{ "uniprot_canonical_ac": "A2ARI4-1", "uniprot_ac": "A2ARI4", "uniprot_id": "LGR4_MOUSE", "mass": { "chemical_mass": 104150.0, "monoisotopic_mass": 104150.0 }, "refseq": { "ac": "NP_766259", "name": "leucine-rich repeat-containing G-protein coupled receptor 4 precursor", "summary": "", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_766259" }, "gene_names": [ { "name": "Lgr4", "resource": "UniProtKB", "type": "recommended", "url": "https://www.uniprot.org/uniprot/A2ARI4", "id": "A2ARI4" }, { "name": "9130225G07; A330106J01Rik; A930009A08Rik; Gpr48", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_766259", "id": "NP_766259" }, { "name": "Gpr48", "resource": "UniProtKB", "type": "synonym", "url": "https://www.uniprot.org/uniprot/A2ARI4", "id": "A2ARI4" }, { "name": "Lgr4", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_766259", "id": "NP_766259" } ], "protein_names": [ { "name": "Leucine-rich repeat-containing G-protein coupled receptor 4", "resource": "UniProtKB", "type": "recommended", "url": "https://www.uniprot.org/uniprot/A2ARI4#names_and_taxonomy", "id": "A2ARI4" }, { "name": "G protein-coupled receptor GPR48; G-protein coupled receptor 48", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_766259", "id": "NP_766259" }, { "name": "G-protein coupled receptor 48", "resource": "UniProtKB", "type": "synonym", "url": "https://www.uniprot.org/uniprot/A2ARI4#names_and_taxonomy", "id": "A2ARI4" }, { "name": "leucine-rich repeat-containing G-protein coupled receptor 4 precursor", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_766259", "id": "NP_766259" } ], "function": [ { "annotation": "Lgr4 Governs a Pro-Inflammatory Program in Macrophages to Antagonize Post-Infarction Cardiac Repair.", "evidence": [ { "database": "RefSeq", "id": "NP_766259", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_766259" }, { "database": "PubMed", "id": "32600176", "url": "https://glygen.org/publication/PubMed/32600176" } ] }, { "annotation": "Lgr4 promotes aerobic glycolysis and differentiation in osteoblasts via the canonical Wnt/beta-catenin pathway.", "evidence": [ { "database": "RefSeq", "id": "NP_766259", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_766259" }, { "database": "PubMed", "id": "33950533", "url": "https://glygen.org/publication/PubMed/33950533" } ] }, { "annotation": "Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and is involved in the formation of various organs. 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. Its function as activator of the Wnt signaling pathway is required for the development of various organs, including liver, kidney, intestine, bone, reproductive tract and eye. May also act as a receptor for norrin (NDP), such results however require additional confirmation in vivo. Required during spermatogenesis to activate the Wnt signaling pathway in peritubular myoid cells. Required for the maintenance of intestinal stem cells and Paneth cell differentiation in postnatal intestinal crypts. Acts as a regulator of bone formation and remodeling. Involved in kidney development; required for maintaining the ureteric bud in an undifferentiated state. Involved in the development of the anterior segment of the eye. Required during erythropoiesis. Also acts as a negative regulator of innate immunity by inhibiting TLR2/TLR4 associated pattern-recognition and proinflammatory cytokine production. Plays an important role in regulating the circadian rhythms of plasma lipids, partially through regulating the rhythmic expression of MTTP (PubMed:24353284).", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4#function" }, { "database": "PubMed", "id": "23589304", "url": "https://glygen.org/publication/PubMed/23589304" }, { "database": "PubMed", "id": "23533175", "url": "https://glygen.org/publication/PubMed/23533175" }, { "database": "PubMed", "id": "21693646", "url": "https://glygen.org/publication/PubMed/21693646" }, { "database": "PubMed", "id": "19605502", "url": "https://glygen.org/publication/PubMed/19605502" }, { "database": "PubMed", "id": "24353284", "url": "https://glygen.org/publication/PubMed/24353284" }, { "database": "PubMed", "id": "21727895", "url": "https://glygen.org/publication/PubMed/21727895" }, { "database": "PubMed", "id": "23393138", "url": "https://glygen.org/publication/PubMed/23393138" }, { "database": "PubMed", "id": "23444378", "url": "https://glygen.org/publication/PubMed/23444378" }, { "database": "PubMed", "id": "18955481", "url": "https://glygen.org/publication/PubMed/18955481" }, { "database": "PubMed", "id": "21508962", "url": "https://glygen.org/publication/PubMed/21508962" } ] }, { "annotation": "Rspo1/Rspo3-LGR4 