Protein: Frizzled-4 (Fz-4) (mFz4) (CD antigen CD344) (Q61088)
Organism: Mus musculus (Mouse)
Function: Receptor for Wnt proteins. Most frizzled receptors are coupled to the beta-catenin (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP). In retina, it can be activated by Wnt protein-binding and also by Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism.
Subcellular location: Cell membrane {ECO:0000269|PubMed:10097073}; Multi-pass membrane protein {ECO:0000255}.
Sequence: MAWPGTGPSSRGAPGGVGLRLGLLLQFLLLLRPTLGFGDEEERRCDPIRIAMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCLSVKRRCEPVLREFGFAWPDTLNCSKFPPQNDHNHMCMEGPGDEEVPLPHKTPIQPGEECHSVGSNSDQYIWVKRSLNCVLKCGYDAGLYSRSAKEFTDIWMAVWASLCFISTTFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAAEPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPATCVIACYFYEISNWALFRYSADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSNRLVNSGKVKREKRGNGWVKPGKGNETVV
InterPro domains: - IPR041765: Frizzled 4, cysteine-rich domain (domain) [42-167]
- IPR036790: Frizzled cysteine-rich domain superfamily (homologous_superfamily) [37-162]
- IPR015526: Frizzled/secreted frizzled-related protein (family) [42-506]
- IPR020067: Frizzled domain (domain) [40-163]
- IPR026551: Frizzled-4, 7TM (domain) [209-509]
- IPR017981: GPCR, family 2-like, 7TM (domain) [219-503]
- IPR000539: Frizzled/Smoothened, 7TM (domain) [209-514]
Interaction partners: - Norrin
- Protein Wnt-5a
- Low-density lipoprotein receptor-related protein 6
- Low-density lipoprotein receptor-related protein 5
- Tetraspanin-12
- Protein Wnt-11
- Protein Wnt-7a
- Protein Wnt-7b
- Proto-oncogene Wnt-1
- Tyrosine-protein kinase RYK
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0060089 (molecular transducer activity), GO:0005488 (binding), GO:0038023 (signaling receptor activity), GO:0005515 (protein binding), GO:0004888 (transmembrane signaling receptor activity), GO:0042813 (Wnt receptor activity)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0000003 (reproduction), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0022414 (reproductive process), GO:0048519 (negative regulation of biological process), GO:0048856 (anatomical structure development), GO:0009653 (anatomical structure morphogenesis), GO:0048870 (cell motility), GO:0008283 (cell population proliferation), GO:0051240 (positive regulation of multicellular organismal process), GO:0007389 (pattern specification process), GO:0051239 (regulation of multicellular organismal process), GO:0003006 (developmental process involved in reproduction), GO:0048646 (anatomical structure formation involved in morphogenesis), GO:0007267 (cell-cell signaling), GO:0050793 (regulation of developmental process), GO:0009719 (response to endogenous stimulus), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0048523 (negative regulation of cellular process), GO:0007165 (signal transduction), GO:0048869 (cellular developmental process), GO:0007275 (multicellular organism development), GO:0019222 (regulation of metabolic process), GO:0009893 (positive regulation of metabolic process), GO:0051094 (positive regulation of developmental process), GO:0007154 (cell communication), GO:0048522 (positive regulation of cellular process), GO:0048729 (tissue morphogenesis), GO:0035148 (tube formation), GO:0060548 (negative regulation of cell death), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0048731 (system development), GO:0048513 (animal organ development), GO:0003279 (cardiac septum development), GO:0070848 (response to growth factor), GO:0071495 (cellular response to endogenous stimulus), GO:0060255 (regulation of macromolecule metabolic process), GO:0048608 (reproductive structure development), GO:0045137 (development of primary sexual characteristics), GO:0035295 (tube development), GO:0009887 (animal organ morphogenesis), GO:0060411 (cardiac septum morphogenesis), GO:0030900 (forebrain development), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0045595 (regulation of cell differentiation), GO:0007166 (cell surface receptor signaling pathway), GO:0009790 (embryo development), GO:0007548 (sex differentiation), GO:0048839 (inner ear development), GO:0030901 (midbrain development), GO:0008284 (positive regulation of cell population proliferation), GO:0016477 (cell migration), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0035239 (tube morphogenesis), GO:0045597 (positive regulation of cell differentiation), GO:0048736 (appendage development), GO:0009798 (axis specification), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0198738 (cell-cell signaling by wnt), GO:0001568 (blood vessel development), GO:1905114 (cell surface receptor signaling pathway involved in cell-cell signaling), GO:0035107 (appendage morphogenesis), GO:0003205 (cardiac chamber development), GO:0009891 (positive regulation of biosynthetic process), GO:0001525 (angiogenesis), GO:0048598 (embryonic morphogenesis), GO:2000026 (regulation of multicellular