UniProt functional annotation for Q6UXX9



	UniProt functional annotation for Q6UXX9

UniProt code: Q6UXX9.

Organism: Homo sapiens (Human).

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

Function: Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway (PubMed:21909076, PubMed:21727895, PubMed:22615920). During embryonic development, plays a crucial role in limb specification, amplifying the Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3, hence governing the number of limbs an embryo should form (PubMed:29769720). {ECO:0000269|PubMed:21727895, ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22615920, ECO:0000269|PubMed:29769720}.

Subunit: Interacts with WNT1 (By similarity). Binds heparin (By similarity). Interacts with LGR4, LGR5 and LGR6 (PubMed:21909076, PubMed:21727895, PubMed:22615920, PubMed:29769720). Interacts with E3 ubiquitin ligases RNF43 and ZNRF3 (PubMed:29769720). {ECO:0000250|UniProtKB:Q8BFU0, ECO:0000269|PubMed:21727895, ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22615920, ECO:0000269|PubMed:29769720}.

Subcellular location: Secreted {ECO:0000250|UniProtKB:Q8BFU0}.

Domain: The FU repeat is required for activation and stabilization of beta-catenin. {ECO:0000250}.

Disease: Tetraamelia syndrome 2 (TETAMS2) [MIM:618021]: A form of tetraamelia, a rare disease characterized by rudimentary appendages or complete absence of all four limbs, and other anomalies such as craniofacial, nervous system, pulmonary, skeletal and urogenital defects. TETAMS2 patients manifest limb deformities, bilateral agenesis of the lungs, abnormalities of the pulmonary vasculature, labioscrotal fold aplasia, and dysmorphic features including bilateral cleft lip/palate, ankyloglossia, mandibular hypoplasia, and microretrognathia. TETAMS2 transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269|PubMed:29769720}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Humerofemoral hypoplasia with radiotibial ray deficiency (HHRRD) [MIM:618022]: A severe disease characterized by reduction of all four limbs as well as hypoplasia of the upper limb girdle and pelvis. Rudimentary finger- or toe-like appendages may be present. HHRRD transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269|PubMed:29769720}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the R-spondin family. {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:		Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway (PubMed:21909076, PubMed:21727895, PubMed:22615920). During embryonic development, plays a crucial role in limb specification, amplifying the Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3, hence governing the number of limbs an embryo should form (PubMed:29769720). {ECO:0000269\|PubMed:21727895, ECO:0000269\|PubMed:21909076, ECO:0000269\|PubMed:22615920, ECO:0000269\|PubMed:29769720}.


Subunit:		Interacts with WNT1 (By similarity). Binds heparin (By similarity). Interacts with LGR4, LGR5 and LGR6 (PubMed:21909076, PubMed:21727895, PubMed:22615920, PubMed:29769720). Interacts with E3 ubiquitin ligases RNF43 and ZNRF3 (PubMed:29769720). {ECO:0000250\|UniProtKB:Q8BFU0, ECO:0000269\|PubMed:21727895, ECO:0000269\|PubMed:21909076, ECO:0000269\|PubMed:22615920, ECO:0000269\|PubMed:29769720}.
Subcellular location:		Secreted {ECO:0000250\|UniProtKB:Q8BFU0}.
Domain:		The FU repeat is required for activation and stabilization of beta-catenin. {ECO:0000250}.
Disease:		Tetraamelia syndrome 2 (TETAMS2) [MIM:618021]: A form of tetraamelia, a rare disease characterized by rudimentary appendages or complete absence of all four limbs, and other anomalies such as craniofacial, nervous system, pulmonary, skeletal and urogenital defects. TETAMS2 patients manifest limb deformities, bilateral agenesis of the lungs, abnormalities of the pulmonary vasculature, labioscrotal fold aplasia, and dysmorphic features including bilateral cleft lip/palate, ankyloglossia, mandibular hypoplasia, and microretrognathia. TETAMS2 transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269\|PubMed:29769720}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Humerofemoral hypoplasia with radiotibial ray deficiency (HHRRD) [MIM:618022]: A severe disease characterized by reduction of all four limbs as well as hypoplasia of the upper limb girdle and pelvis. Rudimentary finger- or toe-like appendages may be present. HHRRD transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269\|PubMed:29769720}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the R-spondin family. {ECO:0000305}.