Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Wnt5a. (This text reflects annotations as of Tuesday, May 21, 2013.) MGI curation of this mouse gene is considered complete, including annotations derived from the biomedical literature as of April 27, 2010. If you know of any additional information regarding this mouse gene please let us know. Please supply mouse gene symbol and a PubMed ID.

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene encodes a member of the WNT family that signals through both the canonical and non-canonical WNT pathways. This protein is a ligand for the seven transmembrane receptor frizzled-5 and the tyrosine kinase orphan receptor 2. This protein plays an essential role in regulating developmental pathways during embryogenesis. This protein may also play a role in oncogenesis. Mutations in this gene are the cause of autosomal dominant Robinow syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Wnt5a
  • participates in the following biological processes:
    • anterior/posterior axis specification, embryo ^[15]
    • axon guidance ^[6]
    • canonical Wnt receptor signaling pathway ^{[38, 43]}
    • cellular response to molecule of bacterial origin ^[7]
    • epithelial cell proliferation involved in mammary gland duct elongation ^[32]
    • hematopoietic stem cell proliferation ^[4]
    • inner ear morphogenesis ^[22]
    • JNK cascade ^[27]
    • lateral sprouting involved in mammary gland duct morphogenesis ^[32]
    • mammary gland branching involved in thelarche ^[32]
    • negative regulation of canonical Wnt receptor signaling pathway ^[11]
    • negative regulation of epithelial cell proliferation ^[32]
    • negative regulation of synapse assembly ^[11]
    • neuron projection morphogenesis ^[6]
    • positive regulation of cartilage development ^[22]
    • positive regulation of cell proliferation ^[4]
    • positive regulation of cell-cell adhesion mediated by cadherin ^[37]
    • positive regulation of interleukin-1 beta secretion ^[28]
    • positive regulation of interleukin-6 production ^[28]
    • positive regulation of interleukin-8 secretion ^[28]
    • positive regulation of JUN kinase activity ^[23]
    • positive regulation of neuron projection development ^[29]
    • positive regulation of protein phosphorylation ^[14]
    • positive regulation of transcription, DNA-dependent ^[38]
    • regulation of branching involved in mammary gland duct morphogenesis ^[32]
    • Wnt receptor signaling pathway, calcium modulating pathway ^[28]
    • Wnt receptor signaling pathway, planar cell polarity pathway ^[8]
  • performs the following molecular functions:
    • cytokine activity ^[11]
    • frizzled-2 binding ^{[33, 37]}
  • is located in the following cellular components:
    • cell surface ^[34]
    • extracellular matrix ^[34]
• The gene product of Wnt5a has been shown to bind to the gene products of Cthrc1, Kl, Lrp6, Ror2, Wls. ^{[8, 12, 21, 27, 42]} Researchers have inferred, based on physical interactions, that the gene product of Wnt5a
  • performs the following molecular functions:
    • frizzled binding ^[13]
    • protein domain specific binding ^[17]
    • receptor binding ^[17]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Wnt5a
  • participates in the following biological processes:
    • ameboidal cell migration ^[9]
    • anterior/posterior pattern specification ^{[2, 24]}
    • axis elongation ^{[2, 9]}
    • canonical Wnt receptor signaling pathway ^[43]
    • cell migration ^[18]
    • cellular protein localization ^[31]
    • cervix development ^[24]
    • cochlea morphogenesis ^[31]
    • convergent extension ^[31]
    • development of primary male sexual characteristics ^[39]
    • digestive tract morphogenesis ^[23]
    • dopaminergic neuron differentiation ^[3]
    • embryo development ^[40]
    • embryonic digit morphogenesis ^[2]
    • embryonic limb morphogenesis ^[40]
    • establishment of planar polarity ^[3]
    • hematopoietic stem cell proliferation ^[4]
    • hindgut morphogenesis ^[1]
    • hypophysis morphogenesis ^[10]
