LGR4_XENTR
ID LGR4_XENTR Reviewed; 955 AA.
AC B0BLW3; F6US71;
DT 26-JUN-2013, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Leucine-rich repeat-containing G-protein coupled receptor 4;
DE Flags: Precursor;
GN Name=lgr4;
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20431018; DOI=10.1126/science.1183670;
RA Hellsten U., Harland R.M., Gilchrist M.J., Hendrix D., Jurka J.,
RA Kapitonov V., Ovcharenko I., Putnam N.H., Shu S., Taher L., Blitz I.L.,
RA Blumberg B., Dichmann D.S., Dubchak I., Amaya E., Detter J.C., Fletcher R.,
RA Gerhard D.S., Goodstein D., Graves T., Grigoriev I.V., Grimwood J.,
RA Kawashima T., Lindquist E., Lucas S.M., Mead P.E., Mitros T., Ogino H.,
RA Ohta Y., Poliakov A.V., Pollet N., Robert J., Salamov A., Sater A.K.,
RA Schmutz J., Terry A., Vize P.D., Warren W.C., Wells D., Wills A.,
RA Wilson R.K., Zimmerman L.B., Zorn A.M., Grainger R., Grammer T.,
RA Khokha M.K., Richardson P.M., Rokhsar D.S.;
RT "The genome of the Western clawed frog Xenopus tropicalis.";
RL Science 328:633-636(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JAN-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=21909076; DOI=10.1038/embor.2011.175;
RA Glinka A., Dolde C., Kirsch N., Huang Y.L., Kazanskaya O., Ingelfinger D.,
RA Boutros M., Cruciat C.M., Niehrs C.;
RT "LGR4 and LGR5 are R-spondin receptors mediating Wnt/beta-catenin and
RT Wnt/PCP signalling.";
RL EMBO Rep. 12:1055-1061(2011).
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 play a role in regulating the circadian rhythms of plasma
CC lipids (By similarity). Required for proper development of GnRH neurons
CC (gonadotropin-releasing hormone expressing neurons) that control the
CC release of reproductive hormones from the pituitary gland (By
CC similarity). {ECO:0000250|UniProtKB:A2ARI4,
CC ECO:0000250|UniProtKB:E7FE13, ECO:0000269|PubMed:21909076}.
CC -!- INTERACTION:
CC B0BLW3; B0BLW3: lgr4; NbExp=3; IntAct=EBI-7425077, EBI-7425077;
CC B0BLW3; Q2MKA7: RSPO1; Xeno; NbExp=2; IntAct=EBI-7425077, EBI-10045219;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9BXB1};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9BXB1}.
CC -!- DEVELOPMENTAL STAGE: Maternally and zygotically expressed. Zygotic
CC expression increases after gastrula stage. Expressed in all three germ
CC layers. {ECO:0000269|PubMed:21909076}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AAMC01072689; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01072690; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01072691; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01072692; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01072693; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01072694; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01072695; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAMC01072696; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC158183; AAI58184.1; -; mRNA.
DR RefSeq; NP_001119970.1; NM_001126498.1.
DR PDB; 4LI1; X-ray; 2.66 A; A/B=23-454.
DR PDB; 4LI2; X-ray; 3.19 A; A=23-454.
DR PDBsum; 4LI1; -.
DR PDBsum; 4LI2; -.
DR AlphaFoldDB; B0BLW3; -.
DR SMR; B0BLW3; -.
DR DIP; DIP-60560N; -.
DR IntAct; B0BLW3; 2.
DR MINT; B0BLW3; -.
DR STRING; 8364.ENSXETP00000061102; -.
DR PaxDb; B0BLW3; -.
DR GeneID; 100144922; -.
DR KEGG; xtr:100144922; -.
DR CTD; 55366; -.
DR Xenbase; XB-GENE-5959108; lgr4.
DR eggNOG; KOG0619; Eukaryota.
DR eggNOG; KOG2087; Eukaryota.
DR OrthoDB; 340670at2759; -.
DR TreeFam; TF316814; -.
DR Reactome; R-XTR-4641263; Regulation of FZD by ubiquitination.
DR Proteomes; UP000008143; Chromosome 4.
DR Proteomes; UP000790000; Unplaced.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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:0007186; P:G protein-coupled receptor signaling pathway; IEA:UniProtKB-KW.
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:0001649; P:osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
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 Pfam; PF00001; 7tm_1; 1.
DR Pfam; PF13855; LRR_8; 4.
DR PRINTS; PR00373; GLYCHORMONER.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM00369; LRR_TYP; 14.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR PROSITE; PS51450; LRR; 15.
