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P22888 (LSHR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 171. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lutropin-choriogonadotropic hormone receptor

Short name=LH/CG-R
Alternative name(s):
Luteinizing hormone receptor
Short name=LHR
Short name=LSH-R
Gene names
Name:LHCGR
Synonyms:LCGR, LGR2, LHRHR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length699 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Gonadal and thyroid cells.

Involvement in disease

Familial male precocious puberty (FMPP) [MIM:176410]: In FMPP the receptor is constitutively activated.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19 Ref.20 Ref.24 Ref.26

Luteinizing hormone resistance (LHR) [MIM:238320]: An autosomal recessive disorder characterized by unresponsiveness to luteinizing hormone, defective sexual development in males, and defective follicular development and ovulation, amenorrhea and infertility in females. Two forms of the disorder have been defined in males. Type 1 is a severe form characterized by complete 46,XY male pseudohermaphroditism, low testosterone and high luteinizing hormone levels, total lack of responsiveness to luteinizing and chorionic gonadotropin hormones, lack of breast development, and absent development of secondary male sex characteristics. Type 2, a milder form, displays a broader range of phenotypic expression ranging from micropenis to severe hypospadias.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.18 Ref.21 Ref.22 Ref.25 Ref.28 Ref.29 Ref.31 Ref.32 Ref.34

Sequence similarities

Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.

Contains 6 LRR (leucine-rich) repeats.

Contains 1 LRRNT domain.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainLeucine-rich repeat
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Traceable author statement Ref.29. Source: ProtInc

G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger

Traceable author statement Ref.18. Source: ProtInc

activation of adenylate cyclase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular response to gonadotropin stimulus

Inferred from sequence or structural similarity. Source: BHF-UCL

cognition

Inferred from mutant phenotype PubMed 23227193. Source: UniProt

development of secondary male sexual characteristics

Inferred from electronic annotation. Source: Ensembl

male genitalia development

Traceable author statement Ref.29. Source: ProtInc

male gonad development

Traceable author statement Ref.18. Source: ProtInc

ovarian follicle development

Inferred from electronic annotation. Source: Ensembl

phospholipase C-activating G-protein coupled receptor signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of cAMP-mediated signaling

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of inositol trisphosphate biosynthetic process

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of steroid hormone biosynthetic process

Inferred from electronic annotation. Source: Ensembl

seminiferous tubule development

Inferred from electronic annotation. Source: Ensembl

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

uterus development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentendosome

Traceable author statement PubMed 10617611. Source: ProtInc

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionchoriogonadotropin hormone binding

Inferred from sequence or structural similarity. Source: BHF-UCL

choriogonadotropin hormone receptor activity

Inferred from sequence or structural similarity. Source: BHF-UCL

luteinizing 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]

Note: Additional isoforms seem to exist.
Isoform Long (identifier: P22888-1)

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 Short (identifier: P22888-2)

The sequence of this isoform differs from the canonical sequence as follows:
     227-289: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 699673Lutropin-choriogonadotropic hormone receptor
PRO_0000012780

Regions

Topological domain27 – 363337Extracellular Potential
Transmembrane364 – 38522Helical; Name=1; Potential
Topological domain386 – 39510Cytoplasmic Potential
Transmembrane396 – 41621Helical; Name=2; Potential
Topological domain417 – 43923Extracellular Potential
Transmembrane440 – 46223Helical; Name=3; Potential
Topological domain463 – 48220Cytoplasmic Potential
Transmembrane483 – 50523Helical; Name=4; Potential
Topological domain506 – 52520Extracellular Potential
Transmembrane526 – 54924Helical; Name=5; Potential
Topological domain550 – 57021Cytoplasmic Potential
Transmembrane571 – 59424Helical; Name=6; Potential
Topological domain595 – 60511Extracellular Potential
Transmembrane606 – 62722Helical; Name=7; Potential
Topological domain628 – 69972Cytoplasmic Potential
Domain27 – 6640LRRNT
Repeat96 – 11520LRR 1
Repeat124 – 14522LRR 2
Repeat149 – 17123LRR 3
Repeat175 – 19622LRR 4
Repeat198 – 22023LRR 5
Repeat223 – 24422LRR 6

