UniProt functional annotation for Q9ULT6



	UniProt functional annotation for Q9ULT6

UniProt code: Q9ULT6.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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). Along with RSPO2 and RNF43, constitutes a master switch that governs limb specification (By similarity). {ECO:0000250|UniProtKB:Q08D68, ECO:0000269|PubMed:22575959}.

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:0000269|PubMed:22575959}.

Pathway: Protein modification; protein ubiquitination.

Subunit: Interacts with LRP6, FZD4, FZD5, FZD6 and FZD8 (PubMed:22575959). Interacts with RSPO1; interaction promotes indirect interaction with LGR4 and membrane clearance of ZNRF3 (PubMed:22575959). Also interacts with RSPO2 (PubMed:29769720). Interacts with LMBR1L (PubMed:31073040). {ECO:0000269|PubMed:22575959, ECO:0000269|PubMed:29769720, ECO:0000305|PubMed:31073040}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:22575959}; Single-pass type I membrane protein {ECO:0000255}.

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

Sequence caution: Sequence=CAG30283.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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). Along with RSPO2 and RNF43, constitutes a master switch that governs limb specification (By similarity). {ECO:0000250\|UniProtKB:Q08D68, ECO:0000269\|PubMed:22575959}.


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:0000269\|PubMed:22575959}.
Pathway:		Protein modification; protein ubiquitination.
Subunit:		Interacts with LRP6, FZD4, FZD5, FZD6 and FZD8 (PubMed:22575959). Interacts with RSPO1; interaction promotes indirect interaction with LGR4 and membrane clearance of ZNRF3 (PubMed:22575959). Also interacts with RSPO2 (PubMed:29769720). Interacts with LMBR1L (PubMed:31073040). {ECO:0000269\|PubMed:22575959, ECO:0000269\|PubMed:29769720, ECO:0000305\|PubMed:31073040}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:22575959}; Single-pass type I membrane protein {ECO:0000255}.
Similarity:		Belongs to the ZNRF3 family. {ECO:0000305}.
Sequence caution:		Sequence=CAG30283.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};