UniProt functional annotation for O75473



	UniProt functional annotation for O75473

UniProt code: O75473.

Organism: Homo sapiens (Human).

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

Function: Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a stem cell marker of the intestinal epithelium and the hair follicle. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates 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. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. Involved in the development and/or maintenance of the adult intestinal stem cells during postembryonic development. {ECO:0000269|PubMed:21693646, ECO:0000269|PubMed:21727895, ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22815884, ECO:0000269|PubMed:23809763}.

Subunit: Identified in a complex composed of RNF43, LGR5 and RSPO1 (PubMed:21909076, PubMed:21727895, PubMed:21693646, PubMed:22815884, PubMed:23809763, PubMed:23756651). Also interacts with other R-spondin ligands, including RSPO2, RSPO3 and RSPO4 (PubMed:21909076, PubMed:21727895, PubMed:21693646, PubMed:29769720). {ECO:0000269|PubMed:21693646, ECO:0000269|PubMed:21727895, ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22815884, ECO:0000269|PubMed:23756651, ECO:0000269|PubMed:23809763, ECO:0000269|PubMed:29769720}.

Subcellular location: Cell membrane; Multi-pass membrane protein. Golgi apparatus, trans-Golgi network membrane; Multi-pass membrane protein. Note=Rapidly and constitutively internalized to the trans-Golgi network at steady state. Internalization to the trans-Golgi network may be the result of phosphorylation at Ser-861 and Ser-864; however, the phosphorylation event has not been proven (PubMed:23439653). {ECO:0000269|PubMed:23439653}.

Tissue specificity: Expressed in skeletal muscle, placenta, spinal cord, and various region of brain. Expressed at the base of crypts in colonic and small mucosa stem cells. In premalignant cancer expression is not restricted to the cript base. Overexpressed in cancers of the ovary, colon and liver. {ECO:0000269|PubMed:12601349, ECO:0000269|PubMed:16575208, ECO:0000269|PubMed:19030762}.

Miscellaneous: LGR5 is used as a marker of adult tissue stem cells in the intestine, stomach, hair follicle, and mammary epithelium. {ECO:0000305|PubMed:19030762}.

Similarity: Belongs to the G-protein coupled receptor 1 family. {ECO:0000255|PROSITE-ProRule:PRU00521}.

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:		Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a stem cell marker of the intestinal epithelium and the hair follicle. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates 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. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. Involved in the development and/or maintenance of the adult intestinal stem cells during postembryonic development. {ECO:0000269\|PubMed:21693646, ECO:0000269\|PubMed:21727895, ECO:0000269\|PubMed:21909076, ECO:0000269\|PubMed:22815884, ECO:0000269\|PubMed:23809763}.


Subunit:		Identified in a complex composed of RNF43, LGR5 and RSPO1 (PubMed:21909076, PubMed:21727895, PubMed:21693646, PubMed:22815884, PubMed:23809763, PubMed:23756651). Also interacts with other R-spondin ligands, including RSPO2, RSPO3 and RSPO4 (PubMed:21909076, PubMed:21727895, PubMed:21693646, PubMed:29769720). {ECO:0000269\|PubMed:21693646, ECO:0000269\|PubMed:21727895, ECO:0000269\|PubMed:21909076, ECO:0000269\|PubMed:22815884, ECO:0000269\|PubMed:23756651, ECO:0000269\|PubMed:23809763, ECO:0000269\|PubMed:29769720}.
Subcellular location:		Cell membrane; Multi-pass membrane protein. Golgi apparatus, trans-Golgi network membrane; Multi-pass membrane protein. Note=Rapidly and constitutively internalized to the trans-Golgi network at steady state. Internalization to the trans-Golgi network may be the result of phosphorylation at Ser-861 and Ser-864; however, the phosphorylation event has not been proven (PubMed:23439653). {ECO:0000269\|PubMed:23439653}.
Tissue specificity:		Expressed in skeletal muscle, placenta, spinal cord, and various region of brain. Expressed at the base of crypts in colonic and small mucosa stem cells. In premalignant cancer expression is not restricted to the cript base. Overexpressed in cancers of the ovary, colon and liver. {ECO:0000269\|PubMed:12601349, ECO:0000269\|PubMed:16575208, ECO:0000269\|PubMed:19030762}.
Miscellaneous:		LGR5 is used as a marker of adult tissue stem cells in the intestine, stomach, hair follicle, and mammary epithelium. {ECO:0000305\|PubMed:19030762}.
Similarity:		Belongs to the G-protein coupled receptor 1 family. {ECO:0000255\|PROSITE-ProRule:PRU00521}.