PE 1: Evidence at protein level;
KW 3D-structure; Biological rhythms; Cell membrane; Developmental protein;
KW Differentiation; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Leucine-rich repeat; Membrane; Receptor; Reference proteome; Repeat;
KW Signal; Transducer; Transmembrane; Transmembrane helix;
KW Wnt signaling pathway.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..955
FT /note="Leucine-rich repeat-containing G-protein coupled
FT receptor 4"
FT /id="PRO_0000422816"
FT TOPO_DOM 22..547
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 548..568
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 569..578
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 579..599
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 600..623
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 624..644
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 645..666
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 667..687
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 688..706
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 707..727
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 728..759
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 760..780
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 781..786
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 787..807
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 808..955
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 26..59
FT /note="LRRNT"
FT REPEAT 57..81
FT /note="LRR 1"
FT REPEAT 83..105
FT /note="LRR 2"
FT REPEAT 106..129
FT /note="LRR 3"
FT REPEAT 131..153
FT /note="LRR 4"
FT REPEAT 155..177
FT /note="LRR 5"
FT REPEAT 178..201
FT /note="LRR 6"
FT REPEAT 203..225
FT /note="LRR 7"
FT REPEAT 226..249
FT /note="LRR 8"
FT REPEAT 250..272
FT /note="LRR 9"
FT REPEAT 274..296
FT /note="LRR 10"
FT REPEAT 320..343
FT /note="LRR 11"
FT REPEAT 345..365
FT /note="LRR 12"
FT REPEAT 366..389
FT /note="LRR 13"
FT REPEAT 390..413
FT /note="LRR 14"
FT REPEAT 415..437
FT /note="LRR 15"
FT CARBOHYD 201
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 316
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 384
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..37
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 35..45
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 341..366
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 472..525
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 473..478
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 621..696
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT STRAND 33..37
FT /evidence="ECO:0007829|PDB:4LI2"
FT STRAND 39..44
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 62..65
FT /evidence="ECO:0007829|PDB:4LI1"
FT TURN 76..81
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:4LI1"
FT TURN 100..105
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:4LI1"
FT TURN 124..129
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:4LI1"
FT TURN 148..153
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:4LI1"
FT HELIX 172..175
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:4LI1"
FT TURN 196..201
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:4LI1"
FT TURN 220..225
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 231..233
FT /evidence="ECO:0007829|PDB:4LI1"
FT HELIX 244..248
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:4LI1"
FT TURN 267..272
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:4LI1"
FT TURN 291..294
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 302..306
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 324..331
FT /evidence="ECO:0007829|PDB:4LI1"
FT HELIX 339..343
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 349..351
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 371..373
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 384..387
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:4LI1"
FT HELIX 407..409
FT /evidence="ECO:0007829|PDB:4LI2"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:4LI1"
FT STRAND 424..426
FT /evidence="ECO:0007829|PDB:4LI2"
FT STRAND 439..442
FT /evidence="ECO:0007829|PDB:4LI1"
FT HELIX 450..452
FT /evidence="ECO:0007829|PDB:4LI1"
SQ SEQUENCE 955 AA; 105725 MW; E36B9BD93557CCA8 CRC64;
MGCPGWPLAL FALLLASCSG GPSGVSSPAP CPAPCACDLD GGADCSGKGL VTVPDGLSVF
THSLDLSMNN ITKLPEGAFK GFPYLEELRL AGNDLSIIHP MALSGLKELK VLTLQNNQLK
TVPSESLKGL VSLQSLRLDA NHIVTVPEDS FEGLVQLRHL WLDDNSLTEV PIRPLSNLPS
LQALTLALNK ISHIPDYAFS NLSSLVVLHL HNNKIRTLGP HCFHGLDNLE ALDLNYNNLI
DFPDSIRSLP NLKELGFHSN SITIIPDGAF VKNPLLRTIH LYDNPLSFVG NSAFQNLSDL
HFLIIRGASN VQWFPNLTGT NNLESLTLTG TKIRSIPIKF CQEQKMLRTL DLSYNEISAL
VGFEGCSSLE EVYLQNNQIQ EVQNETFQGL AALRMLDLSR NRIHTIHKEA FVTLKALTNL
DLSFNDLTAF PTAGLHGLNQ LKLTGNPNFK ETLTAKDLIK LSSVSVPYAY QCCAFSACNS
YMTTTVEEDR LRAQRLLLDH DRAAMDPDYM GTEDDKEHVQ ALIQCNPATG PFKPCEYLLG
SWMIRLTVWF IFLLALIFNV IVIVTMFASC SQLTSSKLFI GLIAVSNLFM GVYTGTLTVL
DTISWGQFAE FGIWWETGNG CKVAGFLAIF SSESAIFFLM LAAIERSLSA KDIIKKEKHQ
HLRKFQVASL LAVLLAAAAG CLPLFHIGEF SSSPLCLPFP TGETPSLGFT VTLVLLNSLA
FLIMVITYTK LYCTIEKEDL SENAESSMIK HVAWLIFTNC IFFCPVAFFS FAPLITAIYI
SPEIMKSVTL IFLPLPACLN PVLYVFFNPK FKEDWKLLRW RLTKRSGSVA VATNSQRGCV
TQDFYYDFGM YSHLQGGNFA VCDYCESVLL KNPPPCKHLI KSHSCPTLAV VPCQRPDNYW
SEFGTQSAHS DCADEEDSFV SDSSDQVQVC GRACFYQSRG LPLVRYAYNI PRMKD
