WNT3A

WNT3A
Identifiers
Aliases	WNT3A , Wnt family member 3A
External IDs	OMIM: 606359; MGI: 98956; HomoloGene: 22528; GeneCards: WNT3A; OMA:WNT3A - orthologs
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1q42.13 Start 228,006,998 bp [1] End 228,061,271 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11 B1.3|11 37.17 cM Start 59,138,859 bp [2] End 59,181,578 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in placenta right lung upper lobe of left lung olfactory zone of nasal mucosa skin of leg skin of abdomen mucosa of esophagus salivary gland minor salivary glands prostate Top expressed in urethra male urethra epithelium of male urethra ejaculatory duct female urethra vagina muscle layer of seminal vesicle prostatic epithelium muscle layer of urethra primitive streak More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein domain specific binding signaling receptor binding co-receptor binding frizzled binding protein binding transcription coactivator activity receptor ligand activity Cellular component endocytic vesicle membrane endoplasmic reticulum lumen extracellular region cell surface extracellular exosome Wnt-Frizzled-LRP5/6 complex early endosome membrane plasma membrane Golgi lumen presynapse extracellular space synapse glutamatergic synapse Biological process somitogenesis cellular response to retinoic acid hemopoiesis positive regulation of protein phosphorylation Wnt signaling pathway involved in forebrain neuroblast division positive regulation of skeletal muscle tissue development positive regulation of receptor internalization axis elongation involved in somitogenesis positive regulation of collateral sprouting in absence of injury mammary gland development platelet activation heart looping positive regulation of cysteine-type endopeptidase activity involved in apoptotic process positive regulation of protein localization to plasma membrane cardiac muscle cell fate commitment mesoderm development cell proliferation in forebrain positive regulation of mesodermal cell fate specification negative regulation of fat cell differentiation canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment regulation of microtubule cytoskeleton organization negative regulation of dopaminergic neuron differentiation cell proliferation in midbrain in utero embryonic development negative regulation of axon extension involved in axon guidance positive regulation of peptidyl-serine phosphorylation positive regulation of transcription, DNA-templated regulation of axonogenesis positive regulation of B cell proliferation post-anal tail morphogenesis positive regulation of cardiac muscle cell differentiation negative regulation of neuron projection development paraxial mesodermal cell fate commitment negative regulation of neurogenesis positive regulation of protein tyrosine kinase activity positive regulation of DNA-binding transcription factor activity extracellular matrix organization positive regulation of neural precursor cell proliferation synaptic vesicle recycling osteoblast differentiation skeletal muscle cell differentiation COP9 signalosome assembly dorsal/ventral neural tube patterning positive regulation of protein binding platelet aggregation midbrain development positive regulation of protein kinase activity positive regulation of cell-cell adhesion mediated by cadherin positive regulation of hepatocyte proliferation neurogenesis spinal cord association neuron differentiation axonogenesis positive regulation of cytokine production positive regulation of dermatome development somatic stem cell division positive regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation axon guidance multicellular organism development determination of left/right symmetry inner ear morphogenesis positive regulation of cell population proliferation regulation of cell differentiation hippocampus development negative regulation of heart induction by canonical Wnt signaling pathway positive regulation of transcription by RNA polymerase II anterior/posterior pattern specification Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation beta-catenin destruction complex disassembly neuron differentiation Wnt signaling pathway positive regulation of canonical Wnt signaling pathway positive regulation of gene expression calcium ion transmembrane transport via low voltage-gated calcium channel presynapse assembly negative regulation of neuron death positive regulation of core promoter binding regulation of RNA biosynthetic process regulation of signaling receptor activity cell population proliferation canonical Wnt signaling pathway secondary palate development cell fate commitment modulation of chemical synaptic transmission regulation of synapse organization postsynapse to nucleus signaling pathway regulation of presynapse assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 89780 22416 Ensembl ENSG00000154342 ENSMUSG00000009900 UniProt P56704 P27467 RefSeq (mRNA) NM_033131 NM_009522 RefSeq (protein) NP_149122 NP_033548 Location (UCSC) Chr 1: 228.01 – 228.06 Mb Chr 11: 59.14 – 59.18 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Protein Wnt-3a is a protein that in humans is encoded by the WNT3A gene. ^[5]

The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins have are critical in tissue homeostasis, embryonic development, and disease.

