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

GO curators for mouse genes have assigned the following annotations to the gene product of Fzd4. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This protein may play a role as a positive regulator of the Wingless type MMTV integration site signaling pathway. A transcript variant retaining intronic sequence and encoding a shorter isoform has been described, however, its expression is not supported by other experimental evidence. [provided by RefSeq, Jul 2008]

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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 Fzd4
  • participates in the following biological processes:
    • canonical Wnt receptor signaling pathway ^[9]
    • extracellular matrix-cell signaling ^[9]
    • positive regulation of sequence-specific DNA binding transcription factor activity ^[9]
    • positive regulation of transcription, DNA-dependent ^[9]
  • is located in the following cellular components:
    • cell-cell junction ^[10]
    • plasma membrane ^{[1, 9]}
• The gene product of Fzd4 has been shown to bind to the gene products of Magi3, Tsku, Wnt2b, Wnt7b. ^{[1, 5, 8, 10]} Researchers have inferred, based on physical interactions, that the gene product of Fzd4
  • performs the following molecular functions:
    • cytokine binding ^[9]
    • Wnt-activated receptor activity ^[4]
    • Wnt-protein binding ^[3]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Fzd4
  • participates in the following biological processes:
    • blood vessel development ^[11]
    • cerebellum vasculature morphogenesis ^[9]
    • locomotion involved in locomotory behavior ^[7]
    • luteinization ^[2]
    • negative regulation of cell-substrate adhesion ^[1]
    • progesterone secretion ^[2]
    • regulation of vascular endothelial growth factor receptor signaling pathway ^[2]
    • retina vasculature morphogenesis in camera-type eye ^[11]
    • retinal blood vessel morphogenesis ^[9]
    • sensory perception of sound ^[7]
    • substrate adhesion-dependent cell spreading ^[1]
    • vasculogenesis ^[2]
  • is located in the following cellular components:
    • plasma membrane ^[1]
• Researchers have inferred, based on genetic interactions, that the gene product of Fzd4
  • participates in the following biological processes:
    • canonical Wnt receptor signaling pathway based on interactions with Wnt3a, Wnt7b ^{[4, 6]}
    • positive regulation of JUN kinase activity based on interactions with Magi3, Vangl2 ^[10]
    • retina vasculature morphogenesis in camera-type eye based on interactions with Lrp5, Ndp ^[11]

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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 Fzd4:
  • participates in the following biological processes:
    • canonical Wnt receptor signaling pathway
    • embryo development
    • negative regulation of cell-substrate adhesion
    • positive regulation of sequence-specific DNA binding transcription factor activity
    • positive regulation of transcription, DNA-dependent
    • regulation of transcription from RNA polymerase II promoter
    • retina vasculature morphogenesis in camera-type eye
    • Wnt receptor signaling pathway
    • Wnt receptor signaling pathway, calcium modulating pathway
  • performs the following molecular functions:
    • cytokine binding
    • PDZ domain binding
    • protein heterodimerization activity
    • protein homodimerization activity
    • ubiquitin protein ligase binding
    • Wnt-activated receptor activity
    • Wnt-protein binding
  • is located in the following cellular components:
    • cell projection
    • cell surface
    • cytoplasm
    • plasma membrane

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Summary text based on GO annotations supported by structural data

• Fzd4 encodes a protein or proteins that contain the following InterPro domains: Frizzled domain, Frizzled protein, Frizzled-4, Frizzled/secreted frizzled-related protein, GPCR, family 2-like, indicating that the gene product:
  • participates in the following biological processes:
    • cell surface receptor signaling pathway
  • performs the following molecular functions:
    • transmembrane signaling receptor activity
  • is located in the following cellular components:
    • membrane

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Fzd4 indicates that it:
  • participates in the following biological processes:
    • G-protein coupled receptor signaling pathway
    • multicellular organismal development
    • signal transduction
  • performs the following molecular functions:
    • G-protein coupled receptor activity
    • signal transducer activity
  • is located in the following cellular components:
    • integral to membrane
    • membrane

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References

1. Dufourcq P et al. (2008) Regulation of endothelial cell cytoskeletal reorganization by a secreted frizzled-related protein-1 and frizzled 4- and frizzled 7-dependent pathway: role in neovessel formation. Am J Pathol, 172:37-49. (PubMed:18156211)
2. Hsieh M et al. (2005) Mice null for Frizzled4 (Fzd4-/-) are infertile and exhibit impaired corpora lutea formation and function. Biol Reprod, 73:1135-46. (PubMed:16093361)
3. Kubo F et al. (2003) Wnt2b controls retinal cell differentiation at the ciliary marginal zone. Development, 130:587-98. (PubMed:12490564)
4. Lobov IB et al. (2005) WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature. Nature, 437:417-21. (PubMed:16163358)
5. Ohta K et al. (2011) Tsukushi functions as a Wnt signaling inhibitor by competing with Wnt2b for binding to transmembrane protein Frizzled4. Proc Natl Acad Sci U S A, 108:14962-7. (PubMed:21856951)
6. 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)
7. Wang Y et al. (2001) Progressive cerebellar, auditory, and esophageal dysfunction caused by targeted disruption of the frizzled-4 gene. J Neurosci, 21:4761-71. (PubMed:11425903)
8. Wang Z et al. (2005) Wnt7b activates canonical signaling in epithelial and vascular smooth muscle cells through interactions with Fzd1, Fzd10, and LRP5. Mol Cell Biol, 25:5022-30. (PubMed:15923619)
9. Xu Q et al. (2004) Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell, 116:883-95. (PubMed:15035989)
10. Yao R et al. (2004) MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap. Oncogene, 23:6023-30. (PubMed:15195140)
11. Ye X et al. (2009) Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization. Cell, 139:285-98. (PubMed:19837032)

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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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