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Protein

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

Gene

Lgr4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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 (PubMed:24353284).10 Publications

GO - Molecular functioni

  • transmembrane signaling receptor activity Source: UniProtKB

GO - Biological processi

  • bone mineralization Source: UniProtKB
  • bone remodeling Source: UniProtKB
  • canonical Wnt signaling pathway involved in metanephric kidney development Source: UniProtKB
  • cell differentiation involved in metanephros development Source: UniProtKB
  • circadian regulation of gene expression Source: UniProtKB
  • circadian rhythm Source: UniProtKB
  • digestive tract development Source: MGI
  • epithelial cell proliferation Source: MGI
  • epithelial cell proliferation involved in renal tubule morphogenesis Source: MGI
  • G-protein coupled receptor signaling pathway Source: UniProtKB-KW
  • hair follicle development Source: MGI
  • innate immune response Source: UniProtKB-KW
  • intestinal stem cell homeostasis Source: MGI
  • male genitalia development Source: MGI
  • metanephric glomerulus development Source: UniProtKB
  • metanephric nephron tubule morphogenesis Source: UniProtKB
  • negative regulation of cytokine secretion Source: UniProtKB
  • negative regulation of toll-like receptor signaling pathway Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • osteoblast differentiation Source: UniProtKB
  • positive regulation of branching involved in ureteric bud morphogenesis Source: UniProtKB
  • positive regulation of canonical Wnt signaling pathway Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • spermatogenesis Source: UniProtKB
  • tube morphogenesis Source: MGI
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-MMU-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1891468. Lgr4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 544520ExtracellularSequence analysisAdd
BLAST
Transmembranei545 – 56521Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini566 – 57510CytoplasmicSequence analysis
Transmembranei576 – 59621Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini597 – 61923ExtracellularSequence analysisAdd
BLAST
Transmembranei620 – 64021Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini641 – 66121CytoplasmicSequence analysisAdd
BLAST
Transmembranei662 – 68221Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini683 – 70321ExtracellularSequence analysisAdd
BLAST
Transmembranei704 – 72421Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini725 – 75632CytoplasmicSequence analysisAdd
BLAST
Transmembranei757 – 77721Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini778 – 7836ExtracellularSequence analysis
Transmembranei784 – 80421Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini805 – 951147CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • integral component of plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Strong variations in phenotypes, probably depending on the strain background used in the different experiments. According to a first report done in a C57BL/6 background, mice show intra-uterine growth retardation leading to embryonic and perinatal lethality (PubMed:15192078). A lethal phenotype was confirmed by other groups. In some cases however, few mice survive until adulthood. Mice that survive show wide spectrum of anterior segment dysgenesis phenotypes, including microphthalmia, iris hypoplasia, irdiocorneal angle malformation, cornea dysgenesis and cataract (PubMed:18424556). Defects in osteoblast differentiation and mineralization during embryonic bone formation are also observed. Postnatal mice that survive show defects in bone remodeling (PubMed:19605502). According to other reports done in other strain backgrounds, mice do not die and display defects in the male reproductive tract during the postnatal period (PubMed:16406039, PubMed:17079737, PubMed:23533175). Mice also show small kidneys, in which the total number and density of the glomeruli are decreased (PubMed:16785743). The use of conditional knockouts, leads to defects in hair placode formation, possibly due to reduced keratinocyte migration (PubMed:17079737, PubMed:17850793). Decrease in epithelial cell proliferation and strong reduction in terminal differentiation of Paneth cells in postnatal intestinal crypts (PubMed:21508962, PubMed:23393138). Fetuses display transient anemia during midgestation and abnormal definitive erythropoiesis (PubMed:18955481). Mice are also more susceptible and have much higher mortality to lipopolysaccharide (LPS) stimulation due to over-activated innate immune response (PubMed:23589304). Conditional knockout of both Lgr4 and Lgr5 in the gut results in Wnt signaling inhibition and results in the rapid demise of intestinal crypts (PubMed:21727895).16 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi755 – 7551T → I: Confers constitutive activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence analysisAdd
BLAST
Chaini25 – 951927Leucine-rich repeat-containing G-protein coupled receptor 4PRO_0000303240Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi29 ↔ 35PROSITE-ProRule annotation
Disulfide bondi33 ↔ 43PROSITE-ProRule annotation
Glycosylationi68 – 681N-linked (GlcNAc...)Sequence analysis
Glycosylationi188 – 1881N-linked (GlcNAc...)Sequence analysis
Glycosylationi199 – 1991N-linked (GlcNAc...)Sequence analysis
Glycosylationi294 – 2941N-linked (GlcNAc...)Sequence analysis
Disulfide bondi339 ↔ 364PROSITE-ProRule annotation
Disulfide bondi470 ↔ 522PROSITE-ProRule annotation
Disulfide bondi471 ↔ 476PROSITE-ProRule annotation
Glycosylationi505 – 5051N-linked (GlcNAc...)Sequence analysis
Disulfide bondi618 ↔ 693PROSITE-ProRule annotation
Modified residuei920 – 9201PhosphoserineBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiA2ARI4.
PaxDbiA2ARI4.
PeptideAtlasiA2ARI4.
PRIDEiA2ARI4.

