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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

BioCyciZFISH:ENSG00000133067-MONOMER.
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)DescriptionActionsGraphical viewLength
Topological domaini25 – 567ExtracellularSequence analysisAdd BLAST543
Transmembranei568 – 588Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini589 – 598CytoplasmicSequence analysis10
Transmembranei599 – 619Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini620 – 644ExtracellularSequence analysisAdd BLAST25
Transmembranei645 – 665Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini666 – 687CytoplasmicSequence analysisAdd BLAST22
Transmembranei688 – 708Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini709 – 727ExtracellularSequence analysisAdd BLAST19
Transmembranei728 – 748Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini749 – 774CytoplasmicSequence analysisAdd BLAST26
Transmembranei775 – 795Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini796 – 809ExtracellularSequence analysisAdd BLAST14
Transmembranei810 – 830Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini831 – 967CytoplasmicSequence analysisAdd BLAST137

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi59352.
OpenTargetsiENSG00000133067.
PharmGKBiPA134927114.

Chemistry databases

GuidetoPHARMACOLOGYi149.

Polymorphism and mutation databases

BioMutaiLGR6.
DMDMi158519993.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000006969925 – 967Leucine-rich repeat-containing G-protein coupled receptor 6Add BLAST943

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi77N-linked (GlcNAc...)Sequence analysis1
Glycosylationi208N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi642 ↔ 717By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9HBX8.
PeptideAtlasiQ9HBX8.
PRIDEiQ9HBX8.

PTM databases

iPTMnetiQ9HBX8.
PhosphoSitePlusiQ9HBX8.

Expressioni

Gene expression databases

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

Organism-specific databases

HPAiHPA008556.

Interactioni

Protein-protein interaction databases

BioGridi121893. 1 interactor.
STRINGi9606.ENSP00000356247.

Structurei

3D structure databases

ProteinModelPortaliQ9HBX8.
SMRiQ9HBX8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 66LRRNTAdd BLAST41
Repeati91 – 112LRR 1Add BLAST22
Repeati115 – 136LRR 2Add BLAST22
Repeati139 – 160LRR 3Add BLAST22
Repeati163 – 186LRR 4Add BLAST24
Repeati187 – 208LRR 5Add BLAST22
Repeati211 – 232LRR 6Add BLAST22
Repeati235 – 256LRR 7Add BLAST22
Repeati258 – 279LRR 8Add BLAST22
Repeati282 – 303LRR 9Add BLAST22
Repeati306 – 328LRR 10Add BLAST23
Repeati329 – 350LRR 11Add BLAST22
Repeati353 – 374LRR 12Add BLAST22
Repeati375 – 396LRR 13Add BLAST22
Repeati399 – 420LRR 14Add BLAST22
Repeati423 – 443LRR 15Add BLAST21

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi952 – 955Poly-Gly4

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)DescriptionActionsGraphical viewLength
Sequence conflicti545 – 549CSPTP → MISPT in BAB89329 (PubMed:12044878).Curated5
Sequence conflicti767W → R in BAB55071 (PubMed:14702039).Curated1
Sequence conflicti963 – 967FASHV → LLHTY in AAG17168 (PubMed:10935549).Curated5

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049413267N → K.Corresponds to variant rs7553800dbSNPEnsembl.1
Natural variantiVAR_033479516A → S.Corresponds to variant rs6668765dbSNPEnsembl.1
Natural variantiVAR_059324592V → A.2 PublicationsCorresponds to variant rs788795dbSNPEnsembl.1
Natural variantiVAR_035762725G → C in a colorectal cancer sample; somatic mutation; no effect Wnt signlaing upon RSPO1-binding. 2 Publications1
Natural variantiVAR_035763928P → H in a colorectal cancer sample; somatic mutation; no effect Wnt signlaing upon RSPO1-binding. 2 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0280061 – 71MPSPP…LTAYL → MRLEGEGRSARAGQNLSRAG SARRGAPR in isoform 1. 1 PublicationAdd BLAST71
Alternative sequenceiVSP_0135961 – 71MPSPP…LTAYL → MGRPRLTLVCQVSIIISAR in isoform 2. 2 PublicationsAdd BLAST71
Alternative sequenceiVSP_028007144 – 239Missing in isoform 1. 1 PublicationAdd BLAST96

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121893. 1 interactor.
STRINGi9606.ENSP00000356247.

Chemistry databases

GuidetoPHARMACOLOGYi149.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ9HBX8.
PhosphoSitePlusiQ9HBX8.

Polymorphism and mutation databases

BioMutaiLGR6.
DMDMi158519993.

Proteomic databases

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.
DisGeNETi59352.
GeneCardsiLGR6.
HGNCiHGNC:19719. LGR6.
HPAiHPA008556.
MIMi606653. gene.
neXtProtiNX_Q9HBX8.
OpenTargetsiENSG00000133067.
PharmGKBiPA134927114.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000133067-MONOMER.
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: November 2, 2016
This is version 144 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.