Amino acid modifications

Lipidation6431S-palmitoyl cysteine Ref.7
Lipidation6441S-palmitoyl cysteine Ref.7
Glycosylation991N-linked (GlcNAc...) Potential
Glycosylation1741N-linked (GlcNAc...) Potential
Glycosylation1951N-linked (GlcNAc...) Potential
Glycosylation2911N-linked (GlcNAc...) Potential
Glycosylation2991N-linked (GlcNAc...) Potential
Glycosylation3131N-linked (GlcNAc...) Potential
Disulfide bond439 ↔ 514 By similarity

Natural variations

Alternative sequence227 – 28963Missing in isoform Short.
VSP_001962
Natural variant181Q → QLQ May be associated with earlier age of onset of breast cancer and poor prognosis.
VAR_003549
Natural variant1311C → R in LHR; Leydig cell hypoplasia type 2. Ref.22
VAR_010154
Natural variant1441V → F in LHR; Leydig cell hypoplasia type 1; exhibits a marked impairment of human chorionic gonadotropin binding; shows the absence of the glycosylated cell surface form; the mutant receptor is retained in the endoplasmic reticulum; mutant receptors do not migrate to the cell surface. Ref.32
Corresponds to variant rs121912539 [ dbSNP | Ensembl ].
VAR_062336
Natural variant1521I → T in LHR; reveals a marked impairment of human chorionic gonadotropin binding and signal transduction. Ref.34
VAR_062337
Natural variant2841N → S. Ref.23
VAR_003550
Natural variant2911N → S.
Corresponds to variant rs12470652 [ dbSNP | Ensembl ].
VAR_055922
Natural variant3061S → N. Ref.23
VAR_003551
Natural variant3121N → S. Ref.1 Ref.4
Corresponds to variant rs2293275 [ dbSNP | Ensembl ].
VAR_060737
Natural variant3431C → S in LHR; Leydig cell hypoplasia type 1; completely devoided of hormone-induced cAMP reporter gene activation; although initial translocation to the endoplasmic reticulum is normal translocation is halted or misrouted and the mutant does not reach the cell surface and cannot bind hormone. Ref.11
VAR_010155
Natural variant3541E → K in LHR; Leydig cell hypoplasia type 1. Ref.25
VAR_003552
Natural variant3681L → P in FMPP; cells expressing the mutation display up to a 12-fold increase in basal cAMP production compared with cells expressing the same number of cell surface wild-type receptor indicating constitutive activation of the mutant receptor. Ref.9
VAR_062338
Natural variant3731A → V in FMPP. Ref.24
VAR_003553
Natural variant3981M → T in FMPP. Ref.20
VAR_003554
Natural variant4571L → R in FMPP. Ref.26
VAR_010156
Natural variant5021L → P in LHR; Leydig cell hypoplasia type 1; shows reduced cAMP production and ligand binding; receptor trafficking is not affected by the mutation. Ref.31
VAR_062339
Natural variant5421I → L in FMPP.
VAR_010157
Natural variant5431C → R in LHR; Leydig cell hypoplasia type 1; completely devoided of hormone-induced cAMP reporter gene activation; although initial translocation to the endoplasmic reticulum is normal translocation is halted or misrouted and the mutant does not reach the cell surface and cannot bind hormone. Ref.11
VAR_010158
Natural variant5641D → G in FMPP. Ref.10
VAR_010159
Natural variant5641D → N in a breast cancer sample; somatic mutation. Ref.33
VAR_035764
Natural variant5681A → V in FMPP. Ref.9 Ref.17
VAR_003555
Natural variant5711M → I in FMPP. Ref.14
VAR_003556
Natural variant5721A → V in FMPP. Ref.16
VAR_003557
Natural variant5751I → L in FMPP.
VAR_010160
Natural variant5771T → I in FMPP. Ref.15 Ref.19
VAR_003558
Natural variant5781D → E in FMPP.
VAR_010161
Natural variant5781D → G in FMPP. Ref.13 Ref.14
VAR_003559
Natural variant5781D → H in Leydig cell tumor; somatic mutation; causes receptor activation and precocious puberty. Ref.30
VAR_010162
Natural variant5781D → Y in FMPP.
VAR_010163
Natural variant5811C → R in FMPP.
VAR_010164
Natural variant5931A → P in LHR; Leydig cell hypoplasia type 1; abolishes signal transduction. Ref.18
VAR_003560
Natural variant608 – 6092Missing in LHR; Leydig cell hypoplasia type 1.
VAR_003561
Natural variant6161S → Y in LHR; Leydig cell hypoplasia type 1; micropenis. Ref.21
VAR_003562
Natural variant6251I → K in LHR; Leydig cell hypoplasia type 2. Ref.29
VAR_003563

Experimental info

Mutagenesis6431C → G: Loss of palmitoylation. Ref.7
Mutagenesis6441C → G: Loss of palmitoylation. Ref.7
Sequence conflict71A → P in AAA70231. Ref.3
Sequence conflict191P → A in AAA70231. Ref.3
Sequence conflict27 – 282EA → R in AAA70231. Ref.3
Sequence conflict44 – 518CPGPTAGL → APAPRPS in AAA70231. Ref.3
Sequence conflict681A → S in AAA70231. Ref.3
Sequence conflict1241R → G in AAA59515. Ref.1
Sequence conflict1241R → G in CAA59234. Ref.4
Sequence conflict262 – 2632RE → KQ in AAA70231. Ref.3
Sequence conflict2701E → R in AAA70231. Ref.3
Sequence conflict2741T → H in AAA70231. Ref.3
Sequence conflict2901Q → L in AAA70231. Ref.3
Sequence conflict311 – 32313Missing in AAA70231. Ref.3
Sequence conflict4481F → L in AAA70231. Ref.3
Sequence conflict5401F → L in AAA70231. Ref.3
Sequence conflict6491E → DP in AAA70231. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified December 15, 2009. Version 4.
Checksum: 2E3D93F4621BA842

FASTA69978,643
        10         20         30         40         50         60 
MKQRFSALQL LKLLLLLQPP LPRALREALC PEPCNCVPDG ALRCPGPTAG LTRLSLAYLP 

        70         80         90        100        110        120 
VKVIPSQAFR GLNEVIKIEI SQIDSLERIE ANAFDNLLNL SEILIQNTKN LRYIEPGAFI 

       130        140        150        160        170        180 
NLPRLKYLSI CNTGIRKFPD VTKVFSSESN FILEICDNLH ITTIPGNAFQ GMNNESVTLK 

       190        200        210        220        230        240 
LYGNGFEEVQ SHAFNGTTLT SLELKENVHL EKMHNGAFRG ATGPKTLDIS STKLQALPSY 

       250        260        270        280        290        300 
GLESIQRLIA TSSYSLKKLP SRETFVNLLE ATLTYPSHCC AFRNLPTKEQ NFSHSISENF 

       310        320        330        340        350        360 
SKQCESTVRK VNNKTLYSSM LAESELSGWD YEYGFCLPKT PRCAPEPDAF NPCEDIMGYD 

       370        380        390        400        410        420 
FLRVLIWLIN ILAIMGNMTV LFVLLTSRYK LTVPRFLMCN LSFADFCMGL YLLLIASVDS 

       430        440        450        460        470        480 
QTKGQYYNHA IDWQTGSGCS TAGFFTVFAS ELSVYTLTVI TLERWHTITY AIHLDQKLRL 

       490        500        510        520        530        540 
RHAILIMLGG WLFSSLIAML PLVGVSNYMK VSICFPMDVE TTLSQVYILT ILILNVVAFF 

       550        560        570        580        590        600 
IICACYIKIY FAVRNPELMA TNKDTKIAKK MAILIFTDFT CMAPISFFAI SAAFKVPLIT 

       610        620        630        640        650        660 
VTNSKVLLVL FYPINSCANP FLYAIFTKTF QRDFFLLLSK FGCCKRRAEL YRRKDFSAYT 

       670        680        690 
SNCKNGFTGS NKPSQSTLKL STLHCQGTAL LDKTRYTEC 

« Hide

Isoform Short [UniParc].

Checksum: 969918F83E700C85
Show »

FASTA63671,615

References

« Hide 'large scale' references
[1]"Cloning and sequencing of human LH/hCG receptor cDNA."
Minegish T., Nakamura K., Takakura Y., Miyamoto K., Hasegawa Y., Ibuki Y., Igarashi M.
Biochem. Biophys. Res. Commun. 172:1049-1054(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-312.
Tissue: Ovary.
[2]"Expression of human luteinizing hormone (LH) receptor: interaction with LH and chorionic gonadotropin from human but not equine, rat, and ovine species."
Jia X.-C., Oikawa M., Bo M., Tanaka T., Ny T., Boime I., Hsueh A.J.W.
Mol. Endocrinol. 5:759-768(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Ovary.
[3]"Isolation of TSH and LH/CG receptor cDNAs from human thyroid: regulation by tissue specific splicing."
Frazier A.L., Robbins L.S., Stork P.J., Sprengel R., Segaloff D.L., Cone R.D.
Mol. Endocrinol. 4:1264-1276(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Thyroid.
[4]"Structure of the human luteinizing hormone-choriogonadotropin receptor gene: unusual promoter and 5' non-coding regions."
Atger M., Misrahi M., Sar S., Leflem L., Dessen P., Milgrom E.
Mol. Cell. Endocrinol. 111:113-123(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-GLN-18 INS AND SER-312.
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Genomic distribution and gonadal mRNA expression of two human luteinizing hormone receptor exon 1 sequences in random populations."
Tsai-Morris C.-H., Geng Y., Buczko E., Dehejia A., Dufau M.L.
Hum. Hered. 49:48-51(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-54, VARIANT LEU-GLN-18 INS.
[7]"Evidence that palmitoylation of carboxyl terminus cysteine residues of the human luteinizing hormone receptor regulates postendocytic processing."
Munshi U.M., Clouser C.L., Peegel H., Menon K.M.
Mol. Endocrinol. 19:749-758(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PALMITOYLATION AT CYS-643 AND CYS-644, MUTAGENESIS OF CYS-643 AND CYS-644.
[8]"Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone-receptor interactions."
Jiang X., Dreano M., Buckler D.R., Cheng S., Ythier A., Wu H., Hendrickson W.A., el Tayar N.
Structure 3:1341-1353(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING OF 51-232.
[9]"Gonadotropin-independent precocious puberty due to luteinizing hormone receptor mutations in Brazilian boys: a novel constitutively activating mutation in the first transmembrane helix."
Latronico A.C., Shinozaki H., Guerra G. Jr., Pereira M.A.A., Lemos Marini S.H.V., Baptista M.T.M., Arnhold I.J.P., Fanelli F., Mendonca B.B., Segaloff D.L.
J. Clin. Endocrinol. Metab. 85:4799-4805(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS FMPP PRO-368 AND VAL-568, CHARACTERIZATION OF VARIANT FMPP PRO-368.
[10]"Nodular Leydig cell hyperplasia in a boy with familial male-limited precocious puberty."
Leschek E.W., Chan W.-Y., Diamond D.A., Kaefer M., Jones J., Barnes K.M., Cutler G.B. Jr.
J. Pediatr. 138:949-951(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FMPP GLY-564.
[11]"Mutant luteinizing hormone receptors in a compound heterozygous patient with complete Leydig cell hypoplasia: abnormal processing causes signaling deficiency."
Martens J.W.M., Lumbroso S., Verhoef-Post M., Georget V., Richter-Unruh A., Szarras-Czapnik M., Romer T.E., Brunner H.G., Themmen A.P.N., Sultan C.
J. Clin. Endocrinol. Metab. 87:2506-2513(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LHR SER-343 AND ARG-543, CHARACTERIZATION OF VARIANTS LHR SER-343 AND ARG-543.
[12]"Luteinizing hormone signaling and breast cancer: polymorphisms and age of onset."
Powell B.L., Piersma D., Kevenaar M.E., van Staveren I.L., Themmen A.P.N., Iacopetta B.J., Berns E.M.J.J.
J. Clin. Endocrinol. Metab. 88:1653-1657(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION OF VARIANT LEU-GLN-18 INS WITH AGE OF BREAST CANCER ONSET.
[13]"A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty."
Shenker A., Laue L., Kosugi S., Merendino J.J. Jr., Minegishi T., Cutler G.B. Jr.
