FZD<sub>5</sub> | Class Frizzled GPCRs | IUPHAR/BPS Guide to PHARMACOLOGY

FZD5

Target id: 233

Nomenclature: FZD5

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 FZD5 in GtoImmuPdb

Gene and Protein Information
Frizzled family G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 585 2q33-q34 FZD5 frizzled class receptor 5 9
Mouse 7 585 1 C2 Fzd5 frizzled class receptor 5
Rat 7 585 9q32 Fzd5 frizzled class receptor 5
Previous and Unofficial Names
frizzled family receptor 5 | Fz5
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
WNTs
Agonist Comments
WNT-3A, WNT-5A and WNT-7A have been shown to bind to the FZD5 receptor using immunoprecipitation. 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. For further information see [3].
Primary Transduction Mechanisms
Comments:  Signal transduction involving G proteins is likely [5].
References: 
Secondary Transduction Mechanisms
Comments:  FZD/beta-catenin signalling (also referred to as canonical WNT signalling) [11].
References: 
Tissue Distribution
Placental villi
Species:  Human
Technique:  Immunohistochemistry
References:  7
Synaptic sites during synapse formation
Species:  Mouse
Technique:  Immunohistochemistry
References:  8
Yolk sac, placental blood vessels of embryonic origin
Species:  Mouse
Technique:  In situ hybridisation
References:  4
Embryonic tissue including telencephalon, optic vesicles and lung buds
Species:  Mouse
Technique:  In situ hybridisation
References:  1
Developing intestinal crypts in neonatal and adult tissue
Species:  Mouse
Technique:  In situ hybridisation
References:  13
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
Overexpression of FZD5 in HEK293T cells strongly induced β-catenin-dependent transactivation of a luciferace reporter plasmid (TOPflash) on stimulation with a Wnt3a-conditioned medium
Species:  Human
Tissue:  HEK 293T cells
Response measured:  β-catenin-dependent transactivation of a luciferace reporter plasmid (TOPflash)
References:  11
Physiological Functions
Regulation of angiogenesis
Species:  Mouse
Tissue:  Yolk sac and placenta
References:  4,14
Involved in directing branching morphogenesis
Species:  Human
Tissue:  Chorionic plate
References:  7
Transducing canonical Wnt signals in Paneth-cell maturation process
Species:  Mouse
Tissue:  Intestine
References:  13
Involved in synaptic assembly
Species:  Rat
Tissue:  Hippocampus
References:  2,8
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Fzd5tm1Cle|Krt19+|Krt19tm1(cre)Mmt Fzd5tm1Cle/Fzd5tm1Cle,Krt19tm1(cre)Mmt/Krt19+
involves: 129P2/OlaHsd
MGI:108571  MGI:96693  MP:0004843 abnormal Paneth cell morphology PMID: 15778706 
Fzd5tm1Mmt Fzd5tm1Mmt/Fzd5tm1Mmt
involves: 129X1/SvJ * C57BL/6
MGI:108571  MP:0008803 abnormal placental labyrinth vasculature morphology PMID: 11092808 
Fzd5tm1Cle|Krt19+|Krt19tm1(cre)Mmt Fzd5tm1Cle/Fzd5tm1Cle,Krt19tm1(cre)Mmt/Krt19+
involves: 129P2/OlaHsd
MGI:108571  MGI:96693  MP:0004841 abnormal small intestine crypts of Lieberkuhn morphology PMID: 15778706 
Fzd5tm1Nat|Fzd5tm2Nat|Tg(Sox2-cre)1Amc Fzd5tm1Nat/Fzd5tm2Nat,Tg(Sox2-cre)1Amc/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL
MGI:108571  MGI:2656537  MP:0000832 abnormal thalamus morphology PMID: 18509025 
Fzd5tm1Nat|Fzd5tm2Nat|Gt(ROSA)26Sortm1(cre/ERT)Nat Fzd5tm1Nat/Fzd5tm2Nat,Gt(ROSA)26Sortm1(cre/ERT)Nat/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL
MGI:104735  MGI:108571  MP:0000832 abnormal thalamus morphology PMID: 18509025 
Fzd5tm1Mmt Fzd5tm1Mmt/Fzd5tm1Mmt
involves: 129X1/SvJ * C57BL/6
MGI:108571  MP:0004076 abnormal vitelline vascular remodeling PMID: 11092808 
Fzd5tm1Mmt Fzd5tm1Mmt/Fzd5tm1Mmt
involves: 129X1/SvJ * C57BL/6
MGI:108571  MP:0001718 abnormal yolk sac morphology PMID: 11092808 
Fzd5tm1Nat|Fzd5tm2Nat|Tg(Sox2-cre)1Amc Fzd5tm1Nat/Fzd5tm2Nat,Tg(Sox2-cre)1Amc/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL
MGI:108571  MGI:2656537  MP:0001265 decreased body size PMID: 18509025 
Fzd5tm1Nat|Fzd5tm2Nat|Tg(Sox2-cre)1Amc Fzd5tm1Nat/Fzd5tm2Nat,Tg(Sox2-cre)1Amc/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL
MGI:108571  MGI:2656537  MP:0001262 decreased body weight PMID: 18509025 
Fzd5tm1Mmt Fzd5tm1Mmt/Fzd5tm1Mmt
involves: 129X1/SvJ * C57BL/6
MGI:108571  MP:0001723 disorganized yolk sac vascular plexus PMID: 11092808 
Fzd5tm1Mmt Fzd5tm1Mmt/Fzd5tm1Mmt
involves: 129X1/SvJ * C57BL/6
MGI:108571  MP:0006207 embryonic lethality during organogenesis PMID: 11092808 
Fzd5tm1Nat Fzd5tm1Nat/Fzd5tm1Nat
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:108571  MP:0006207 embryonic lethality during organogenesis PMID: 18509025 
Fzd5tm1Mmt Fzd5tm1Mmt/Fzd5tm1Mmt
involves: 129X1/SvJ * C57BL/6
MGI:108571  MP:0001914 hemorrhage PMID: 11092808 
Fzd5tm1Nat|Fzd5tm2Nat|Tg(Sox2-cre)1Amc Fzd5tm1Nat/Fzd5tm2Nat,Tg(Sox2-cre)1Amc/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL
MGI:108571  MGI:2656537  MP:0001405 impaired coordination PMID: 18509025 
Fzd5tm1Mmt Fzd5tm1Mmt/Fzd5tm1Mmt
involves: 129X1/SvJ * C57BL/6
MGI:108571  MP:0001722 pale yolk sac PMID: 11092808 
Fzd5tm1Nat|Fzd5tm2Nat|Tg(Sox2-cre)1Amc Fzd5tm1Nat/Fzd5tm2Nat,Tg(Sox2-cre)1Amc/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL
MGI:108571  MGI:2656537  MP:0001326 retinal degeneration PMID: 18509025 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Alzheimer disease
Synonyms: Alzheimer's disease [Disease Ontology: DOID:10652]
Disease Ontology: DOID:10652
OMIM: 104300
References:  6
Disease:  Cancer
Disease Ontology: DOID:162
References:  12
Disease:  Rheumatoid arthritis
Disease Ontology: DOID:7148
OMIM: 180300
References:  10