signaling inhibits hepatic cholesterol synthesis through the AMPKalpha-SREBP2 pathway.", "evidence": [ { "database": "RefSeq", "id": "NP_766259", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_766259" }, { "database": "PubMed", "id": "32926477", "url": "https://glygen.org/publication/PubMed/32926477" } ] } ], "disease": [ { "disease_id": "DOID:11476", "recommended_name": { "id": "DOID:11476", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:11476", "name": "osteoporosis", "description": "A bone resorption disease characterized by decreased density of normally mineralized bone which results_in the thinning of bone tissue and decreased mechanical strength." }, "synonyms": [ { "id": "MONDO:0005298", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005298", "name": "osteoporosis", "description": "A condition of reduced bone mass, with decreased cortical thickness and a decrease in the number and size of the trabeculae of cancellous bone (but normal chemical composition), resulting in increased fracture incidence. Osteoporosis is classified as primary (Type 1, postmenopausal osteoporosis; Type 2, age-associated osteoporosis; and idiopathic, which can affect juveniles, premenopausal women, and middle-aged men) and secondary osteoporosis (which results from an identifiable cause of bone mass loss)." }, { "id": "MONDO:0005298", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005298", "name": "osteoporosis, involutional", "description": "" }, { "id": "MONDO:0005298", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005298", "name": "fracture, hip, susceptibility to", "description": "" }, { "id": "MIM:166710", "resource": "MIM", "url": "https://www.omim.org/entry/166710", "name": "Osteoporosis", "description": "Osteoporosis" } ], "evidence": [ { "id": "11476", "database": "Alliance of Genome Resources", "url": "https://www.alliancegenome.org/disease/DOID:11476" } ] }, { "disease_id": "DOID:1686", "recommended_name": { "id": "DOID:1686", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:1686", "name": "glaucoma", "description": "An eye disease that is characterized by an unstable or a sustained increase in the intraocular pressure which the eye cannot withstand without damage to its structure or impairment of its function." }, "synonyms": [], "evidence": [ { "id": "1686", "database": "Alliance of Genome Resources", "url": "https://www.alliancegenome.org/disease/DOID:1686" } ] } ], "snv": [], "mutagenesis": [ { "start_pos": 755, "end_pos": 755, "sequence_org": "T", "sequence_mut": "I", "comment": "Confers constitutive activity.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" }, { "database": "PubMed", "id": "23589304", "url": "https://glygen.org/publication/PubMed/23589304" } ] } ], "expression_tissue": [], "expression_disease": [], "species": [ { "name": "Mus musculus", "taxid": 10090, "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "common_name": "Mouse" } ], "gene": [ { "name": "Lgr4", "url": "https://www.uniprot.org/uniprot/A2ARI4", "locus": { "chromosome": "2", "start_pos": 109917647, "end_pos": 110014257, "strand": "+", "evidence": [ { "database": "Ensembl Gene", "id": "ENSMUSG00000050199", "url": "https://www.ensembl.org/id/ENSMUSG00000050199" } ] } } ], "crossref": [ { "id": "ENSMUSG00000050199", "url": "https://bgee.org/?page=gene&gene_id=ENSMUSG00000050199", "database": "Bgee" }, { "id": "107515", "url": "https://www.ncbi.nlm.nih.gov/gene/107515", "database": "GeneID" }, { "id": "GPDB0001721", "url": "https://acgg.asia/gpdb2/GPDB0001721", "database": "GlycoProtDB" }, { "id": "GPDB0001722", "url": "https://acgg.asia/gpdb2/GPDB0001722", "database": "GlycoProtDB" }, { "id": "IPR000276", "url": "https://www.ebi.ac.uk/interpro/entry/IPR000276", "database": "InterPro" }, { "id": "IPR000372", "url": "https://www.ebi.ac.uk/interpro/entry/IPR000372", "database": "InterPro" }, { "id": "IPR001611", "url": "https://www.ebi.ac.uk/interpro/entry/IPR001611", "database": "InterPro" }, { "id": "IPR002131", "url": "https://www.ebi.ac.uk/interpro/entry/IPR002131", "database": "InterPro" }, { "id": "IPR003591", "url": "https://www.ebi.ac.uk/interpro/entry/IPR003591", "database": "InterPro" }, { "id": "IPR017452", "url": "https://www.ebi.ac.uk/interpro/entry/IPR017452", "database": "InterPro" }, { "id": "IPR032675", "url": "https://www.ebi.ac.uk/interpro/entry/IPR032675", "database": "InterPro" }, { "id": "mmu:107515", "url": "https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+mmu:107515", "database": "KEGG Pathway" }, { "id": "1891468", "url": "http://www.informatics.jax.org/marker/MGI:1891468", "database": "MGI" }, { "id": "LFHGGEY", "url": "https://omabrowser.org/oma/group/LFHGGEY/", "database": "OMA" }, { "id": "PF00001", "url": "http://pfam.xfam.org/family/PF00001", "database": "Pfam" }, { "id": "PF01462", "url": "http://pfam.xfam.org/family/PF01462", "database": "Pfam" }, { "id": "PF13855", "url": "http://pfam.xfam.org/family/PF13855", "database": "Pfam" }, { "id": "PR_A2ARI4", "url": "http://purl.obolibrary.org/obo/PR_A2ARI4", "database": "PRO" }, { "id": "NP_766259", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_766259", "database": "RefSeq" }, { "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4", "database": "UniProtKB" }, { "id": "A2ARI4-1", "url": "https://www.uniprot.org/uniprot/A2ARI4-1", "database": "UniProtKB" }, { "id": "A2ARI4-2", "url": "https://www.uniprot.org/uniprot/A2ARI4-2", "database": "UniProtKB" } ], "sequence": { "sequence": "MPGPLRLLCFFALGLLGSAGPSGAAPPLCAAPCSCDGDRRVDCSGKGLTAVPEGLSAFTQALDISMNNITQLPEDAFKNFPFLEELQLAGNDLSFIHPKALSGLKELKVLTLQNNQLKTVPSEAIRGLSALQSLRLDANHITSVPEDSFEGLVQLRHLWLDDNILTEVPVRPLSNLPTLQALTLALNNISSIPDFAFTNLSSLVVLHLHNNKIKSLSQHCFDGLDNLETLDLNYNNLDEFPQAIKALPSLKELGFHSNSISVIPDGAFAGNPLLRTIHLYDNPLSFVGNSAFHNLSDLHSLVIRGASLVQWFPNLAGTVHLESLTLTGTKISSIPDDLCQNQKMLRTLDLSYNDIRDLPSFNGCRALEEISLQRNQISLIKETTFQGLTSLRILDLSRNLIREIHSGAFAKLGTITNLDVSFNELTSFPTEGLNGLNQLKLVGNFQLKDALAARDFANLRSLSVPYAYQCCAFWGCDSYANLNTEDNSPQDHSVTKEKGATDAANATSTAESEEHSQIIIHCTPSTGAFKPCEYLLGSWMIRLTVWFIFLVALLFNLLVILTVFASCSSLPASKLFIGLISVSNLLMGIYTGILTFLDAVSWGRFAEFGIWWETGSGCKVAGSLAVFSSESAVFLLTLAAVERSVFAKDVMKNGKSSHLRQFQVAALVALLGAAIAGCFPLFHGGQYSASPLCLPFPTGETPSLGFTVTLVLLNSLAFLLMAIIYTKLYCNLEKEDPSENSQSSMIKHVAWLIFTNCIFFCPVAFFSFAPLITAISISPEIMKSVTLIFFPLPACLNPVLYVFFNPKFKDDWKLLKRRVTRKHGSVSVSISSQGGCGEQDFYYDCGMYSHLQGNLTVCDCCESFLLTKPVSCKHLIKSHSCPVLTVASCQRPEAYWSDCGTQSAHSDYADEEDSFVSDSSDQVQACGRACFYQSRGFPLVRYAYNLPRVRD", "length": 951, "header": "sp|A2ARI4-1|LGR4_MOUSE Isoform 1 of Leucine-rich repeat-containing G-protein coupled receptor 4 OS=Mus musculus OX=10090 GN=Lgr4 PE=1 SV=1 CANONICAL=A2ARI4-1" }, "isoforms": [ { "isoform_ac": "A2ARI4-1", "url": "https://www.uniprot.org/uniprot/A2ARI4#A2ARI4-1", "sequence": { "sequence": "MPGPLRLLCFFALGLLGSAGPSGAAPPLCAAPCSCDGDRRVDCSGKGLTAVPEGLSAFTQALDISMNNITQLPEDAFKNFPFLEELQLAGNDLSFIHPKALSGLKELKVLTLQNNQLKTVPSEAIRGLSALQSLRLDANHITSVPEDSFEGLVQLRHLWLDDNILTEVPVRPLSNLPTLQALTLALNNISSIPDFAFTNLSSLVVLHLHNNKIKSLSQHCFDGLDNLETLDLNYNNLDEFPQAIKALPSLKELGFHSNSISVIPDGAFAGNPLLRTIHLYDNPLSFVGNSAFHNLSDLHSLVIRGASLVQWFPNLAGTVHLESLTLTGTKISSIPDDLCQNQKMLRTLDLSYNDIRDLPSFNGCRALEEISLQRNQISLIKETTFQGLTSLRILDLSRNLIREIHSGAFAKLGTITNLDVSFNELTSFPTEGLNGLNQLKLVGNFQLKDALAARDFANLRSLSVPYAYQCCAFWGCDSYANLNTEDNSPQDHSVTKEKGATDAANATSTAESEEHSQIIIHCTPSTGAFKPCEYLLGSWMIRLTVWFIFLVALLFNLLVILTVFASCSSLPASKLFIGLISVSNLLMGIYTGILTFLDAVSWGRFAEFGIWWETGSGCKVAGSLAVFSSESAVFLLTLAAVERSVFAKDVMKNGKSSHLRQFQVAALVALLGAAIAGCFPLFHGGQYSASPLCLPFPTGETPSLGFTVTLVLLNSLAFLLMAIIYTKLYCNLEKEDPSENSQSSMIKHVAWLIFTNCIFFCPVAFFSFAPLITAISISPEIMKSVTLIFFPLPACLNPVLYVFFNPKFKDDWKLLKRRVTRKHGSVSVSISSQGGCGEQDFYYDCGMYSHLQGNLTVCDCCESFLLTKPVSCKHLIKSHSCPVLTVASCQRPEAYWSDCGTQSAHSDYADEEDSFVSDSSDQVQACGRACFYQSRGFPLVRYAYNLPRVRD", "length": 951, "header": "sp|A2ARI4-1|LGR4_MOUSE