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FLASH GENE
Symbol WNT5A contributors: shn/ - updated : 21-07-2010
HGNC name wingless-type MMTV integration site family, member 5A
HGNC id 12784
Corresponding disease
RBNS2 Robinow syndrome 2
Location 3p14.3      Physical location : 55.499.743 - 55.521.331
Synonym name
  • WNT-5A protein
  • protein Wnt-5a
  • oncogen WNT5A
  • Synonym symbol(s) hWNT5A
    DNA
    TYPE functioning gene
    STRUCTURE 21.59 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map pter - D3S3717 - D3S3719 - WNT5A - D3S1606 - D3S2408 - cen
    Physical map
    LOC285398 3p21.31 hypothetical protein LOC285398 RFT1 3p21.31 putative endoplasmic reticulum multispan transmembrane protein PRKCD 3p21.31 protein kinase C, delta TKT 3p14.3 transketolase (Wernicke-Korsakoff syndrome) HSA275986 3p21.31 transcription factor SMIF LOC391539 3 similar to 40S ribosomal protein S25 CACNA1D 3p14.3 calcium channel, voltage-dependent, L type, alpha 1D subunit CHDH 3p21.1 choline dehydrogenase IL17RB 3p21.1 interleukin 17 receptor B ACTR8 3p21.31 ARP8 actin-related protein 8 homolog (yeast) SELK 3p21.31 selenoprotein K LOC266954 3p21.31 calcium-binding tyrosine phosphorylation-regulated protein pseudogene CACNA2D3 3p21.1 calcium channel, voltage-dependent, alpha 2/delta 3 subunit HT017 3p21.2 calcium channel, voltage-dependent, alpha 2/delta 3 subunit WNT5A 3p21.1 wingless-type MMTV integration site family, member 5A CAST 5q15-q21 calpastatin C1orf1 1p36.2 chromosome 1 open reading frame 1 RAP140 3p21.31 retinoblastoma-associated protein 140 ARHGEF3 3p21-p13 Rho guanine nucleotide exchange factor (GEF) 3 SPATA12 3p21.2 spermatogenesis associated 12 IL17RD 3p21.1 interleukin 17 receptor D HESX1 3p21.2-p21.1 homeo box (expressed in ES cells) 1 APPL 3p21.1-p14.3 homeo box (expressed in ES cells) 1 ASB14 3p21.1 ankyrin repeat and SOCS box-containing 14 FLJ40427 3p21.2 hypothetical protein FLJ40427 FLJ44290 3p21.2 FLJ44290 protein DKFZp667B1218 3p21.2 hypothetical protein DKFZp667B1218 ARF4 3p21.2-p21.1 ADP-ribosylation factor 4 FLJ34969 3p21.2 hypothetical protein FLJ34969 SLMAP 3p21.2-p14.3 sarcolemma associated protein LOC344797 3p21.2 similar to peptidylprolyl isomerase A
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 5855 - 380 - -
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   lowly
     brain   lowly
    Reproductivefemale systemovary  moderately Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductiveepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, neonatal, pregnancy
    Text
  • developing face, ventral area of midbrain and limbs
  • neonatal heart and lung
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a hydrophobic signal sequence
  • 21 conserved cysteine residues
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to Drosophila wingless (wg) segment polarity gene
    ortholog to Wnt5a, Mus musculus
    ortholog to Wnt5a, Rattus norvegicus
    ortholog to wnt5a, Danio rerio
    Homologene
    FAMILY
  • WNT gene family
  • CATEGORY protooncogene , signaling
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • modulating cell fate and cell behavior during vertebrate development
  • regulates hematopoiesis by the antagonism of the canonical Wnt pathway, resulting in a pool of quiescent hematopoietic stem cells, and regulates hematopoietic stem cell function in a paracrine fashion through several distinct mechanisms including modulating canonical Wnt signaling
  • involved in control cell orientation, polarity, and directional movement in response to positional cues from chemokine gradients
  • have crucial roles in adipogenesis as positive regulator
  • acts in vivo to promote beta-catenin degradation in regulating mammalian limb development and possibly in suppressing tumor formation
  • acts through noncanonical Wnt signaling to promote angiogenesis
  • activating TMOD1, while gelsolin, known as an actin-severing protein, is down-regulated by WNT5A
  • promotes axon differentiation
  • critically involved in inflammatory macrophage signaling in sepsis and is a target for antiinflammatory mediators
  • Wnt5a-mediated non-canonical Wnt signalling regulated endothelial cell proliferation
