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Protein

Leucine-rich repeat-containing G-protein coupled receptor 6

Gene

LGR6

Organism
Homo sapiens (Human)
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 acts as a marker of multipotent stem cells in the epidermis. 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. May act as a tumor suppressor.2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Leucine-rich repeat-containing G-protein coupled receptor 6
Gene namesi
Name:LGR6
ORF Names:UNQ6427/PRO21331, VTS20631
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:19719. LGR6.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 567543ExtracellularSequence analysisAdd
BLAST
Transmembranei568 – 58821Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini589 – 59810CytoplasmicSequence analysis
Transmembranei599 – 61921Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini620 – 64425ExtracellularSequence analysisAdd
BLAST
Transmembranei645 – 66521Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini666 – 68722CytoplasmicSequence analysisAdd
BLAST
Transmembranei688 – 70821Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini709 – 72719ExtracellularSequence analysisAdd
BLAST
Transmembranei728 – 74821Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini749 – 77426CytoplasmicSequence analysisAdd
BLAST
Transmembranei775 – 79521Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini796 – 80914ExtracellularSequence analysisAdd
BLAST
Transmembranei810 – 83021Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini831 – 967137CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

PharmGKBiPA134927114.

Chemistry

GuidetoPHARMACOLOGYi149.

Polymorphism and mutation databases

BioMutaiLGR6.
DMDMi158519993.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence analysisAdd
BLAST
Chaini25 – 967943Leucine-rich repeat-containing G-protein coupled receptor 6PRO_0000069699Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi77 – 771N-linked (GlcNAc...)Sequence analysis
Glycosylationi208 – 2081N-linked (GlcNAc...)Sequence analysis
Disulfide bondi642 ↔ 717By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9HBX8.
PaxDbiQ9HBX8.
PeptideAtlasiQ9HBX8.
PRIDEiQ9HBX8.

PTM databases

iPTMnetiQ9HBX8.
PhosphoSiteiQ9HBX8.

Expressioni

Gene expression databases

BgeeiENSG00000133067.
CleanExiHS_LGR6.
ExpressionAtlasiQ9HBX8. baseline and differential.
GenevisibleiQ9HBX8. HS.

Organism-specific databases

HPAiHPA008556.

Interactioni

Protein-protein interaction databases

BioGridi121893. 1 interaction.
STRINGi9606.ENSP00000356247.

Structurei

3D structure databases

ProteinModelPortaliQ9HBX8.
SMRiQ9HBX8. Positions 31-556.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini26 – 6641LRRNTAdd
BLAST
Repeati91 – 11222LRR 1Add
BLAST
Repeati115 – 13622LRR 2Add
BLAST
Repeati139 – 16022LRR 3Add
BLAST
Repeati163 – 18624LRR 4Add
BLAST
Repeati187 – 20822LRR 5Add
BLAST
Repeati211 – 23222LRR 6Add
BLAST
Repeati235 – 25622LRR 7Add
BLAST
Repeati258 – 27922LRR 8Add
BLAST
Repeati282 – 30322LRR 9Add
BLAST
Repeati306 – 32823LRR 10Add
BLAST
Repeati329 – 35022LRR 11Add
BLAST
Repeati353 – 37422LRR 12Add
BLAST
Repeati375 – 39622LRR 13Add
BLAST
Repeati399 – 42022LRR 14Add
BLAST
Repeati423 – 44321LRR 15Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi952 – 9554Poly-Gly

Sequence similaritiesi

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.
HOVERGENiHBG031675.
InParanoidiQ9HBX8.
KOiK08399.
OrthoDBiEOG091G0QA0.
PhylomeDBiQ9HBX8.
TreeFamiTF316814.

Family and domain databases

Gene3Di3.80.10.10. 3 hits.
InterProiIPR000276. GPCR_Rhodpsn.
IPR002131. Gphrmn_rcpt_fam.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000372. LRRNT.
[Graphical view]
PfamiPF13855. LRR_8. 4 hits.
[Graphical view]
PRINTSiPR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.
SMARTiSM00369. LRR_TYP. 14 hits.
SM00013. LRRNT. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 1 hit.
PROSITEiPS51450. LRR. 13 hits.
[Graphical view]

