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FLASH GENE

Symbol

WNT5A

contributors: shn/ - updated : 27-01-2018

HGNC name	wingless-type MMTV integration site family, member 5A
HGNC id	12784

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003392 5 - 5855 NP_003383 - 380 - -

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain       lowly Reproductive female system ovary     moderately Homo sapiens Skeleton appendicular skeleton         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective dense ligament peridontal ligament highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Reproductive epithelial cell Homo sapiens Skeleton osteoblast 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 Ca²&
	8314; in nerve cells under physiological and pathological conditions
	WNT5A and WNT11 are essential regulators of the response of second heart field progenitors to WNT/CTNNB1 signaling and they act by restraining WNT/CTNNB1 signaling during cardiac development
	WNT5A and ROR2 signaling are of substantial importance for BMP2-mediated osteoblastic differentiation
	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
	WNT5A and WNT11 regulate epithelial-mesenchymal transition (EMT) by inducing p38 (MAPK14) phosphorylation

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
	WNT5A/ROR2 signaling appears to be involved in BMP2-mediated osteoblast differentiation in a Smad independent pathway
	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
	WNT5A activates noncanonical WNT signaling through ROR2
	WNT5A signaling is a substantial constituent for BMP2-mediated osteoblastic differentiation
	CAMK2A is crucial for the regulation between NOTCH1 and WNT5A signaling
	WNT5A inhibited the physical association between RBPJ and NCOR2 suggesting that WNT5A induced CAMK2A activation plays a critical role in the endogenous RBPJ-NCOR2 binding
	FHL2 controls the osteogenic differentiation of mesenchymal stromal cells (MSC), bone formation and bone mass through modulation of WNT molecules, WNT10B, WNT3A, WNT5A
	MCAM acting potentially as a functional WNT5A receptor in regulating cell migration and convergent extension, turning off the canonical Wnt signalling branch
	monocyte-secreted WNT5A interacts with FZD5 in microvascular endothelial cells and induces angiogenesis through tissue factor signaling
	WNT5A expressed in periodontal ligament (PDL) tissue plays specific roles in inducing collagen production by PDL cells through TGFB1-mediated upregulation of periostin expression
	RNA helicase MOV10 plays a role in WNT5A synthesis and secretion
	ROR1 is a receptor for WNT5A and related Wnt proteins, that play an important role during embryonic development by regulating cell migration, cell polarity, neural patterning, and organogenesis

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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 tumoral     --over   in melanoma and is thought to be a critical regulator of cell movement during metastasis

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     WNT5A-ROR2 signaling can be a target of cancer therapies to prevent cancer cells from undergoing invasion and metastasis cancer reproductive ovary 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