Nomenclature: FZD2

Family: Frizzled Class GPCRs

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
Frizzled family G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 565 17q21.1 FZD2 frizzled family receptor 2 13
Mouse 7 570 11 E1 Fzd2 frizzled homolog 2 (Drosophila) 5
Rat 7 570 10q32.1 Fzd2 frizzled family receptor 2 2
Previous and Unofficial Names
frizzled homolog 2 (Drosophila)
Fz2
Hfz2
hFz2
Frizzled-2
frizzled (Drosophila) homolog 2
frizzled 2, seven transmembrane spanning receptor
Fz-10
Fzd10
Drosophila polarity gene (frizzled) homologue
Drosophila polarity gene homolog 2
frizzled family receptor 2
frizzled homolog 2
fz-2
rFz2
Mfz10
Mfz10a
Fz10
AW456835
Database Links
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligand(s)
Wnt-5a {Sp: Human}
Agonist Comments
Endogenous protein WNT-5A binds to the FZD2 receptor [1,3-4].

Due to the lack of purified and biologically active WNTs hardly any information on the specificity and pharmacology of FZD-WNT interaction is available. Extensive and quantitative binding assays have not been performed with mammalian FZDs. The references above contain data showing the direct activation/interaction of FZD2 by individual WNTs.
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Other - See Comments
Comments:  Even though data argue strongly for FZD2 signalling via heterotrimeric G proteins, no direct interaction between FZD2 and the G protein has been shown yet. Thus direct proof for G protein-coupling of this receptor is still not available.
References:  1,3-4
Tissue Distribution
Arthritic synovial tissue.
Species:  Human
Technique:  RT-PCR.
References:  8
Adult heart, fetal brain, lung, kidney.
Species:  Human
Technique:  Northern blotting.
References:  6
Fetal brain, lung, kidney, adult heart, skeletal muscle, ovary, testis, pancreas > fetal liver, adult lung, liver, prostate, colon, small intestine > adult brain, placenta, spleen, leukocytes, thymus.
Species:  Human
Technique:  Northern blotting.
References:  13
Brain, eye, heart, kidney, lung, spleen, testis.
Species:  Mouse
Technique:  Northern blotting.
References:  11
Developing mouse thoracic arterial system and heart.
Species:  Mouse
Technique:  Whole mount in situ hybridisation.
References:  10
Adult: kidney, liver, uterus, ovary, heart > brain, small intestine > calvaria, lung, mammary gland, testis.
Species:  Rat
Technique:  Northern blotting.
References:  2
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of cGMP levels in mouse F9 teratocarcinoma cells expressing the rat FZD2 receptor.
Species:  Rat
Tissue:  Mouse F9 cells.
Response measured:  WNT-5A conditioned medium-induced decrease in cGMP levels.
References:  1
Measurement of intracellular Ca2+ levels, NFAT-reporter activity and PKG activity via Gt2 and Go in mouse F9 teratocarcinoma cells expressing the rat FZD2 receptor.
Species:  Rat
Tissue:  Mouse F9 cells.
Response measured:  WNT-5A-induced and PTX-sensitive increase in Ca2+ mobilisation, NFAT-reporter activity and PKG activity.
References:  3
Measurement of ATF-2 phosphorylation, p38 kinase activity and phosphorylation, PKG activity and cGMP levels, intracellular Ca2+ mobilisation and PDE activity in mouse F9 cells and HEK 293 cells expressing the rat FXD2 receptor.
Species:  Rat
Tissue:  Mouse F9 cells, HEK 293 cells.
Response measured:  WNT-5A-induced, PTX-sensitive increase in ATF-2 phosphorylation, p38 activity/phosphorylation, decrease in PKG activity and cGMP levels, mobilisation of Ca2+ and increase in PDE activity.
References:  4
Physiological Consequences of Altering Gene Expression
FZD2 receptor knockout mice are viable and normal.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  9
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0002622 abnormal cochlear hair cell morphology PMID: 20940229 
Fzd2tm1.1Nat|Vangl2+|Vangl2Lp Fzd2tm1.1Nat/Fzd2tm1.1Nat,Vangl2Lp/Vangl2+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * LPT/LeJ
MGI:1888513  MGI:2135272  MP:0002622 abnormal cochlear hair cell morphology PMID: 20940229 
Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0004406 abnormal cochlear hair cell number PMID: 20940229 