Isoform 1 of Leucine-rich repeat-containing G-protein coupled receptor 4 OS=Mus musculus OX=10090 GN=Lgr4 PE=1 SV=1 CANONICAL=A2ARI4-1" }, "locus": { "chromosome": "2", "start_pos": 109842869, "end_pos": 109748466, "strand": "-", "evidence": [ { "database": "Ensembl Transcript", "id": "ENSMUST00000046548", "url": "https://www.ensembl.org/id/ENSMUST00000046548" }, { "database": "Ensembl Peptide", "id": "ENSMUSP00000047325", "url": "https://www.ensembl.org/id/ENSMUSP00000047325" } ] } }, { "isoform_ac": "A2ARI4-2", "url": "https://www.uniprot.org/uniprot/A2ARI4#A2ARI4-2", "sequence": { "sequence": "MPGPLRLLCFFALGLLGSAGPSGAAPPLCAAPCSCDGDRRVDCSGKGLTAVPEGLSAFTQALQLAGNDLSFIHPKALSGLKELKVLTLQNNQLKTVPSEAIRGLSALQSLRLDANHITSVPEDSFEGLVQLRHLWLDDNILTEVPVRPLSNLPTLQALTLALNNISSIPDFAFTNLSSLVVLHLHNNKIKSLSQHCFDGLDNLETLDLNYNNLDEFPQAIKALPSLKELGFHSNSISVIPDGAFAGNPLLRTIHLYDNPLSFVGNSAFHNLSDLHSLVIRGASLVQWFPNLAGTVHLESLTLTGTKISSIPDDLCQNQKMLRTLDLSYNDIRDLPSFNGCRALEEISLQRNQISLIKETTFQGLTSLRILDLSRNLIREIHSGAFAKLGTITNLDVSFNELTSFPTEGLNGLNQLKLVGNFQLKDALAARDFANLRSLSVPYAYQCCAFWGCDSYANLNTEDNSPQDHSVTKEKGATDAANATSTAESEEHSQIIIHCTPSTGAFKPCEYLLGSWMIRLTVWFIFLVALLFNLLVILTVFASCSSLPASKLFIGLISVSNLLMGIYTGILTFLDAVSWGRFAEFGIWWETGSGCKVAGSLAVFSSESAVFLLTLAAVERSVFAKDVMKNGKSSHLRQFQVAALVALLGAAIAGCFPLFHGGQYSASPLCLPFPTGETPSLGFTVTLVLLNSLAFLLMAIIYTKLYCNLEKEDPSENSQSSMIKHVAWLIFTNCIFFCPVAFFSFAPLITAISISPEIMKSVTLIFFPLPACLNPVLYVFFNPKFKDDWKLLKRRVTRKHGSVSVSISSQGGCGEQDFYYDCGMYSHLQGNLTVCDCCESFLLTKPVSCKHLIKSHSCPVLTVASCQRPEAYWSDCGTQSAHSDYADEEDSFVSDSSDQVQACGRACFYQSRGFPLVRYAYNLPRVRD", "length": 927, "header": "sp|A2ARI4-2|LGR4_MOUSE Isoform 2 of Leucine-rich repeat-containing G-protein coupled receptor 4 OS=Mus musculus OX=10090 GN=Lgr4 PE=1 SV=1 CANONICAL=A2ARI4-1" }, "locus": { "chromosome": "2", "start_pos": 109842869, "end_pos": 109748466, "strand": "-", "evidence": [ { "database": "Ensembl Transcript", "id": "ENSMUST00000111037", "url": "https://www.ensembl.org/id/ENSMUST00000111037" }, { "database": "Ensembl Peptide", "id": "ENSMUSP00000106666", "url": "https://www.ensembl.org/id/ENSMUSP00000106666" } ] } } ], "glycosylation": [ { "glytoucan_ac": "", "type": "N-linked", "subtype": "", "site_category": "predicted", "site_seq": "N", "relation": "attached", "comment": "N-linked (GlcNAc...) asparagine", "start_pos": 188, "start_aa": "Asn", "end_pos": 188, "end_aa": "Asn", "residue": "Asn", "evidence": [ { "id": "A2ARI4", "database": "UniProtKB", "url": "https://www.uniprot.org/uniprot/A2ARI4#ptm_processing" } ] }, { "glytoucan_ac": "", "type": "N-linked", "subtype": "", "site_category": "predicted", "site_seq": "N", "relation": "attached", "comment": "N-linked (GlcNAc...) asparagine", "start_pos": 199, "start_aa": "Asn", "end_pos": 199, "end_aa": "Asn", "residue": "Asn", "evidence": [ { "id": "A2ARI4", "database": "UniProtKB", "url": "https://www.uniprot.org/uniprot/A2ARI4#ptm_processing" } ] }, { "glytoucan_ac": "", "type": "N-linked", "subtype": "", "site_category": "predicted", "site_seq": "N", "relation": "attached", "comment": "N-linked (GlcNAc...) asparagine", "start_pos": 294, "start_aa": "Asn", "end_pos": 294, "end_aa": "Asn", "residue": "Asn", "evidence": [ { "id": "A2ARI4", "database": "UniProtKB", "url": "https://www.uniprot.org/uniprot/A2ARI4#ptm_processing" } ] }, { "glytoucan_ac": "", "type": "N-linked", "subtype": "", "site_category": "predicted", "site_seq": "N", "relation": "attached", "comment": "N-linked (GlcNAc...) asparagine", "start_pos": 505, "start_aa": "Asn", "end_pos": 505, "end_aa": "Asn", "residue": "Asn", "evidence": [ { "id": "A2ARI4", "database": "UniProtKB", "url": "https://www.uniprot.org/uniprot/A2ARI4#ptm_processing" } ] }, { "glytoucan_ac": "", "type": "N-linked", "subtype": "", "site_category": "predicted", "site_seq": "N", "relation": "attached", "comment": "N-linked (GlcNAc...) asparagine", "start_pos": 68, "start_aa": "Asn", "end_pos": 68, "end_aa": "Asn", "residue": "Asn", "evidence": [ { "id": "A2ARI4", "database": "UniProtKB", "url": "https://www.uniprot.org/uniprot/A2ARI4#ptm_processing" } ] } ], "phosphorylation": [ { "start_pos": 920, "end_pos": 920, "kinase_uniprot_canonical_ac": "", "kinase_gene_name": "", "residue": "Ser", "comment": "Phosphoserine", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ] } ], "glycation": [], "keywords": [ "glycoprotein", "glycoprotein_predicted" ], "publication": [ { "title": "The G protein-coupled receptor repertoires of human and mouse.", "journal": "Proc. Natl. Acad. Sci. U.S.A.", "date": "2003", "authors": "Bergmann J.E., Brown A., Gaitanaris G.A., Hohmann J.G., Li F., Mortrud M.T., Ranchalis J.E., Rodriguez S.S., Vassilatis D.K., Weller J.R., Wright A.C., Zeng H.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "12679517", "url": "https://glygen.org/publication/PubMed/12679517" } ] }, { "title": "Leucine-rich repeat-containing, G protein-coupled receptor 4 null mice exhibit intrauterine growth retardation associated with embryonic and perinatal lethality.", "journal": "Mol. Endocrinol.", "date": "2004", "authors": "Tessier-Lavigne M., Mazerbourg S., Sudo S., Kawamura K., Hsueh A.J., Goodrich L.V., Bouley D.M., Rayburn H., Klein C.A., Zhang J.V.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "15192078", "url": "https://glygen.org/publication/PubMed/15192078" } ] }, { "title": "Defective postnatal development of the male reproductive tract in LGR4 knockout mice.", "journal": "Dev. Biol.", "date": "2006", "authors": "Vassart G., Laurent P., Mendive F., Pochet R., Skarnes W., Van Schoore G.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "16406039", "url": "https://glygen.org/publication/PubMed/16406039" } ] }, { "title": "Leucine-rich repeat-containing G protein-coupled receptor-4 (LGR4, Gpr48) is essential for renal development in mice.", "journal": "Nephron Exp. Nephrol.", "date": "2006", "authors": "Kato S., Nishimori K., Matsubara M., Matsuo T., Mohri Y., Umezawa A., Hatano R., Kazama I.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "16785743", "url": "https://glygen.org/publication/PubMed/16785743" } ] }, { "title": "LGR4 regulates the postnatal development and integrity of male reproductive tracts in mice.", "journal": "Biol. Reprod.", "date": "2007", "authors": "Araki K., Nakagata N., Takeya M., Yamamura K., Hoshii T., Takeo T.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "17079737", "url": "https://glygen.org/publication/PubMed/17079737" } ] }, { "title": "Eye-open at birth phenotype with reduced keratinocyte motility in LGR4 null mice.", "journal": "FEBS Lett.", "date": "2007", "authors": "Kato S., Nishimori K., Ogawa E., Okuyama R., Matsuo T., Mohri Y., Umezawa A.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "17850793", "url": "https://glygen.org/publication/PubMed/17850793" } ] }, { "title": "Deletion of G protein-coupled receptor 48 leads to ocular anterior segment dysgenesis (ASD) through down-regulation of Pitx2.", "journal": "Proc. Natl. Acad. Sci. U.S.A.", "date": "2008", "authors": "Liu M., Luo J., Martin J.F., Wang J., Zhou X., Cheng X., Li D., Qu J., Jin C., Tu L., Weng J., Amendt B.A., Ai D.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "18424556", "url": "https://glygen.org/publication/PubMed/18424556" } ] }, { "title": "Impaired hair placode formation with reduced expression of hair follicle-related genes in mice lacking Lgr4.", "journal": "Dev. Dyn.", "date": "2008", "authors": "Kato S., Nishimori K., Okuyama R., Mohri Y., Umezawa A.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "18651655", "url": "https://glygen.org/publication/PubMed/18651655" } ] }, { "title": "Inactivation of G-protein-coupled receptor 48 (Gpr48/Lgr4) impairs definitive erythropoiesis at midgestation through down-regulation of the ATF4 signaling pathway.", "journal": "J. Biol. Chem.", "date": "2008", "authors": "Liu M., Luo J., Luo W., Song H., Wang Z., Li D., Li B., Weng J.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "18955481", "url": "https://glygen.org/publication/PubMed/18955481" } ] }, { "title": "Regulation of bone formation and remodeling by G-protein-coupled receptor 48.", "journal": "Development", "date": "2009", "authors": "Li C., Liu M., Luo J., Wu X., Zhou X., Zhou W., Li D., Li X.Y., de Crombrugghe B., Cho S.G., Yi Z., Yi T., Weng J., Hook M.