LGR6_MOUSE
ID LGR6_MOUSE Reviewed; 967 AA.
AC Q3UVD5; B2RUL8; Q80UB8; Q8R301;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Leucine-rich repeat-containing G-protein coupled receptor 6;
DE Flags: Precursor;
GN Name=Lgr6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 748-909.
RX PubMed=12679517; DOI=10.1073/pnas.0230374100;
RA Vassilatis D.K., Hohmann J.G., Zeng H., Li F., Ranchalis J.E.,
RA Mortrud M.T., Brown A., Rodriguez S.S., Weller J.R., Wright A.C.,
RA Bergmann J.E., Gaitanaris G.A.;
RT "The G protein-coupled receptor repertoires of human and mouse.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:4903-4908(2003).
RN [5]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=20223988; DOI=10.1126/science.1184733;
RA Snippert H.J., Haegebarth A., Kasper M., Jaks V., van Es J.H., Barker N.,
RA van de Wetering M., van den Born M., Begthel H., Vries R.G., Stange D.E.,
RA Toftgard R., Clevers H.;
RT "Lgr6 marks stem cells in the hair follicle that generate all cell lineages
RT of the skin.";
RL Science 327:1385-1389(2010).
RN [6]
RP DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=29769720; DOI=10.1038/s41586-018-0118-y;
RA Szenker-Ravi E., Altunoglu U., Leushacke M., Bosso-Lefevre C., Khatoo M.,
RA Thi Tran H., Naert T., Noelanders R., Hajamohideen A., Beneteau C.,
RA de Sousa S.B., Karaman B., Latypova X., Basaran S., Yuecel E.B., Tan T.T.,
RA Vlaminck L., Nayak S.S., Shukla A., Girisha K.M., Le Caignec C.,
RA Soshnikova N., Uyguner Z.O., Vleminckx K., Barker N., Kayserili H.,
RA Reversade B.;
RT "RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently
RT of LGR4/5/6.";
RL Nature 557:564-569(2018).
CC -!- FUNCTION: Receptor for R-spondins that potentiates the canonical Wnt
CC signaling pathway and acts as a marker of multipotent stem cells in the
CC epidermis. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4),
CC associates with phosphorylated LRP6 and frizzled receptors that are
CC activated by extracellular Wnt receptors, triggering the canonical Wnt
CC signaling pathway to increase expression of target genes. In contrast
CC to classical G-protein coupled receptors, does not activate
CC heterotrimeric G-proteins to transduce the signal (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in multipotent stem cells in
CC the epidermis. {ECO:0000269|PubMed:20223988}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the earliest embryonic hair placodes.
CC In adult hair follicles, present in a region directly above the
CC follicle bulge. Specifically present in prenatal cells establishing the
CC hair follicle, sebaceous gland and interfollicular epidermis.
CC Postnatally, present in cells generating sebaceous gland and
CC interfollicular epidermis (PubMed:20223988). During limb development,
CC at 14.5 dpc, expressed in the ectoderm overlying the limb buds and at
CC the apical ectodermal ridge. In the developing lungs, at 14.5 dpc,
CC expressed in smooth muscle cells (PubMed:29769720).
CC {ECO:0000269|PubMed:20223988, ECO:0000269|PubMed:29769720}.
CC -!- DISRUPTION PHENOTYPE: Simultaneous knockdown of LGR4, LGR5 and LGR6
CC results in developmental phenotypes, such as cleft palate and
CC ankyloglossia, but not in tetra-amelia with lung agenesis.
CC {ECO:0000269|PubMed:29769720}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000305}.
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DR EMBL; AK137380; BAE23335.1; -; mRNA.
DR EMBL; GL456086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026896; AAH26896.1; -; mRNA.
DR EMBL; BC141210; AAI41211.1; -; mRNA.
DR EMBL; AY255562; AAO85074.1; -; mRNA.
DR CCDS; CCDS15314.1; -.
DR RefSeq; NP_001028581.1; NM_001033409.3.
DR AlphaFoldDB; Q3UVD5; -.
DR SMR; Q3UVD5; -.
DR IntAct; Q3UVD5; 1.
DR STRING; 10090.ENSMUSP00000035444; -.
DR GlyGen; Q3UVD5; 2 sites.
DR PhosphoSitePlus; Q3UVD5; -.
DR PaxDb; Q3UVD5; -.
DR PRIDE; Q3UVD5; -.
DR ProteomicsDB; 252469; -.
DR Antibodypedia; 34525; 362 antibodies from 33 providers.
DR Ensembl; ENSMUST00000044828; ENSMUSP00000035444; ENSMUSG00000042793.
DR GeneID; 329252; -.
DR KEGG; mmu:329252; -.
DR UCSC; uc007csq.1; mouse.
DR CTD; 59352; -.
DR MGI; MGI:2441805; Lgr6.
DR VEuPathDB; HostDB:ENSMUSG00000042793; -.
DR eggNOG; KOG0619; Eukaryota.
DR eggNOG; KOG2087; Eukaryota.
DR GeneTree; ENSGT00940000159939; -.
DR HOGENOM; CLU_006843_0_0_1; -.
DR InParanoid; Q3UVD5; -.
DR OMA; RRLWPCT; -.
DR OrthoDB; 340670at2759; -.
DR PhylomeDB; Q3UVD5; -.
DR TreeFam; TF316814; -.
DR BioGRID-ORCS; 329252; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Lgr6; mouse.
DR PRO; PR:Q3UVD5; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q3UVD5; protein.
DR Bgee; ENSMUSG00000042793; Expressed in ascending aorta and 150 other tissues.