PTM databases

PhosphoSiteiA2ARI4.

Expressioni

Inductioni

Expressed in a circadian manner in the liver.1 Publication

Gene expression databases

BgeeiA2ARI4.
GenevisibleiA2ARI4. MM.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000047325.

Structurei

3D structure databases

ProteinModelPortaliA2ARI4.
SMRiA2ARI4. Positions 26-533, 540-809.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini25 – 5733LRRNTAdd
BLAST
Repeati58 – 7922LRR 1Add
BLAST
Repeati82 – 10322LRR 2Add
BLAST
Repeati106 – 12722LRR 3Add
BLAST
Repeati130 – 15122LRR 4Add
BLAST
Repeati154 – 17724LRR 5Add
BLAST
Repeati178 – 19922LRR 6Add
BLAST
Repeati202 – 22322LRR 7Add
BLAST
Repeati226 – 24722LRR 8Add
BLAST
Repeati249 – 27022LRR 9Add
BLAST
Repeati273 – 29422LRR 10Add
BLAST
Repeati320 – 34122LRR 11Add
BLAST
Repeati344 – 36522LRR 12Add
BLAST
Repeati366 – 38722LRR 13Add
BLAST
Repeati390 – 41122LRR 14Add
BLAST
Repeati414 – 43522LRR 15Add
BLAST

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.
InParanoidiA2ARI4.
KOiK04309.
OMAiCSCDGDR.
OrthoDBiEOG7DNNTF.
PhylomeDBiA2ARI4.
TreeFamiTF316814.

Family and domain databases

Gene3Di3.80.10.10. 3 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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: A2ARI4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

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

D
Length:951
Mass (Da):104,150
Last modified:February 20, 2007 - v1
Checksum:iAD41C68730A19C6B
GO
Isoform 2 (identifier: A2ARI4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     62-85: Missing.

Show »
Length:927
Mass (Da):101,341
Checksum:i2290E2B445926227
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti668 – 6681V → L in AAH56637 (PubMed:15489334).Curated
Sequence conflicti684 – 6841G → R in AAH56637 (PubMed:15489334).Curated
Sequence conflicti730 – 7301C → F in BAC31882 (PubMed:16141072).Curated
Sequence conflicti928 – 9281R → P in AAH56637 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei62 – 8524Missing in isoform 2. CuratedVSP_047137Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL845423, AL928922 Genomic DNA. Translation: CAM17466.1.
AL928922, AL845423 Genomic DNA. Translation: CAM24131.1.
BX294391 Genomic DNA. No translation available.
AY255619 mRNA. Translation: AAO85131.1.
AK044357 mRNA. Translation: BAC31882.1.
BC056637 mRNA. Translation: AAH56637.1.
CCDSiCCDS38195.1. [A2ARI4-1]
RefSeqiNP_766259.2. NM_172671.2. [A2ARI4-1]
UniGeneiMm.277351.
Mm.485992.

