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P22888

- LSHR_HUMAN

UniProt

P22888 - LSHR_HUMAN

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Protein

Lutropin-choriogonadotropic hormone receptor

Gene

LHCGR

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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

GO - Molecular functioni

  1. choriogonadotropin hormone binding Source: BHF-UCL
  2. choriogonadotropin hormone receptor activity Source: BHF-UCL
  3. luteinizing hormone receptor activity Source: InterPro

GO - Biological processi

  1. activation of adenylate cyclase activity Source: BHF-UCL
  2. cellular response to gonadotropin stimulus Source: BHF-UCL
  3. cognition Source: UniProt
  4. development of secondary male sexual characteristics Source: Ensembl
  5. G-protein coupled receptor signaling pathway Source: ProtInc
  6. G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
  7. male genitalia development Source: ProtInc
  8. male gonad development Source: ProtInc
  9. ovarian follicle development Source: Ensembl
  10. phospholipase C-activating G-protein coupled receptor signaling pathway Source: BHF-UCL
  11. positive regulation of cAMP-mediated signaling Source: BHF-UCL
  12. positive regulation of inositol trisphosphate biosynthetic process Source: BHF-UCL
  13. regulation of steroid hormone biosynthetic process Source: Ensembl
  14. seminiferous tubule development Source: Ensembl
  15. spermatogenesis Source: Ensembl
  16. uterus development Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_16942. Hormone ligand-binding receptors.
REACT_19327. G alpha (s) signalling events.
SignaLinkiP22888.

Names & Taxonomyi

Protein namesi
Recommended name:
Lutropin-choriogonadotropic hormone receptor
Short name:
LH/CG-R
Alternative name(s):
Luteinizing hormone receptor
Short name:
LHR
Short name:
LSH-R
Gene namesi
Name:LHCGR
Synonyms:LCGR, LGR2, LHRHR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:6585. LHCGR.

Subcellular locationi

GO - Cellular componenti

  1. endosome Source: ProtInc
  2. integral component of plasma membrane Source: BHF-UCL
  3. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Familial male precocious puberty (FMPP) [MIM:176410]: In FMPP the receptor is constitutively activated.11 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti368 – 3681L → 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. 1 Publication
VAR_062338
Natural varianti373 – 3731A → V in FMPP. 1 Publication
VAR_003553
Natural varianti398 – 3981M → T in FMPP. 1 Publication
VAR_003554
Natural varianti457 – 4571L → R in FMPP. 1 Publication
VAR_010156
Natural varianti542 – 5421I → L in FMPP.
VAR_010157
Natural varianti564 – 5641D → G in FMPP. 1 Publication
VAR_010159
Natural varianti568 – 5681A → V in FMPP. 2 Publications
VAR_003555
Natural varianti571 – 5711M → I in FMPP. 1 Publication
VAR_003556
Natural varianti572 – 5721A → V in FMPP. 1 Publication
VAR_003557
Natural varianti575 – 5751I → L in FMPP.
VAR_010160
Natural varianti577 – 5771T → I in FMPP. 2 Publications
VAR_003558
Natural varianti578 – 5781D → E in FMPP.
VAR_010161
Natural varianti578 – 5781D → G in FMPP. 2 Publications
VAR_003559
Natural varianti578 – 5781D → Y in FMPP.
VAR_010163
Natural varianti581 – 5811C → R in FMPP.
VAR_010164
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.10 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti131 – 1311C → R in LHR; Leydig cell hypoplasia type 2. 1 Publication
VAR_010154
Natural varianti144 – 1441V → 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. 1 Publication
Corresponds to variant rs121912539 [ dbSNP | Ensembl ].
VAR_062336
Natural varianti152 – 1521I → T in LHR; reveals a marked impairment of human chorionic gonadotropin binding and signal transduction. 1 Publication
VAR_062337
Natural varianti343 – 3431C → 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. 1 Publication
VAR_010155
Natural varianti354 – 3541E → K in LHR; Leydig cell hypoplasia type 1. 1 Publication
VAR_003552
Natural varianti502 – 5021L → P in LHR; Leydig cell hypoplasia type 1; shows reduced cAMP production and ligand binding; receptor trafficking is not affected by the mutation. 1 Publication
VAR_062339
Natural varianti543 – 5431C → 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. 1 Publication
VAR_010158
Natural varianti593 – 5931A → P in LHR; Leydig cell hypoplasia type 1; abolishes signal transduction. 1 Publication
VAR_003560
Natural varianti608 – 6092Missing in LHR; Leydig cell hypoplasia type 1. 1 Publication
VAR_003561
Natural varianti616 – 6161S → Y in LHR; Leydig cell hypoplasia type 1; micropenis. 1 Publication
VAR_003562
Natural varianti625 – 6251I → K in LHR; Leydig cell hypoplasia type 2. 1 Publication
VAR_003563

