WNT5A

Wingless-type MMTV integration site family, member 5A
Identifiers
Symbols	WNT5A ; hWNT5A
External IDs	OMIM: 164975 MGI: 98958 HomoloGene: 20720 GeneCards: WNT5A Gene
Gene ontology Molecular function • transcription factor activity, sequence-specific DNA binding • frizzled binding • frizzled-2 binding • receptor tyrosine kinase-like orphan receptor binding • cytokine activity • protein domain specific binding • transcription regulatory region DNA binding • receptor agonist activity Cellular component • extracellular region • proteinaceous extracellular matrix • extracellular space • endoplasmic reticulum lumen • Golgi lumen • plasma membrane • cell surface • clathrin-coated endocytic vesicle membrane • extracellular exosome Biological process • activation of MAPK activity • ameboidal-type cell migration • establishment of planar polarity • somitogenesis • epithelial to mesenchymal transition • positive regulation of endothelial cell proliferation • heart looping • positive regulation of mesenchymal cell proliferation • lens development in camera-type eye • positive regulation of cytokine secretion involved in immune response • type B pancreatic cell development • optic cup formation involved in camera-type eye development • Wnt signaling pathway, calcium modulating pathway • activation of JUN kinase activity • axon guidance • hindgut morphogenesis • midgut development • male gonad development • anterior/posterior axis specification, embryo • response to organic substance • positive regulation of endothelial cell migration • positive regulation of peptidyl-threonine phosphorylation • positive regulation of T cell chemotaxis • positive regulation of neuron projection development • Wnt signaling pathway • olfactory bulb interneuron development • neuron differentiation • keratinocyte differentiation • lung development • negative regulation of BMP signaling pathway • positive regulation of cGMP metabolic process • midbrain development • activation of protein kinase B activity • positive regulation of interferon-gamma production • positive regulation of interleukin-6 production • positive regulation of peptidyl-serine phosphorylation • cellular protein localization • post-anal tail morphogenesis • non-canonical Wnt signaling pathway via JNK cascade • negative regulation of fibroblast growth factor receptor signaling pathway • wound healing • embryonic digit morphogenesis • positive regulation of macrophage activation • negative regulation of apoptotic process • positive regulation of chemokine biosynthetic process • cell fate commitment • negative regulation of fat cell differentiation • positive regulation of protein catabolic process • positive regulation of angiogenesis • positive regulation of ossification • positive regulation of endocytosis • positive regulation of meiotic nuclear division • negative regulation of transcription, DNA-templated • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • negative regulation of melanin biosynthetic process • positive regulation of fibroblast proliferation • embryonic skeletal system development • genitalia development • negative regulation of axon extension involved in axon guidance • hypophysis morphogenesis • negative regulation of epithelial cell proliferation • positive regulation of interleukin-1 beta secretion • positive regulation of inflammatory response • negative chemotaxis • positive regulation of NF-kappaB transcription factor activity • cartilage development • negative regulation of synapse assembly • palate development • convergent extension involved in organogenesis • uterus development • cervix development • vagina development • canonical Wnt signaling pathway • urinary bladder development • face development • positive regulation of type I interferon-mediated signaling pathway • lateral sprouting involved in mammary gland duct morphogenesis • mesenchymal-epithelial cell signaling • negative regulation of prostatic bud formation • mammary gland branching involved in thelarche • epithelial cell proliferation involved in mammary gland duct elongation • positive regulation of response to cytokine stimulus • regulation of branching involved in mammary gland duct morphogenesis • positive regulation of macrophage cytokine production • positive regulation of cartilage development • planar cell polarity pathway involved in outflow tract morphogenesis • planar cell polarity pathway involved in ventricular septum morphogenesis • planar cell polarity pathway involved in cardiac right atrium morphogenesis • planar cell polarity pathway involved in cardiac muscle tissue morphogenesis • planar cell polarity pathway involved in pericardium morphogenesis • positive regulation of thymocyte apoptotic process • cellular response to lipopolysaccharide • cellular response to calcium ion • cellular response to retinoic acid • cellular response to interferon-gamma • hematopoietic stem cell proliferation • dopaminergic neuron differentiation • cellular response to transforming growth factor beta stimulus • negative regulation of mesenchymal cell proliferation • primitive streak formation • positive regulation of protein kinase C signaling • negative regulation of canonical Wnt signaling pathway • cochlea morphogenesis • planar cell polarity pathway involved in neural tube closure • melanocyte proliferation • positive regulation of protein kinase C activity • positive regulation of cell-cell adhesion mediated by cadherin • positive regulation of non-canonical Wnt signaling pathway • positive regulation of interleukin-8 secretion Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7474	22418
Ensembl	ENSG00000114251	ENSMUSG00000021994
UniProt	P41221	P22725
RefSeq (mRNA)	NM_001256105	NM_001256224
RefSeq (protein)	NP_001243034	NP_001243153
Location (UCSC)	Chr 3: 55.47 – 55.49 Mb	Chr 14: 28.5 – 28.53 Mb
PubMed search

Protein Wnt-5a is a protein that in humans is encoded by the WNT5A gene.^[1][2]

The WNT gene family consists of structurally related genes that encode secreted signaling lipid modified glycoproteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis.^[3] This gene is a member of the WNT gene family. The WNT5A is highly expressed in the dermal papilla of depilated skin. It encodes a protein showing 98%, 98%, and 87% amino acid identity to the mouse, rat and the xenopus Wnt5A protein, respectively. The experiments performed in Xenopus laevis embryos identified that human frizzled-5 (hFz5) is the receptor for the Wnt5A ligand and the Wnt5A/hFz5 signaling mediates axis induction.^[2]

The Wnt5a gene is also a key component in posterior development of the female reproductive tract, development of the uterine glands postnatally, and the process of estrogen mediated cellular and molecular responses.^[4] Wnt5a is expressed throughout the endometrial stroma of the mammalian female reproductive tracts and is required in the development of the posterior formation of the Müllerian ducts (cervix, vagina).^[5] A Wnt5a absence study was performed by Mericskay et al. on mice and showed the anterior Müllerian-derived structures (oviducts and uterine horns) could easily be identified, and the posterior derived structures (cervix and vagina) were absent showing that this gene is a requirement for its development.^[6] Other members of the WNT family that are required for the development of the reproductive tract are Wnt4 and Wnt7a.^[7] Failure to develop reproductive tract will result in infertility. Not only is the Wnt5a gene responsible for this formation but also is significate in the postnatal production of the uterine glands otherwise known as adenogenesis which is essential for adult function.^[8] In addition to these two developments Wnt5a it needed for the complete process of estrogen mediated cellular and molecular responses.^[9]

References

1. Clark CC, Cohen I, Eichstetter I, Cannizzaro LA, McPherson JD, Wasmuth JJ, Iozzo RV (Feb 1994). "Molecular cloning of the human proto-oncogene Wnt-5A and mapping of the gene (WNT5A) to chromosome 3p14-p21". Genomics 18 (2): 249–60. doi:10.1006/geno.1993.1463. PMID 8288227.
2. "Entrez Gene: WNT5A wingless-type MMTV integration site family, member 5A".
3. Bhatt PM, Malgor R (September 2014). "Wnt5a: A player in the pathogenesis of atherosclerosis and other inflammatory disorders". Atherosclerosis 237 (1): 155–62. doi:10.1016/j.atherosclerosis.2014.08.027. PMID 25240110.
4. Mericskay, Mathias (22 January 2004). "Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus". Development 131: 2061–2072. doi:10.1242/dev.01090.
5. Hayashi, K.; Yoshioka, S.; Reardon, S. N.; Rucker, E. B.; Spencer, T. E.; DeMayo, F. J.; Lydon, J. P.; MacLean, J. A. (20 October 2010). "WNTs in the Neonatal Mouse Uterus: Potential Regulation of Endometrial Gland Development". Biology of Reproduction 84 (2): 308–319. doi:10.1095/biolreprod.110.088161.
6. Mericskay, Mathias (22 January 2004). "Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus". Development 131: 2061–2072. doi:10.1242/dev.01090.
7. Hayashi, K.; Yoshioka, S.; Reardon, S. N.; Rucker, E. B.; Spencer, T. E.; DeMayo, F. J.; Lydon, J. P.; MacLean, J. A. (20 October 2010). "WNTs in the Neonatal Mouse Uterus: Potential Regulation of Endometrial Gland Development". Biology of Reproduction 84 (2): 308–319. doi:10.1095/biolreprod.110.088161.
8. Mericskay, Mathias (22 January 2004). "Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus". Development 131: 2061–2072. doi:10.1242/dev.01090.
9. Mericskay, Mathias (22 January 2004). "Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus". Development 131: 2061–2072. doi:10.1242/dev.01090.

Mericskay, M. (31 March 2004). "Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus". Development 131 (9): 2061–2072. doi:10.1242/dev.01090. Hayashi, K.; Yoshioka, S.; Reardon, S. N.; Rucker, E. B.; Spencer, T. E.; DeMayo, F. J.; Lydon, J. P.; MacLean, J. A. (20 October 2010). "WNTs in the Neonatal Mouse Uterus: Potential Regulation of Endometrial Gland Development". Biology of Reproduction 84 (2): 308–319. doi:10.1095/biolreprod.110.088161.

Further reading

• "Wnt5a". Signaling Gateway Molecule Pages.

