O75473 (LGR5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	LGR5
Synonyms:	GPR49, GPR67

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	907 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Orphan receptor. Stem cell marker of the intestinal epithelium and the hair follicle. Target gene of Wnt signaling.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	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. Ref.5 Ref.6 Ref.7
Sequence similarities	Belongs to the G-protein coupled receptor 1 family. Contains 16 LRR (leucine-rich) repeats. Contains 1 LRRNT domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Leucine-rich repeat Repeat Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	inner ear development Inferred from electronic annotation. Source: Compara
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	G-protein coupled receptor activity Traceable author statement Ref.1. Source: ProtInc protein-hormone receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O75473-1)

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.

Isoform 2 (identifier: O75473-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 907	886	Leucine-rich repeat-containing G-protein coupled receptor 5		PRO_0000012794
Regions
	Topological domain	22 – 561	540	Extracellular Potential
	Transmembrane	562 – 582	21	Helical; Name=1; Potential
	Topological domain	583 – 593	11	Cytoplasmic Potential
	Transmembrane	594 – 614	21	Helical; Name=2; Potential
	Topological domain	615 – 638	24	Extracellular Potential
	Transmembrane	639 – 659	21	Helical; Name=3; Potential
	Topological domain	660 – 682	23	Cytoplasmic Potential
	Transmembrane	683 – 703	21	Helical; Name=4; Potential
	Topological domain	704 – 722	19	Extracellular Potential
	Transmembrane	723 – 743	21	Helical; Name=5; Potential
	Topological domain	744 – 767	24	Cytoplasmic Potential
	Transmembrane	768 – 788	21	Helical; Name=6; Potential
	Topological domain	789 – 802	14	Extracellular Potential
	Transmembrane	803 – 823	21	Helical; Name=7; Potential
	Topological domain	824 – 907	84	Cytoplasmic Potential
	Domain	25 – 66	42	LRRNT
	Repeat	67 – 90	24	LRR 1
	Repeat	91 – 112	22	LRR 2
	Repeat	115 – 136	22	LRR 3
	Repeat	139 – 160	22	LRR 4
	Repeat	163 – 184	22	LRR 5
	Repeat	187 – 208	22	LRR 6
	Repeat	211 – 232	22	LRR 7
	Repeat	235 – 256	22	LRR 8
	Repeat	258 – 279	22	LRR 9
	Repeat	282 – 303	22	LRR 10
	Repeat	306 – 328	23	LRR 11
	Repeat	329 – 350	22	LRR 12
	Repeat	353 – 374	22	LRR 13
	Repeat	375 – 396	22	LRR 14
	Repeat	399 – 420	22	LRR 15
	Repeat	423 – 446	24	LRR 16
Amino acid modifications
	Glycosylation	63	1	N-linked (GlcNAc...) Potential
	Glycosylation	77	1	N-linked (GlcNAc...) Potential
	Glycosylation	208	1	N-linked (GlcNAc...) Potential
	Glycosylation	500	1	N-linked (GlcNAc...) Potential
	Glycosylation	792	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	263 – 286	24	Missing in isoform 2.		VSP_037746
	Natural variant	383	1	H → R. Corresponds to variant rs12303775 [ dbSNP | Ensembl ].		VAR_049411
	Natural variant	666	1	V → A. Ref.4 Corresponds to variant rs17109924 [ dbSNP | Ensembl ].		VAR_049412
Experimental info
	Sequence conflict	90	1	R → H in AAC77911. Ref.2
	Sequence conflict	212	1	L → W in AAC77911. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 822D5C5E6F0D9092	FASTA	907	99,998
	10 20 30 40 50 60 MDTSRLGVLL SLPVLLQLAT GGSSPRSGVL LRGCPTHCHC EPDGRMLLRV DCSDLGLSEL 70 80 90 100 110 120 PSNLSVFTSY LDLSMNNISQ LLPNPLPSLR FLEELRLAGN ALTYIPKGAF TGLYSLKVLM 130 140 150 160 170 180 LQNNQLRHVP TEALQNLRSL QSLRLDANHI SYVPPSCFSG LHSLRHLWLD DNALTEIPVQ 190 200 210 220 230 240 AFRSLSALQA MTLALNKIHH IPDYAFGNLS SLVVLHLHNN RIHSLGKKCF DGLHSLETLD 250 260 270 280 290 300 LNYNNLDEFP TAIRTLSNLK ELGFHSNNIR SIPEKAFVGN PSLITIHFYD NPIQFVGRSA 310 320 330 340 350 360 FQHLPELRTL TLNGASQITE FPDLTGTANL ESLTLTGAQI SSLPQTVCNQ LPNLQVLDLS 370 380 390 400 410 420 YNLLEDLPSF SVCQKLQKID LRHNEIYEIK VDTFQQLLSL RSLNLAWNKI AIIHPNAFST 430 440 450 460 470 480 LPSLIKLDLS SNLLSSFPIT GLHGLTHLKL TGNHALQSLI SSENFPELKV IEMPYAYQCC 490 500 510 520 530 540 AFGVCENAYK ISNQWNKGDN SSMDDLHKKD AGMFQAQDER DLEDFLLDFE EDLKALHSVQ 550 560 570 580 590 600 CSPSPGPFKP CEHLLDGWLI RIGVWTIAVL ALTCNALVTS TVFRSPLYIS PIKLLIGVIA 610 620 630 640 650 660 AVNMLTGVSS AVLAGVDAFT FGSFARHGAW WENGVGCHVI GFLSIFASES SVFLLTLAAL 670 680 690 700 710 720 ERGFSVKYSA KFETKAPFSS LKVIILLCAL LALTMAAVPL LGGSKYGASP LCLPLPFGEP 730 740 750 760 770 780 STMGYMVALI LLNSLCFLMM TIAYTKLYCN LDKGDLENIW DCSMVKHIAL LLFTNCILNC 790 800 810 820 830 840 PVAFLSFSSL INLTFISPEV IKFILLVVVP LPACLNPLLY ILFNPHFKED LVSLRKQTYV 850 860 870 880 890 900 WTRSKHPSLM SINSDDVEKQ SCDSTQALVT FTSSSITYDL PPSSVPSPAY PVTESCHLSS VAFVPCL
	Isoform 2 [UniParc]. Checksum: 50B293FCFCAED440	FASTA	883	97,404
	10 20 30 40 50 60 MDTSRLGVLL SLPVLLQLAT GGSSPRSGVL LRGCPTHCHC EPDGRMLLRV DCSDLGLSEL 70 80 90 100 110 120 PSNLSVFTSY LDLSMNNISQ LLPNPLPSLR FLEELRLAGN ALTYIPKGAF TGLYSLKVLM 130 140 150 160 170 180 LQNNQLRHVP TEALQNLRSL QSLRLDANHI SYVPPSCFSG LHSLRHLWLD DNALTEIPVQ 190 200 210 220 230 240 AFRSLSALQA MTLALNKIHH IPDYAFGNLS SLVVLHLHNN RIHSLGKKCF DGLHSLETLD 250 260 270 280 290 300 LNYNNLDEFP TAIRTLSNLK ELHFYDNPIQ FVGRSAFQHL PELRTLTLNG ASQITEFPDL 310 320 330 340 350 360 TGTANLESLT LTGAQISSLP QTVCNQLPNL QVLDLSYNLL EDLPSFSVCQ KLQKIDLRHN 370 380 390 400 410 420 EIYEIKVDTF QQLLSLRSLN LAWNKIAIIH PNAFSTLPSL IKLDLSSNLL SSFPITGLHG 430 440 450 460 470 480 LTHLKLTGNH ALQSLISSEN FPELKVIEMP YAYQCCAFGV CENAYKISNQ WNKGDNSSMD 490 500 510 520 530 540 DLHKKDAGMF QAQDERDLED FLLDFEEDLK ALHSVQCSPS PGPFKPCEHL LDGWLIRIGV 550 560 570 580 590 600 WTIAVLALTC NALVTSTVFR SPLYISPIKL LIGVIAAVNM LTGVSSAVLA GVDAFTFGSF 610 620 630 640 650 660 ARHGAWWENG VGCHVIGFLS IFASESSVFL LTLAALERGF SVKYSAKFET KAPFSSLKVI 670 680 690 700 710 720 ILLCALLALT MAAVPLLGGS KYGASPLCLP LPFGEPSTMG YMVALILLNS LCFLMMTIAY 730 740 750 760 770 780 TKLYCNLDKG DLENIWDCSM VKHIALLLFT NCILNCPVAF LSFSSLINLT FISPEVIKFI 790 800 810 820 830 840 LLVVVPLPAC LNPLLYILFN PHFKEDLVSL RKQTYVWTRS KHPSLMSINS DDVEKQSCDS 850 860 870 880 TQALVTFTSS SITYDLPPSS VPSPAYPVTE SCHLSSVAFV PCL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and cloning of an orphan G protein-coupled receptor of the glycoprotein hormone receptor subfamily." McDonald T., Wang R., Bailey W., Xie G., Chen F., Caskey C.T., Liu Q. Biochem. Biophys. Res. Commun. 247:266-270(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Characterization of two LGR genes homologous to gonadotropin and thyrotropin receptors with extracellular leucine-rich repeats and a G protein-coupled, seven-transmembrane region." Hsu S.Y., Liang S.-G., Hsueh A.J.W. Mol. Endocrinol. 12:1830-1845(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[3]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT ALA-666.
[5]	"Overexpression of orphan G-protein-coupled receptor, Gpr49, in human hepatocellular carcinomas with beta-catenin mutations." Yamamoto Y., Sakamoto M., Fujii G., Tsuiji H., Kenetaka K., Asaka M., Hirohashi S. Hepatology 37:528-533(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"Identification of overexpression of orphan G protein-coupled receptor GPR49 in human colon and ovarian primary tumors." McClanahan T., Koseoglu S., Smith K., Grein J., Gustafson E., Black S., Kirschmeier P., Samatar A.A. Cancer Biol. Ther. 5:419-426(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Immunostaining of Lgr5, an intestinal stem cell marker, in normal and premalignant human gastrointestinal tissue." Becker L., Huang Q., Mashimo H. ScientificWorldJournal 8:1168-1176(2008) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF062006 mRNA. Translation: AAC28019.1. AF061444 mRNA. Translation: AAC77911.1. 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.
IPI	IPI00021131. IPI00940760.
PIR	JE0176.
RefSeq	NP_001264155.1. NM_001277226.1. NP_003658.1. NM_003667.3.
UniGene	Hs.658889.
3D structure databases
ProteinModelPortal	O75473.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000266674.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	O75473.
Proteomic databases
PaxDb	O75473.
PRIDE	O75473.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000266674; ENSP00000266674; ENSG00000139292. ENST00000540815; ENSP00000441035; ENSG00000139292.
GeneID	8549.
KEGG	hsa:8549.
UCSC	uc001swl.3. human. uc001swm.3. human.
Organism-specific databases
CTD	8549.
GeneCards	GC12P071833.
HGNC	HGNC:4504. LGR5.
HPA	HPA012530.
MIM	606667. gene.
neXtProt	NX_O75473.
PharmGKB	PA28894.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4886.
HOGENOM	HOG000231829.
HOVERGEN	HBG031675.
InParanoid	O75473.
KO	K04308.
OMA	FNPHFKE.
OrthoDB	EOG46143B.
PhylomeDB	O75473.
Gene expression databases
ArrayExpress	O75473.
Bgee	O75473.
CleanEx	HS_LGR5.
Genevestigator	O75473.
GermOnline	ENSG00000139292. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR002131. Gphrmn_rcpt. IPR001611. Leu-rich_rpt. IPR003591. Leu-rich_rpt_typical-subtyp. IPR000372. LRR-contain_N. IPR026906. LRR_5. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. PF00560. LRR_1. 1 hit. PF13306. LRR_5. 1 hit. PF01462. LRRNT. 1 hit. [Graphical view]
PRINTS	PR00373. GLYCHORMONER. PR00237. GPCRRHODOPSN.
SMART	SM00369. LRR_TYP. 8 hits. SM00013. LRRNT. 1 hit. [Graphical view]
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. False negative. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. PS51450. LRR. 15 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	8549.
NextBio	32032.
SOURCE	Search...

Entry information

Entry name

LGR5_HUMAN

Accession

Primary (citable) accession number: O75473
Secondary accession number(s): Q4VAM0, Q4VAM2, Q9UP75

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2002
Last sequence update:	November 1, 1998
Last modified:	May 29, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.