LGR4_DANRE
ID LGR4_DANRE Reviewed; 971 AA.
AC E7FE13;
DT 26-JUN-2013, integrated into UniProtKB/Swiss-Prot.
DT 08-MAR-2011, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Leucine-rich repeat-containing G-protein coupled receptor 4;
DE Flags: Precursor;
GN Name=lgr4;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP DEVELOPMENTAL STAGE.
RX PubMed=21570488; DOI=10.1016/j.gep.2011.04.002;
RA Hirose K., Shimoda N., Kikuchi Y.;
RT "Expression patterns of lgr4 and lgr6 during zebrafish development.";
RL Gene Expr. Patterns 11:378-383(2011).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32493844; DOI=10.1172/jci.insight.133434;
RA Mancini A., Howard S.R., Marelli F., Cabrera C.P., Barnes M.R.,
RA Sternberg M.J., Leprovots M., Hadjidemetriou I., Monti E., David A.,
RA Wehkalampi K., Oleari R., Lettieri A., Vezzoli V., Vassart G., Cariboni A.,
RA Bonomi M., Garcia M.I., Guasti L., Dunkel L.;
RT "LGR4 deficiency results in delayed puberty through impaired Wnt/beta-
RT catenin signaling.";
RL JCI Insight 5:0-0(2020).
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. 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 (PubMed:32493844).
CC {ECO:0000250|UniProtKB:A2ARI4, ECO:0000250|UniProtKB:B0BLW3,
CC ECO:0000269|PubMed:32493844}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9BXB1};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9BXB1}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the neural plate border, Kupffer's
CC vesicle, neural tube, otic vesicles, midbrain, eyes, forebrain and
CC brain ventricular zone by 24 hours post-fertilization (hpf). From 36 to
CC 96 hpf, expression is detected in the midbrain-hindbrain boundary, otic
CC vesicles, pharyngeal arches, cranial cartilages such as Meckel's
CC cartilages, palatoquadrates, and ceratohyals, cranial cavity, pectoral
CC fin buds, brain ventricular zone, ciliary marginal zone, and digestive
CC organs such as the intestine, liver and pancreas.
CC {ECO:0000269|PubMed:21570488}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown results in disorganization
CC of the olfactory bulbs with a significant reduction of GnRH neuronal
CC development compared with uninjected embryos.
CC {ECO:0000269|PubMed:32493844}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; BX511109; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_687184.4; XM_682092.8.
DR AlphaFoldDB; E7FE13; -.
DR SMR; E7FE13; -.
DR STRING; 7955.ENSDARP00000079854; -.
DR PaxDb; E7FE13; -.
DR Ensembl; ENSDART00000169588; ENSDARP00000137036; ENSDARG00000060542.
DR GeneID; 558825; -.
DR CTD; 55366; -.
DR ZFIN; ZDB-GENE-111013-1; lgr4.
DR eggNOG; KOG0619; Eukaryota.
DR eggNOG; KOG2087; Eukaryota.
DR GeneTree; ENSGT00940000157925; -.
DR InParanoid; E7FE13; -.
DR OMA; DLFWMCL; -.
DR OrthoDB; 159438at2759; -.
DR PhylomeDB; E7FE13; -.
DR TreeFam; TF316814; -.
DR PRO; PR:E7FE13; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 7.
DR Bgee; ENSDARG00000060542; Expressed in swim bladder and 38 other tissues.
DR ExpressionAtlas; E7FE13; baseline.
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:0007186; P:G protein-coupled receptor signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0021888; P:hypothalamus gonadotrophin-releasing hormone neuron development; IMP:ZFIN.
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; 15.
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;
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..971
FT /note="Leucine-rich repeat-containing G-protein coupled
FT receptor 4"
FT /id="PRO_0000422815"
FT TOPO_DOM 22..531
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 532..552
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 553..563
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 564..584
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 585..608
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 609..629
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 630..658
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 659..679
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 680..699
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 700..720
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 721..744
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 745..765
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 766..782
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 783..803
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 804..971
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..60
FT /note="LRRNT"
FT REPEAT 58..82
FT /note="LRR 1"
FT REPEAT 84..106
FT /note="LRR 2"
FT REPEAT 107..130
FT /note="LRR 3"
FT REPEAT 131..154
FT /note="LRR 4"
FT REPEAT 156..178
FT /note="LRR 5"
FT REPEAT 179..202
FT /note="LRR 6"
FT REPEAT 204..226
FT /note="LRR 7"
FT REPEAT 227..250
FT /note="LRR 8"
FT REPEAT 251..273
FT /note="LRR 9"
FT REPEAT 275..297
FT /note="LRR 10"
FT REPEAT 299..321
FT /note="LRR 11"
FT REPEAT 322..344
FT /note="LRR 12"
FT REPEAT 345..366
FT /note="LRR 13"
FT REPEAT 367..390
FT /note="LRR 14"
FT REPEAT 391..414
FT /note="LRR 15"
FT REPEAT 416..438
FT /note="LRR 16"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 32..38
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 36..46
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 342..367
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 473..510
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 607..689
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 971 AA; 105210 MW; EF2FAA1ED5663987 CRC64;
MALLAVRMLV LGLCVGGQAA AAGEGQSTPA TCSPLCRCDE DGGADCSGRG LTSVPTGLSA
FTYYLDISMN NITELPANVF RNLPYLEELR LAGNDLAFIH PEALSGLHQL KVLMLQNNQL
KTVPSAALKN LNALQSLRLD ANHITSVPED SFEGLQQLRH LWLDDNSLTE VPISPLQHQS
NLQALTLALN RITHIPDNAF ANLSSLVVLH LHNNRIQEIG KNCFNGLDNL ETLDLNFNNL
KIFPEAIQML PKLKELGFHS NNIASIPEGA FCRNSLLRTI HLFDNPLSFV GTTAFQNLSD
LHSLMLRGAS MMQDFPSLTG TINLESLTLT GTKIRSIPAD LCEDLTVLRT VDLSYNDIED
LPSFQGCVRL QDINLQHNQI KQIDRGTFQG MTSLRVLDLS RNQIKFIHRD AFLSLSALTN
LDLSLNSLAS VPTAGLSALN QLKLTGNMEL RNGLMSKTLP KLRSITVPYA YQCCAFVAYD
SAVNPAEDDE RRNAFGGEED MERIPMVMHC SPLPGAFKPC EHLLGSWMIR LTVWFICLVA
LLFNCLVLAA TFSPRTSSLS PSRFLVALLA SANLLTGVYV AALTLLDTVT WGSFAEYGVW
WETGAGCQVV GFLAVFSSEW AVLLLALAAV ERCLAVRALM GKAGALRSRG ERRERRRRFA
IAALLLGLVS VAAACLSLYH GSAMGSPLCL PFSEGSSPGL GFTVALVLMN TLAYLLSAVV
YTRLYCRLGR AQLADPEQAG SVRHIAWLIF TNCIFFCPVA AFSFAPLLAG TSNAVGGPEM
AKSVTLIFFP LSACLNPVLY VCFSPSFRYD WLHLRGRGRT GGCGRLVAKT VTKGTVAGGS
PVSDDGEGLS SDCGMYTKLH GDSRGMCEHC DAALHIRTSS SSGSSSSSAC RHLVKSHSCP
ALMGNVPQCL SSEGYWPDTG TLSAQSEYGD EGDSFVSDSS EQVQACGRAC FCQSRGLPLV
HYSYNIPRMT D