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 3 (identifier: Q9HBX8-3) [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
MPSPPGLRAL WLCAALCASR RAGGAPQPGP GPTACPAPCH CQEDGIMLSA
60 70 80 90 100
DCSELGLSAV PGDLDPLTAY LDLSMNNLTE LQPGLFHHLR FLEELRLSGN
110 120 130 140 150
HLSHIPGQAF SGLYSLKILM LQNNQLGGIP AEALWELPSL QSLRLDANLI
160 170 180 190 200
SLVPERSFEG LSSLRHLWLD DNALTEIPVR ALNNLPALQA MTLALNRISH
210 220 230 240 250
IPDYAFQNLT SLVVLHLHNN RIQHLGTHSF EGLHNLETLD LNYNKLQEFP
260 270 280 290 300
VAIRTLGRLQ ELGFHNNNIK AIPEKAFMGN PLLQTIHFYD NPIQFVGRSA
310 320 330 340 350
FQYLPKLHTL SLNGAMDIQE FPDLKGTTSL EILTLTRAGI RLLPSGMCQQ
360 370 380 390 400
LPRLRVLELS HNQIEELPSL HRCQKLEEIG LQHNRIWEIG ADTFSQLSSL
410 420 430 440 450
QALDLSWNAI RSIHPEAFST LHSLVKLDLT DNQLTTLPLA GLGGLMHLKL
460 470 480 490 500
KGNLALSQAF SKDSFPKLRI LEVPYAYQCC PYGMCASFFK ASGQWEAEDL
510 520 530 540 550
HLDDEESSKR PLGLLARQAE NHYDQDLDEL QLEMEDSKPH PSVQCSPTPG
560 570 580 590 600
PFKPCEYLFE SWGIRLAVWA IVLLSVLCNG LVLLTVFAGG PVPLPPVKFV
610 620 630 640 650
VGAIAGANTL TGISCGLLAS VDALTFGQFS EYGARWETGL GCRATGFLAV
660 670 680 690 700
LGSEASVLLL TLAAVQCSVS VSCVRAYGKS PSLGSVRAGV LGCLALAGLA
710 720 730 740 750
AALPLASVGE YGASPLCLPY APPEGQPAAL GFTVALVMMN SFCFLVVAGA
760 770 780 790 800
YIKLYCDLPR GDFEAVWDCA MVRHVAWLIF ADGLLYCPVA FLSFASMLGL
810 820 830 840 850
FPVTPEAVKS VLLVVLPLPA CLNPLLYLLF NPHFRDDLRR LRPRAGDSGP
860 870 880 890 900
LAYAAAGELE KSSCDSTQAL VAFSDVDLIL EASEAGRPPG LETYGFPSVT
910 920 930 940 950
LISCQQPGAP RLEGSHCVEP EGNHFGNPQP SMDGELLLRA EGSTPAGGGL
960
SGGGGFQPSG LAFASHV
Length:967
Mass (Da):104,298
Last modified:September 11, 2007 - v3
Checksum:i22E332E85DF8DCE0
GO
Isoform 1 (identifier: Q9HBX8-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-71: MPSPPGLRAL...GDLDPLTAYL → MRLEGEGRSARAGQNLSRAGSARRGAPR
     144-239: Missing.

Show »
Length:828
Mass (Da):89,302
Checksum:i1B5971445AA2D8B4
GO
Isoform 2 (identifier: Q9HBX8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-71: MPSPPGLRAL...GDLDPLTAYL → MGRPRLTLVCQVSIIISAR

Show »
Length:915
Mass (Da):99,295
Checksum:i2925C7AC50B8CEF7
GO

Sequence cautioni

The sequence BAB55071 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti545 – 5495CSPTP → MISPT in BAB89329 (PubMed:12044878).Curated
Sequence conflicti767 – 7671W → R in BAB55071 (PubMed:14702039).Curated
Sequence conflicti963 – 9675FASHV → LLHTY in AAG17168 (PubMed:10935549).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti267 – 2671N → K.
Corresponds to variant rs7553800 [ dbSNP | Ensembl ].
VAR_049413
Natural varianti516 – 5161A → S.
Corresponds to variant rs6668765 [ dbSNP | Ensembl ].
VAR_033479
Natural varianti592 – 5921V → A.2 Publications
Corresponds to variant rs788795 [ dbSNP | Ensembl ].
VAR_059324
Natural varianti725 – 7251G → C in a colorectal cancer sample; somatic mutation; no effect Wnt signlaing upon RSPO1-binding. 2 Publications
VAR_035762
Natural varianti928 – 9281P → H in a colorectal cancer sample; somatic mutation; no effect Wnt signlaing upon RSPO1-binding. 2 Publications
VAR_035763

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 7171MPSPP…LTAYL → MRLEGEGRSARAGQNLSRAG SARRGAPR in isoform 1. 1 PublicationVSP_028006Add
BLAST
Alternative sequencei1 – 7171MPSPP…LTAYL → MGRPRLTLVCQVSIIISAR in isoform 2. 2 PublicationsVSP_013596Add
BLAST
Alternative sequencei144 – 23996Missing in isoform 1. 1 PublicationVSP_028007Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF190501 mRNA. Translation: AAG17168.1.
AY358119 mRNA. Translation: AAQ88486.1.
AL356953 Genomic DNA. Translation: CAI15927.1.
AL356953 Genomic DNA. Translation: CAI15929.1.
AL356953 Genomic DNA. Translation: CAI15930.1.
BC047905 mRNA. Translation: AAH47905.2.
AB049405 mRNA. Translation: BAB39854.1.
AB083616 Genomic DNA. Translation: BAB89329.1.
AK027377 mRNA. Translation: BAB55071.1. Different initiation.
CCDSiCCDS1424.1. [Q9HBX8-2]
CCDS30971.1. [Q9HBX8-3]
CCDS30972.1. [Q9HBX8-1]
RefSeqiNP_001017403.1. NM_001017403.1. [Q9HBX8-3]
NP_001017404.1. NM_001017404.1. [Q9HBX8-1]
NP_067649.2. NM_021636.2. [Q9HBX8-2]
UniGeneiHs.497402.

