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LHCGR (luteinizing hormone/choriogonadotropin receptor)

Identity

Other namesLHR (Luteinizing hormone receptor).
LCGR
LGR2
LHCGR (luteinizing hormone/choriogonadotropin receptor)
LH/CG-R, LSH-R (lutropin-choriogonadotropic hormone receptor)
HGNC (Hugo) LHCGR
Location 2p21
Location_base_pair Starts at 48767417 and ends at 48836384 bp from pter ( according to hg18-Mar_2006)  [Mapping]
 
  Human LHR gene organization (Upper panel), 5' flanking regulatory domains and 176 bp promoter with its functional domains, associated transcription factors and silencing regulatory complex (HDAC/mSin3A) (lower panel). Triangle: multiple transcriptional start sites. PA: poly adenylation sites. Open arrow, up: activation, down: inhibition. ERE: estrogen responsive element. DR: direct repeat. OR: orphan receptor. Sp1 I, Sp1 II: Sp1 sites. PIC: preinitiation complex.
Note The LHR belongs to the glycoprotein hormone receptor subfamily, with leucine rich repeat motifs, of the G protein-coupled receptor family (GPCR).

DNA/RNA

 
  Schematic representation of human LHR variants, as deduced from the alternative splicing of the transcripts.
Description The genomic size of human LHR gene is about 80 Kb and consists of 11 coding exons separated by 10 introns. At least three alternatively spliced variants of the hLHR (deletion of exon 8 or 9 or 10) were reported.
Transcription Multiple LHR mRNA transcriptional start sites are located within the -176 bp TATA-less 5' flanking promoter domain. Additional upstream transcriptional start sites (> -176 bp) were identified in human testicular mRNA and human choriocarcinoma JAR cell. EREhs (-161 to -171 bp) and upstream sequences (-177 to -2056 bp) are inhibitory. Activation of the human LHR promoter through Sp1/3 factors at Sp1 sites is negatively regulated by cross talk among the transcription factors EAR3/COUP-TFI, Sp1, TFIIB, and independently by histone deacetylase-mSin3A complex at the Sp1 I site.
Pseudogene No known pseudogenes

Protein

 
  Legend diagram: EC: Extracellular domain. TM: Transmembrane domain. IC: Intracellular domain. Triangle box: the putative signal peptide. Vertical lines indicate exons. Normal amino acid residue (white circle). X: Stop. Activating mutations noted as green in familial male precocious puberty (FMPP)-autosomal dominant and/or sporadic male-limited precocious puberty (SMPP) or other; inactivating mutations in Leydig cells hypoplasia (LCH) noted in yellow. Polymorphism noted in blue. Underlined: N-glycosylation sites.
Description The cDNA for the human LHR encodes 699 amino acids. The receptor is composed of two functional units: the extracellular hormone-binding domain and the seven-membrane transmembrane/cytoplasmic module, which is the anchoring unit that transduces the signal initiated in the extracellular domain and couples to G proteins. The large extracellular domain binds LH and hCG with high affinity.
Expression LHR is predominantly expressed in gonads. The LHR has also been identified in several non-gonadal tissues, including human nonpregnant uterus, placenta, fallopian tubes, uterine vessels, umbilical cord, brain, and lymphocyte.
Localisation Predominantly localized in the cell membrane.
Function The LHR mediates gonadotropin signaling and triggers intracellular responses that participate in gonadal maturation and function, as well as in the regulation of steroidogenesis and gametogenesis. Luteinizing hormone through its surface receptors on the Leydig cell maintains general metabolic processes and steroidogenic enzymes to regulate the production of androgens. In the ovary, LH promotes follicular development, at stages beyond early antral follicles including the formation of preovulatory follicles and corpora lutea.
Homology The percent identity below represents identity using Global pairwise alignment function (GAP): M. musculus: 83.2; R. Norvegicus: 85.2; D. Melanogaster: 40.1; A. gambiae: 39.7; C. elegans: 30.7

Mutations

Note Polymorphism detected in exon 1, 8, 10 and 11. Nucleotides insertion/deletion, single nucleotide mutation detected in exon 1, 5, 7, 8, 10 and 11. Deletions of exon 8 or 9 or 10 (splice variants).

Polymorphism: N291S, N312S. Deletion - L204, D355. Insertion at aa 18 - IQ

Activating mutation: A373V, M398T, L457R, I542L, D564G, A568V, M571I, A572V, I575L, T577I, D578G/Y/H/E, C581R

Inhibiting mutation: C131R, F194V, C343S, E354K, W491X, C543R, C545X, R554X, A593P, S616Y and I625K. Deletion - L608, V609, aa 203-227 (exon 8), aa 228-289 (exon 9), and aa 290-316 (exon 10). Insertion: aa18 - LLKLLLLLQLQ.

Implicated in

Note
  • Activating mutations: Human familial male precocious puberty (FMPP) and sporadic male-limited precocious puberty (SMPP)- gonadotropin independent precocious puberty with Leydig cell hyperplasia.
  • Inactivating mutations: Male: Leydig cell hypoplasia (LCH) with various degree of hypogonadism severity, pseudohermaphroditism. Female: Infertility hypergonadotropic hypogonadism and primary amenorrhea.
  • Association of FMPP and testicular seminoma (D578G) - 1 patient or nodular Leydig cell hyperplasia (D578G) - 1 patient.
  • Somatic mutation of the LHR (D578H) with Leydig cell adenoma and no history of FMPP (3 patients).
  • Mutations may be linked to breast cancer prognosis (18LQ insert)
    •   