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi643 – 6431C → G: Loss of palmitoylation. 1 Publication
Mutagenesisi644 – 6441C → G: Loss of palmitoylation. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi152790. gene+phenotype.
176410. phenotype.
238320. phenotype.
Orphaneti3000. 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.
PharmGKBiPA30357.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626Sequence AnalysisAdd
BLAST
Chaini27 – 699673Lutropin-choriogonadotropic hormone receptorPRO_0000012780Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi99 – 991N-linked (GlcNAc...)Sequence Analysis
Glycosylationi174 – 1741N-linked (GlcNAc...)Sequence Analysis
Glycosylationi195 – 1951N-linked (GlcNAc...)Sequence Analysis
Glycosylationi291 – 2911N-linked (GlcNAc...)Sequence Analysis
Glycosylationi299 – 2991N-linked (GlcNAc...)Sequence Analysis
Glycosylationi313 – 3131N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi439 ↔ 514PROSITE-ProRule annotation
Lipidationi643 – 6431S-palmitoyl cysteine1 Publication
Lipidationi644 – 6441S-palmitoyl cysteine1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP22888.
PRIDEiP22888.

PTM databases

PhosphoSiteiP22888.

Expressioni

Tissue specificityi

Gonadal and thyroid cells.

Gene expression databases

BgeeiP22888.
CleanExiHS_LHCGR.
ExpressionAtlasiP22888. baseline and differential.
GenevestigatoriP22888.

Organism-specific databases

HPAiCAB009814.

Interactioni

Protein-protein interaction databases

BioGridi110161. 4 interactions.
STRINGi9606.ENSP00000294954.

Structurei

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LUTmodel-A51-232[»]
1XULmodel-C51-232[»]
ProteinModelPortaliP22888.
SMRiP22888. Positions 54-645.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini27 – 363337ExtracellularSequence AnalysisAdd
BLAST
Topological domaini386 – 39510CytoplasmicSequence Analysis
Topological domaini417 – 43923ExtracellularSequence AnalysisAdd
BLAST
Topological domaini463 – 48220CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini506 – 52520ExtracellularSequence AnalysisAdd
BLAST
Topological domaini550 – 57021CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini595 – 60511ExtracellularSequence AnalysisAdd
BLAST
Topological domaini628 – 69972CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei364 – 38522Helical; Name=1Sequence AnalysisAdd
BLAST
Transmembranei396 – 41621Helical; Name=2Sequence AnalysisAdd
BLAST
Transmembranei440 – 46223Helical; Name=3Sequence AnalysisAdd
BLAST
Transmembranei483 – 50523Helical; Name=4Sequence AnalysisAdd
BLAST
Transmembranei526 – 54924Helical; Name=5Sequence AnalysisAdd
BLAST
Transmembranei571 – 59424Helical; Name=6Sequence AnalysisAdd
BLAST
Transmembranei606 – 62722Helical; Name=7Sequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini27 – 6640LRRNTAdd
BLAST
Repeati96 – 11520LRR 1Add
BLAST
Repeati124 – 14522LRR 2Add
BLAST
Repeati149 – 17123LRR 3Add
BLAST
Repeati175 – 19622LRR 4Add
BLAST
Repeati198 – 22023LRR 5Add
BLAST
Repeati223 – 24422LRR 6Add
BLAST

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.PROSITE-ProRule annotation
Contains 6 LRR (leucine-rich) repeats.Curated
Contains 1 LRRNT domain.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG285844.
GeneTreeiENSGT00760000119088.
HOGENOMiHOG000045902.
HOVERGENiHBG003521.
InParanoidiP22888.
KOiK04248.
OMAiIYFAVQN.
OrthoDBiEOG73BVCG.
PhylomeDBiP22888.
TreeFamiTF316814.