Nature 365:652-654(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FMPP GLY-578.
[14]"Cosegregation of missense mutations of the luteinizing hormone receptor gene with familial male-limited precocious puberty."
Kremer H., Mariman E., Otten B.J., Moll G.W. Jr., Stoelinga G.B.A., Wit J.M., Jansen M., Drop S.L., Faas B., Ropers H.-H., Brunner H.G.
Hum. Mol. Genet. 2:1779-1783(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS FMPP ILE-571 AND GLY-578.
[15]"Characterization of heterogeneous mutations causing constitutive activation of the luteinizing hormone receptor in familial male precocious puberty."
Kosugi S., van Dop C., Geffner M.E., Rabl W., Carel J.-C., Chaussain J.-L., Mori T., Merendino J.J. Jr., Shenker A.
Hum. Mol. Genet. 4:183-188(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FMPP ILE-577.
[16]"A new constitutively activating point mutation in the luteinizing hormone/choriogonadotropin receptor gene in cases of male-limited precocious puberty."
Yano K., Saji M., Hidaka A., Moriya N., Okuno A., Kohn L.D., Cutler G.B. Jr.
J. Clin. Endocrinol. Metab. 80:1162-1168(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FMPP VAL-572.
[17]"A novel mutation of the luteinizing hormone receptor gene causing male gonadotropin-independent precocious puberty."
Latronico A.C., Anasti J., Arnhold I.J., Mendonca B.B., Domenice S., Albano M.C., Zachman K., Wajchenberg B.L., Tsigos C.
J. Clin. Endocrinol. Metab. 80:2490-2494(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FMPP VAL-568.
[18]"Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene."
Kremer H., Kraaij R., Toledo S.P.A., Post M., Fridman J.B., Hayashida C.Y., van Reen M., Milgrom E., Ropers H.-H., Mariman E., Themmen A.P.N., Brunner H.G.
Nat. Genet. 9:160-164(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LHR PRO-593.
[19]"A missense (T577I) mutation in the luteinizing hormone receptor gene associated with familial male-limited precocious puberty."
Cocco S., Meloni A., Marini M.G., Cao A., Moi P.
Hum. Mutat. 7:164-166(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FMPP ILE-577.
[20]"A new point mutation in the luteinising hormone receptor gene in familial and sporadic male limited precocious puberty: genotype does not always correlate with phenotype."
Evans B.A.J., Bowen D.J., Smith P.J., Clayton P.E., Gregory J.W.
J. Med. Genet. 33:143-147(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FMPP THR-398.
[21]"Testicular and ovarian resistance to luteinizing hormone caused by inactivating mutations of the luteinizing hormone-receptor gene."
Latronico A.C., Anasti J., Arnhold I.J.P., Rapaport R., Mendonca B.B., Bloise W., Castro M., Tsigos C., Chrousos G.P.
N. Engl. J. Med. 334:507-512(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LHR TYR-616.
[22]"Comparison of immunocytochemical and molecular features with the phenotype in a case of incomplete male pseudohermaphroditism associated with a mutation of the luteinizing hormone receptor."
Misrahi M., Meduri G., Pissard S., Bouvattier C., Beau I., Loosfelt H., Jolivet A., Rappaport R., Milgrom E., Bougneres P.
J. Clin. Endocrinol. Metab. 82:2159-2165(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LHR ARG-131.
[23]"Polymorphisms in the coding exons of the human luteinizing hormone receptor gene."
Wu S.-M., Jose M., Hallermeier K., Rennert O.M., Chan W.-Y.
Hum. Mutat. 11:333-334(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LEU-GLN-18 INS; SER-284 AND ASN-306.
[24]"A mutation in the first transmembrane domain of the lutropin receptor causes male precocious puberty."
Gromoll J., Partsch C.-J., Simoni M., Nordhoff V., Sippell W.G., Nieschlag E., Saxena B.B.
J. Clin. Endocrinol. Metab. 83:476-480(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FMPP VAL-373.
[25]"A novel mutation of the human luteinizing hormone receptor in 46XY and 46XX sisters."
Stavrou S.S., Zhu Y.S., Cai L.Q., Katz M.D., Herrera C., Defillo-Ricart M., Imperato-Mcginley J.
