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FLASH GENE
Symbol WWC1 contributors: mct - updated : 27-12-2016
HGNC name WW and C2 domain containing 1
HGNC id 29435
Location 5q34      Physical location : 167.719.064 - 167.899.306
Synonym name
  • WW, C2 and coiled-coil domain containing 1
  • KIBRA protein
  • kidney and brain protein
  • HBeAg-binding protein 3
  • protein WWC1
  • protein phosphatase 1, regulatory subunit 168
  • Synonym symbol(s) KIBRA, KIAA0869, FLJ10865, FLJ23369, HBEBP36, HBEBP3, MEMRYQTL, PPP1R168
    DNA
    TYPE functioning gene
    STRUCTURE 177.67 kb     23 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 - 6753 125.77 1119 - 2003 12559952
    23 - 6735 125.17 1113 - 2003 12559952
    23 - 6750 125.65 1118 - 2003 12559952
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainlimbic systemhippocampus predominantly Homo sapiens
     braindiencephalonhypothalamus moderately Homo sapiens
     brainforebraincerebral lobetemporal lobehighly Homo sapiens
    Reproductivemale systemprostate  highly
    Urinarykidneytubulecollecting duct predominantly Homo sapiens
     kidneynephronrenal capsuleglomerulus  Homo sapiens
     kidneytubuleconvoluted tubule   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Urinarypodocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two amino-terminal WW domains (amino acids 739 for WW1 and amino acids 5486 for WW2), that are required to interact with LATS2 and to regulate YAP1 phosphorylation
  • an internal C2-like domain
  • a PPPY motif
  • a C-terminal glutamic acid-rich stretch
  • conjugated PhosphoP
    HOMOLOGY
    Homologene
    FAMILY
  • WWC family
  • KIBRA subfamily
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus
    text
  • a cytoplasmic and a perinuclear localization
  • in primary hippocampal neurons, displays a somatodendritic distribution and an enrichment at the postsynaptic density
  • mainly cytoplasmic in interphase, but also associates with the microtubule motor protein dynein light chain 1, and may also be a component of the mitotic apparatus
  • basic FUNCTION
  • playing a role in memory
  • promotes the collagen-stimulated activation of the MAPK cascade
  • directly bound to synaptopodin, an essential organizer of the podocyte cytoskeleton
  • modulates the motility of podocytes by linking polarity proteins and cytoskeleton-associated protein complexes
  • involved in brain development and memory formation as a postsynaptic scaffold protein connecting cytoskeletal and signaling molecules
  • WWC1 and CLSTN2 interactively modulate episodic memory performance, and underscore the need for delineating the interactive effects of multiple genes on brain and behavior
  • involved in synaptic plasticity
  • participates in the control of episodic memory
  • promotes LATS1 and LATS2 kinase activity by stimulating phosphorylation on their hydrophobic sites
  • novel regulator of the Hippo pathway, which controls tissue growth and tumorigenesis by inhibiting cell proliferation and promoting apoptosis
  • function as an upstream member of the Hippo pathway by influencing the phosphorylation of LATS and YAP
  • activates the Aurora kinases and is required for full activation of Aurora kinases during mitosis
  • implicated in higher brain function
  • is involved in other physiological processes including cell polarity, membrane/vesicular trafficking, mitosis and cell migration )
  • plays an important role in synaptic plasticity in human hippocampus related to cognitive function
  • potential role in cell cycle progression through phosphoregulation by the Aurora-PPP1CC mitotic complex
  • is a tumor promoter in prostate cancer
  • is a novel bidirectional regulator of synaptic and structural plasticity in hippocampal neurons, and of long-term memory, highly relevant to cognitive processes and their pathologies
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • regulatory roles of WWC1 and PTPN14 in the Hippo pathway
  • a component
  • WWC1-DLC1 complex is recruited to ER-responsive promoters (essential for ER transactivation in breast cancer cells)
  • WWC1-Aurora-LATS2 protein complexes form a novel axis that regulates precise mitosis
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with DLC1 (is mandatory for the recruitment and transactivation functions of ER or DLC1 to the target chromatin)
  • interacts with histone H3 via its glutamic acid-rich region and such interaction might play a mechanistic role in conferring an optimal ER transactivation function as well as the proliferation of ligand-stimulated breast cancer cells
  • protein kinase C (PRKCZ) zeta is a WWC1-interacting protein (known to play an important role in synaptic plasticity and memory formation)
  • interacts with the postsynaptic protein dendrin and synaptopodin via its WW domains and is thought to play a role in synaptic plasticity and cell migration of podocytes
  • binds to a WW domain binding motif, PPXY, in the tyrosine kinase receptor DDR1
  • interaction partner of INADL (the last four AAs of WWC1 mediated binding to the eighth PDZ domain of INADL)
  • interacting with CLSTN2
  • associates with and activates LATS (large tumor suppressor) LATS1 and LATS2 kinases by stimulating their phosphorylation on the hydrophobic motif
  • connection between WWC1 and mammalian Hippo signaling
  • binding between WWC1 and LATS2 requires the N-terminal 86 AAs of WWC1 and the PPPY motif and AAs 667788 in LATS2
  • interacting with PRKCI (WWC1 suppresses apical exocytosis through inhibition of PRKCI activity in epithelial cells)
  • associates with NF2/Merlin in a Ser539 phosphorylation-dependent manner
  • PPP1CC interacts with and dephosphorylates WWC1
  • tissue-specific differences in the regulation of WWC1 gene expression involve transcription factor TCF7L2 and a complex alternative promoter system
  • PTPN14 and WWC1 can induce the LATS1 activation independently and cooperatively
  • is a physiologically interacting reversible substrate of ataxia telangiectasia mutated (ATM) kinase
  • memory associated WWC1 is a target of MECP2 in regulating dendritic growth
  • cell & other
    REGULATION
    Phosphorylated by AURKA, AURKB
    also phosphorylated by CDK1 (cyclin-dependent kinase 1) in response to spindle damage stress
    Other its phosphorylation is regulated in a cell cycle-dependent manner with the highest level of phosphorylated WWC1detected in mitosis
    phospho-regulation of WWC1 by CDK1 and CDC14A is involved in mitotic exit under spindle stress
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in human prostate tumors
    constitutional     --low  
    in Alzheimer patients with dementia, enhanced tau acetylation is linked to loss of WWC1
    Susceptibility
  • to variation of memory performance
  • to specific phenotypes of patients with Alzheimer disease
  • Variant & Polymorphism SNP
  • C/C genotype might have an impact on memory performance (T allele carriers had significantly better verbal memory, attention/concentration and delayed recall performance than the C/C carriers)
  • rs17070145 affects specific phenotypes of patients with AD
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS