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Protein

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

Gene

LGR5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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.5 Publications

Miscellaneous

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

GO - Molecular functioni

  • G protein-coupled peptide receptor activity Source: GO_Central
  • G protein-coupled receptor activity Source: ProtInc
  • protein-hormone receptor activity Source: InterPro
  • transmembrane signaling receptor activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-4641263 Regulation of FZD by ubiquitination
SIGNORiO75473

Names & Taxonomyi

Protein namesi
Recommended name:
Leucine-rich repeat-containing G-protein coupled receptor 5
Alternative name(s):
G-protein coupled receptor 49
G-protein coupled receptor 67
G-protein coupled receptor HG38
Gene namesi
Name:LGR5
Synonyms:GPR49, GPR67
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000139292.12
HGNCiHGNC:4504 LGR5
MIMi606667 gene
neXtProtiNX_O75473

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 – 722ExtracellularSequence analysisAdd BLAST19
Transmembranei723 – 743Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini744 – 767CytoplasmicSequence analysisAdd BLAST24
Transmembranei768 – 788Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini789 – 802ExtracellularSequence analysisAdd BLAST14
Transmembranei803 – 823Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini824 – 907CytoplasmicSequence analysisAdd BLAST84

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi146D → F: Abolishes activation of Wnt signaling. 1 Publication1
Mutagenesisi170D → F: Abolishes activation of Wnt signaling. 1 Publication1
Mutagenesisi190A → D: Abolishes activation of Wnt signaling. 1 Publication1
Mutagenesisi861S → A: Impaired internalization to the trans-Golgi network; when associated with A-864. 1 Publication1
Mutagenesisi864S → A: Impaired internalization to the trans-Golgi network; when associated with A-861. 1 Publication1

Organism-specific databases

DisGeNETi8549
OpenTargetsiENSG00000139292
PharmGKBiPA28894

Chemistry databases

GuidetoPHARMACOLOGYi148

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000001279422 – 907Leucine-rich repeat-containing G-protein coupled receptor 5Add BLAST886

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi34 ↔ 40
Disulfide bondi38 ↔ 52
Glycosylationi63N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi77N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi208N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi348 ↔ 373
Disulfide bondi479 ↔ 541
Glycosylationi500N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi637 ↔ 712PROSITE-ProRule annotation
Glycosylationi792N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiO75473
PaxDbiO75473
PeptideAtlasiO75473
PRIDEiO75473
ProteomicsDBi50034
50035 [O75473-2]

PTM databases

iPTMnetiO75473
PhosphoSitePlusiO75473

Expressioni

Tissue specificityi

Expressed in skeletal muscle, placenta, spinal cord, and various region of brain. Expressed at the base of crypts in colonic and small mucosa stem cells. In premalignant cancer expression is not restricted to the cript base. Overexpressed in cancers of the ovary, colon and liver.3 Publications

Gene expression databases

BgeeiENSG00000139292 Expressed in 162 organ(s), highest expression level in endometrium
CleanExiHS_LGR5
ExpressionAtlasiO75473 baseline and differential
GenevisibleiO75473 HS

Organism-specific databases

HPAiHPA012530

Interactioni

Subunit structurei

Identified in a complex composed of RNF43, LGR5 and RSPO1 (PubMed:21909076, PubMed:21727895, PubMed:21693646, PubMed:22815884, PubMed:23809763, PubMed:23756651). Also interacts with other R-spondin ligands, including RSPO2, RSPO3 and RSPO4 (PubMed:21909076, PubMed:21727895, PubMed:21693646, PubMed:29769720).7 Publications

Protein-protein interaction databases

BioGridi114119, 7 interactors
CORUMiO75473
STRINGi9606.ENSP00000266674

Structurei

Secondary structure

1907
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO75473
SMRiO75473
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 66LRRNTAdd BLAST42
Repeati67 – 90LRR 1Add BLAST24
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 – 328LRR 11Add BLAST23
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

Keywords - Domaini

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

Phylogenomic databases

eggNOGiKOG0619 Eukaryota
KOG2087 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00760000119088
HOGENOMiHOG000231829
HOVERGENiHBG031675
InParanoidiO75473
KOiK04308
OMAiKCSAKFE
OrthoDBiEOG091G0QA0
PhylomeDBiO75473
TreeFamiTF316814

Family and domain databases

Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR002131 Gphrmn_rcpt_fam
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000372 LRRNT
PfamiView protein in Pfam
PF00560 LRR_1, 1 hit
PF13855 LRR_8, 4 hits
PF01462 LRRNT, 1 hit
PRINTSiPR00373 GLYCHORMONER
PR00237 GPCRRHODOPSN
SMARTiView protein in SMART
SM00369 LRR_TYP, 15 hits
SM00013 LRRNT, 1 hit
PROSITEiView protein in PROSITE
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
PS51450 LRR, 15 hits

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: O75473-1) [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
MDTSRLGVLL SLPVLLQLAT GGSSPRSGVL LRGCPTHCHC EPDGRMLLRV
60 70 80 90 100
DCSDLGLSEL PSNLSVFTSY LDLSMNNISQ LLPNPLPSLR FLEELRLAGN
110 120 130 140 150
ALTYIPKGAF TGLYSLKVLM LQNNQLRHVP TEALQNLRSL QSLRLDANHI
160 170 180 190 200
SYVPPSCFSG LHSLRHLWLD DNALTEIPVQ AFRSLSALQA MTLALNKIHH
210 220 230 240 250
IPDYAFGNLS SLVVLHLHNN RIHSLGKKCF DGLHSLETLD LNYNNLDEFP
260 270 280 290 300
TAIRTLSNLK ELGFHSNNIR SIPEKAFVGN PSLITIHFYD NPIQFVGRSA
310 320 330 340 350
FQHLPELRTL TLNGASQITE FPDLTGTANL ESLTLTGAQI SSLPQTVCNQ
360 370 380 390 400
LPNLQVLDLS YNLLEDLPSF SVCQKLQKID LRHNEIYEIK VDTFQQLLSL
410 420 430 440 450
RSLNLAWNKI AIIHPNAFST LPSLIKLDLS SNLLSSFPIT GLHGLTHLKL
460 470 480 490 500
TGNHALQSLI SSENFPELKV IEMPYAYQCC AFGVCENAYK ISNQWNKGDN
510 520 530 540 550
SSMDDLHKKD AGMFQAQDER DLEDFLLDFE EDLKALHSVQ CSPSPGPFKP
560 570 580 590 600
CEHLLDGWLI RIGVWTIAVL ALTCNALVTS TVFRSPLYIS PIKLLIGVIA
610 620 630 640 650
AVNMLTGVSS AVLAGVDAFT FGSFARHGAW WENGVGCHVI GFLSIFASES
660 670 680 690 700
SVFLLTLAAL ERGFSVKYSA KFETKAPFSS LKVIILLCAL LALTMAAVPL
710 720 730 740 750
LGGSKYGASP LCLPLPFGEP STMGYMVALI LLNSLCFLMM TIAYTKLYCN
760 770 780 790 800
LDKGDLENIW DCSMVKHIAL LLFTNCILNC PVAFLSFSSL INLTFISPEV
810 820 830 840 850
IKFILLVVVP LPACLNPLLY ILFNPHFKED LVSLRKQTYV WTRSKHPSLM
860 870 880 890 900
SINSDDVEKQ SCDSTQALVT FTSSSITYDL PPSSVPSPAY PVTESCHLSS

VAFVPCL
Length:907
Mass (Da):99,998
Last modified:November 1, 1998 - v1
Checksum:i822D5C5E6F0D9092
GO
Isoform 2 (identifier: O75473-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     263-286: Missing.

Show »
Length:883
Mass (Da):97,404
Checksum:i50B293FCFCAED440
GO
Isoform 3 (identifier: O75473-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     143-214: Missing.

Show »
Length:835
Mass (Da):92,006
Checksum:i352096C4523C1E2F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti90R → H in AAC77911 (PubMed:9849958).Curated1
Sequence conflicti212L → W in AAC77911 (PubMed:9849958).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049411383H → R. Corresponds to variant dbSNP:rs12303775Ensembl.1
Natural variantiVAR_049412666V → A1 PublicationCorresponds to variant dbSNP:rs17109924Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_054782143 – 214Missing in isoform 3. 1 PublicationAdd BLAST72
Alternative sequenceiVSP_037746263 – 286Missing in isoform 2. 1 PublicationAdd BLAST24

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF062006 mRNA Translation: AAC28019.1
AF061444 mRNA Translation: AAC77911.1
FN820440 mRNA Translation: CBL95002.2
AC078860 Genomic DNA No translation available.
AC090116 Genomic DNA No translation available.
BC096324 mRNA Translation: AAH96324.1
BC096325 mRNA Translation: AAH96325.1
BC096326 mRNA Translation: AAH96326.1
BC099650 mRNA Translation: AAH99650.1
CCDSiCCDS61194.1 [O75473-2]
CCDS61195.1 [O75473-3]
CCDS9000.1 [O75473-1]
PIRiJE0176
RefSeqiNP_001264155.1, NM_001277226.1 [O75473-2]
NP_001264156.1, NM_001277227.1 [O75473-3]
NP_003658.1, NM_003667.3 [O75473-1]
UniGeneiHs.658889

Genome annotation databases

EnsembliENST00000266674; ENSP00000266674; ENSG00000139292 [O75473-1]
ENST00000536515; ENSP00000443033; ENSG00000139292 [O75473-3]
ENST00000540815; ENSP00000441035; ENSG00000139292 [O75473-2]
GeneIDi8549
KEGGihsa:8549
UCSCiuc001swl.5 human [O75473-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF062006 mRNA Translation: AAC28019.1
AF061444 mRNA Translation: AAC77911.1
FN820440 mRNA Translation: CBL95002.2
AC078860 Genomic DNA No translation available.
AC090116 Genomic DNA No translation available.
BC096324 mRNA Translation: AAH96324.1
BC096325 mRNA Translation: AAH96325.1
BC096326 mRNA Translation: AAH96326.1
BC099650 mRNA Translation: AAH99650.1
CCDSiCCDS61194.1 [O75473-2]
CCDS61195.1 [O75473-3]
CCDS9000.1 [O75473-1]
PIRiJE0176
RefSeqiNP_001264155.1, NM_001277226.1 [O75473-2]
NP_001264156.1, NM_001277227.1 [O75473-3]
NP_003658.1, NM_003667.3 [O75473-1]
UniGeneiHs.658889

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BSRX-ray3.20A/B22-543[»]
4BSSX-ray3.20A/B/E/F22-543[»]
4BSTX-ray4.30A/B22-543[»]
4BSUX-ray3.20A/B/E/F22-543[»]
4KNGX-ray2.50A/B32-557[»]
4UFRX-ray2.20A/C32-486[»]
A/C538-544[»]
4UFSX-ray4.80A32-486[»]
A538-544[»]
ProteinModelPortaliO75473
SMRiO75473
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114119, 7 interactors
CORUMiO75473
STRINGi9606.ENSP00000266674

Chemistry databases

GuidetoPHARMACOLOGYi148

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiO75473
PhosphoSitePlusiO75473

Proteomic databases

MaxQBiO75473
PaxDbiO75473
PeptideAtlasiO75473
PRIDEiO75473
ProteomicsDBi50034
50035 [O75473-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000266674; ENSP00000266674; ENSG00000139292 [O75473-1]
ENST00000536515; ENSP00000443033; ENSG00000139292 [O75473-3]
ENST00000540815; ENSP00000441035; ENSG00000139292 [O75473-2]
GeneIDi8549
KEGGihsa:8549
UCSCiuc001swl.5 human [O75473-1]

Organism-specific databases

CTDi8549
DisGeNETi8549
EuPathDBiHostDB:ENSG00000139292.12
GeneCardsiLGR5
HGNCiHGNC:4504 LGR5
HPAiHPA012530
MIMi606667 gene
neXtProtiNX_O75473
OpenTargetsiENSG00000139292
PharmGKBiPA28894
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0619 Eukaryota
KOG2087 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00760000119088
HOGENOMiHOG000231829
HOVERGENiHBG031675
InParanoidiO75473
KOiK04308
OMAiKCSAKFE
OrthoDBiEOG091G0QA0
PhylomeDBiO75473
TreeFamiTF316814

Enzyme and pathway databases

ReactomeiR-HSA-4641263 Regulation of FZD by ubiquitination
SIGNORiO75473

Miscellaneous databases

ChiTaRSiLGR5 human
GeneWikiiLGR5
GenomeRNAii8549
PROiPR:O75473
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139292 Expressed in 162 organ(s), highest expression level in endometrium
CleanExiHS_LGR5
ExpressionAtlasiO75473 baseline and differential
GenevisibleiO75473 HS

Family and domain databases

Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR002131 Gphrmn_rcpt_fam
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000372 LRRNT
PfamiView protein in Pfam
PF00560 LRR_1, 1 hit
PF13855 LRR_8, 4 hits
PF01462 LRRNT, 1 hit
PRINTSiPR00373 GLYCHORMONER
PR00237 GPCRRHODOPSN
SMARTiView protein in SMART
SM00369 LRR_TYP, 15 hits
SM00013 LRRNT, 1 hit
PROSITEiView protein in PROSITE
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
PS51450 LRR, 15 hits
ProtoNetiSearch...

Entry informationi

Entry nameiLGR5_HUMAN
AccessioniPrimary (citable) accession number: O75473
Secondary accession number(s): D8MCT0
, Q4VAM0, Q4VAM2, Q9UP75
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2002
Last sequence update: November 1, 1998
Last modified: November 7, 2018
This is version 168 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  7. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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