J. Clin. Endocrinol. Metab. 83:2091-2098(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LHR LYS-354.
[26]"A unique constitutively activating mutation in third transmembrane helix of luteinizing hormone receptor causes sporadic male gonadotropin-independent precocious puberty."
Latronico A.C., Abell A.N., Arnhold I.J., Liu X., Lins T.S., Brito V.N., Billerbeck A.E., Segaloff D.L., Mendonca B.B.
J. Clin. Endocrinol. Metab. 83:2435-2440(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FMPP ARG-457.
[27]"Evidences for an allelic variant of the human LC/CG receptor rather than a gene duplication: functional comparison of wild-type and variant receptors."
Rodien P., Cetani F., Costagliola S., Tonacchera M., Duprez L., Minegishi T., Govaerts C., Vassart G.
J. Clin. Endocrinol. Metab. 83:4431-4434(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LEU-GLN-18 INS.
[28]"A homozygous microdeletion in helix 7 of the luteinizing hormone receptor associated with familial testicular and ovarian resistance is due to both decreased cell surface expression and impaired effector activation by the cell surface receptor."
Latronico A.C., Chai Y., Arnhold I.J.P., Liu X., Mendonca B.B., Segaloff D.L.
Mol. Endocrinol. 12:442-450(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LHR 608-LEU-VAL-609 DEL.
[29]"A homozygous mutation in the luteinizing hormone receptor causes partial Leydig cell hypoplasia: correlation between receptor activity and phenotype."
Martens J.W., Verhoef-Post M., Abelin N., Ezabella M., Toledo S.P., Brunner H.G., Themmen A.P.
Mol. Endocrinol. 12:775-784(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LHR LYS-625.
[30]"Leydig-cell tumors caused by an activating mutation of the gene encoding the luteinizing hormone receptor."
Liu G., Duranteau L., Carel J.-C., Monroe J., Doyle D.A., Shenker A.
N. Engl. J. Med. 341:1731-1736(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LEYDIG CELL TUMOR HIS-578.
[31]"A novel missense homozygous inactivating mutation in the fourth transmembrane helix of the luteinizing hormone receptor in Leydig cell hypoplasia."
Leung M.Y.-K., Al-Muslim O., Wu S.-M., Aziz A., Inam S., Awadh M., Rennert O.M., Chan W.-Y.
Am. J. Med. Genet. A 130:146-153(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LHR PRO-502, CHARACTERIZATION OF VARIANT LCH PRO-502.
[32]"Leydig cell hypoplasia: absent luteinizing hormone receptor cell surface expression caused by a novel homozygous mutation in the extracellular domain."
Richter-Unruh A., Verhoef-Post M., Malak S., Homoki J., Hauffa B.P., Themmen A.P.N.
J. Clin. Endocrinol. Metab. 89:5161-5167(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LHR PHE-144, CHARACTERIZATION OF VARIANT LCH PHE-144.
[33]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-564.
[34]"A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism."
Qiao J., Han B., Liu B.-L., Chen X., Ru Y., Cheng K.-X., Chen F.-G., Zhao S.-X., Liang J., Lu Y.-L., Tang J.-F., Wu Y.-X., Wu W.-L., Chen J.-L., Chen M.-D., Song H.-D.
Hum. Mutat. 30:E855-E865(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LHR THR-152, CHARACTERIZATION OF VARIANT LHR THR-152.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M63108 mRNA. Translation: AAA59515.1.
S57793 mRNA. Translation: AAB19917.2.
M73746 mRNA. Translation: AAA70231.1.
X84753 expand/collapse EMBL AC list , X84754, X84755, X84756, X84757, X84758, X84759, X84760, X84761, X84762, X84763 Genomic DNA. Translation: CAA59234.1.
AC073082 Genomic DNA. No translation available.
AC087816 Genomic DNA. No translation available.
AF082076 Genomic DNA. Translation: AAC98291.1.
AF024642 Genomic DNA. Translation: AAB88417.1.
CCDSCCDS1842.1. [P22888-1]
PIRQRHUUT. A36243.
RefSeqNP_000224.2. NM_000233.3. [P22888-1]
UniGeneHs.468490.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LUTmodel-A51-232[»]
1XULmodel-C51-232[»]
ProteinModelPortalP22888.
SMRP22888. Positions 7-645.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110161. 4 interactions.
STRING9606.ENSP00000294954.