  • role in regulation of ventral midbrain morphogenesis, dopaminergic progenitor cell division, and differentiation of NR4A2+ dopaminergic precursors
  • activates calpain-1, leading to the cleavage of filamin A, resulting in a remodeling of the cytoskeleton and an increase in melanoma cell motility
  • negatively regulates both proliferation and migration of dental papilla cells, suggesting its important role in odontogenesis via controlling the dental papilla cells
  • critical mediator of CXCL12-CXCR4 signaling and migration in human and murine T cells
  • enhances cardiac gene expressions of endothelial progenitor cells via an activation of PKC delta
  • a regulator of fibroblast proliferation and resistance to apoptosis
  • regulates skin epidermal differentiation
  • regulates signaling pathways by binding to FZD2
  • regulates the assembly and function of the excitatory postsynaptic region in the mature central nervous system
  • stimulates focal adhesion dynamics through DVL1 and APC
  • in addition to the planar cell polarity pathway, WNT5a has been shown to activate at least two other branches of the non-canonical Wnt pathway
  • antagonizes canonical WNT/CTNNB1 signaling and induces cellular senescence by activating the histone repressor A/promyelocytic leukemia senescence pathway
  • WNT5a/FZD2 signaling pathway contributed to increasing intracellular Ca˛&
  • 8314; in nerve cells under physiological and pathological conditions
  • mediates CTNNB1–independent signaling and promotes Rho/Rac GTPase activity in specific cell types
  • stimulated bacterial internalization and restricted killing
  • may exert its stimulatory effects on macrophages through autocrine and/or paracrine modes upon binding to the FZD5 receptor
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
  • WNT5A–FZD5 signaling in macrophages promotes phagocytosis through lipid raft clustering concomitant with RAC1–PI3 kinase–IKB kinase activation
  • potentially part of the PRICKLE1/WNT5A/PCP signaling, regulating cell polarity and affecting expression of multiple factors to stunt limb growth through altered patterns of gene expression, including the PCP genes WNT5a and VANGL2
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • frizzled homolog 1, FZD1 (Gazit et al, 1999)
  • receptor tyrosine kinase-like orphan receptor 2, ROR2
  • FZD2
  • ability of WNT5A–FZD5 signaling to stimulate phagocytosis of E. coli but not its killing makes it a likely mediator of uncontrolled inflammation or sepsis during infection
  • ROR2 binds to WNT5A directly through its Fz-like CRD and may serve as a co-receptor in WNT5A-induced signaling
  • WNT5A-ROR2 signaling might be required for expression of MMP13 gene during the development of the cartilaginous tissue
  • WNT5A potentiates PGC chemotaxis toward secreted KITLG by redistribution of ROR2 within the cell
  • MCAM acting potentially as a functional WNT5A receptor in regulating cell migration and convergent extension, turning off the canonical Wnt signalling branch
  • cell & other
    REGULATION
    Other regulated by PAX2 and may be involved in blastemal predominant Wilms tumorigenesis (importance of PAX2 in the regulation of WNT5A)
    stimulated by CaSR in myofibroblasts
    ASSOCIATED DISORDERS
    corresponding disease(s) RBNS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    aberrantly methylated from the early stages of colorectal cancers
    tumoral       loss of function
    inactivated by aberrant methylation in acute lymphoblastic leukaemia
    tumoral     --over  
    by hypomethylation in prostate cancer
    tumoral     --low  
    in epithelial ovarian cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    WNT5A-ROR2 signaling can be a target of cancer therapies to prevent cancer cells from undergoing invasion and metastasis
    cancerreproductiveovary
    by reconstituting WNT5A signaling may offer an effective new strategy for EOC therapy
    ANIMAL & CELL MODELS
  • Wnt5a-/- mice exhibit dwarfism, facial abnormalities, short limbs and tails, dysplasia of lungs and genitals, and ventricular septal defects
  • Wnt5a-/- mice display a defect in (mid)brain morphogenesis, including an impairment in midbrain elongation and a rounded ventricular cavity