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "19605502", "url": "https://glygen.org/publication/PubMed/19605502" } ] }, { "title": "Reduced fertility with impairment of early-stage embryos observed in mice lacking Lgr4 in epithelial tissues.", "journal": "Fertil. Steril.", "date": "2010", "authors": "Kato S., Nishimori K., Mohri Y., Akamatsu A., Hidema S., Nawa A., Tomisawa H., Umezu T.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "20638054", "url": "https://glygen.org/publication/PubMed/20638054" } ] }, { "title": "Lgr4 is required for Paneth cell differentiation and maintenance of intestinal stem cells ex vivo.", "journal": "EMBO Rep.", "date": "2011", "authors": "Libert F., Vassart G., Lefort A., Garcia M.I., Mustata R.C., Strollo S., Van Loy T.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "21508962", "url": "https://glygen.org/publication/PubMed/21508962" } ] }, { "title": "Lgr4-deficient mice showed premature differentiation of ureteric bud with reduced expression of Wnt effector Lef1 and Gata3.", "journal": "Dev. Dyn.", "date": "2011", "authors": "Kato S., Nishimori K., Mohri Y., Akamatsu A., Oyama K.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "21523854", "url": "https://glygen.org/publication/PubMed/21523854" } ] }, { "title": "R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling.", "journal": "Proc. Natl. Acad. Sci. U.S.A.", "date": "2011", "authors": "Liu Q., Lin Q., Gong X., Thomas A., Carmon K.S.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "21693646", "url": "https://glygen.org/publication/PubMed/21693646" } ] }, { "title": "Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling.", "journal": "Nature", "date": "2011", "authors": "Heck A.J., Mohammed S., Peters P.J., Nishimori K., Clevers H., van de Wetering M., Kujala P., Barker N., Guardavaccaro D., Teunissen H., Haegebarth A., Koo B.K., Low T.Y., Stange D.E., Li V.S., Mohri Y., Schasfoort R.B., de Lau W., van Es J.E.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "21727895", "url": "https://glygen.org/publication/PubMed/21727895" } ] }, { "title": "Lgr4 gene deficiency increases susceptibility and severity of dextran sodium sulfate-induced inflammatory bowel disease in mice.", "journal": "J. Biol. Chem.", "date": "2013", "authors": "Li L., Liu M., Liu S., Lu X., Pan H., Qian Y., Zhang L., Zhao Y., Li D., Guan Y., Guan X., Wei G.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "23393138", "url": "https://glygen.org/publication/PubMed/23393138" } ] }, { "title": "Multi-functional norrin is a ligand for the LGR4 receptor.", "journal": "J. Cell Sci.", "date": "2013", "authors": "Reddy P., Cheng Y., Deng C., Hsiao C.L., Luo C.W., Hsueh A.J.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "23444378", "url": "https://glygen.org/publication/PubMed/23444378" } ] }, { "title": "Lgr4-mediated Wnt/beta-catenin signaling in peritubular myoid cells is essential for spermatogenesis.", "journal": "Development", "date": "2013", "authors": "Li L., Li X., Liu M., Liu S., Lu Y., Pan H., Qian Y., Zhao Y., Li D., Guan Y., Gao N., Guan X., Qiu Z.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "23533175", "url": "https://glygen.org/publication/PubMed/23533175" } ] }, { "title": "Lgr4/Gpr48 negatively regulates TLR2/4 associated pattern recognition and innate immunity by targeting CD14 expression.", "journal": "J. Biol. Chem.", "date": "2013", "authors": "Li R., Liu M., Lu X., Luo W., Zhang D., Zhao Y., Han H., Li D., Qian M., Tan B., Du B.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "23589304", "url": "https://glygen.org/publication/PubMed/23589304" } ] }, { "title": "LGR4 acts as a link between the peripheral circadian clock and lipid metabolism in liver.", "journal": "J. Mol. Endocrinol.", "date": "2014", "authors": "Li X., Liu M., Liu R., Ma Q., Wang F., Wang J., Wang R., Zhang X., Chen M., Ning G., Fan N.