Genome annotation databases

EnsembliENSMUST00000046548; ENSMUSP00000047325; ENSMUSG00000050199. [A2ARI4-1]
ENSMUST00000111037; ENSMUSP00000106666; ENSMUSG00000050199. [A2ARI4-2]
GeneIDi107515.
KEGGimmu:107515.
UCSCiuc008lmq.1. mouse. [A2ARI4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL845423, AL928922 Genomic DNA. Translation: CAM17466.1.
AL928922, AL845423 Genomic DNA. Translation: CAM24131.1.
BX294391 Genomic DNA. No translation available.
AY255619 mRNA. Translation: AAO85131.1.
AK044357 mRNA. Translation: BAC31882.1.
BC056637 mRNA. Translation: AAH56637.1.
CCDSiCCDS38195.1. [A2ARI4-1]
RefSeqiNP_766259.2. NM_172671.2. [A2ARI4-1]
UniGeneiMm.277351.
Mm.485992.

3D structure databases

ProteinModelPortaliA2ARI4.
SMRiA2ARI4. Positions 26-533, 540-809.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000047325.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiA2ARI4.

Proteomic databases

MaxQBiA2ARI4.
PaxDbiA2ARI4.
PeptideAtlasiA2ARI4.
PRIDEiA2ARI4.

Protocols and materials databases

DNASUi107515.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000046548; ENSMUSP00000047325; ENSMUSG00000050199. [A2ARI4-1]
ENSMUST00000111037; ENSMUSP00000106666; ENSMUSG00000050199. [A2ARI4-2]
GeneIDi107515.
KEGGimmu:107515.
UCSCiuc008lmq.1. mouse. [A2ARI4-1]

Organism-specific databases

CTDi55366.
MGIiMGI:1891468. Lgr4.

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
KOG2087. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00760000119088.
HOGENOMiHOG000231829.
HOVERGENiHBG031675.
InParanoidiA2ARI4.
KOiK04309.
OMAiCSCDGDR.
OrthoDBiEOG7DNNTF.
PhylomeDBiA2ARI4.
TreeFamiTF316814.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiLgr4. mouse.
PROiA2ARI4.
SOURCEiSearch...

Gene expression databases

BgeeiA2ARI4.
GenevisibleiA2ARI4. MM.