    External links

    Nomenclature
    HGNC (Hugo)LHCGR   6585
    Entrez_Gene (NCBI)LHCGR  3973  luteinizing hormone/choriogonadotropin receptor
    Cards
    AtlasLHRID288
    GeneCards (Weizmann)LHCGR
    Ensembl (Hinxton)ENSG00000138039 [Gene_View]  LHCGR [Vega]
    AceView (NCBI)LHCGR
    Genatlas (Paris)LHCGR
    euGene (Indiana)3973
    SOURCE (Stanford)NM_000233
    Gene Expression (Array Express) ENSG00000138039
    Genomic and cartography
    GoldenPath (UCSC)LHCGR  -  2p21   chr2:48767417-48836384 -  2p21   [Description]    (hg18-Mar_2006)
    EnsemblLHCGR - 2p21 [CytoView]
    Mapping of homologs : NCBILHCGR [Mapview]
    OMIM152790   176410   238320   
    Gene and transcription
    Gene : Genbank (Entrez)AK123498 BC156303 BC157028 BX101581 DA376746
    Reference sequence (RefSeq transcript) :SRSNM_000233
    Reference transcript : EntrezNM_000233
    RefSeq genomic : SRSAC_000045 AC_000134 NC_000002 NG_008193 NT_022184 NW_001838769 NW_927719
    RefSeq genomic : EntrezAC_000045 AC_000134 NC_000002 NG_008193 NT_022184 NW_001838769 NW_927719
    Consensus coding sequences : CCDS NCBILHCGR
    Cluster EST : UnigeneHs.468490 [ SRS ] Hs.468490 [ NCBI ]
    Alternative Splicing : Fast-db (Paris)5040
    Protein : pattern, domain, 3D structure
    Protein : UniProt/SwissProtP22888 (SRS) P22888 (Expasy) P22888 (Uniprot)
    With graphics : InterProP22888
    Splice isoforms : VarSplice FASTAP22888(VarSplice FASTA)
    Domaine pattern : Prosite (SRS)G_PROTEIN_RECEP_F1_1 (PS00237)    G_PROTEIN_RECEP_F1_2 (PS50262)   
    Domain pattern : Prosite (Expaxy)G_PROTEIN_RECEP_F1_1 (PS00237)    G_PROTEIN_RECEP_F1_2 (PS50262)   
    Domains : Interpro (SRS)7TM_GPCR_Rhodpsn    GPCR_Rhodpsn_supfam    Gphrmn_rcpt    LRR-contain_N    LSH_rcpt   
    Domains : Interpro (EBI)7TM_GPCR_Rhodpsn    GPCR_Rhodpsn_supfam    Gphrmn_rcpt    LRR-contain_N    LSH_rcpt   
    Related proteins : CluSTrP22888
    Domain families : Pfam SRS7tm_1 (PF00001)   
    Domain families : Pfam Sanger7tm_1 (PF00001)   
    Domain families : Pfam NCBIpfam00001   
    Domain families : Smart EMBLLRRNT (SM00013)  
    Blocks (Seattle)P22888
    Crystal structure of protein : PDB SRS1LUT    1XUL   
    Crystal structure of protein : PDBSum1LUT    1XUL   
    Crystal structure of protein : IMB1LUT    1XUL   
    Crystal structure of protein : PDB RSDB1LUT    1XUL   
    HPRD01073
    Protein Interaction databases
    DIP (DOE-UCLA)P22888
    IntAct (EBI)P22888
    Polymorphism : SNP, mutations, diseases
    Single Nucleotide Polymorphism (SNP) : dbSNP NCBILHCGR
    SNP : GeneSNP UtahLHCGR
    SNP : HGBaseLHCGR
    Genetic variants : HAPMAPLHCGR
    Somatic Mutations in Cancer : COSMICLHCGR 
    Mutations and Diseases : HGMDLHCGR
    Hereditary diseases : OMIM152790    176410    238320   
    Hereditary diseases : GENETests152790    176410    238320   
    Diseases : Genetic AssociationLHCGR
    General knowledge
    Homologs : HomoloGeneLHCGR
    Homology/Alignments : Family Browser UCSCLHCGR
    Phylogenetic Trees/Animal Genes : TreeFamLHCGR
    Chemical/Protein Interactions : CTD3973
    Keywords Ontology : AmiGOreceptor activity  lutropin-choriogonadotropic hormone receptor activity  extracellular space  nucleus  cytoplasm  lysosome  endosome  endoplasmic reticulum  plasma membrane  integral to plasma membrane  protein targeting to lysosome  signal transduction  G-protein signaling, coupled to cAMP nucleotide second messenger  activation of adenylate cyclase activity  activation of phospholipase C activity by G-protein coupled receptor protein signaling pathway coupled to IP3 second messenger  peptide receptor activity, G-protein coupled  male gonad development  hormone-mediated signaling pathway  peptide hormone binding  male genitalia development  intrinsic to external side of plasma membrane  response to drug  luteinizing hormone signaling pathway  protein homodimerization activity  receptor complex  positive regulation of hormone biosynthetic process  arachidonic acid secretion  regulation of steroid biosynthetic process  positive regulation of calcium-mediated signaling  ATPase binding  positive regulation of release of sequestered calcium ion into cytosol  
    Keywords Ontology : EGO-EBIreceptor activity  lutropin-choriogonadotropic hormone receptor activity  extracellular space  nucleus  cytoplasm  lysosome  endosome  endoplasmic reticulum  plasma membrane  integral to plasma membrane  protein targeting to lysosome  signal transduction  G-protein signaling, coupled to cAMP nucleotide second messenger  activation of adenylate cyclase activity  activation of phospholipase C activity by G-protein coupled receptor protein signaling pathway coupled to IP3 second messenger  peptide receptor activity, G-protein coupled  male gonad development  hormone-mediated signaling pathway  peptide hormone binding  male genitalia development  intrinsic to external side of plasma membrane  response to drug  luteinizing hormone signaling pathway  protein homodimerization activity  receptor complex  positive regulation of hormone biosynthetic process  arachidonic acid secretion  regulation of steroid biosynthetic process  positive regulation of calcium-mediated signaling  ATPase binding  positive regulation of release of sequestered calcium ion into cytosol  
    Pathways : BIOCARTA
    Pathways : KEGGCalcium signaling pathwayNeuroactive ligand-receptor interaction
    Other databases
    Probes
    Probes : ImagenesLHCGR Related clones (RZPD - Berlin)
    Literature
    PubMed127 Pubmed reference(s) in Entrez
    PubGeneLHCGR

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    REVIEW articlesautomatic search in PubMed
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    Contributor(s)

    Written08-2004Chon-Hwa Tsai-Morris, Maria L Dufau
    Endocrinology Section, NICHD, NIH, Bldg. 49 Rm. 6A-36, Bethesda MD 20892-4510, USA

    Citation

    This paper should be referenced as such :
    Tsai-Morris CH, Dufau ML . LHCGR (luteinizing hormone/choriogonadotropin receptor). Atlas Genet Cytogenet Oncol Haematol. August 2004 .
    URL : http://AtlasGeneticsOncology.org/Genes/LHRID288.html

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    indexed on : Sat Feb 27 10:52:45 CET 2010
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