References

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1. Borello U, Buffa V, Sonnino C, Melchionna R, Vivarelli E, Cossu G. (1999) Differential expression of the Wnt putative receptors Frizzled during mouse somitogenesis. Mech Dev, 89: 173-177. [PMID:10559494]

2. Dickins EM, Salinas PC. (2013) Wnts in action: from synapse formation to synaptic maintenance. Front Cell Neurosci, 7: 162. [PMID:24223536]

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. Ishikawa T, Tamai Y, Zorn AM, Yoshida H, Seldin MF, Nishikawa S, Taketo MM. (2001) Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis. Development, 128 (1): 25-33. [PMID:11092808]

5. Kilander MB, Dijksterhuis JP, Ganji RS, Bryja V, Schulte G. (2011) WNT-5A stimulates the GDP/GTP exchange at pertussis toxin-sensitive heterotrimeric G proteins. Cell. Signal., 23 (3): 550-4. [PMID:21070854]

6. Li B, Zhong L, Yang X, Andersson T, Huang M, Tang SJ. (2011) WNT5A signaling contributes to Aβ-induced neuroinflammation and neurotoxicity. PLoS ONE, 6 (8): e22920. [PMID:21857966]

7. Lu J, Zhang S, Nakano H, Simmons DG, Wang S, Kong S, Wang Q, Shen L, Tu Z, Wang W et al.. (2013) A positive feedback loop involving Gcm1 and Fzd5 directs chorionic branching morphogenesis in the placenta. PLoS Biol., 11 (4): e1001536. [PMID:23610556]

8. Sahores M, Gibb A, Salinas PC. (2010) Frizzled-5, a receptor for the synaptic organizer Wnt7a, regulates activity-mediated synaptogenesis. Development, 137 (13): 2215-25. [PMID:20530549]

9. Saitoh T, Hirai M, Katoh M. (2001) Molecular cloning and characterization of human Frizzled-5 gene on chromosome 2q33.3-q34 region. Int. J. Oncol., 19 (1): 105-10. [PMID:11408929]

10. 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]

11. Tauriello DV, Jordens I, Kirchner K, Slootstra JW, Kruitwagen T, Bouwman BA, Noutsou M, Rüdiger SG, Schwamborn K, Schambony A et al.. (2012) Wnt/β-catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled. Proc. Natl. Acad. Sci. U.S.A., 109 (14): E812-20. [PMID:22411803]

12. Ueno K, Hirata H, Hinoda Y, Dahiya R. (2013) Frizzled homolog proteins, microRNAs and Wnt signaling in cancer. Int. J. Cancer, 132 (8): 1731-40. [PMID:22833265]

13. van Es JH, Jay P, Gregorieff A, van Gijn ME, Jonkheer S, Hatzis P, Thiele A, van den Born M, Begthel H, Brabletz T et al.. (2005) Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nat. Cell Biol., 7 (4): 381-6. [PMID:15778706]

14. Zerlin M, Julius MA, Kitajewski J. (2008) Wnt/Frizzled signaling in angiogenesis. Angiogenesis, 11 (1): 63-9. [PMID:18253847]

Contributors

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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: FZD5. Last modified on 17/02/2015. Accessed on 16/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=233.