Family and domain databases

Gene3Di3.80.10.10. 3 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...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 63-196.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 74-951.
    Strain: C57BL/6J.
    Tissue: Retina.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 464-951.
    Strain: Czech II.
    Tissue: Mammary tumor.
  5. "Leucine-rich repeat-containing, G protein-coupled receptor 4 null mice exhibit intrauterine growth retardation associated with embryonic and perinatal lethality."
    Mazerbourg S., Bouley D.M., Sudo S., Klein C.A., Zhang J.V., Kawamura K., Goodrich L.V., Rayburn H., Tessier-Lavigne M., Hsueh A.J.
    Mol. Endocrinol. 18:2241-2254(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  6. "Defective postnatal development of the male reproductive tract in LGR4 knockout mice."
    Mendive F., Laurent P., Van Schoore G., Skarnes W., Pochet R., Vassart G.
    Dev. Biol. 290:421-434(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  7. "Leucine-rich repeat-containing G protein-coupled receptor-4 (LGR4, Gpr48) is essential for renal development in mice."
    Kato S., Matsubara M., Matsuo T., Mohri Y., Kazama I., Hatano R., Umezawa A., Nishimori K.
    Nephron Exp. Nephrol. 104:E63-E75(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  8. "LGR4 regulates the postnatal development and integrity of male reproductive tracts in mice."
    Hoshii T., Takeo T., Nakagata N., Takeya M., Araki K., Yamamura K.
    Biol. Reprod. 76:303-313(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  9. "Eye-open at birth phenotype with reduced keratinocyte motility in LGR4 null mice."
    Kato S., Mohri Y., Matsuo T., Ogawa E., Umezawa A., Okuyama R., Nishimori K.
    FEBS Lett. 581:4685-4690(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  10. "Impaired hair placode formation with reduced expression of hair follicle-related genes in mice lacking Lgr4."
    Mohri Y., Kato S., Umezawa A., Okuyama R., Nishimori K.
    Dev. Dyn. 237:2235-2242(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  11. "Inactivation of G-protein-coupled receptor 48 (Gpr48/Lgr4) impairs definitive erythropoiesis at midgestation through down-regulation of the ATF4 signaling pathway."
    Song H., Luo J., Luo W., Weng J., Wang Z., Li B., Li D., Liu M.
    J. Biol. Chem. 283:36687-36697(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  12. "Deletion of G protein-coupled receptor 48 leads to ocular anterior segment dysgenesis (ASD) through down-regulation of Pitx2."
    Weng J., Luo J., Cheng X., Jin C., Zhou X., Qu J., Tu L., Ai D., Li D., Wang J., Martin J.F., Amendt B.A., Liu M.
    Proc. Natl. Acad. Sci. U.S.A. 105:6081-6086(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  13. "Regulation of bone formation and remodeling by G-protein-coupled receptor 48."
    Luo J., Zhou W., Zhou X., Li D., Weng J., Yi Z., Cho S.G., Li C., Yi T., Wu X., Li X.Y., de Crombrugghe B., Hook M., Liu M.
    Development 136:2747-2756(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  14. "Reduced fertility with impairment of early-stage embryos observed in mice lacking Lgr4 in epithelial tissues."
    Mohri Y., Umezu T., Hidema S., Tomisawa H., Akamatsu A., Kato S., Nawa A., Nishimori K.
    Fertil. Steril. 94:2878-2881(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  15. "Lgr4-deficient mice showed premature differentiation of ureteric bud with reduced expression of Wnt effector Lef1 and Gata3."
    Mohri Y., Oyama K., Akamatsu A., Kato S., Nishimori K.
    Dev. Dyn. 240:1626-1634(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  16. "Lgr4 is required for Paneth cell differentiation and maintenance of intestinal stem cells ex vivo."
    Mustata R.C., Van Loy T., Lefort A., Libert F., Strollo S., Vassart G., Garcia M.I.
    EMBO Rep. 12:558-564(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  17. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  18. "R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling."
    Carmon K.S., Gong X., Lin Q., Thomas A., Liu Q.
    Proc. Natl. Acad. Sci. U.S.A. 108:11452-11457(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RSPO1; RSPO2; RSPO3 AND RSPO4.
  19. "Lgr4-mediated Wnt/beta-catenin signaling in peritubular myoid cells is essential for spermatogenesis."
    Qian Y., Liu S., Guan Y., Pan H., Guan X., Qiu Z., Li L., Gao N., Zhao Y., Li X., Lu Y., Liu M., Li D.
    Development 140:1751-1761(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  20. "Lgr4 gene deficiency increases susceptibility and severity of dextran sodium sulfate-induced inflammatory bowel disease in mice."
    Liu S., Qian Y., Li L., Wei G., Guan Y., Pan H., Guan X., Zhang L., Lu X., Zhao Y., Liu M., Li D.
    J. Biol. Chem. 288:8794-8803(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  21. "Lgr4/Gpr48 negatively regulates TLR2/4 associated pattern recognition and innate immunity by targeting CD14 expression."
    Du B., Luo W., Li R., Tan B., Han H., Lu X., Li D., Qian M., Zhang D., Zhao Y., Liu M.
    J. Biol. Chem. 288:15131-15141(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF THR-755.
  22. "Multi-functional norrin is a ligand for the LGR4 receptor."
    Deng C., Reddy P., Cheng Y., Luo C.W., Hsiao C.L., Hsueh A.J.
    J. Cell Sci. 126:2060-2068(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  23. "LGR4 acts as a link between the peripheral circadian clock and lipid metabolism in liver."
    Wang F., Zhang X., Wang J., Chen M., Fan N., Ma Q., Liu R., Wang R., Li X., Liu M., Ning G.
    J. Mol. Endocrinol. 52:133-143(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.

Entry informationi

Entry nameiLGR4_MOUSE
AccessioniPrimary (citable) accession number: A2ARI4
Secondary accession number(s): A2ARI3
, Q6PHA3, Q80T31, Q8BXS9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: February 20, 2007
Last modified: July 6, 2016
This is version 85 of the entry and version 1 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. 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.