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Protein

Leucine-rich repeat-containing G-protein coupled receptor 4

Gene

Lgr4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and is involved in the formation of various organs. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. Its function as activator of the Wnt signaling pathway is required for the development of various organs, including liver, kidney, intestine, bone, reproductive tract and eye. May also act as a receptor for norrin (NDP), such results however require additional confirmation in vivo. Required during spermatogenesis to activate the Wnt signaling pathway in peritubular myoid cells. Required for the maintenance of intestinal stem cells and Paneth cell differentiation in postnatal intestinal crypts. Acts as a regulator of bone formation and remodeling. Involved in kidney development; required for maintaining the ureteric bud in an undifferentiated state. Involved in the development of the anterior segment of the eye. Required during erythropoiesis. Also acts as a negative regulator of innate immunity by inhibiting TLR2/TLR4 associated pattern-recognition and proinflammatory cytokine production. Plays an important role in regulating the circadian rhythms of plasma lipids, partially through regulating the rhythmic expression of MTTP.By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Biological rhythms, Differentiation, Immunity, Innate immunity, Spermatogenesis, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-RNO-4641263. Regulation of FZD by ubiquitination.

Names & Taxonomyi

Protein namesi
Recommended name:
Leucine-rich repeat-containing G-protein coupled receptor 4
Alternative name(s):
G-protein coupled receptor 48
Gene namesi
Name:Lgr4
Synonyms:Gpr48
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi628615. Lgr4.

Subcellular locationi

  • Cell membrane By similarity; Multi-pass membrane protein By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 544ExtracellularSequence analysisAdd BLAST520
Transmembranei545 – 565Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini566 – 575CytoplasmicSequence analysis10
Transmembranei576 – 596Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini597 – 619ExtracellularSequence analysisAdd BLAST23
Transmembranei620 – 640Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini641 – 661CytoplasmicSequence analysisAdd BLAST21
Transmembranei662 – 682Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini683 – 703ExtracellularSequence analysisAdd BLAST21
Transmembranei704 – 724Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini725 – 756CytoplasmicSequence analysisAdd BLAST32
Transmembranei757 – 777Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini778 – 783ExtracellularSequence analysis6
Transmembranei784 – 804Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini805 – 951CytoplasmicSequence analysisAdd BLAST147

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000001279325 – 951Leucine-rich repeat-containing G-protein coupled receptor 4Add BLAST927

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi29 ↔ 35PROSITE-ProRule annotation
Disulfide bondi33 ↔ 43PROSITE-ProRule annotation
Glycosylationi68N-linked (GlcNAc...)Sequence analysis1
Glycosylationi188N-linked (GlcNAc...)Sequence analysis1
Glycosylationi199N-linked (GlcNAc...)Sequence analysis1
Glycosylationi294N-linked (GlcNAc...)Sequence analysis1
Glycosylationi314N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi339 ↔ 364PROSITE-ProRule annotation
Disulfide bondi470 ↔ 522PROSITE-ProRule annotation
Disulfide bondi471 ↔ 476PROSITE-ProRule annotation
Glycosylationi505N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi618 ↔ 693PROSITE-ProRule annotation
Modified residuei920PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9Z2H4.
PRIDEiQ9Z2H4.

PTM databases

PhosphoSitePlusiQ9Z2H4.

Expressioni

Gene expression databases

BgeeiENSRNOG00000005715.
GenevisibleiQ9Z2H4. RN.

Interactioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000007681.

Structurei

3D structure databases

ProteinModelPortaliQ9Z2H4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 57LRRNTAdd BLAST33
Repeati58 – 79LRR 1Add BLAST22
Repeati82 – 103LRR 2Add BLAST22
Repeati106 – 127LRR 3Add BLAST22
Repeati130 – 151LRR 4Add BLAST22
Repeati154 – 177LRR 5Add BLAST24
Repeati178 – 199LRR 6Add BLAST22
Repeati202 – 223LRR 7Add BLAST22
Repeati226 – 247LRR 8Add BLAST22
Repeati249 – 270LRR 9Add BLAST22
Repeati273 – 294LRR 10Add BLAST22
Repeati320 – 341LRR 11Add BLAST22
Repeati344 – 365LRR 12Add BLAST22
Repeati366 – 387LRR 13Add BLAST22
Repeati390 – 411LRR 14Add BLAST22
Repeati414 – 435LRR 15Add BLAST22

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation
Contains 15 LRR (leucine-rich) repeats.Curated
Contains 1 LRRNT domain.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
KOG2087. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00760000119088.
HOGENOMiHOG000231829.
HOVERGENiHBG031675.
InParanoidiQ9Z2H4.
KOiK04309.
OMAiCAAPCSC.
OrthoDBiEOG091G0QA0.
TreeFamiTF316814.

Family and domain databases

Gene3Di3.80.10.10. 4 hits.
InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002131. Gphrmn_rcpt_fam.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000372. LRRNT.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
PF13855. LRR_8. 4 hits.
PF01462. LRRNT. 1 hit.
[Graphical view]
PRINTSiPR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.
SMARTiSM00369. LRR_TYP. 15 hits.
SM00013. LRRNT. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
PS51450. LRR. 15 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9Z2H4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPGPLRLLCF FALGLLGSAG PSGAAPPLCA APCSCDGDRR VDCSGKGLTA
60 70 80 90 100
VPEGLSAFTQ ALDISMNNIT QLPEDAFKSF PFLEELQLAG NDLSFIHPKA
110 120 130 140 150
LSGLKELKVL TLQNNQLRTV PSEAIHGLSA LQSLRLDANH ITSVPEDSFE
160 170 180 190 200
GLVQLRHLWL DDNSLTEVPV RPLSNLPTLQ ALTLALNNIS SIPDFAFTNL
210 220 230 240 250
SSLVVLHLHN NKIKSLSQHC FDGLDNLETL DLNYNNLDEF PQAIKALPSL
260 270 280 290 300
KELGFHSNSI SVIPDGAFGG NPLLRTIHLY DNPLSFVGNS AFHNLSDLHS
310 320 330 340 350
LVIRGASLVQ WFPNLTGTVH LESLTLTGTK ISSIPDDLCQ NQKMLRTLDL
360 370 380 390 400
SYNNIRDLPS FNGCRALEEI SLQRNQISLI KENTFQGLTS LRILDLSRNL
410 420 430 440 450
IREIHSGAFA KLGTITNLDV SFNELTSFPT EGLNGLNQLK LVGNFKLKDA
460 470 480 490 500
LAARDFANLR SLSVPYAYQC CAFWGCDSYA NLNTEDNSPQ EHSVTKEKGA
510 520 530 540 550
TDAANVTSTA ENEEHSQIII HCTPSTGAFK PCEYLLGSWM IRLTVWFIFL
560 570 580 590 600
VALLFNLLVI LTVFASCSSL PASKLFIGLI SVSNLLMGIY TGILTFLDAV
610 620 630 640 650
SWGRFAEFGI WWETGSGCKV AGSLAVFSSE SAVFLLTLAA VERSVFAKDL
660 670 680 690 700
MKHGKSSHLR QFQVAALLAL LGAAVAGCFP LFHGGQYSAS PLCLPFPTGE
710 720 730 740 750
TPSLGFTVTL VLLNSLAFLL MAIIYTKLYC NLEKEDLSEN SQSSVIKHVA
760 770 780 790 800
WLIFTNCIFF CPVAFFSFAP LITAISISPE IMKSVTLIFF PLPACLNPVL
810 820 830 840 850
YVFFNPKFKE DWKLLKRRVT RKHGSVSVSI SSQGGCGEQD FYYDCGMYSH
860 870 880 890 900
LQGNLTVCDC CESFLLTKPV SCKHLIKSHS CPVLTAASCQ RPEAYWSDCG
910 920 930 940 950
TQSAHSDYAD EEDSFVSDSS DQVQACGRAC FYQSRGFPLV RYAYNLQRVR

D
Length:951
Mass (Da):104,241
Last modified:June 26, 2013 - v2
Checksum:i457798D5408DC403
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6R → G in AAC77910 (PubMed:9849958).Curated1
Sequence conflicti11F → L in AAC77910 (PubMed:9849958).Curated1
Sequence conflicti95F → L in AAC77910 (PubMed:9849958).Curated1
Sequence conflicti236N → Y in AAC77910 (PubMed:9849958).Curated1
Sequence conflicti300S → C in AAC77910 (PubMed:9849958).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF061443 mRNA. Translation: AAC77910.1.
AABR06025467 Genomic DNA. No translation available.
AABR06025468 Genomic DNA. No translation available.
AABR06025469 Genomic DNA. No translation available.
AABR06025470 Genomic DNA. No translation available.
AABR06025471 Genomic DNA. No translation available.
CH473949 Genomic DNA. Translation: EDL79759.1.
RefSeqiNP_775450.1. NM_173328.1.
UniGeneiRn.162671.

Genome annotation databases

EnsembliENSRNOT00000007681; ENSRNOP00000007681; ENSRNOG00000005715.
GeneIDi286994.
KEGGirno:286994.
UCSCiRGD:628615. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF061443 mRNA. Translation: AAC77910.1.
AABR06025467 Genomic DNA. No translation available.
AABR06025468 Genomic DNA. No translation available.
AABR06025469 Genomic DNA. No translation available.
AABR06025470 Genomic DNA. No translation available.
AABR06025471 Genomic DNA. No translation available.
CH473949 Genomic DNA. Translation: EDL79759.1.
RefSeqiNP_775450.1. NM_173328.1.
UniGeneiRn.162671.

3D structure databases

ProteinModelPortaliQ9Z2H4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000007681.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSitePlusiQ9Z2H4.

Proteomic databases

PaxDbiQ9Z2H4.
PRIDEiQ9Z2H4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000007681; ENSRNOP00000007681; ENSRNOG00000005715.
GeneIDi286994.
KEGGirno:286994.
UCSCiRGD:628615. rat.

Organism-specific databases

CTDi55366.
RGDi628615. Lgr4.

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
KOG2087. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00760000119088.
HOGENOMiHOG000231829.
HOVERGENiHBG031675.
InParanoidiQ9Z2H4.
KOiK04309.
OMAiCAAPCSC.
OrthoDBiEOG091G0QA0.
TreeFamiTF316814.

Enzyme and pathway databases

ReactomeiR-RNO-4641263. Regulation of FZD by ubiquitination.

Miscellaneous databases

PROiQ9Z2H4.

Gene expression databases

BgeeiENSRNOG00000005715.
GenevisibleiQ9Z2H4. RN.

Family and domain databases

Gene3Di3.80.10.10. 4 hits.
InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002131. Gphrmn_rcpt_fam.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000372. LRRNT.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
PF13855. LRR_8. 4 hits.
PF01462. LRRNT. 1 hit.
[Graphical view]
PRINTSiPR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.
SMARTiSM00369. LRR_TYP. 15 hits.
SM00013. LRRNT. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
PS51450. LRR. 15 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLGR4_RAT
AccessioniPrimary (citable) accession number: Q9Z2H4
Secondary accession number(s): G3V6R1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2002
Last sequence update: June 26, 2013
Last modified: November 2, 2016
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.