    • inner ear morphogenesis ^[22]
    • limb morphogenesis ^[2]
    • lung development ^[19]
    • male gonad development ^{[1, 39]}
    • mesenchymal-epithelial cell signaling ^[24]
    • midgut development ^[9]
    • morphogenesis of an epithelium ^[24]
    • negative regulation of BMP signaling pathway ^[30]
    • negative regulation of canonical Wnt receptor signaling pathway ^{[20, 36]}
    • negative regulation of epithelial cell proliferation ^[32]
    • negative regulation of fibroblast growth factor receptor signaling pathway ^[30]
    • negative regulation of prostatic bud formation ^[1]
    • non-canonical Wnt receptor signaling pathway via JNK cascade ^[5]
    • olfactory bulb interneuron development ^[29]
    • planar cell polarity pathway involved in cardiac muscle tissue morphogenesis ^[8]
    • planar cell polarity pathway involved in cardiac right atrium morphogenesis ^[8]
    • planar cell polarity pathway involved in neural tube closure ^[8]
    • planar cell polarity pathway involved in outflow tract morphogenesis ^[8]
    • planar cell polarity pathway involved in pericardium morphogenesis ^[8]
    • planar cell polarity pathway involved in ventricular septum morphogenesis ^[8]
    • positive regulation of cartilage development ^[22]
    • positive regulation of cell proliferation ^[4]
    • positive regulation of epithelial cell proliferation ^[9]
    • positive regulation of interferon-gamma production ^[7]
    • positive regulation of JNK cascade ^[5]
    • positive regulation of JUN kinase activity ^[23]
    • positive regulation of mesenchymal cell proliferation ^[9]
    • positive regulation of thymocyte apoptotic process ^[20]
    • post-anal tail morphogenesis ^[2]
    • tube closure ^[9]
    • type B pancreatic cell development ^[18]
    • urinary bladder development ^[1]
    • uterus development ^[24]
    • vagina development ^[24]
    • Wnt receptor signaling pathway, calcium modulating pathway ^[20]
    • Wnt receptor signaling pathway, planar cell polarity pathway ^{[23, 31]}
• Researchers have inferred, based on genetic interactions, that the gene product of Wnt5a
  • participates in the following biological processes:
    • canonical Wnt receptor signaling pathway based on interactions with Fzd4 ^[25]
    • cell migration based on interactions with Gsk3a, Gsk3b ^[41]
    • cochlea morphogenesis based on interactions with Vangl2 ^[31]
    • convergent extension involved in organogenesis based on interactions with Lrp6, Vangl2 ^{[2, 31]}
    • dopaminergic neuron differentiation based on interactions with Rac1 ^[3]
    • heart looping based on interactions with Lrp6 ^[2]
    • negative chemotaxis based on interactions with Ryk ^[17]
    • negative regulation of axon extension involved in axon guidance based on interactions with Ryk ^[17]
    • negative regulation of canonical Wnt receptor signaling pathway based on interactions with Fzd2, Ror2, Wnt3a ^{[25, 33]}
    • neural tube closure based on interactions with Lrp6, Vangl2 ^{[2, 31]}
    • neural tube development based on interactions with Lrp6 ^[2]
    • pericardium morphogenesis based on interactions with Lrp6 ^[2]
    • positive regulation of meiosis based on interactions with Wnt4 ^[26]
    • positive regulation of peptidyl-serine phosphorylation based on interactions with Gsk3a, Gsk3b ^[41]
    • positive regulation of peptidyl-threonine phosphorylation based on interactions with Gsk3a, Gsk3b ^[41]
    • post-anal tail morphogenesis based on interactions with Lrp6 ^[2]
    • primitive streak formation based on interactions with Lrp6 ^[2]
    • protein phosphorylation based on interactions with Tgfb1 ^[32]
    • regulation of branching involved in mammary gland duct morphogenesis based on interactions with Hgf, Tgfb1 ^[32]
    • somitogenesis based on interactions with Lrp6 ^[2]
    • Wnt receptor signaling pathway based on interactions with Fzd3, Fzd4, Fzd5, Fzd8 ^{[16, 35]}
    • Wnt receptor signaling pathway, planar cell polarity pathway based on interactions with Rac1, Vangl2 ^{[3, 31]}