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "24353284", "url": "https://glygen.org/publication/PubMed/24353284" } ] }, { "title": "RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently of LGR4/5/6.", "journal": "Nature", "date": "2018", "authors": "Kayserili H., Reversade B., Beneteau C., Barker N., Girisha K.M., Shukla A., Le Caignec C., Latypova X., Altunoglu U., de Sousa S.B., Tan T.T., Karaman B., Basaran S., Vleminckx K., Uyguner Z.O., Soshnikova N., Bosso-Lefevre C., Hajamohideen A., Khatoo M., Leushacke M., Naert T., Nayak S.S., Noelanders R., Szenker-Ravi E., Thi Tran H., Vlaminck L., Yuecel E.B.", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "reference": [ { "type": "PubMed", "id": "29769720", "url": "https://glygen.org/publication/PubMed/29769720" } ] }, { "title": "Lgr4 Governs a Pro-Inflammatory Program in Macrophages to Antagonize Post-Infarction Cardiac Repair.", "journal": "Circulation research", "date": "2020", "authors": "Huang CK, Dai D, Xie H, Zhu Z, Hu J, Su M, Liu M, Lu L, Shen W, Ning G, Wang J, Zhang R, Yan X", "evidence": [ { "database": "RefSeq", "id": "NP_766259", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_766259" } ], "reference": [ { "type": "PubMed", "id": "32600176", "url": "https://glygen.org/publication/PubMed/32600176" } ] }, { "title": "Rspo1/Rspo3-LGR4 signaling inhibits hepatic cholesterol synthesis through the AMPKalpha-SREBP2 pathway.", "journal": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology", "date": "2020", "authors": "Liu S, Gao Y, Zhang L, Yin Y, Zhang W", "evidence": [ { "database": "RefSeq", "id": "NP_766259", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_766259" } ], "reference": [ { "type": "PubMed", "id": "32926477", "url": "https://glygen.org/publication/PubMed/32926477" } ] }, { "title": "Lgr4 promotes aerobic glycolysis and differentiation in osteoblasts via the canonical Wnt/beta-catenin pathway.", "journal": "Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research", "date": "2021", "authors": "Yang YY, Zhou YM, Xu JZ, Sun LH, Tao B, Wang WQ, Wang JQ, Zhao HY, Liu JM", "evidence": [ { "database": "RefSeq", "id": "NP_766259", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_766259" } ], "reference": [ { "type": "PubMed", "id": "33950533", "url": "https://glygen.org/publication/PubMed/33950533" } ] } ], "pathway": [ { "id": "mmu:107515", "name": "", "url": "https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+mmu:107515", "resource": "KEGG Pathway" } ], "orthologs": [ { "uniprot_canonical_ac": "Q9BXB1-1", "protein_name": "Leucine-rich repeat-containing G-protein coupled receptor 4", "gene_name": "LGR4", "tax_id": 9606, "organism": "Homo sapiens", "sequence": { "sequence": "MPGPLGLLCFLALGLLGSAGPSGAAPPLCAAPCSCDGDRRVDCSGKGLTAVPEGLSAFTQALDISMNNITQLPEDAFKNFPFLEELQLAGNDLSFIHPKALSGLKELKVLTLQNNQLKTVPSEAIRGLSALQSLRLDANHITSVPEDSFEGLVQLRHLWLDDNSLTEVPVHPLSNLPTLQALTLALNKISSIPDFAFTNLSSLVVLHLHNNKIRSLSQHCFDGLDNLETLDLNYNNLGEFPQAIKALPSLKELGFHSNSISVIPDGAFDGNPLLRTIHLYDNPLSFVGNSAFHNLSDLHSLVIRGASMVQQFPNLTGTVHLESLTLTGTKISSIPNNLCQEQKMLRTLDLSYNNIRDLPSFNGCHALEEISLQRNQIYQIKEGTFQGLISLRILDLSRNLIHEIHSRAFATLGPITNLDVSFNELTSFPTEGLNGLNQLKLVGNFKLKEALAAKDFVNLRSLSVPYAYQCCAFWGCDSYANLNTEDNSLQDHSVAQEKGTADAANVTSTLENEEHSQIIIHCTPSTGAFKPCEYLLGSWMIRLTVWFIFLVALFFNLLVILTTFASCTSLPSSKLFIGLISVSNLFMGIYTGILTFLDAVSWGRFAEFGIWWETGSGCKVAGFLAVFSSESAIFLLMLATVERSLSAKDIMKNGKSNHLKQFRVAALLAFLGATVAGCFPLFHRGEYSASPLCLPFPTGETPSLGFTVTLVLLNSLAFLLMAVIYTKLYCNLEKEDLSENSQSSMIKHVAWLIFTNCIFFCPVAFFSFAPLITAISISPEIMKSVTLIFFPLPACLNPVLYVFFNPKFKEDWKLLKRRVTKKSGSVSVSISSQGGCLEQDFYYDCGMYSHLQGNLTVCDCCESFLLTKPVSCKHLIKSHSCPALAVASCQRPEGYWSDCGTQSAHSDYADEEDSFVSDSSDQVQACGRACFYQSRGFPLVRYAYNLPRVKD", "length": 951 }, "evidence": [ { "id": 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"10226", "url": "http://www.informatics.jax.org/homology/10226", "database": "MGI" } ], "common_name": "Rat" } ], "go_annotation": { "categories": [ { "name": "Molecular Function", "total": 4, "go_terms": [ { "name": "protein-hormone receptor activity", "id": "GO:0016500", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0016500", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "" }, { "name": "transmembrane signaling receptor activity", "id": "GO:0004888", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0004888", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "21693646" }, { "name": "heparin