ID LGR4_RAT Reviewed; 951 AA.
AC Q9Z2H4; G3V6R1;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2013, sequence version 2.
DT 27-MAR-2024, entry version 156.
DE RecName: Full=Leucine-rich repeat-containing G-protein coupled receptor 4;
DE AltName: Full=G-protein coupled receptor 48;
DE Flags: Precursor;
GN Name=Lgr4; Synonyms=Gpr48;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RX PubMed=9849958; DOI=10.1210/mend.12.12.0211;
RA Hsu S.Y., Liang S.-G., Hsueh A.J.W.;
RT "Characterization of two LGR genes homologous to gonadotropin and
RT thyrotropin receptors with extracellular leucine-rich repeats and a G
RT protein-coupled, seven-transmembrane region.";
RL Mol. Endocrinol. 12:1830-1845(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Receptor for R-spondins that potentiates the canonical Wnt
CC signaling pathway and is involved in the formation of various organs.
CC Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates
CC with phosphorylated LRP6 and frizzled receptors that are activated by
CC extracellular Wnt receptors, triggering the canonical Wnt signaling
CC pathway to increase expression of target genes. In contrast to
CC classical G-protein coupled receptors, does not activate heterotrimeric
CC G-proteins to transduce the signal. Its function as activator of the
CC Wnt signaling pathway is required for the development of various
CC organs, including liver, kidney, intestine, bone, reproductive tract
CC and eye. May also act as a receptor for norrin (NDP), such results
CC however require additional confirmation in vivo. Required during
CC spermatogenesis to activate the Wnt signaling pathway in peritubular
CC myoid cells. Required for the maintenance of intestinal stem cells and
CC Paneth cell differentiation in postnatal intestinal crypts. Acts as a
CC regulator of bone formation and remodeling. Involved in kidney
CC development; required for maintaining the ureteric bud in an
CC undifferentiated state. Involved in the development of the anterior
CC segment of the eye. Required during erythropoiesis. Also acts as a
CC negative regulator of innate immunity by inhibiting TLR2/TLR4
CC associated pattern-recognition and pro-inflammatory cytokine
CC production. Plays an important role in regulating the circadian rhythms
CC of plasma lipids, partially through regulating the rhythmic expression
CC of MTTP. Required for proper development of GnRH neurons (gonadotropin-
CC releasing hormone expressing neurons) that control the release of
CC reproductive hormones from the pituitary gland (By similarity).
CC {ECO:0000250|UniProtKB:A2ARI4, ECO:0000250|UniProtKB:Q9BXB1}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9BXB1};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9BXB1}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF061443; AAC77910.1; -; mRNA.
DR EMBL; AABR06025467; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06025468; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06025469; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06025470; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06025471; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473949; EDL79759.1; -; Genomic_DNA.
DR RefSeq; NP_775450.1; NM_173328.1.
DR AlphaFoldDB; Q9Z2H4; -.
DR SMR; Q9Z2H4; -.
DR STRING; 10116.ENSRNOP00000007681; -.
DR GlyCosmos; Q9Z2H4; 6 sites, No reported glycans.
DR GlyGen; Q9Z2H4; 6 sites.
DR PhosphoSitePlus; Q9Z2H4; -.
DR PaxDb; 10116-ENSRNOP00000007681; -.
DR Ensembl; ENSRNOT00000007681.5; ENSRNOP00000007681.3; ENSRNOG00000005715.6.
DR Ensembl; ENSRNOT00055040404; ENSRNOP00055032823; ENSRNOG00055023472.
DR Ensembl; ENSRNOT00060002720; ENSRNOP00060001787; ENSRNOG00060001759.
DR Ensembl; ENSRNOT00065026804; ENSRNOP00065021049; ENSRNOG00065016106.
DR GeneID; 286994; -.
DR KEGG; rno:286994; -.
DR UCSC; RGD:628615; rat.
DR AGR; RGD:628615; -.
DR CTD; 55366; -.
DR RGD; 628615; Lgr4.
DR eggNOG; KOG0619; Eukaryota.
DR eggNOG; KOG2087; Eukaryota.
DR GeneTree; ENSGT00940000157925; -.
DR HOGENOM; CLU_006843_0_0_1; -.
DR InParanoid; Q9Z2H4; -.
DR OMA; PPGNCSM; -.
DR OrthoDB; 4257264at2759; -.
DR TreeFam; TF316814; -.
DR PRO; PR:Q9Z2H4; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Proteomes; UP000234681; Chromosome 3.
DR Bgee; ENSRNOG00000005715; Expressed in stomach and 19 other cell types or tissues.
DR Genevisible; Q9Z2H4; RN.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IBA:GO_Central.
DR GO; GO:0016500; F:protein-hormone receptor activity; IEA:InterPro.
DR GO; GO:0048495; F:Roundabout binding; IBA:GO_Central.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISS:UniProtKB.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0030282; P:bone mineralization; ISS:UniProtKB.
DR GO; GO:0046849; P:bone remodeling; ISS:UniProtKB.
DR GO; GO:0061290; P:canonical Wnt signaling pathway involved in metanephric kidney development; ISO:RGD.
DR GO; GO:0072202; P:cell differentiation involved in metanephros development; ISO:RGD.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; ISO:RGD.
DR GO; GO:0048565; P:digestive tract development; ISO:RGD.
DR GO; GO:0050673; P:epithelial cell proliferation; ISO:RGD.
DR GO; GO:2001013; P:epithelial cell proliferation involved in renal tubule morphogenesis; ISO:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0001942; P:hair follicle development; ISO:RGD.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0036335; P:intestinal stem cell homeostasis; ISO:RGD.
DR GO; GO:0030539; P:male genitalia development; ISO:RGD.
DR GO; GO:0072224; P:metanephric glomerulus development; ISO:RGD.
DR GO; GO:0072282; P:metanephric nephron tubule morphogenesis; ISO:RGD.
DR GO; GO:0050919; P:negative chemotaxis; IBA:GO_Central.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:RGD.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; ISO:RGD.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0035239; P:tube morphogenesis; ISO:RGD.
DR CDD; cd15361; 7tmA_LGR4; 1.
DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR002131; Gphrmn_rcpt_fam.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000372; LRRNT.
DR PANTHER; PTHR24372; GLYCOPROTEIN HORMONE RECEPTOR; 1.
DR PANTHER; PTHR24372:SF77; GPR INSULIN LIKE RECEPTOR 1; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR Pfam; PF00560; LRR_1; 1.
DR Pfam; PF13855; LRR_8; 4.
DR Pfam; PF01462; LRRNT; 1.
DR PRINTS; PR00373; GLYCHORMONER.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM00364; LRR_BAC; 10.
DR SMART; SM00365; LRR_SD22; 6.
DR SMART; SM00369; LRR_TYP; 15.
DR SMART; SM00013; LRRNT; 1.
DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR SUPFAM; SSF52058; L domain-like; 2.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR PROSITE; PS51450; LRR; 15.
