Class Frizzled GPCRs C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

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Receptors of the Class Frizzled (FZD, nomenclature as agreed by the NC-IUPHAR subcommittee on the Class Frizzled GPCRs [12]), are GPCRs originally identified in Drosophila [4], which are highly conserved across species. While SMO shows structural resemblance to the 10 FZDs, it is functionally separated as it mediates effects in the Hedgehog signaling pathway [12]. FZDs are activated by WNTs, which are cysteine-rich lipoglycoproteins with fundamental functions in ontogeny and tissue homeostasis. FZD signalling was initially divided into two pathways, being either dependent on the accumulation of the transcription regulator β-catenin (CTNNB1, P35222) or being β-catenin-independent (often referred to as canonical vs. non-canonical WNT/FZD signalling, respectively). WNT stimulation of FZDs can, in cooperation with the low density lipoprotein receptors LRP5 (O75197) and LRP6 (O75581), lead to the inhibition of a constitutively active destruction complex, which results in the accumulation of β-catenin and subsequently its translocation to the nucleus. β-Catenin, in turn, modifies gene transcription by interacting with TCF/LEF transcription factors. β-Catenin-independent FZD signalling is far more complex with regard to the diversity of the activated pathways. WNT/FZD signalling can lead to the activation of heterotrimeric G proteins [6], the elevation of intracellular calcium [13], activation of cGMP-specific PDE6 [1] and elevation of cAMP as well as RAC-1, JNK, Rho and Rho kinase signalling [7]. Furthermore, the phosphoprotein Dishevelled constitutes a key player in WNT/FZD signalling. As with other GPCRs, members of the Frizzled family are functionally dependent on the arrestin scaffolding protein for internalization [5], as well as for β-catenin-dependent [2] and -independent [3,9] signalling. The pattern of cell signalling is complicated by the presence of additional ligands, which can enhance or inhibit FZD signalling (secreted Frizzled-related proteins (sFRP), Wnt-inhibitory factor (WIF1, Q9Y5W5) (WIF), sclerostin (SOST, Q9BQB4) or Dickkopf (DKK)), as well as modulatory (co)-receptors with Ryk, ROR1, ROR2 and Kremen, which may also function as independent signalling proteins.


FZD1 C Show summary » More detailed page

FZD2 C Show summary » More detailed page

FZD3 C Show summary » More detailed page

FZD4 C Show summary » More detailed page

FZD5 C Show summary » More detailed page

FZD6 C Show summary » More detailed page

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FZD8 C Show summary » More detailed page

FZD9 C Show summary » More detailed page

FZD10 C Show summary » More detailed page

SMO C Show summary » More detailed page


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Further reading

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NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation:

Gunnar Schulte, Jacomijn Dijksterhuis, Julian Petersen, Elisa Arthofer, Belma Hot, Katerina Strakova, Shane Wright, Jana Valnohova, Matthias Lauth. Class Frizzled GPCRs. Accessed on 21/11/2017. IUPHAR/BPS Guide to PHARMACOLOGY,

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Davenport AP, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: G protein-coupled receptors. Br J Pharmacol. 172: 5744-5869.