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Wnt5a:
  • participates in the following biological processes:
    • activation of JUN kinase activity
    • activation of MAPK activity
    • activation of protein kinase B activity
    • cell fate commitment
    • cellular protein localization
    • embryonic skeletal system development
    • face development
    • genitalia development
    • hematopoietic stem cell proliferation
    • negative regulation of apoptotic process
    • negative regulation of canonical Wnt receptor signaling pathway
    • negative regulation of fat cell differentiation
    • negative regulation of mesenchymal cell proliferation
    • negative regulation of transcription, DNA-dependent
    • palate development
    • positive regulation of angiogenesis
    • positive regulation of cell-cell adhesion
    • positive regulation of cGMP metabolic process
    • positive regulation of chemokine biosynthetic process
    • positive regulation of cytokine secretion involved in immune response
    • positive regulation of endothelial cell migration
    • positive regulation of endothelial cell proliferation
    • positive regulation of fibroblast proliferation
    • positive regulation of inflammatory response
    • positive regulation of interleukin-1 beta secretion
    • positive regulation of interleukin-6 production
    • positive regulation of macrophage activation
    • positive regulation of macrophage cytokine production
    • positive regulation of NF-kappaB transcription factor activity
    • positive regulation of ossification
    • positive regulation of protein catabolic process
    • positive regulation of protein kinase C signaling cascade
    • positive regulation of response to cytokine stimulus
    • positive regulation of T cell chemotaxis
    • positive regulation of transcription from RNA polymerase II promoter
    • positive regulation of transcription, DNA-dependent
    • positive regulation of type I interferon-mediated signaling pathway
    • Wnt receptor signaling pathway
    • Wnt receptor signaling pathway, calcium modulating pathway
    • Wnt receptor signaling pathway, planar cell polarity pathway
    • wound healing
  • performs the following molecular functions:
    • frizzled binding
    • receptor tyrosine kinase-like orphan receptor binding
    • sequence-specific DNA binding transcription factor activity
    • transcription regulatory region DNA binding
  • is located in the following cellular components:
    • cytoplasm
    • extracellular space