binding", "id": "GO:0008201", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0008201", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "21873635" }, { "name": "Roundabout binding", "id": "GO:0048495", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0048495", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "21873635" } ] }, { "name": "Cellular Component", "total": 1, "go_terms": [ { "name": "integral component of plasma membrane", "id": "GO:0005887", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005887", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "21693646" } ] }, { "name": "Biological Process", "total": 28, "go_terms": [ { "name": "G protein-coupled receptor signaling pathway", "id": "GO:0007186", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0007186", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "" }, { "name": "spermatogenesis", "id": "GO:0007283", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0007283", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "23393138" }, { "name": "innate immune response", "id": "GO:0045087", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0045087", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "" }, { "name": "negative regulation of transcription, DNA-templated", "id": "GO:0045892", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0045892", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "21523854" }, { "name": "positive regulation of transcription, DNA-templated", "id": "GO:0045893", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0045893", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "21523854" }, { "name": "circadian rhythm", "id": "GO:0007623", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0007623", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "24353284" }, { "name": "bone remodeling", "id": "GO:0046849", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0046849", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "19605502" }, { "name": "positive regulation of branching involved in ureteric bud morphogenesis", "id": "GO:0090190", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0090190", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "21523854" }, { "name": "hair follicle development", "id": "GO:0001942", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0001942", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "24680895" }, { "name": "positive regulation of canonical Wnt signaling pathway", "id": "GO:0090263", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0090263", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "21693646" }, { "name": "osteoblast differentiation", "id": "GO:0001649", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0001649", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "19605502" }, { "name": "digestive tract development", "id": "GO:0048565", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0048565", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "24680895" }, { "name": "negative chemotaxis", "id": "GO:0050919", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0050919", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "21873635" }, { "name": "circadian regulation of gene expression", "id": "GO:0032922", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0032922", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "24353284" }, { "name": "negative regulation of toll-like receptor signaling pathway", "id": "GO:0034122", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0034122", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "23589304" }, { "name": "axon guidance", "id": "GO:0007411", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0007411", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "21873635" }, { "name": "male genitalia development", "id": "GO:0030539", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0030539", "evidence": [ { "database": "UniProtKB", "id": "A2ARI4", "url": "https://www.uniprot.org/uniprot/A2ARI4" } ], "pmid": "16406039" }, { "name": "bone mineralization", "id": "GO:0030282", 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