Chemistry

ChEMBLCHEMBL1854.
DrugBankDB00050. Cetrorelix.
DB00097. Choriogonadotropin alfa.
DB00014. Goserelin.
DB00044. Lutropin alfa.
DB00032. Menotropins.
GuidetoPHARMACOLOGY254.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP22888.

Polymorphism databases

DMDM281185513.

Proteomic databases

PaxDbP22888.
PRIDEP22888.

Protocols and materials databases

DNASU3973.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000294954; ENSP00000294954; ENSG00000138039. [P22888-1]
GeneID3973.
KEGGhsa:3973.
UCSCuc002rwu.4. human. [P22888-1]

Organism-specific databases

CTD3973.
GeneCardsGC02M048825.
HGNCHGNC:6585. LHCGR.
HPACAB009814.
MIM152790. gene+phenotype.
176410. phenotype.
238320. phenotype.
neXtProtNX_P22888.
Orphanet3000. Familial male-limited precocious puberty.
96265. Leydig cell hypoplasia due to complete LH resistance.
96266. Leydig cell hypoplasia due to partial LH resistance.
619. Primary ovarian failure.
PharmGKBPA30357.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG285844.
HOGENOMHOG000045902.
HOVERGENHBG003521.
InParanoidP22888.
KOK04248.
OMAIYFAVQN.
OrthoDBEOG73BVCG.
PhylomeDBP22888.
TreeFamTF316814.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkP22888.

Gene expression databases

ArrayExpressP22888.
BgeeP22888.
CleanExHS_LHCGR.
GenevestigatorP22888.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002131. Gphrmn_rcpt_fam.
IPR000372. LRR-contain_N.
IPR026906. LRR_5.
IPR002273. LSH_rcpt.
[Graphical view]
PANTHERPTHR24372. PTHR24372. 1 hit.
PTHR24372:SF1. PTHR24372:SF1. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
PF13306. LRR_5. 2 hits.
[Graphical view]
PRINTSPR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.
PR01144. LSHRECEPTOR.
SMARTSM00013. LRRNT. 1 hit.
[Graphical view]
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiLuteinizing_hormone/choriogonadotropin_receptor.
GenomeRNAi3973.
NextBio15574.
PROP22888.
SOURCESearch...

Entry information

Entry nameLSHR_HUMAN
AccessionPrimary (citable) accession number: P22888
Secondary accession number(s): Q14751, Q15996, Q9UEW9
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: December 15, 2009
Last modified: July 9, 2014
This is version 171 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries