LGR4_BOVIN
ID LGR4_BOVIN Reviewed; 951 AA.
AC F1MLX5;
DT 26-JUN-2013, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2013, sequence version 3.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Leucine-rich repeat-containing G-protein coupled receptor 4;
DE Flags: Precursor;
GN Name=LGR4;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
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 required 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; DAAA02041144; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001192440.1; NM_001205511.1.
DR AlphaFoldDB; F1MLX5; -.
DR SMR; F1MLX5; -.
DR STRING; 9913.ENSBTAP00000003370; -.
DR PaxDb; F1MLX5; -.
DR PRIDE; F1MLX5; -.
DR Ensembl; ENSBTAT00000073630; ENSBTAP00000058722; ENSBTAG00000002606.
DR GeneID; 505423; -.
DR KEGG; bta:505423; -.
DR CTD; 55366; -.
DR VEuPathDB; HostDB:ENSBTAG00000002606; -.
DR VGNC; VGNC:30861; LGR4.
DR eggNOG; KOG0619; Eukaryota.
DR eggNOG; KOG2087; Eukaryota.
DR GeneTree; ENSGT00940000157925; -.
DR HOGENOM; CLU_006843_0_0_1; -.
DR InParanoid; F1MLX5; -.
DR OMA; DLFWMCL; -.
DR OrthoDB; 340670at2759; -.
DR TreeFam; TF316814; -.
DR Proteomes; UP000009136; Chromosome 15.
DR Bgee; ENSBTAG00000002606; Expressed in abomasum and 106 other tissues.
DR ExpressionAtlas; F1MLX5; baseline and differential.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016500; F:protein-hormone receptor activity; IEA:InterPro.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISS:UniProtKB.
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; IEA:Ensembl.
DR GO; GO:0072202; P:cell differentiation involved in metanephros development; IEA:Ensembl.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0048565; P:digestive tract development; IEA:Ensembl.
DR GO; GO:2001013; P:epithelial cell proliferation involved in renal tubule morphogenesis; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0036335; P:intestinal stem cell homeostasis; IEA:Ensembl.
DR GO; GO:0030539; P:male genitalia development; IEA:Ensembl.
DR GO; GO:0072224; P:metanephric glomerulus development; IEA:Ensembl.
DR GO; GO:0072282; P:metanephric nephron tubule morphogenesis; IEA:Ensembl.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IEA:Ensembl.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; IEA:Ensembl.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR Gene3D; 3.80.10.10; -; 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 Pfam; PF00001; 7tm_1; 1.
DR Pfam; PF13855; LRR_8; 4.
DR Pfam; PF01462; LRRNT; 1.
DR PRINTS; PR00373; GLYCHORMONER.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM00369; LRR_TYP; 15.
DR SMART; SM00013; LRRNT; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR PROSITE; PS51450; LRR; 15.
PE 3: Inferred from homology;
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..19
FT /evidence="ECO:0000255"
FT CHAIN 20..951
FT /note="Leucine-rich repeat-containing G-protein coupled
FT receptor 4"
FT /id="PRO_0000422814"
FT TOPO_DOM 20..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 35..58
FT /note="LRR 1"
FT REPEAT 59..79
FT /note="LRR 2"
FT REPEAT 81..103
FT /note="LRR 3"
FT REPEAT 104..127
FT /note="LRR 4"
FT REPEAT 128..151
FT /note="LRR 5"
FT REPEAT 153..175
FT /note="LRR 6"
FT REPEAT 176..199
FT /note="LRR 7"
FT REPEAT 201..223
FT /note="LRR 8"
FT REPEAT 224..247
FT /note="LRR 9"
FT REPEAT 248..270
FT /note="LRR 10"
FT REPEAT 272..294
FT /note="LRR 11"
FT REPEAT 318..341
FT /note="LRR 12"
FT REPEAT 342..363
FT /note="LRR 13"
FT REPEAT 364..387
FT /note="LRR 14"
FT REPEAT 388..411
FT /note="LRR 15"
FT REPEAT 413..435
FT /note="LRR 16"
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 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 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"
SQ SEQUENCE 951 AA; 104466 MW; AA84520D44C80361 CRC64;
MPGPLGLLCF LALGLRGSAE PSGAAPPLCA APCSCDGDRR VDCSGKGLTA VPEGLSAFTQ
LLDISMNNIT QLPEDAFKNF PFLEELRLAG NDLSFIHPKA LSGLKELKVL TLQNNQLKTV
PSEAIRGLSS LQSLRLDANH ITSVPEDSFE GLTQLRHLWL DDNSLTEVPV HPLSNLPTLQ
ALTLALNKIS SIPDFAFTNL SSLVVLHLHN NKIKSLGQHC FDGLDNLETL DLNYNNLGEF
PQAIKALPSL KELLFHSNSI SVIPDGAFDG NPLLKTIHLY DNPLSFVGNS AFHNLSELHS
LVIRGASMVQ RFPNLTGTVR LESLTLTGTK ISSISNNLCQ EQKRLRTLDL SYNSIKDLPS
FNGCHALEEI SLQRNQIHQI KEDTFQGLTS LKILDLSRNL IHEIDDRAFA KLGSITNLDV
SFNELTSFPT EGLNGLNQLK LVGNFKLKEA LAAKDFVNLR SLSVPYAYQC CAFWGCDSYT
HSNTEDNSLQ DHSGSKDKGL SDVAGVTSSA ENEEHSQIII HCTPSTGAFK PCEYLLGSWM
IRLTVWFIFL VALFFNLLVI LTTFASCTSV PSSKLFIGLI SVSNLFMGAY TGILTFLDAV
SWGRFAEFGI WWEIGSGCKI AGFLAVFSSE SAIFLLMLAA VERSLSAKDM MKNGKSNHLR
QFRIAALLAF LGAAVAGSFP LFHRGEYSAS PLCLPFPTGE TPSLGFTVTL VLLNSLAFLL
MAIIYTKLYC NLEKEDLSES SQSSMIKHVA WLIFTNCIFF CPVAFFSFAP LITAVSISPE
IMKSVTLIFF PLPACLNPVL YVFFNPKFKE DWKLLKRHVS KKSGSASVSI SSQAGCVEQD
FYYDCGMYSH LQGNLTVCDC CEAFLLTKPV SCKHLIKSHS CPALTVGSCQ RPDGYWSDCG
TQSAHSDYAD EEDSFVSDSS DQVQACGRAC FYQSRGFPLV RYAYNLPRVK D
