome arms in prophase, whereas centromeric cohesin is protected from WAPAL until anaphase onset
  • C-terminal kinase domain of HASPIN (Haspin-KD) binds and phosphorylates the YSR motif of WAPAL
  • SGO1 binds directly to STAG2 and further shields cohesin from WAPL, protecting sister-chromatid cohesion during mitosis, particularly at centromeres
  • cell & other
    REGULATION
    induced by human papillomavirus (HPV) E6 and E7 oncoproteins
    Phosphorylated by NEK1
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in cervical cancer, and overexpression of WAPL may play an important role in occurrence and development of cervical cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS