UniProt functional annotation for Q5SSZ7



	UniProt functional annotation for Q5SSZ7

UniProt code: Q5SSZ7.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

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). {ECO:0000250|UniProtKB:Q08D68, ECO:0000269|PubMed:22575959, ECO:0000269|PubMed:22895187}.

Catalytic activity: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;

Activity regulation: Negatively regulated by R-spondin proteins such as RSPO1: interaction with RSPO1 induces the indirect association between ZNRF3 and LGR4, promoting membrane clearance of ZNRF3. {ECO:0000250}.

Pathway: Protein modification; protein ubiquitination.

Subunit: Interacts with LRP6, FZD4, FZD5, FZD6 and FZD8 (By similarity). Interacts with RSPO1; interaction promotes indirect interaction with LGR4 and membrane clearance of ZNRF3 (By similarity). Interacts with LMBR1L (PubMed:31073040). {ECO:0000250|UniProtKB:Q9ULT6, ECO:0000269|PubMed:31073040}.

Subcellular location: Cell membrane {ECO:0000250|UniProtKB:Q9ULT6}; Single-pass type I membrane protein {ECO:0000255}.

Developmental stage: During limb development, at 14.5 dpc, ubiquitously expressed in the limb bud. In developing lungs, at 14.5 dpc, ubiquitously expressed. {ECO:0000269|PubMed:29769720}.

Disruption phenotype: Embryos die around birth due to activation of Wnt signaling pathway. Embryos display a lack of lens formation due to Wnt activation. Conditional knockout mice lacking both Rnf43 and Znrf3 in intestine show a marked expansion of the proliferative compartment, resembling the effects of acute deletion of Apc. {ECO:0000269|PubMed:22575959, ECO:0000269|PubMed:22895187}.

Similarity: Belongs to the ZNRF3 family. {ECO:0000305}.

Sequence caution: Sequence=AAI51081.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAI51084.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



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). {ECO:0000250\|UniProtKB:Q08D68, ECO:0000269\|PubMed:22575959, ECO:0000269\|PubMed:22895187}.


Catalytic activity:		Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;
Activity regulation:		Negatively regulated by R-spondin proteins such as RSPO1: interaction with RSPO1 induces the indirect association between ZNRF3 and LGR4, promoting membrane clearance of ZNRF3. {ECO:0000250}.
Pathway:		Protein modification; protein ubiquitination.
Subunit:		Interacts with LRP6, FZD4, FZD5, FZD6 and FZD8 (By similarity). Interacts with RSPO1; interaction promotes indirect interaction with LGR4 and membrane clearance of ZNRF3 (By similarity). Interacts with LMBR1L (PubMed:31073040). {ECO:0000250\|UniProtKB:Q9ULT6, ECO:0000269\|PubMed:31073040}.
Subcellular location:		Cell membrane {ECO:0000250\|UniProtKB:Q9ULT6}; Single-pass type I membrane protein {ECO:0000255}.
Developmental stage:		During limb development, at 14.5 dpc, ubiquitously expressed in the limb bud. In developing lungs, at 14.5 dpc, ubiquitously expressed. {ECO:0000269\|PubMed:29769720}.
Disruption phenotype:		Embryos die around birth due to activation of Wnt signaling pathway. Embryos display a lack of lens formation due to Wnt activation. Conditional knockout mice lacking both Rnf43 and Znrf3 in intestine show a marked expansion of the proliferative compartment, resembling the effects of acute deletion of Apc. {ECO:0000269\|PubMed:22575959, ECO:0000269\|PubMed:22895187}.
Similarity:		Belongs to the ZNRF3 family. {ECO:0000305}.
Sequence caution:		Sequence=AAI51081.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAI51084.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};