PE 2: Evidence at transcript level;
KW Biological rhythms; Cell membrane; Developmental protein; Differentiation;
KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Immunity;
KW Innate immunity; Leucine-rich repeat; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Spermatogenesis; Transducer;
KW Transmembrane; Transmembrane helix; Wnt signaling pathway.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..951
FT /note="Leucine-rich repeat-containing G-protein coupled
FT receptor 4"
FT /id="PRO_0000012793"
FT TOPO_DOM 25..544
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 545..565
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 566..575
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 576..596
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 597..619
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 620..640
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 641..661
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 662..682
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 683..703
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 704..724
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 725..756
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 757..777
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 778..783
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 784..804
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 805..951
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..57
FT /note="LRRNT"
FT REPEAT 58..79
FT /note="LRR 1"
FT REPEAT 82..103
FT /note="LRR 2"
FT REPEAT 106..127
FT /note="LRR 3"
FT REPEAT 130..151
FT /note="LRR 4"
FT REPEAT 154..177
FT /note="LRR 5"
FT REPEAT 178..199
FT /note="LRR 6"
FT REPEAT 202..223
FT /note="LRR 7"
FT REPEAT 226..247
FT /note="LRR 8"
FT REPEAT 249..270
FT /note="LRR 9"
FT REPEAT 273..294
FT /note="LRR 10"
FT REPEAT 320..341
FT /note="LRR 11"
FT REPEAT 344..365
FT /note="LRR 12"
FT REPEAT 366..387
FT /note="LRR 13"
FT REPEAT 390..411
FT /note="LRR 14"
FT REPEAT 414..435
FT /note="LRR 15"
FT MOD_RES 920
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BXB1"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 314
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 505
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..35
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 33..43
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 339..364
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 470..522
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 471..476
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 618..693
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT CONFLICT 6
FT /note="R -> G (in Ref. 1; AAC77910)"
FT /evidence="ECO:0000305"
FT CONFLICT 11
FT /note="F -> L (in Ref. 1; AAC77910)"
FT /evidence="ECO:0000305"
FT CONFLICT 95
FT /note="F -> L (in Ref. 1; AAC77910)"
FT /evidence="ECO:0000305"
FT CONFLICT 236
FT /note="N -> Y (in Ref. 1; AAC77910)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="S -> C (in Ref. 1; AAC77910)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 951 AA; 104241 MW; 457798D5408DC403 CRC64;
MPGPLRLLCF FALGLLGSAG PSGAAPPLCA APCSCDGDRR VDCSGKGLTA VPEGLSAFTQ
ALDISMNNIT QLPEDAFKSF PFLEELQLAG NDLSFIHPKA LSGLKELKVL TLQNNQLRTV
PSEAIHGLSA LQSLRLDANH ITSVPEDSFE GLVQLRHLWL DDNSLTEVPV RPLSNLPTLQ
ALTLALNNIS SIPDFAFTNL SSLVVLHLHN NKIKSLSQHC FDGLDNLETL DLNYNNLDEF
PQAIKALPSL KELGFHSNSI SVIPDGAFGG NPLLRTIHLY DNPLSFVGNS AFHNLSDLHS
LVIRGASLVQ WFPNLTGTVH LESLTLTGTK ISSIPDDLCQ NQKMLRTLDL SYNNIRDLPS
FNGCRALEEI SLQRNQISLI KENTFQGLTS LRILDLSRNL IREIHSGAFA KLGTITNLDV
SFNELTSFPT EGLNGLNQLK LVGNFKLKDA LAARDFANLR SLSVPYAYQC CAFWGCDSYA
NLNTEDNSPQ EHSVTKEKGA TDAANVTSTA ENEEHSQIII HCTPSTGAFK PCEYLLGSWM
IRLTVWFIFL VALLFNLLVI LTVFASCSSL PASKLFIGLI SVSNLLMGIY TGILTFLDAV
SWGRFAEFGI WWETGSGCKV AGSLAVFSSE SAVFLLTLAA VERSVFAKDL MKHGKSSHLR
QFQVAALLAL LGAAVAGCFP LFHGGQYSAS PLCLPFPTGE TPSLGFTVTL VLLNSLAFLL
MAIIYTKLYC NLEKEDLSEN SQSSVIKHVA WLIFTNCIFF CPVAFFSFAP LITAISISPE
IMKSVTLIFF PLPACLNPVL YVFFNPKFKE DWKLLKRRVT RKHGSVSVSI SSQGGCGEQD
FYYDCGMYSH LQGNLTVCDC CESFLLTKPV SCKHLIKSHS CPVLTAASCQ RPEAYWSDCG
TQSAHSDYAD EEDSFVSDSS DQVQACGRAC FYQSRGFPLV RYAYNLQRVR D
//
