Wnt domain found in proto-oncogene Wnt-3 and similar proteins
Wnt-3, also called proto-oncogene Int-4, functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family. It is required for normal embryonic development, and especially for limb development. Wnt-3a functions in the canonical Wnt signaling pathway and plays crucial roles in both proliferation and differentiation processes in several types of stem cells. Wnt3a stimulates the migration and invasion of trophoblasts and induce the survival, proliferation, and migration of human embryonic kidney (HEK) 293 cells. It also up-regulates genes implicated in melanocyte differentiation and increases the expression and nuclear localization of the transcriptional co-activator with PDZ-binding motif (TAZ), a transcriptional modulator involved in activating osteoblastic differentiation. Wnt genes have been identified in vertebrates and invertebrates, but not in plants, unicellular eukaryotes, or prokaryotes. In humans, 19 WNT proteins are known. Because of their insolubility little is known about Wnt protein structure, but all have 23 or 24 Cys residues whose spacing is highly conserved. Signal transduction by Wnt proteins (including the Wnt/beta-catenin, the Wnt/Ca++, and the Wnt/polarity pathway) is mediated by receptors of the Frizzled and LDL-receptor-related protein (LRP) families. The Wnt signaling mediated by Wnt proteins that orchestrate and influence a myriad of cellular processes, such as cell proliferation, differentiation, tumorigenesis, apoptosis, and participation in immune defense during microbe infection.
Feature 1:Frizzled receptor binding site [polypeptide binding site]
Evidence:
Comment:The structure of Xenopus Wnt8 (XWnt8) in complex with mouse Frizzled-8 (Fz8) cysteine-rich domain (CRD) reveals an unusual two-domain Wnt structure, not obviously related to known protein folds, resembling a "hand" with "thumb" and "index" fingers extended to grasp the Fz8-CRD at two distinct binding sites.
Comment:Based on the structure of Xenopus laevis Wnt8 (4F0A) in complex with the cysteine-rich domain of frizzled 8.
Jiyao W et al.(2023). "The conserved domain database in 2023.",