Signaling and Related Genes

WNT3A is highly related to the WNT3 gene in sequence and protein function. WNT3A and WNT3 signal similarly through primarily the beta-catenin/Tcf pathway. WNT3A is located in the genome beside the WNT9A gene across many vertebrates. Similarly, the WNT3 gene occurs in the genome beside the WNT9B gene. WNT9A and WNT9B signal through the beta-catenin/Tcf pathway but do not play related roles as WNT3A and WNT3 in the same cellular processes.

Role in Disease

WNT3A is not linked to particular genetic disorder in humans. Mice that have a genetic mutation in the WNT3A die during early embryogenesis and fail to correctly form axial tissues. ^[6] Rodent Wnt3a promotes the beta-catenin/Tcf pathway which is tumor inducing and can cause cancer when expressed in particular cell populations. ^[7]

Role in embryonic development

Embryonic development is the process where the body plan is created. From studies in vertebrate model systems we can infer the roles of particular genes in human anatomical structures. Wnt3a plays a role in these processes:

Body plan - Torso

Wnt3A patterns a multipotent stem cell population that form neurons, muscles, bones, and cartilage of the torso region. Wnt3a instructs these multipotent stems cells to form muscle, bone, and cartilage progenitors over forming neurons. ^[8] Wnt3A also regulates the Notch pathway to control the segmentation clock needed for normal torso development ^{[9] [10]}

Left-Right patterning

Wnt3a is in a signaling pathway that activates the gene Nodal which is left side signaling determinant ^[11]

Intestine - Colon

The colon portion of the gastrointestinal tract is completely dependent on Wnt3a and Wnt3a selectively causes the growth of colon progenitors ^[12]

Neural crest

Wnt3a expands neural crest cells during early development ^[13]

Blood cells

Wnt3a promotes hematopoietic stem cell self-renewal. Wnt3a is needed for myeloid but not B-lymphoid development at the progenitor level, and affected immature thymocyte differentiation ^[14]

Brain - Hippocampus

Wnt3a is needed for formation of the hippocampus portion of the brain ^[15]

Teeth

Wnt3a promotes stem cell properties of dental pulp stem cells ^[16]