DR ExpressionAtlas; Q3UVD5; baseline and differential.
DR Genevisible; Q3UVD5; MM.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031982; C:vesicle; ISO:MGI.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0016500; F:protein-hormone receptor activity; IEA:InterPro.
DR GO; GO:1990523; P:bone regeneration; IMP:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISO:MGI.
DR GO; GO:0042246; P:tissue regeneration; IMP:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR002131; Gphrmn_rcpt_fam.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000372; LRRNT.
DR Pfam; PF13855; LRR_8; 4.
DR PRINTS; PR00373; GLYCHORMONER.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM00369; LRR_TYP; 14.
DR SMART; SM00013; LRRNT; 1.
DR PROSITE; PS51450; LRR; 14.
PE 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Leucine-rich repeat; Membrane; Receptor; Reference proteome; Repeat;
KW Signal; Transducer; Transmembrane; Transmembrane helix;
KW Wnt signaling pathway.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..967
FT /note="Leucine-rich repeat-containing G-protein coupled
FT receptor 6"
FT /id="PRO_0000303884"
FT TOPO_DOM 25..567
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 568..588
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 589..598
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 599..619
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 620..644
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 645..665
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 666..687
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 688..708
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 709..727
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 728..748
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 749..774
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 775..795
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 796..809
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 810..830
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 831..967
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 26..66
FT /note="LRRNT"
FT REPEAT 91..112
FT /note="LRR 1"
FT REPEAT 115..136
FT /note="LRR 2"
FT REPEAT 139..160
FT /note="LRR 3"
FT REPEAT 163..186
FT /note="LRR 4"
FT REPEAT 187..208
FT /note="LRR 5"
FT REPEAT 211..232
FT /note="LRR 6"
FT REPEAT 235..256
FT /note="LRR 7"
FT REPEAT 258..279
FT /note="LRR 8"
FT REPEAT 282..302
FT /note="LRR 9"
FT REPEAT 303..325
FT /note="LRR 10"
FT REPEAT 329..350
FT /note="LRR 11"
FT REPEAT 353..374
FT /note="LRR 12"
FT REPEAT 375..396
FT /note="LRR 13"
FT REPEAT 399..420
FT /note="LRR 14"
FT REPEAT 423..443
FT /note="LRR 15"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 208
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 642..717
FT /evidence="ECO:0000250"
FT CONFLICT 22
FT /note="A -> G (in Ref. 3; AAI41211)"
FT /evidence="ECO:0000305"
FT CONFLICT 280
FT /note="S -> N (in Ref. 3; AAI41211)"
FT /evidence="ECO:0000305"
FT CONFLICT 540
FT /note="H -> N (in Ref. 3; AAH26896/AAI41211)"
FT /evidence="ECO:0000305"
FT CONFLICT 611
FT /note="S -> T (in Ref. 3; AAH26896/AAI41211)"
FT /evidence="ECO:0000305"
FT CONFLICT 918
FT /note="V -> I (in Ref. 3; AAH26896/AAI41211)"
FT /evidence="ECO:0000305"
FT CONFLICT 952
FT /note="V -> M (in Ref. 3; AAH26896)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 967 AA; 104267 MW; 06FE0A7E7FA5083B CRC64;
MHSPPGLLAL WLCAVLCASA RAGSDPQPGP GRPACPAPCH CQEDGIMLSA DCSELGLSVV
PADLDPLTAY LDLSMNNLTE LQPGLFHHLR FLEELRLSGN HLSHIPGQAF SGLHSLKILM
LQSNQLRGIP AEALWELPSL QSLRLDANLI SLVPERSFEG LSSLRHLWLD DNALTEIPVR
ALNNLPALQA MTLALNHIRH IPDYAFQNLT SLVVLHLHNN RIQHVGTHSF EGLHNLETLD
LNYNELQEFP LAIRTLGRLQ ELGFHNNNIK AIPEKAFMGS PLLQTIHFYD NPIQFVGRSA
FQYLSKLHTL SLNGATDIQE FPDLKGTTSL EILTLTRAGI RLLPPGVCQQ LPRLRILELS
HNQIEELPSL HRCQKLEEIG LRHNRIKEIG ADTFSQLGSL QALDLSWNAI RAIHPEAFST
LRSLVKLDLT DNQLTTLPLA GLGGLMHLKL KGNLALSQAF SKDSFPKLRI LEVPYAYQCC
AYGICASFFK TSGQWQAEDF HPEEEEAPKR PLGLLAGQAE NHYDLDLDEL QMGTEDSKPH
PSVQCSPVPG PFKPCEHLFE SWGIRLAVWA IVLLSVLCNG LVLLTVFASG PSPLSPVKLV
VGAMAGANAL SGISCGLLAS VDALTYGQFA EYGARWESGL GCQATGFLAV LGSEASVLLL
TLAAVQCSIS VTCVRAYGKA PSPGSVRAGA LGCLALAGLA AALPLASVGE YGASPLCLPY
APPEGRPAAL GFAVALVMMN SLCFLVVAGA YIKLYCDLPR GDFEAVWDCA MVRHVAWLIF
ADGLLYCPVA FLSFASMLGL FPVTPEAVKS VLLVVLPLPA CLNPLLYLLF NPHFRDDLRR
LWPSPRSPGP LAYAAAGELE KSSCDSTQAL VAFSDVDLIL EASEAGQPPG LETYGFPSVT
LISRHQPGAT RLEGNHFVES DGTKFGNPQP PMKGELLLKA EGATLAGCGS SVGGALWPSG
SLFASHL
