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Gene Review

LGR4  -  leucine-rich repeat containing G protein...

Homo sapiens

Synonyms: BNMD17, G-protein coupled receptor 48, GPR48, Leucine-rich repeat-containing G-protein coupled receptor 4
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Disease relevance of LGR4


High impact information on LGR4


Biological context of LGR4

  • Comparison of overall amino acid sequences indicated that LGR4 and LGR5 are closely related to each other but diverge, during evolution, from the homologous receptor found in snail and the mammalian glycoprotein hormone receptors [4].
  • The leucine-rich repeats in LGR4 and LGR5 are arrays of 24 amino acids showing similarity to repeats found in the acid labile subunit of the insulin-like growth factor (IGF)/IGF binding protein complexes as well as slit, decorin, and Toll proteins [4].
  • Tissues expressing LGR4 were analyzed based on histochemical staining of the transgene driven by the endogenous LGR4 promoter [1].
  • To elucidate the functions of this subgroup of LGRs, LGR4 null mice were generated using a secretory trap approach to delete the majority of the LGR4 gene after the insertion of a beta-galactosidase reporter gene immediately after exon 1 [1].
  • We have mapped this receptor to human chromosome 11p14-->p13 by several approaches, including radiation hybrid and interspecific backcross mapping, and show that GPR48 is close to BDNF [5].

Anatomical context of LGR4

  • In contrast to the restricted tissue expression of gonadotropin and TSH receptors in gonads and thyroid, respectively, LGR4 is expressed in diverse tissues including ovary, testis, adrenal, placenta, thymus, spinal cord, and thyroid, whereas LGR5 is found in muscle, placenta, spinal cord, and brain [4].
  • Northern blot analysis demonstrated high expression of GPR48 in the adult human pancreas, with moderate levels of expression in placenta, kidney, brain, and heart [6].

Associations of LGR4 with chemical compounds

  • Phylogenetic analysis showed that there are three LGR subgroups: the known glycoprotein hormone receptors; LGR4 to 6; and a third subgroup represented by LGR7 [7].
  • The cellular cyclic AMP level in HEK293 cells was increased following transfection of wild-type GPR48 in a dose-dependent manner [8].

Other interactions of LGR4


  1. Leucine-rich repeat-containing, G protein-coupled receptor 4 null mice exhibit intrauterine growth retardation associated with embryonic and perinatal lethality. Mazerbourg, S., Bouley, D.M., Sudo, S., Klein, C.A., Zhang, J.V., Kawamura, K., Goodrich, L.V., Rayburn, H., Tessier-Lavigne, M., Hsueh, A.J. Mol. Endocrinol. (2004) [Pubmed]
  2. Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma cell invasiveness and metastasis. Gao, Y., Kitagawa, K., Hiramatsu, Y., Kikuchi, H., Isobe, T., Shimada, M., Uchida, C., Hattori, T., Oda, T., Nakayama, K., Nakayama, K.I., Tanaka, T., Konno, H., Kitagawa, M. Cancer Res. (2006) [Pubmed]
  3. Molecular cloning, genomic organization, developmental regulation, and a knock-out mutant of a novel leu-rich repeats-containing G protein-coupled receptor (DLGR-2) from Drosophila melanogaster. Eriksen, K.K., Hauser, F., Schiøtt, M., Pedersen, K.M., Søndergaard, L., Grimmelikhuijzen, C.J. Genome Res. (2000) [Pubmed]
  4. Characterization of two LGR genes homologous to gonadotropin and thyrotropin receptors with extracellular leucine-rich repeats and a G protein-coupled, seven-transmembrane region. Hsu, S.Y., Liang, S.G., Hsueh, A.J. Mol. Endocrinol. (1998) [Pubmed]
  5. Chromosomal localization of GPR48, a novel glycoprotein hormone receptor like GPCR, in human and mouse with radiation hybrid and interspecific backcross mapping. Loh, E.D., Broussard, S.R., Liu, Q., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Kolakowski, L.F. Cytogenet. Cell Genet. (2000) [Pubmed]
  6. Molecular characterization of a novel glycoprotein hormone G-protein-coupled receptor. Loh, E.D., Broussard, S.R., Kolakowski, L.F. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  7. The three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for LGR7. Hsu, S.Y., Kudo, M., Chen, T., Nakabayashi, K., Bhalla, A., van der Spek, P.J., van Duin, M., Hsueh, A.J. Mol. Endocrinol. (2000) [Pubmed]
  8. Generation of a constitutively active mutant of human GPR48/LGR4, a G-protein-coupled receptor. Gao, Y., Kitagawa, K., Shimada, M., Uchida, C., Hattori, T., Oda, T., Kitagawa, M. Hokkaido Igaku Zasshi (2006) [Pubmed]
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