References

1. GRCh38: Ensembl release 89: ENSG00000154342 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000009900 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: WNT3A wingless-type MMTV integration site family, member 3A".
6. Yoshikawa Y, Fujimori T, McMahon AP, Takada S (March 1997). "Evidence that absence of Wnt-3a signaling promotes neuralization instead of paraxial mesoderm development in the mouse". Developmental Biology. 183 (2): 234–42. doi: 10.1006/dbio.1997.8502 . PMID   9126297.
7. Pashirzad M, Fiuji H, Khazei M, Moradi-Binabaj M, Ryzhikov M, Shabani M, et al. (October 2019). "Role of Wnt3a in the pathogenesis of cancer, current status and prospective". Molecular Biology Reports. 46 (5): 5609–5616. doi:10.1007/s11033-019-04895-4. PMID   31236761. S2CID   195329662.
8. Garriock RJ, Chalamalasetty RB, Kennedy MW, Canizales LC, Lewandoski M, Yamaguchi TP (May 2015). "Lineage tracing of neuromesodermal progenitors reveals novel Wnt-dependent roles in trunk progenitor cell maintenance and differentiation". Development. 142 (9): 1628–38. doi:10.1242/dev.111922. PMC   4419273 . PMID   25922526.
9. Aulehla A, Wehrle C, Brand-Saberi B, Kemler R, Gossler A, Kanzler B, Herrmann BG (March 2003). "Wnt3a plays a major role in the segmentation clock controlling somitogenesis". Developmental Cell. 4 (3): 395–406. doi: 10.1016/s1534-5807(03)00055-8 . PMID   12636920.
10. Nakaya MA, Biris K, Tsukiyama T, Jaime S, Rawls JA, Yamaguchi TP (December 2005). "Wnt3a links left-right determination with segmentation and anteroposterior axis elongation". Development. 132 (24): 5425–36. doi:10.1242/dev.02149. PMC   1389788 . PMID   16291790.
11. Nakaya MA, Biris K, Tsukiyama T, Jaime S, Rawls JA, Yamaguchi TP (December 2005). "Wnt3a links left-right determination with segmentation and anteroposterior axis elongation". Development. 132 (24): 5425–36. doi:10.1242/dev.02149. PMC   1389788 . PMID   16291790.
12. Garriock RJ, Chalamalasetty RB, Zhu J, Kennedy MW, Kumar A, Mackem S, Yamaguchi TP (April 2020). "A dorsal-ventral gradient of Wnt3a/β-catenin signals controls mouse hindgut extension and colon formation". Development. 147 (8): dev185108. doi:10.1242/dev.185108. PMC   7174843 . PMID   32156757.
13. Ikeya M, Lee SM, Johnson JE, McMahon AP, Takada S (October 1997). "Wnt signalling required for expansion of neural crest and CNS progenitors". Nature. 389 (6654): 966–70. Bibcode:1997Natur.389..966I. doi:10.1038/40146. PMID   9353119. S2CID   4359867.
14. Luis TC, Weerkamp F, Naber BA, Baert MR, de Haas EF, Nikolic T, et al. (January 2009). "Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and leads to defects in progenitor cell differentiation". Blood. 113 (3): 546–54. doi: 10.1182/blood-2008-06-163774 . hdl: 1765/19345 . PMID   18832654. S2CID   1932170.
15. Lee SM, Tole S, Grove E, McMahon AP (February 2000). "A local Wnt-3a signal is required for development of the mammalian hippocampus". Development. 127 (3): 457–67. doi:10.1242/dev.127.3.457. PMID   10631167.
16. Uribe-Etxebarria V, García-Gallastegui P, Pérez-Garrastachu M, Casado-Andrés M, Irastorza I, Unda F, et al. (March 2020). "Wnt-3a Induces Epigenetic Remodeling in Human Dental Pulp Stem Cells". Cells. 9 (3): E652. doi: 10.3390/cells9030652 . PMC   7140622 . PMID   32156036.