Family and domain databases

Gene3Di1.20.1070.10. 1 hit.
InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002131. Gphrmn_rcpt_fam.
IPR000372. LRR-contain_N.
IPR026906. LRR_5.
IPR002273. LSH_rcpt.
[Graphical view]
PANTHERiPTHR24372. PTHR24372. 1 hit.
PTHR24372:SF1. PTHR24372:SF1. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
PF13306. LRR_5. 2 hits.
[Graphical view]
PRINTSiPR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.
PR01144. LSHRECEPTOR.
SMARTiSM00013. LRRNT. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Note: Additional isoforms seem to exist.

Isoform Long (identifier: P22888-1) [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
MKQRFSALQL LKLLLLLQPP LPRALREALC PEPCNCVPDG ALRCPGPTAG
60 70 80 90 100
LTRLSLAYLP VKVIPSQAFR GLNEVIKIEI SQIDSLERIE ANAFDNLLNL
110 120 130 140 150
SEILIQNTKN LRYIEPGAFI NLPRLKYLSI CNTGIRKFPD VTKVFSSESN
160 170 180 190 200
FILEICDNLH ITTIPGNAFQ GMNNESVTLK LYGNGFEEVQ SHAFNGTTLT
210 220 230 240 250
SLELKENVHL EKMHNGAFRG ATGPKTLDIS STKLQALPSY GLESIQRLIA
260 270 280 290 300
TSSYSLKKLP SRETFVNLLE ATLTYPSHCC AFRNLPTKEQ NFSHSISENF
310 320 330 340 350
SKQCESTVRK VNNKTLYSSM LAESELSGWD YEYGFCLPKT PRCAPEPDAF
360 370 380 390 400
NPCEDIMGYD FLRVLIWLIN ILAIMGNMTV LFVLLTSRYK LTVPRFLMCN
410 420 430 440 450
LSFADFCMGL YLLLIASVDS QTKGQYYNHA IDWQTGSGCS TAGFFTVFAS
460 470 480 490 500
ELSVYTLTVI TLERWHTITY AIHLDQKLRL RHAILIMLGG WLFSSLIAML
510 520 530 540 550
PLVGVSNYMK VSICFPMDVE TTLSQVYILT ILILNVVAFF IICACYIKIY
560 570 580 590 600
FAVRNPELMA TNKDTKIAKK MAILIFTDFT CMAPISFFAI SAAFKVPLIT
610 620 630 640 650
VTNSKVLLVL FYPINSCANP FLYAIFTKTF QRDFFLLLSK FGCCKRRAEL
660 670 680 690
YRRKDFSAYT SNCKNGFTGS NKPSQSTLKL STLHCQGTAL LDKTRYTEC
Length:699
Mass (Da):78,643
Last modified:December 15, 2009 - v4
Checksum:i2E3D93F4621BA842
GO
Isoform Short (identifier: P22888-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:636
Mass (Da):71,615
Checksum:i969918F83E700C85
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti7 – 71A → P in AAA70231. (PubMed:2293030)Curated
Sequence conflicti19 – 191P → A in AAA70231. (PubMed:2293030)Curated
Sequence conflicti27 – 282EA → R in AAA70231. (PubMed:2293030)Curated
Sequence conflicti44 – 518CPGPTAGL → APAPRPS in AAA70231. (PubMed:2293030)Curated
Sequence conflicti68 – 681A → S in AAA70231. (PubMed:2293030)Curated
Sequence conflicti124 – 1241R → G in AAA59515. (PubMed:2244890)Curated
Sequence conflicti124 – 1241R → G in CAA59234. (PubMed:7556872)Curated
Sequence conflicti262 – 2632RE → KQ in AAA70231. (PubMed:2293030)Curated
Sequence conflicti270 – 2701E → R in AAA70231. (PubMed:2293030)Curated
Sequence conflicti274 – 2741T → H in AAA70231. (PubMed:2293030)Curated
Sequence conflicti290 – 2901Q → L in AAA70231. (PubMed:2293030)Curated
Sequence conflicti311 – 32313Missing in AAA70231. (PubMed:2293030)CuratedAdd
BLAST
Sequence conflicti448 – 4481F → L in AAA70231. (PubMed:2293030)Curated
Sequence conflicti540 – 5401F → L in AAA70231. (PubMed:2293030)Curated
Sequence conflicti649 – 6491E → DP in AAA70231. (PubMed:2293030)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti18 – 181Q → QLQ May be associated with earlier age of onset of breast cancer and poor prognosis. 2 Publications
VAR_003549
Natural varianti131 – 1311C → R in LHR; Leydig cell hypoplasia type 2. 1 Publication