Genome annotation databases

EnsembliENST00000255432; ENSP00000255432; ENSG00000133067. [Q9HBX8-2]
ENST00000367278; ENSP00000356247; ENSG00000133067. [Q9HBX8-3]
ENST00000439764; ENSP00000387869; ENSG00000133067. [Q9HBX8-1]
GeneIDi59352.
KEGGihsa:59352.
UCSCiuc001gxu.4. human. [Q9HBX8-3]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF190501 mRNA. Translation: AAG17168.1.
AY358119 mRNA. Translation: AAQ88486.1.
AL356953 Genomic DNA. Translation: CAI15927.1.
AL356953 Genomic DNA. Translation: CAI15929.1.
AL356953 Genomic DNA. Translation: CAI15930.1.
BC047905 mRNA. Translation: AAH47905.2.
AB049405 mRNA. Translation: BAB39854.1.
AB083616 Genomic DNA. Translation: BAB89329.1.
AK027377 mRNA. Translation: BAB55071.1. Different initiation.
CCDSiCCDS1424.1. [Q9HBX8-2]
CCDS30971.1. [Q9HBX8-3]
CCDS30972.1. [Q9HBX8-1]
RefSeqiNP_001017403.1. NM_001017403.1. [Q9HBX8-3]
NP_001017404.1. NM_001017404.1. [Q9HBX8-1]
NP_067649.2. NM_021636.2. [Q9HBX8-2]
UniGeneiHs.497402.

3D structure databases

ProteinModelPortaliQ9HBX8.
SMRiQ9HBX8. Positions 31-556.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121893. 1 interaction.
STRINGi9606.ENSP00000356247.

Chemistry

GuidetoPHARMACOLOGYi149.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ9HBX8.
PhosphoSiteiQ9HBX8.

Polymorphism and mutation databases

BioMutaiLGR6.
DMDMi158519993.

Proteomic databases

MaxQBiQ9HBX8.
PaxDbiQ9HBX8.
PeptideAtlasiQ9HBX8.
PRIDEiQ9HBX8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000255432; ENSP00000255432; ENSG00000133067. [Q9HBX8-2]
ENST00000367278; ENSP00000356247; ENSG00000133067. [Q9HBX8-3]
ENST00000439764; ENSP00000387869; ENSG00000133067. [Q9HBX8-1]
GeneIDi59352.
KEGGihsa:59352.
UCSCiuc001gxu.4. human. [Q9HBX8-3]

Organism-specific databases

CTDi59352.
GeneCardsiLGR6.
HGNCiHGNC:19719. LGR6.
HPAiHPA008556.
MIMi606653. gene.
neXtProtiNX_Q9HBX8.
PharmGKBiPA134927114.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
KOG2087. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00760000119088.
HOVERGENiHBG031675.
InParanoidiQ9HBX8.
KOiK08399.
OrthoDBiEOG091G0QA0.
PhylomeDBiQ9HBX8.
TreeFamiTF316814.

Enzyme and pathway databases

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

Miscellaneous databases

GeneWikiiLGR6.
GenomeRNAii59352.
PROiQ9HBX8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000133067.
CleanExiHS_LGR6.
ExpressionAtlasiQ9HBX8. baseline and differential.
GenevisibleiQ9HBX8. HS.

Family and domain databases

Gene3Di3.80.10.10. 3 hits.
InterProiIPR000276. GPCR_Rhodpsn.
IPR002131. Gphrmn_rcpt_fam.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000372. LRRNT.
[Graphical view]
PfamiPF13855. LRR_8. 4 hits.
[Graphical view]
PRINTSiPR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.
SMARTiSM00369. LRR_TYP. 14 hits.
SM00013. LRRNT. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 1 hit.
PROSITEiPS51450. LRR. 13 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLGR6_HUMAN
AccessioniPrimary (citable) accession number: Q9HBX8
Secondary accession number(s): Q5T509
, Q5T512, Q6UY15, Q86VU0, Q96K69, Q9BYD7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: September 11, 2007
Last modified: September 7, 2016
This is version 142 of the entry and version 3 of the sequence. [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

Complete proteome, Reference proteome

Documents

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