• Smolich BD, McMahon JA, McMahon AP, Papkoff J (1994). "Wnt family proteins are secreted and associated with the cell surface.". Mol. Biol. Cell 4 (12): 1267–75. Bibcode:1994JPhy3...4.1267H. doi:10.1051/jp3:1994201. PMC: 275763. PMID 8167409.
• Danielson KG, Pillarisetti J, Cohen IR, et al. (1996). "Characterization of the complete genomic structure of the human WNT-5A gene, functional analysis of its promoter, chromosomal mapping, and expression in early human embryogenesis.". J. Biol. Chem. 270 (52): 31225–34. doi:10.1074/jbc.270.52.31225. PMID 8537388.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• He X, Saint-Jeannet JP, Wang Y, et al. (1997). "A member of the Frizzled protein family mediating axis induction by Wnt-5A.". Science 275 (5306): 1652–4. doi:10.1126/science.275.5306.1652. PMID 9054360.
• Wright M, Aikawa M, Szeto W, Papkoff J (1999). "Identification of a Wnt-responsive signal transduction pathway in primary endothelial cells.". Biochem. Biophys. Res. Commun. 263 (2): 384–8. doi:10.1006/bbrc.1999.1344. PMID 10491302.
• Gazit A, Yaniv A, Bafico A, et al. (1999). "Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response.". Oncogene 18 (44): 5959–66. doi:10.1038/sj.onc.1202985. PMID 10557084.
• Saitoh T, Mine T, Katoh M (2002). "Frequent up-regulation of WNT5A mRNA in primary gastric cancer.". Int. J. Mol. Med. 9 (5): 515–9. doi:10.3892/ijmm.9.5.515. PMID 11956659.
• Weeraratna AT, Jiang Y, Hostetter G, et al. (2002). "Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma.". Cancer Cell 1 (3): 279–88. doi:10.1016/S1535-6108(02)00045-4. PMID 12086864.
• Saitoh T, Katoh M (2003). "Expression and regulation of WNT5A and WNT5B in human cancer: up-regulation of WNT5A by TNFalpha in MKN45 cells and up-regulation of WNT5B by beta-estradiol in MCF-7 cells.". Int. J. Mol. Med. 10 (3): 345–9. doi:10.3892/ijmm.10.3.345. PMID 12165812.
• Murphy LL, Hughes CC (2002). "Endothelial cells stimulate T cell NFAT nuclear translocation in the presence of cyclosporin A: involvement of the wnt/glycogen synthase kinase-3 beta pathway.". J. Immunol. 169 (7): 3717–25. doi:10.4049/jimmunol.169.7.3717. PMID 12244165.
• Thrasivoulou, C, Millar, M and Ahmed, A (2013). "Activation of intracellular calcium by multiple Wnt ligands and translocation of ß-catenin into the nucleus: a convergent model of Wnt/Ca2+ and Wnt/ß-catenin pathways". J. Biol. Chem. 288 (50): 35651–35659. doi:10.1074/jbc.M112.437913. PMID 24158438.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC: 139241. PMID 12477932.
• Ishitani T, Kishida S, Hyodo-Miura J, et al. (2003). "The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling.". Mol. Cell. Biol. 23 (1): 131–9. doi:10.1128/MCB.23.1.131-139.2003. PMC: 140665. PMID 12482967.
• Hocevar BA, Mou F, Rennolds JL, et al. (2003). "Regulation of the Wnt signaling pathway by disabled-2 (Dab2).". EMBO J. 22 (12): 3084–94. doi:10.1093/emboj/cdg286. PMC: 162138. PMID 12805222.
• Taki M, Kamata N, Yokoyama K, et al. (2004). "Down-regulation of Wnt-4 and up-regulation of Wnt-5a expression by epithelial-mesenchymal transition in human squamous carcinoma cells.". Cancer Sci. 94 (7): 593–7. doi:10.1111/j.1349-7006.2003.tb01488.x. PMID 12841867.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Glinsky GV, Glinskii AB, Stephenson AJ, et al. (2004). "Gene expression profiling predicts clinical outcome of prostate cancer.". J. Clin. Invest. 113 (6): 913–23. doi:10.1172/JCI20032. PMC: 362118. PMID 15067324.
• Nishioka K, Dennis JE, Gao J, et al. (2005). "Sustained Wnt protein expression in chondral constructs from mesenchymal stem cells.". J. Cell. Physiol. 203 (1): 6–14. doi:10.1002/jcp.20196. PMID 15389636.
• Blanc E, Roux GL, Bénard J, Raguénez G (2005). "Low expression of Wnt-5a gene is associated with high-risk neuroblastoma.". Oncogene 24 (7): 1277–83. doi:10.1038/sj.onc.1208255. PMID 15592517.
• Kremenevskaja N, von Wasielewski R, Rao AS, et al. (2005). "Wnt-5a has tumor suppressor activity in thyroid carcinoma.". Oncogene 24 (13): 2144–54. doi:10.1038/sj.onc.1208370. PMID 15735754.
• Wang Q, Symes AJ, Kane CA, Freeman A, Nariculam J, et al. (2010). Hotchin NA, ed. "A Novel Role for Wnt/Ca2+ Signaling in Actin Cytoskeleton Remodeling and Cell Motility in Prostate Cancer". PLoS ONE 5 (5): e10456. Bibcode:2010PLoSO...510456W. doi:10.1371/journal.pone.0010456. PMC: 2864254. PMID 20454608.