VAR_010154
Natural varianti144 – 1441V → 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. 1 Publication
Corresponds to variant rs121912539 [ dbSNP | Ensembl ].
VAR_062336
Natural varianti152 – 1521I → T in LHR; reveals a marked impairment of human chorionic gonadotropin binding and signal transduction. 1 Publication
VAR_062337
Natural varianti284 – 2841N → S.1 Publication
VAR_003550
Natural varianti291 – 2911N → S.
Corresponds to variant rs12470652 [ dbSNP | Ensembl ].
VAR_055922
Natural varianti306 – 3061S → N.1 Publication
VAR_003551
Natural varianti312 – 3121N → S.2 Publications
Corresponds to variant rs2293275 [ dbSNP | Ensembl ].
VAR_060737
Natural varianti343 – 3431C → 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. 1 Publication
VAR_010155
Natural varianti354 – 3541E → K in LHR; Leydig cell hypoplasia type 1. 1 Publication
VAR_003552
Natural varianti368 – 3681L → 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. 1 Publication
VAR_062338
Natural varianti373 – 3731A → V in FMPP. 1 Publication
VAR_003553
Natural varianti398 – 3981M → T in FMPP. 1 Publication
VAR_003554
Natural varianti457 – 4571L → R in FMPP. 1 Publication
VAR_010156
Natural varianti502 – 5021L → P in LHR; Leydig cell hypoplasia type 1; shows reduced cAMP production and ligand binding; receptor trafficking is not affected by the mutation. 1 Publication
VAR_062339
Natural varianti542 – 5421I → L in FMPP.
VAR_010157
Natural varianti543 – 5431C → 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. 1 Publication
VAR_010158
Natural varianti564 – 5641D → G in FMPP. 1 Publication
VAR_010159
Natural varianti564 – 5641D → N in a breast cancer sample; somatic mutation. 1 Publication
VAR_035764
Natural varianti568 – 5681A → V in FMPP. 2 Publications
VAR_003555
Natural varianti571 – 5711M → I in FMPP. 1 Publication
VAR_003556
Natural varianti572 – 5721A → V in FMPP. 1 Publication
VAR_003557
Natural varianti575 – 5751I → L in FMPP.
VAR_010160
Natural varianti577 – 5771T → I in FMPP. 2 Publications
VAR_003558
Natural varianti578 – 5781D → E in FMPP.
VAR_010161
Natural varianti578 – 5781D → G in FMPP. 2 Publications
VAR_003559
Natural varianti578 – 5781D → H in Leydig cell tumor; somatic mutation; causes receptor activation and precocious puberty. 1 Publication
VAR_010162
Natural varianti578 – 5781D → Y in FMPP.
VAR_010163
Natural varianti581 – 5811C → R in FMPP.
VAR_010164
Natural varianti593 – 5931A → P in LHR; Leydig cell hypoplasia type 1; abolishes signal transduction. 1 Publication
VAR_003560
Natural varianti608 – 6092Missing in LHR; Leydig cell hypoplasia type 1. 1 Publication
VAR_003561
Natural varianti616 – 6161S → Y in LHR; Leydig cell hypoplasia type 1; micropenis. 1 Publication
VAR_003562
Natural varianti625 – 6251I → K in LHR; Leydig cell hypoplasia type 2. 1 Publication
VAR_003563

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei227 – 28963Missing in isoform Short. CuratedVSP_001962Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M63108 mRNA. Translation: AAA59515.1.
S57793 mRNA. Translation: AAB19917.2.
M73746 mRNA. Translation: AAA70231.1.
X84753
, 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.
CCDSiCCDS1842.1. [P22888-1]
PIRiA36243. QRHUUT.
RefSeqiNP_000224.2. NM_000233.3. [P22888-1]
UniGeneiHs.468490.

