FZD<sub>2</sub> | Class Frizzled GPCRs | IUPHAR/BPS Guide to PHARMACOLOGY

FZD2

Target id: 230

Nomenclature: FZD2

Family: Class Frizzled GPCRs

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

   GtoImmuPdb view: OFF :     Currently no data for FZD2 in GtoImmuPdb

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 class receptor 2 15
Mouse 7 570 11 E1; 11 66.45 cM Fzd2 frizzled class receptor 2 6
Rat 7 570 10q32.1 Fzd2 frizzled class receptor 2 2
Previous and Unofficial Names
Fz2 | Frizzled-2 | Drosophila polarity gene homolog 2 | frizzled family receptor 2 | Fzd10 | Fz10
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
Wnt-5a {Sp: Human}
Agonist Comments
FZDs are receptors for WNT proteins. Until now FZD2 has been proven to bind to WNT 2, 3, 3A, 5A, 6, 7A and 8B. For more detail information see [3].
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
G protein (identity unknown)
Calcium channel
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.

WNT-5A/FZD2 binding in F9 cells induced a PTX-sensitive and PDE6-dependent decrease in cGMP and increase in Ca2+ suggesting a very likely involvement of heterotrimeric G proteins [1].
References:  1,4-5
Tissue Distribution
Adult heart, fetal brain, lung, kidney.
Species:  Human
Technique:  Northern blotting.
References:  7
Arthritic synovial tissue.
Species:  Human
Technique:  RT-PCR.
References:  9
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:  15
Brain, eye, heart, kidney, lung, spleen, testis.
Species:  Mouse
Technique:  Northern blotting.
References:  12
Developing mouse thoracic arterial system and heart.
Species:  Mouse
Technique:  Whole mount in situ hybridisation
References:  11
Adult: kidney, liver, uterus, ovary, heart > brain, small intestine > calvaria, lung, mammary gland, testis.
Species:  Rat
Technique:  Northern blotting.
References:  2
Expression Datasets

Show »

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]

There should be a chart of expression data here, you may need to enable JavaScript!
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:  4
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:  5
Physiological Consequences of Altering Gene Expression
FZD2 receptor knockout mice are viable and normal.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  10
∼50% of Fz2–/– mice had a cleft palate and died as neonates, and the ∼50% that survived exhibited a variable degree of runting that developed during the early postnatal period
Species:  Mouse
Tissue:  Brain
Technique:  Gene knockouts
References:  14
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

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 [8,13].

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

Show »

1. Ahumada A, Slusarski DC, Liu X, Moon RT, Malbon CC, Wang HY. (2002) Signaling of rat Frizzled-2 through phosphodiesterase and cyclic GMP. Science, 298: 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 Chem, 267: 25202-25207. [PMID:1334084]

3. Dijksterhuis JP, Petersen J, Schulte G. (2013) WNT/Frizzled signaling: receptor-ligand selectivity with focus on FZD-G protein signaling and its physiological relevance. Br J Pharmacol,. [PMID:24032637]

4. Ma L, Wang HY. (2006) Suppression of cyclic GMP-dependent protein kinase is essential to the Wnt/cGMP/Ca2+ pathway. J Biol Chem, 281: 30990-31001. [PMID:16920709]

5. Ma L, Wang HY. (2007) Mitogen-activated Protein Kinase p38 Regulates the Wnt/Cyclic GMP/Ca2+ Non-canonical Pathway. J Biol Chem, 282: 28980-28990. [PMID:17684012]

6. Malik TH, Shivdasani RA. (2000) Structure and expression of a novel frizzled gene isolated from the developing mouse gut. Biochem J, 349 Pt 3: 829-834. [PMID:10903145]

7. 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 Commun, 252: 117-122. [PMID:9813155]

8. 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 Neurochem, 92: 1550-1553. [PMID:15748172]

9. 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 A, 97: 2791-2796. [PMID:10688908]

10. van Amerongen R, Berns A. (2006) Knockout mouse models to study Wnt signal transduction. Trends Genet, 22: 678-689. [PMID:17045694]

11. 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]

12. 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 Chem, 271: 4468-4476. [PMID:8626800]

13. 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. Nature, 423: 448-452. [PMID:12717451]

14. Yu H, Smallwood PM, Wang Y, Vidaltamayo R, Reed R, Nathans J. (2010) Frizzled 1 and frizzled 2 genes function in palate, ventricular septum and neural tube closure: general implications for tissue fusion processes. Development, 137 (21): 3707-17. [PMID:20940229]

15. 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. Genomics, 27: 370-373. [PMID:7558010]

Contributors

Show »

How to cite this page

Gunnar Schulte, Jacomijn Dijksterhuis, Julian Petersen, Elisa Arthofer, Belma Hot, Katerina Strakova, Shane Wright, Jana Valnohova, Matthias Lauth.
Class Frizzled GPCRs: FZD2. Last modified on 14/07/2015. Accessed on 17/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=230.