Fzd2tm1.1Nat|Vangl2+|Vangl2Lp Fzd2tm1.1Nat/Fzd2tm1.1Nat,Vangl2Lp/Vangl2+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * LPT/LeJ
MGI:1888513  MGI:2135272  MP:0004406 abnormal cochlear hair cell number PMID: 20940229 
Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0000266 abnormal heart morphology PMID: 20940229 
Fzd1tm1.1Nat|Fzd2+|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0000266 abnormal heart morphology PMID: 20940229 
Fzd1+|Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1+,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0000266 abnormal heart morphology PMID: 20940229 
Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0000452 abnormal mouth morphology PMID: 20940229 
Fzd2tm1.1Nat Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1888513  MP:0002272 abnormal nervous system electrophysiology PMID: 20940229 
Fzd2tm1.1Nat Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1888513  MP:0001983 abnormal olfactory system physiology PMID: 20940229 
Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0004491 abnormal orientation of outer hair cell stereociliary bundles PMID: 20940229 
Fzd2tm1.1Nat|Vangl2+|Vangl2Lp Fzd2tm1.1Nat/Fzd2tm1.1Nat,Vangl2Lp/Vangl2+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * LPT/LeJ
MGI:1888513  MGI:2135272  MP:0004491 abnormal orientation of outer hair cell stereociliary bundles PMID: 20940229 
Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0009653 abnormal palate development PMID: 20940229 
Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0000111 cleft palate PMID: 20940229 
Fzd1tm1.1Nat|Fzd2+|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0000111 cleft palate PMID: 20940229 
Fzd2tm1.1Nat Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1888513  MP:0000111 cleft palate PMID: 20940229 
Fzd2tm1.1Nat|Vangl2+|Vangl2Lp Fzd2tm1.1Nat/Fzd2tm1.1Nat,Vangl2Lp/Vangl2+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * LPT/LeJ
MGI:1888513  MGI:2135272  MP:0000111 cleft palate PMID: 20940229 
Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0001575 cyanosis PMID: 20940229 
Fzd2tm1.1Nat Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1888513  MP:0001265 decreased body size PMID: 20940229 
Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0000284 double outlet heart right ventricle PMID: 20940229 
Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0009886 failure of palatal shelf elevation PMID: 20940229 
Fzd2tm1.1Nat Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1888513  MP:0002058 neonatal lethality PMID: 20940229 
Fzd1+|Fzd1tm1.1Nat|Fzd2+|Fzd2tm1.1Nat|Vangl2+|Vangl2Lp Fzd1tm1.1Nat/Fzd1+,Fzd2tm1.1Nat/Fzd2+,Vangl2Lp/Vangl2+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * LPT/LeJ
MGI:1196625  MGI:1888513  MGI:2135272  MP:0000929 open neural tube PMID: 20940229 
Fzd2tm1.1Nat|Vangl2+|Vangl2Lp Fzd2tm1.1Nat/Fzd2tm1.1Nat,Vangl2Lp/Vangl2+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * LPT/LeJ
MGI:1888513  MGI:2135272  MP:0000929 open neural tube PMID: 20940229 
Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0000273 overriding aorta PMID: 20940229 
Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0009888 palatal shelves fail to meet at midline PMID: 20940229 
Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0000088 short mandible PMID: 20940229 
Fzd1tm1.1Nat|Fzd2tm1.1Nat Fzd1tm1.1Nat/Fzd1tm1.1Nat,Fzd2tm1.1Nat/Fzd2tm1.1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
MGI:1196625  MGI:1888513  MP:0010402 ventricular septal defect PMID: 20940229 
Fzd1+|Fzd1tm1.1Nat|Fzd2+|Fzd2tm1.1Nat|Vangl2+|Vangl2Lp Fzd1tm1.1Nat/Fzd1+,Fzd2tm1.1Nat/Fzd2+,Vangl2Lp/Vangl2+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * LPT/LeJ
MGI:1196625  MGI:1888513  MGI:2135272  MP:0010402 ventricular septal defect PMID: 20940229 
Fzd2tm1.1Nat|Vangl2+|Vangl2Lp Fzd2tm1.1Nat/Fzd2tm1.1Nat,Vangl2Lp/Vangl2+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * LPT/LeJ
MGI:1888513  MGI:2135272  MP:0010402 ventricular septal defect PMID: 20940229 
General Comments
The WNTs that are available in purified and active form for a pharmacological characterisation to date are WNT-3A and WNT-5A [7,12].