Further reading

• Smolich BD, McMahon JA, McMahon AP, Papkoff J (December 1993). "Wnt family proteins are secreted and associated with the cell surface". Molecular Biology of the Cell. 4 (12): 1267–75. doi:10.1091/mbc.4.12.1267. PMC   275763 . PMID   8167409.
• Huguet EL, McMahon JA, McMahon AP, Bicknell R, Harris AL (May 1994). "Differential expression of human Wnt genes 2, 3, 4, and 7B in human breast cell lines and normal and disease states of human breast tissue". Cancer Research. 54 (10): 2615–21. PMID   8168088.
• Gazit A, Yaniv A, Bafico A, Pramila T, Igarashi M, Kitajewski J, Aaronson SA (October 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.
• Tanaka K, Okabayashi K, Asashima M, Perrimon N, Kadowaki T (July 2000). "The evolutionarily conserved porcupine gene family is involved in the processing of the Wnt family". European Journal of Biochemistry. 267 (13): 4300–11. doi:10.1046/j.1432-1033.2000.01478.x. PMID   10866835.
• Katoh M (February 2002). "Regulation of WNT3 and WNT3A mRNAs in human cancer cell lines NT2, MCF-7, and MKN45". International Journal of Oncology. 20 (2): 373–7. doi:10.3892/ijo.20.2.373. PMID   11788904.
• Katoh M (March 2002). "Molecular cloning and expression of mouse Wnt14, and structural comparison between mouse Wnt14-Wnt3a gene cluster and human WNT14-WNT3A gene cluster". International Journal of Molecular Medicine. 9 (3): 221–7. doi:10.3892/ijmm.9.3.221. PMID   11836627.
• Filali M, Cheng N, Abbott D, Leontiev V, Engelhardt JF (September 2002). "Wnt-3A/beta-catenin signaling induces transcription from the LEF-1 promoter". The Journal of Biological Chemistry. 277 (36): 33398–410. doi: 10.1074/jbc.M107977200 . PMID   12052822.
• Hering H, Sheng M (June 2002). "Direct interaction of Frizzled-1, -2, -4, and -7 with PDZ domains of PSD-95". FEBS Letters. 521 (1–3): 185–9. doi: 10.1016/S0014-5793(02)02831-4 . PMID   12067714. S2CID   39243103.
• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Hino S, Michiue T, Asashima M, Kikuchi A (April 2003). "Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is essential for Wnt-3a-induced accumulation of beta-catenin". The Journal of Biological Chemistry. 278 (16): 14066–73. doi: 10.1074/jbc.M213265200 . PMID   12556519.
• Qiang YW, Endo Y, Rubin JS, Rudikoff S (March 2003). "Wnt signaling in B-cell neoplasia". Oncogene. 22 (10): 1536–45. doi: 10.1038/sj.onc.1206239 . PMID   12629517.
• Hocevar BA, Mou F, Rennolds JL, Morris SM, Cooper JA, Howe PH (June 2003). "Regulation of the Wnt signaling pathway by disabled-2 (Dab2)". The EMBO Journal. 22 (12): 3084–94. doi:10.1093/emboj/cdg286. PMC   162138 . PMID   12805222.
• Liu G, Bafico A, Harris VK, Aaronson SA (August 2003). "A novel mechanism for Wnt activation of canonical signaling through the LRP6 receptor". Molecular and Cellular Biology. 23 (16): 5825–35. doi:10.1128/MCB.23.16.5825-5835.2003. PMC   166321 . PMID   12897152.
• Swiatek W, Tsai IC, Klimowski L, Pepler A, Barnette J, Yost HJ, Virshup DM (March 2004). "Regulation of casein kinase I epsilon activity by Wnt signaling". The Journal of Biological Chemistry. 279 (13): 13011–7. doi: 10.1074/jbc.M304682200 . PMID   14722104.
• Zilberberg A, Yaniv A, Gazit A (April 2004). "The low density lipoprotein receptor-1, LRP1, interacts with the human frizzled-1 (HFz1) and down-regulates the canonical Wnt signaling pathway". The Journal of Biological Chemistry. 279 (17): 17535–42. doi: 10.1074/jbc.M311292200 . PMID   14739301.
• Lu W, Yamamoto V, Ortega B, Baltimore D (October 2004). "Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth". Cell. 119 (1): 97–108. doi: 10.1016/j.cell.2004.09.019 . PMID   15454084. S2CID   18567677.
• Capurro MI, Shi W, Sandal S, Filmus J (December 2005). "Processing by convertases is not required for glypican-3-induced stimulation of hepatocellular carcinoma growth". The Journal of Biological Chemistry. 280 (50): 41201–6. doi: 10.1074/jbc.M507004200 . PMID   16227623.
• Thrasivoulou C, Millar M, Ahmed A (December 2013). "Activation of intracellular calcium by multiple Wnt ligands and translocation of β-catenin into the nucleus: a convergent model of Wnt/Ca2+ and Wnt/β-catenin pathways". The Journal of Biological Chemistry. 288 (50): 35651–9. doi: 10.1074/jbc.M112.437913 . PMC   3861617 . PMID   24158438.