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Protein

Leucine-rich repeat-containing G-protein coupled receptor 5

Gene

Lgr5

Organism
Mus musculus (Mouse)
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 acts as a stem cell marker of the intestinal epithelium and the hair follicle. 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. Involved in the development and/or maintenance of the adult intestinal stem cells during postembryonic development.1 Publication

GO - Molecular functioni

  • transmembrane signaling receptor activity Source: UniProtKB

GO - Biological processi

  • epithelial cell proliferation involved in renal tubule morphogenesis Source: MGI
  • G-protein coupled receptor signaling pathway Source: UniProtKB-KW
  • hair follicle development Source: MGI
  • inner ear development Source: MGI
  • oocyte differentiation Source: MGI
  • positive regulation of canonical Wnt signaling pathway Source: UniProtKB
  • regulation of cell proliferation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

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 5
Alternative name(s):
G-protein coupled receptor 49
Orphan G-protein coupled receptor FEX
Gene namesi
Name:Lgr5
Synonyms:Fex, Gpr49
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1341817. Lgr5.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 561ExtracellularSequence analysisAdd BLAST540
Transmembranei562 – 582Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini583 – 593CytoplasmicSequence analysisAdd BLAST11
Transmembranei594 – 614Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini615 – 638ExtracellularSequence analysisAdd BLAST24
Transmembranei639 – 659Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini660 – 682CytoplasmicSequence analysisAdd BLAST23
Transmembranei683 – 703Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini704 – 723ExtracellularSequence analysisAdd BLAST20
Transmembranei724 – 744Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini745 – 767CytoplasmicSequence analysisAdd BLAST23
Transmembranei768 – 788Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini789 – 802ExtracellularSequence analysisAdd BLAST14
Transmembranei803 – 823Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini824 – 907CytoplasmicSequence analysisAdd BLAST84

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice exhibit malformation of the tongue and of lower jam causing newborns to swallow air leading to 100% neonatal lethality. 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).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000001279522 – 907Leucine-rich repeat-containing G-protein coupled receptor 5Add BLAST886

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi34 ↔ 40PROSITE-ProRule annotation
Disulfide bondi38 ↔ 52PROSITE-ProRule annotation
Glycosylationi63N-linked (GlcNAc...)Sequence analysis1
Glycosylationi77N-linked (GlcNAc...)Sequence analysis1
Glycosylationi208N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi348 ↔ 373PROSITE-ProRule annotation
Disulfide bondi479 ↔ 541PROSITE-ProRule annotation
Disulfide bondi637 ↔ 712PROSITE-ProRule annotation
Glycosylationi792N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9Z1P4.
PRIDEiQ9Z1P4.

PTM databases

iPTMnetiQ9Z1P4.
PhosphoSitePlusiQ9Z1P4.

Expressioni

Tissue specificityi

Expressed in the gonads, the adrenal gland, and in the brain. In the central nervous system expression is restricted to the olfactory bulb. In the adrenal gland detected only in the neural-crest derived chromaffin cells of the medulla, but not in the cells of the adrenal cortex. In the gonads, the expression is high in Graafian follicle, but absent from primary and secondary follicles. In the intestine, exclusively expressed in cycling crypt base columnar cells. Expressed in the lower bulge and secondary germ area of telogen hair follicles and in the lower outer root sheath of anagen hair follicle.3 Publications

Developmental stagei

Expressed from embryonic day 10.5 (E10.58) in the developing spinal cord and in the neuroepithelia of the myel-, met-, mes-, and diencephalon. Expression is transitory and the pattern changed rapidly.

Gene expression databases

BgeeiENSMUSG00000020140.
ExpressionAtlasiQ9Z1P4. baseline and differential.
GenevisibleiQ9Z1P4. MM.

Interactioni

Subunit structurei

Identified in a complex composed of RNF43, LGR5 and RSPO1.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000020350.

Structurei

3D structure databases

ProteinModelPortaliQ9Z1P4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 66LRRNTAdd BLAST42
Repeati67 – 88LRR 1Add BLAST22
Repeati91 – 112LRR 2Add BLAST22
Repeati115 – 136LRR 3Add BLAST22
Repeati139 – 160LRR 4Add BLAST22
Repeati163 – 184LRR 5Add BLAST22
Repeati187 – 208LRR 6Add BLAST22
Repeati211 – 232LRR 7Add BLAST22
Repeati235 – 256LRR 8Add BLAST22
Repeati258 – 279LRR 9Add BLAST22
Repeati282 – 303LRR 10Add BLAST22
Repeati306 – 325LRR 11Add BLAST20
Repeati329 – 350LRR 12Add BLAST22
Repeati353 – 374LRR 13Add BLAST22
Repeati375 – 396LRR 14Add BLAST22
Repeati399 – 420LRR 15Add BLAST22
Repeati423 – 446LRR 16Add BLAST24

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation
Contains 16 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.
InParanoidiQ9Z1P4.
KOiK04308.
OMAiLENIWDC.
OrthoDBiEOG091G0QA0.
PhylomeDBiQ9Z1P4.
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. 13 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.

Q9Z1P4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDTSCVHMLL SLLALLQLVA AGSSPGPDAI PRGCPSHCHC ELDGRMLLRV
60 70 80 90 100
DCSDLGLSEL PSNLSVFTSY LDLSMNNISQ LPASLLHRLC FLEELRLAGN
110 120 130 140 150
ALTHIPKGAF TGLHSLKVLM LQNNQLRQVP EEALQNLRSL QSLRLDANHI
160 170 180 190 200
SYVPPSCFSG LHSLRHLWLD DNALTDVPVQ AFRSLSALQA MTLALNKIHH
210 220 230 240 250
IADYAFGNLS SLVVLHLHNN RIHSLGKKCF DGLHSLETLD LNYNNLDEFP
260 270 280 290 300
TAIKTLSNLK ELGFHSNNIR SIPERAFVGN PSLITIHFYD NPIQFVGVSA
310 320 330 340 350
FQHLPELRTL TLNGASHITE FPHLTGTATL ESLTLTGAKI SSLPQAVCDQ
360 370 380 390 400
LPNLQVLDLS YNLLEDLPSL SGCQKLQKID LRHNEIYEIK GSTFQQLFNL
410 420 430 440 450
RSLNLAWNKI AIIHPNAFST LPSLIKLDLS SNLLSSFPVT GLHGLTHLKL
460 470 480 490 500
TGNRALQSLI PSANFPELKI IEMPSAYQCC AFGGCENVYK ISNQWNKDDG
510 520 530 540 550
NSVDDLHKKD AGLFQVQDER DLEDFLLDFE EDLKALHSVQ CSPSPGPFKP
560 570 580 590 600
CEHLFGSWLI RIGVWTTAVL ALSCNALVAL TVFRTPLYIS SIKLLIGVIA
610 620 630 640 650
VVDILMGVSS AVLAAVDAFT FGRFAQHGAW WEDGIGCQIV GFLSIFASES
660 670 680 690 700
SIFLLTLAAL ERGFSVKCSS KFEVKAPLFS LRAIVLLCVL LALTIATIPL
710 720 730 740 750
LGGSKYNASP LCLPLPFGEP STTGYMVALV LLNSLCFLIM TIAYTKLYCS
760 770 780 790 800
LEKGELENLW DCSMVKHIAL LLFANCILYC PVAFLSFSSL LNLTFISPDV
810 820 830 840 850
IKFILLVIVP LPSCLNPLLY IVFNPHFKED MGSLGKHTRF WMRSKHASLL
860 870 880 890 900
SINSDDVEKR SCESTQALVS FTHASIAYDL PSTSGASPAY PMTESCHLSS

VAFVPCL
Length:907
Mass (Da):99,666
Last modified:July 28, 2009 - v2
Checksum:i5E202CB356DB12CF
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti128Q → K in AAD14684 (PubMed:9920770).Curated1
Sequence conflicti534K → N in AAD14684 (PubMed:9920770).Curated1
Sequence conflicti571A → T in AAD14684 (PubMed:9920770).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF110818 mRNA. Translation: AAD14684.1.
AK132387 mRNA. Translation: BAE21138.1.
CH466539 Genomic DNA. Translation: EDL21773.1.
CCDSiCCDS24180.1.
PIRiJG0193.
RefSeqiNP_034325.2. NM_010195.2.
UniGeneiMm.42103.

Genome annotation databases

EnsembliENSMUST00000020350; ENSMUSP00000020350; ENSMUSG00000020140.
GeneIDi14160.
KEGGimmu:14160.
UCSCiuc007hbi.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF110818 mRNA. Translation: AAD14684.1.
AK132387 mRNA. Translation: BAE21138.1.
CH466539 Genomic DNA. Translation: EDL21773.1.
CCDSiCCDS24180.1.
PIRiJG0193.
RefSeqiNP_034325.2. NM_010195.2.
UniGeneiMm.42103.

3D structure databases

ProteinModelPortaliQ9Z1P4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000020350.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ9Z1P4.
PhosphoSitePlusiQ9Z1P4.

Proteomic databases

PaxDbiQ9Z1P4.
PRIDEiQ9Z1P4.

Protocols and materials databases

DNASUi14160.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020350; ENSMUSP00000020350; ENSMUSG00000020140.
GeneIDi14160.
KEGGimmu:14160.
UCSCiuc007hbi.1. mouse.

Organism-specific databases

CTDi8549.
MGIiMGI:1341817. Lgr5.

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
KOG2087. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00760000119088.
HOGENOMiHOG000231829.
HOVERGENiHBG031675.
InParanoidiQ9Z1P4.
KOiK04308.
OMAiLENIWDC.
OrthoDBiEOG091G0QA0.
PhylomeDBiQ9Z1P4.
TreeFamiTF316814.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ9Z1P4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020140.
ExpressionAtlasiQ9Z1P4. baseline and differential.
GenevisibleiQ9Z1P4. 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. 13 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 nameiLGR5_MOUSE
AccessioniPrimary (citable) accession number: Q9Z1P4
Secondary accession number(s): Q3V1L2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2002
Last sequence update: July 28, 2009
Last modified: November 2, 2016
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

LGR5 is used as a marker of adult tissue stem cells in the intestine, stomach, hair follicle, and mammary epithelium.1 Publication

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.