UniProt functional annotation for Q68DV7



	UniProt functional annotation for Q68DV7

UniProt code: Q68DV7.

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, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled. Acts on both canonical and non-canonical Wnt signaling pathway (PubMed:18313049, PubMed:22575959, PubMed:22895187). Along with RSPO2 and ZNRF3, constitutes a master switch that governs limb specification (By similarity). {ECO:0000250|UniProtKB:P0DPR2, ECO:0000269|PubMed:18313049, 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;

Pathway: Protein modification; protein ubiquitination.

Subunit: Interacts with AKAP8L, NONO and SFPQ (PubMed:18313049, PubMed:18655028). Interacts with FZD5 (PubMed:22895187). Identified in a complex composed of RNF43, LGR5 and RSPO1 (PubMed:23756651). Interacts with RSPO2 (PubMed:29769720). Interacts with LMBR1L (By similarity). {ECO:0000250|UniProtKB:Q5NCP0, ECO:0000269|PubMed:18313049, ECO:0000269|PubMed:18655028, ECO:0000269|PubMed:22895187, ECO:0000269|PubMed:23756651, ECO:0000269|PubMed:29769720}.

Subcellular location: Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Nucleus envelope. Note=According to a report, may be secreted. {ECO:0000269|PubMed:15492824}.

Tissue specificity: Expressed in fetal kidney, fetal lung, in colon cancer tissues, hepatocellular carcinomas and lung adenocarcinomas. Overexpressed in colorectal cancer cell lines. {ECO:0000269|PubMed:15492824, ECO:0000269|PubMed:18313049}.

Ptm: Autoubiquitinated. {ECO:0000269|PubMed:18313049}.

Disease: Sessile serrated polyposis cancer syndrome (SSPCS) [MIM:617108]: A rare disease characterized by multiple and/or large serrated polyps developing in the colon, and an increased personal and familial risk of colorectal cancer. A patient is diagnosed with SSPCS if at least one of the following criteria is met: the presence of at least five sessile serrated polyps proximal to the sigmoid colon, two of which are greater than 10 mm in diameter; the presence of any number of serrated polyps occurring proximal to the sigmoid colon in an individual who has a first-degree relative with serrated polyposis; the presence of more than 20 serrated polyps of any size distributed throughout the colon. Sessile serrated polyps are also known as sessile serrated adenomas (SSA) and are estimated to be responsible for 20 to 35% of all colon cancers. Individuals with SSPCS may have a strong personal or family history of extracolonic cancers. {ECO:0000269|PubMed:24512911, ECO:0000269|PubMed:27081527}. Note=Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Miscellaneous: Acts as a cytotoxic T-lymphocyte tumor antigen, suggesting that it may be used as a target for cancer immunotherapy. {ECO:0000305|PubMed:15623641}.

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

Sequence caution: Sequence=BAH12871.1; 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, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled. Acts on both canonical and non-canonical Wnt signaling pathway (PubMed:18313049, PubMed:22575959, PubMed:22895187). Along with RSPO2 and ZNRF3, constitutes a master switch that governs limb specification (By similarity). {ECO:0000250\|UniProtKB:P0DPR2, ECO:0000269\|PubMed:18313049, 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;
Pathway:		Protein modification; protein ubiquitination.
Subunit:		Interacts with AKAP8L, NONO and SFPQ (PubMed:18313049, PubMed:18655028). Interacts with FZD5 (PubMed:22895187). Identified in a complex composed of RNF43, LGR5 and RSPO1 (PubMed:23756651). Interacts with RSPO2 (PubMed:29769720). Interacts with LMBR1L (By similarity). {ECO:0000250\|UniProtKB:Q5NCP0, ECO:0000269\|PubMed:18313049, ECO:0000269\|PubMed:18655028, ECO:0000269\|PubMed:22895187, ECO:0000269\|PubMed:23756651, ECO:0000269\|PubMed:29769720}.
Subcellular location:		Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Nucleus envelope. Note=According to a report, may be secreted. {ECO:0000269\|PubMed:15492824}.
Tissue specificity:		Expressed in fetal kidney, fetal lung, in colon cancer tissues, hepatocellular carcinomas and lung adenocarcinomas. Overexpressed in colorectal cancer cell lines. {ECO:0000269\|PubMed:15492824, ECO:0000269\|PubMed:18313049}.
Ptm:		Autoubiquitinated. {ECO:0000269\|PubMed:18313049}.
Disease:		Sessile serrated polyposis cancer syndrome (SSPCS) [MIM:617108]: A rare disease characterized by multiple and/or large serrated polyps developing in the colon, and an increased personal and familial risk of colorectal cancer. A patient is diagnosed with SSPCS if at least one of the following criteria is met: the presence of at least five sessile serrated polyps proximal to the sigmoid colon, two of which are greater than 10 mm in diameter; the presence of any number of serrated polyps occurring proximal to the sigmoid colon in an individual who has a first-degree relative with serrated polyposis; the presence of more than 20 serrated polyps of any size distributed throughout the colon. Sessile serrated polyps are also known as sessile serrated adenomas (SSA) and are estimated to be responsible for 20 to 35% of all colon cancers. Individuals with SSPCS may have a strong personal or family history of extracolonic cancers. {ECO:0000269\|PubMed:24512911, ECO:0000269\|PubMed:27081527}. Note=Disease susceptibility may be associated with variants affecting the gene represented in this entry.
Miscellaneous:		Acts as a cytotoxic T-lymphocyte tumor antigen, suggesting that it may be used as a target for cancer immunotherapy. {ECO:0000305\|PubMed:15623641}.
Similarity:		Belongs to the ZNRF3 family. {ECO:0000305}.
Sequence caution:		Sequence=BAH12871.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};