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Summary text based on GO annotations supported by structural data

• Wnt5a encodes a protein or proteins that contain the following InterPro domains: Wnt, Wnt protein, conserved site, Wnt-5a protein, indicating that the gene product:
  • participates in the following biological processes:
    • multicellular organismal development
  • is located in the following cellular components:
    • extracellular region

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Wnt5a indicates that it:
  • participates in the following biological processes:
    • cartilage development
    • cell differentiation
    • multicellular organismal development
  • is located in the following cellular components:
    • extracellular region
    • proteinaceous extracellular matrix

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References

1. Allgeier SH et al. (2008) WNT5A selectively inhibits mouse ventral prostate development. Dev Biol, 324:10-7. (PubMed:18804104)
2. Andersson ER et al. (2009) Genetic interaction between Lrp6 and Wnt5a during mouse development. Dev Dyn, 239:237-245. (PubMed:19795512)
3. Andersson ER et al. (2008) Wnt5a regulates ventral midbrain morphogenesis and the development of A9-A10 dopaminergic cells in vivo. PLoS ONE, 3:e3517. (PubMed:18953410)
4. Austin TW et al. (1997) A role for the Wnt gene family in hematopoiesis: expansion of multilineage progenitor cells. Blood, 89:3624-35. (PubMed:9160667)
5. Bilkovski R et al. (2010) Role of WNT-5a in the determination of human mesenchymal stem cells into preadipocytes. J Biol Chem, 285:6170-8. (PubMed:20032469)
6. Blakely BD et al. (2011) Wnt5a regulates midbrain dopaminergic axon growth and guidance. PLoS One, 6:e18373. (PubMed:21483795)
7. Blumenthal A et al. (2006) The Wingless homolog WNT5A and its receptor Frizzled-5 regulate inflammatory responses of human mononuclear cells induced by microbial stimulation. Blood, 108:965-73. (PubMed:16601243)
8. Bryja V et al. (2009) The extracellular domain of Lrp5/6 inhibits noncanonical Wnt signaling in vivo. Mol Biol Cell, 20:924-36. (PubMed:19056682)
9. Cervantes S et al. (2009) Wnt5a is essential for intestinal elongation in mice. Dev Biol, 326:285-94. (PubMed:19100728)
10. Cha KB et al. (2004) WNT5A signaling affects pituitary gland shape. Mech Dev, 121:183-94. (PubMed:15037319)
11. Davis EK et al. (2008) Wnts acting through canonical and noncanonical signaling pathways exert opposite effects on hippocampal synapse formation. Neural Dev, 3:32. (PubMed:18986540)
12. Fu J et al. (2009) Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for embryonic axis formation. Proc Natl Acad Sci U S A, 106:18598-603. (PubMed:19841259)
13. Gazit A et al. (1999) Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response. Oncogene, 18:5959-66. (PubMed:10557084)
14. Gonzalez-Sancho JM et al. (2004) Wnt proteins induce dishevelled phosphorylation via an LRP5/6- independent mechanism, irrespective of their ability to stabilize beta-catenin. Mol Cell Biol, 24:4757-68. (PubMed:15143170)
15. He X et al. (1997) A member of the Frizzled protein family mediating axis induction by Wnt-5A. Science, 275:1652-4. (PubMed:9054360)
16. Ishikawa T et al. (2001) Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis. Development, 128:25-33. (PubMed:11092808)
17. Keeble TR et al. (2006) The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum. J Neurosci, 26:5840-8. (PubMed:16723543)
18. Kim HJ et al. (2005) Wnt5 signaling in vertebrate pancreas development. BMC Biol, 3:23. (PubMed:16246260)
19. Li C et al. (2002) Wnt5a participates in distal lung morphogenesis. Dev Biol, 248:68-81. (PubMed:12142021)
20. Liang H et al. (2007) Noncanonical Wnt signaling promotes apoptosis in thymocyte development. J Exp Med, 204:3077-84. (PubMed:18070933)
21. Liu H et al. (2007) Augmented Wnt signaling in a mammalian model of accelerated aging. Science, 317:803-6. (PubMed:17690294)
22. Liu W et al. (2008) Coordinated molecular control of otic capsule differentiation: functional role of Wnt5a signaling and opposition by sfrp3 activity. Growth Factors, 26:343-54. (PubMed:18991062)
23. Matsuyama M et al. (2009) Sfrp controls apicobasal polarity and oriented cell division in developing gut epithelium. PLoS Genet, 5:e1000427. (PubMed:19300477)
24. Mericskay M et al. (2004) Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus. Development, 131:2061-72. (PubMed:15073149)
25. Mikels AJ et al. (2006) Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol, 4:e115. (PubMed:16602827)
26. Naillat F et al. (2010) Wnt4/5a signalling coordinates cell adhesion and entry into meiosis during presumptive ovarian follicle development. Hum Mol Genet, 19:1539-50. (PubMed:20106871)
27. Oishi I et al. (2003) The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway. Genes Cells, 8:645-54. (PubMed:12839624)
28. Pereira C et al. (2008) Wnt5A/CaMKII signaling contributes to the inflammatory response of macrophages and is a target for the antiinflammatory action of activated protein C and interleukin-10. Arterioscler Thromb Vasc Biol, 28:504-10. (PubMed:18174455)
29. Pino D et al. (2011) Wnt5a controls neurite development in olfactory bulb interneurons. ASN Neuro, 3:e00059. (PubMed:21539518)
30. Potok MA et al. (2008) WNT signaling affects gene expression in the ventral diencephalon and pituitary gland growth. Dev Dyn, 237:1006-20. (PubMed:18351662)
31. Qian D et al. (2007) Wnt5a functions in planar cell polarity regulation in mice. Dev Biol, 306:121-33. (PubMed:17433286)
32. Roarty K et al. (2007) Wnt5a is required for proper mammary gland development and TGF-{beta}-mediated inhibition of ductal growth. Development, 134:3929-39. (PubMed:17898001)
33. Sato A et al. (2010) Wnt5a regulates distinct signalling pathways by binding to Frizzled2. EMBO J, 29:41-54. (PubMed:19910923)
34. Smolich BD et al. (1993) Wnt Family Proteins Are Secreted and Associated with the Cell Surface Mol Biol Cell, 4:1267-1275. (PubMed:8167409)
35. Takada R et al. (2005) Analysis of combinatorial effects of Wnts and Frizzleds on beta-catenin/armadillo stabilization and Dishevelled phosphorylation. Genes Cells, 10:919-28. (PubMed:16115200)
36. Topol L et al. (2003) Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation. J Cell Biol, 162:899-908. (PubMed:12952940)
37. Toyofuku T et al. (2000) Wnt/frizzled-2 signaling induces aggregation and adhesion among cardiac myocytes by increased cadherin-beta-catenin complex. J Cell Biol, 150:225-41. (PubMed:10893270)
38. Verkaar F et al. (2009) Stably overexpressed human Frizzled-2 signals through the beta-catenin pathway and does not activate Ca2+-mobilization in Human Embryonic Kidney 293 cells. Cell Signal, 21:22-33. (PubMed:18929644)
39. Warr N et al. (2009) Sfrp1 and Sfrp2 are required for normal male sexual development in mice. Dev Biol, 326:273-84. (PubMed:19100252)
40. Yamaguchi TP et al. (1999) A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development, 126:1211-23. (PubMed:10021340)
41. Yamamoto H et al. (2007) Wnt5a modulates glycogen synthase kinase 3 to induce phosphorylation of receptor tyrosine kinase Ror2. Genes Cells, 12:1215-23. (PubMed:17986005)
42. Yamamoto S et al. (2008) Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex. Dev Cell, 15:23-36. (PubMed:18606138)
43. Zaghetto AA et al. (2007) Activation of the Wnt-beta catenin pathway in a cell population on the surface of the forebrain is essential for the establishment of olfactory axon connections. J Neurosci, 27:9757-68. (PubMed:17804636)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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