Protein
E3 ubiquitin-protein ligase ZNRF3
Function
E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination and subsequent degradation of Wnt receptor complex components Frizzled and LRP6. Acts on both canonical and non-canonical Wnt signaling pathway. Acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway, thereby resticting the size of the intestinal stem cell zone (PubMed:22575959, PubMed:22895187). Along with RSPO2 and RNF43, constitutes a master switch that governs limb specification (By similarity).
Similarity
Belongs to the ZNRF3 family.
Sequence
MRPRSGGRPGAPGRRRRRLRRGPRGRRLPPPPPLPLLLGLLLAAAGPGAARAKETAFVEVVLFESSPSGDYTTHTTGLTGRFSRAGAMLSAEGEIVQMHPLGLCNNNDEEDLYEYGWVGVVKLEQPELDPKPCLTVLGKAKRAVQRGATAVIFDVSENPEAIDQLNQGSEDPLKRPVVYVKGADAIKLMNIVNKQKVARARIQHLPPRQPTEYFDMGIFLAFFVVVSLVCLILLVKIKLKQRRSQNSMNRLAVQALEKMETRKFNSKSKGRREGSCGALDTLSSGSTSDCAICLEKYIDGEELRVIPCTHRFHRKCVDPWLLQHHTCPHCRHNIIEQKGNPGAVCVETSNLTRGRQPRVTLPVHYPGRVHRTNAIPAYPTRTSMDSHGNPVTLLTMDRHGEQNLYSPQTPTYVRGYPPLHLDHTLAPHRCSLEHRAYSPAHPFRRPKFSSRSFSKAACFSQYETMYQHYYFQGLSYPEQEGQTIPSVTPRGQSRAFPPSGASSLLFPTMVHVAPPTHVESGSTSSFSCYHGHRSVCSGYLADCPGSDSSSNSSGQCRCSSSDSVVDCTEVSNQGVYGSCSTFRSSLSSDYDPFIYRSRGPAVHLEGSPPPEELPAGHSQSAGRGEPWLGPASPSGDQLSTCSLEMNYSSNSSLEPRGPNSSTSEVGLEVSPGAALDLRRTWKGGPEGPSCACCFEPQPFPPGSGIETSAGGSSLFLGPRLLEDCNPPSGEPQLGSSQGLYGLHSDHYPRTDGVKYEGLPCCFYEEKQVAHSAGRGNGCYTEDYSVSVQYTLTEEPPPSCYAGPRDLSQRIPIIPEDVDCDLGLPQDCHGMHNHSPWGGALSLDVPRLHWSLGTTREEEQAPCYQAEVQPGCSPEEAGASRASLSSAPQDTQESHALAAEASGPGSGPGIGTGA