FZD2 (mouse) shows high homology to FZD10 (mouse). Since these receptors are encoded by two genes on different chromosomes, they should be seen as two receptor subtypes.

REFERENCES

1. Ahumada A, Slusarski DC, Liu X, Moon RT, Malbon CC, Wang HY. (2002) Signaling of rat Frizzled-2 through phosphodiesterase and cyclic GMP. Science298: 2006-2010. [PMID:12471263]

2. Chan SD, Karpf DB, Fowlkes ME, Hooks M, Bradley MS, Vuong V, Bambino T, Liu MY, Arnaud CD, Strewler GJ. (1992) Two homologs of the Drosophila polarity gene frizzled (fz) are widely expressed in mammalian tissues. J Biol Chem267: 25202-25207. [PMID:1334084]

3. Ma L, Wang HY. (2006) Suppression of cyclic GMP-dependent protein kinase is essential to the Wnt/cGMP/Ca2+ pathway. J Biol Chem281: 30990-31001. [PMID:16920709]

4. Ma L, Wang HY. (2007) Mitogen-activated Protein Kinase p38 Regulates the Wnt/Cyclic GMP/Ca2+ Non-canonical Pathway. J Biol Chem282: 28980-28990. [PMID:17684012]

5. Malik TH, Shivdasani RA. (2000) Structure and expression of a novel frizzled gene isolated from the developing mouse gut. Biochem J349 Pt 3: 829-834. [PMID:10903145]

6. Sagara N, Toda G, Hirai M, Terada M, Katoh M. (1998) Molecular cloning, differential expression, and chromosomal localization of human frizzled-1, frizzled-2, and frizzled-7. Biochem Biophys Res Commun252: 117-122. [PMID:9813155]

7. Schulte G, Bryja V, Rawal N, Castelo-Branco G, Sousa KM, Arenas E. (2005) Purified Wnt-5a increases differentiation of midbrain dopaminergic cells and dishevelled phosphorylation. J Neurochem92: 1550-1553. [PMID:15748172]

8. Sen M, Lauterbach K, El-Gabalawy H, Firestein GS, Corr M, Carson DA. (2000) Expression and function of wingless and frizzled homologs in rheumatoid arthritis. Proc Natl Acad Sci U S A97: 2791-2796. [PMID:10688908]

9. van Amerongen R, Berns A. (2006) Knockout mouse models to study Wnt signal transduction. Trends Genet22: 678-689. [PMID:17045694]

10. van Gijn ME, Blankesteijn WM, Smits JF, Hierck B, Gittenberger-de Groot AC. (2001) Frizzled 2 is transiently expressed in neural crest-containing areas during development of the heart and great arteries in the mouse. Anat Embryol (Berl)203: 185-192. [PMID:11303904]

11. Wang Y, Macke JP, Abella BS, Andreasson K, Worley P, Gilbert DJ, Copeland NG, Jenkins NA, Nathans J. (1996) A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled. J Biol Chem271: 4468-4476. [PMID:8626800]

12. Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, Yates JR, Nusse R. (2003) Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature423: 448-452. [PMID:12717451]

13. Zhao Z, Lee CC, Baldini A, Caskey CT. (1995) A human homologue of the Drosophila polarity gene frizzled has been identified and mapped to 17q21.1. Genomics27: 370-373. [PMID:7558010]

To cite this database page, please use the following:

Jacomijn Dijksterhuis, Matthias Lauth, Tilman Polonio, Gunnar Schulte.
Frizzled Class GPCRs: FZD2. Last modified on 16/01/2013. Accessed on 17/04/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=230.

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