organismal development), GO:0042127 (regulation of cell population proliferation), GO:0010941 (regulation of cell death), GO:0009888 (tissue development), GO:0003002 (regionalization), GO:0031325 (positive regulation of cellular metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0003206 (cardiac chamber morphogenesis), GO:0031323 (regulation of cellular metabolic process), GO:0060021 (roof of mouth development), GO:0080090 (regulation of primary metabolic process), GO:0046661 (male sex differentiation), GO:0060037 (pharyngeal system development), GO:0060562 (epithelial tube morphogenesis), GO:0042733 (embryonic digit morphogenesis), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0043069 (negative regulation of programmed cell death), GO:0043067 (regulation of programmed cell death), GO:0016055 (Wnt signaling pathway), GO:0001944 (vasculature development), GO:0090596 (sensory organ morphogenesis), GO:0048732 (gland development), GO:0007369 (gastrulation), GO:0008406 (gonad development), GO:0046546 (development of primary male sexual characteristics), GO:0002009 (morphogenesis of an epithelium), GO:0016331 (morphogenesis of embryonic epithelium), GO:0010468 (regulation of gene expression), GO:0060976 (coronary vasculature development), GO:0048754 (branching morphogenesis of an epithelial tube), GO:0048568 (embryonic organ development), GO:0003007 (heart morphogenesis), GO:0007399 (nervous system development), GO:0001501 (skeletal system development), GO:0072359 (circulatory system development), GO:0007417 (central nervous system development), GO:0072164 (mesonephric tubule development), GO:0051252 (regulation of RNA metabolic process), GO:2000027 (regulation of animal organ morphogenesis), GO:0007507 (heart development), GO:0003281 (ventricular septum development), GO:0061458 (reproductive system development), GO:1901215 (negative regulation of neuron death), GO:0042472 (inner ear morphogenesis), GO:0048562 (embryonic organ morphogenesis), GO:0007423 (sensory organ development), GO:1901214 (regulation of neuron death), GO:0010628 (positive regulation of gene expression), GO:0035108 (limb morphogenesis), GO:0001667 (ameboidal-type cell migration), GO:0072175 (epithelial tube formation), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0060412 (ventricular septum morphogenesis), GO:0048514 (blood vessel morphogenesis), GO:0031326 (regulation of cellular biosynthetic process), GO:0060606 (tube closure), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0060173 (limb development), GO:0035113 (embryonic appendage morphogenesis), GO:0060429 (epithelium development), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0071363 (cellular response to growth factor stimulus), GO:0009952 (anterior/posterior pattern specification), GO:0009792 (embryo development ending in birth or egg hatching), GO:0001838 (embryonic epithelial tube formation), GO:0042981 (regulation of apoptotic process), GO:0001892 (embryonic placenta development), GO:2001141 (regulation of RNA biosynthetic process), GO:0043583 (ear development), GO:0043523 (regulation of neuron apoptotic process), GO:0001843 (neural tube closure), GO:0090175 (regulation of establishment of planar polarity), GO:0045446 (endothelial cell differentiation), GO:0043524 (negative regulation of neuron apoptotic process), GO:0001841 (neural tube formation), GO:1902680 (positive regulation of RNA biosynthetic process), GO:0048844 (artery morphogenesis), GO:0030326 (embryonic limb morphogenesis), GO:0043408 (regulation of MAPK cascade), GO:0043009 (chordate embryonic development), GO:0043066 (negative regulation of apoptotic process), GO:0006355 (regulation of DNA-templated transcription), GO:0008584 (male gonad development), GO:0031175 (neuron projection development), GO:0003158 (endothelium development), GO:0014032 (neural crest cell development), GO:0071773 (cellular response to BMP stimulus), GO:0060039 (pericardium development), GO:0035115 (embryonic forelimb morphogenesis), GO:0001701 (in utero embryonic development), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0045893 (positive regulation of DNA-templated transcription), GO:0014020 (primary neural tube formation), GO:0060071 (Wnt signaling pathway, planar cell polarity pathway)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0009986 (cell surface), GO:0071944 (cell periphery), GO:0005737 (cytoplasm), GO:0031090 (organelle membrane), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0030139 (endocytic vesicle), GO:0030135 (coated vesicle), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0031982 (vesicle), GO:0012506 (vesicle membrane), GO:0030659 (cytoplasmic vesicle membrane), GO:0030136 (clathrin-coated vesicle), GO:0030666 (endocytic vesicle membrane), GO:0030662 (coated vesicle membrane), GO:0045334 (clathrin-coated endocytic vesicle), GO:0097708 (intracellular vesicle), GO:0030669 (clathrin-coated endocytic vesicle membrane), GO:0030665 (clathrin-coated vesicle membrane)