Genome annotation databases

EnsembliENST00000294954; ENSP00000294954; ENSG00000138039. [P22888-1]
GeneIDi3973.
KEGGihsa:3973.
UCSCiuc002rwu.4. human. [P22888-1]

Polymorphism databases

DMDMi281185513.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

GRIS

Glycoprotein-hormone Receptors Information System

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Sequence-structure-function-analysis of glycoprotein hormone receptors

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M63108 mRNA. Translation: AAA59515.1 .
S57793 mRNA. Translation: AAB19917.2 .
M73746 mRNA. Translation: AAA70231.1 .
X84753
, 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 .
CCDSi CCDS1842.1. [P22888-1 ]
PIRi A36243. QRHUUT.
RefSeqi NP_000224.2. NM_000233.3. [P22888-1 ]
UniGenei Hs.468490.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1LUT model - A 51-232 [» ]
1XUL model - C 51-232 [» ]
ProteinModelPortali P22888.
SMRi P22888. Positions 54-645.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110161. 4 interactions.
STRINGi 9606.ENSP00000294954.

Chemistry

ChEMBLi CHEMBL1854.
DrugBanki DB06719. Buserelin.
DB00050. Cetrorelix.
DB00097. Choriogonadotropin alfa.
DB00014. Goserelin.
DB00044. Lutropin alfa.
DB00032. Menotropins.
GuidetoPHARMACOLOGYi 254.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei P22888.

Polymorphism databases

DMDMi 281185513.

Proteomic databases

PaxDbi P22888.
PRIDEi P22888.

Protocols and materials databases

DNASUi 3973.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000294954 ; ENSP00000294954 ; ENSG00000138039 . [P22888-1 ]
GeneIDi 3973.
KEGGi hsa:3973.
UCSCi uc002rwu.4. human. [P22888-1 ]

Organism-specific databases

CTDi 3973.
GeneCardsi GC02M048862.
HGNCi HGNC:6585. LHCGR.
HPAi CAB009814.
MIMi 152790. gene+phenotype.
176410. phenotype.
238320. phenotype.
neXtProti NX_P22888.
Orphaneti 3000. 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.
PharmGKBi PA30357.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG285844.
GeneTreei ENSGT00760000119088.
HOGENOMi HOG000045902.
HOVERGENi HBG003521.
InParanoidi P22888.
KOi K04248.
OMAi IYFAVQN.
OrthoDBi EOG73BVCG.
PhylomeDBi P22888.
TreeFami TF316814.

Enzyme and pathway databases

Reactomei REACT_16942. Hormone ligand-binding receptors.
REACT_19327. G alpha (s) signalling events.
SignaLinki P22888.

Miscellaneous databases

GeneWikii Luteinizing_hormone/choriogonadotropin_receptor.
GenomeRNAii 3973.
NextBioi 15574.
PROi P22888.
SOURCEi Search...

Gene expression databases

Bgeei P22888.
CleanExi HS_LHCGR.
ExpressionAtlasi P22888. baseline and differential.
Genevestigatori P22888.

Family and domain databases

Gene3Di 1.20.1070.10. 1 hit.
InterProi IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002131. Gphrmn_rcpt_fam.
IPR000372. LRR-contain_N.
IPR026906. LRR_5.
IPR002273. LSH_rcpt.
[Graphical view ]
PANTHERi PTHR24372. PTHR24372. 1 hit.
PTHR24372:SF1. PTHR24372:SF1. 1 hit.
Pfami PF00001. 7tm_1. 1 hit.
PF13306. LRR_5. 2 hits.
[Graphical view ]
PRINTSi PR00373. GLYCHORMONER.
PR00237. GPCRRHODOPSN.
PR01144. LSHRECEPTOR.
SMARTi SM00013. LRRNT. 1 hit.
[Graphical view ]
PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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.
    , 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. 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. 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.

Entry informationi

Entry nameiLSHR_HUMAN
AccessioniPrimary (citable) accession number: P22888
Secondary accession number(s): Q14751, Q15996, Q9UEW9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: December 15, 2009
Last modified: October 29, 2014
This is version 174 of the entry and version 4 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 2
    Human chromosome 2: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

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