LHCGR (luteinizing hormone/choriogonadotropin receptor)

Identity

Other names	LHR (Luteinizing hormone receptor).
	LCGR
	LGR2
	LHCGR (luteinizing hormone/choriogonadotropin receptor)
	LH/CG-R, LSH-R (lutropin-choriogonadotropic hormone receptor)
HGNC	LHCGR
Location	2p21
Location_base_pair	Starts at 48767417 and ends at 48836384 bp from pter ( according to hg18-Mar_2006).
	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	LHCGR   6585
Entrez_Gene	LHCGR  3973  luteinizing hormone/choriogonadotropin receptor
	Cards
Atlas	LHRID288
GeneCards	LHCGR
Ensembl	ENSG00000138039 [Gene_View]  LHCGR [Vega]
Genatlas	LHCGR
	Genomic and cartography
GoldenPath	LHCGR  -  2p21   chr2:48767417-48836384 -  2p21   [Description]    (hg18-Mar_2006)
Ensembl	LHCGR - 2p21 [CytoView]
NCBI	Mapview
OMIM	152790 Disease map [OMIM]
OMIM	176410 Disease map [OMIM]
HomoloGene	LHCGR
	Gene and transcription
Genbank	AK123498 [ ENTREZ ]
Genbank	BC156303 [ ENTREZ ]
Genbank	BC157028 [ ENTREZ ]
Genbank	BX101581 [ ENTREZ ]
Genbank	DA376746 [ ENTREZ ]
RefSeq	NM_000233 [ SRS ]    NM_000233 [ ENTREZ ]
RefSeq	AC_000045 [ SRS ]    AC_000045 [ ENTREZ ]
RefSeq	AC_000134 [ SRS ]    AC_000134 [ ENTREZ ]
RefSeq	NC_000002 [ SRS ]    NC_000002 [ ENTREZ ]
RefSeq	NG_008193 [ SRS ]    NG_008193 [ ENTREZ ]
RefSeq	NT_022184 [ SRS ]    NT_022184 [ ENTREZ ]
RefSeq	NW_001838769 [ SRS ]    NW_001838769 [ ENTREZ ]
RefSeq	NW_927719 [ SRS ]    NW_927719 [ ENTREZ ]
CCDS	LHCGR CCDS - NCBI
AceView	LHCGR AceView - NCBI
Unigene	Hs.468490 [ SRS ]    Hs.468490 [ NCBI ]
Fast-db	5040 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P22888 [ SRS]    P22888 [ EXPASY ]     P22888 [ INTERPRO ]     P22888 [ UNIPROT ] P22888 [ VarSplice FASTA ]
Prosite	PS00237 G_PROTEIN_RECEP_F1_1 [ SRS ]    PS00237 G_PROTEIN_RECEP_F1_1 [ Expasy ]
Prosite	PS50262 G_PROTEIN_RECEP_F1_2 [ SRS ]    PS50262 G_PROTEIN_RECEP_F1_2 [ Expasy ]
Interpro	IPR000276 GPCR_Rhodpsn [ SRS ]    IPR000276 GPCR_Rhodpsn [ EBI ]
Interpro	IPR017452 GPCR_Rhodpsn_supfam [ SRS ]    IPR017452 GPCR_Rhodpsn_supfam [ EBI ]
Interpro	IPR002131 Gphrmn_rcpt [ SRS ]    IPR002131 Gphrmn_rcpt [ EBI ]
Interpro	IPR000372 LRR_cys_N [ SRS ]    IPR000372 LRR_cys_N [ EBI ]
Interpro	IPR002273 LSH_rcpt [ SRS ]    IPR002273 LSH_rcpt [ EBI ]
CluSTr	P22888
Pfam	PF00001 7tm_1 [ SRS ]    PF00001 7tm_1 [ Sanger ]    pfam00001 [ NCBI-CDD ]
Smart	SM00013 LRRNT [EMBL]
Blocks	P22888
PDB	1LUT [ SRS ]    1LUT [ PdbSum ],   1LUT [ IMB ]   1LUT [ RSDB ]
PDB	1XUL [ SRS ]    1XUL [ PdbSum ],   1XUL [ IMB ]   1XUL [ RSDB ]
HPRD	01073
	Protein Interaction databases
DIP	P22888
IntAct	P22888
	Polymorphism : SNP, mutations, diseases
OMIM	152790    [ map ]
OMIM	176410    [ map ]
GENETests	152790
GENETests	176410
SNP	LHCGR [dbSNP-NCBI]
SNP	NM_000233 [SNP-NCI]
SNP	LHCGR [GeneSNPs - Utah]  LHCGR] [HGBASE - SRS]
HAPMAP	LHCGR [HAPMAP]
HGMD	LHCGR
Genetic Association	LHCGR
CDC HuGE	LHCGR
	General knowledge
Family Browser	LHCGR [UCSC Family Browser]
SOURCE	NM_000233
SMD	Hs.468490
SAGE	Hs.468490
GO	receptor activity [Amigo]  receptor activity
GO	lutropin-choriogonadotropic hormone receptor activity [Amigo]  lutropin-choriogonadotropic hormone receptor activity
GO	endosome [Amigo]  endosome
GO	plasma membrane [Amigo]  plasma membrane
GO	integral to plasma membrane [Amigo]  integral to plasma membrane
GO	signal transduction [Amigo]  signal transduction
GO	G-protein signaling, coupled to cyclic nucleotide second messenger [Amigo]  G-protein signaling, coupled to cyclic nucleotide second messenger
GO	male gonad development [Amigo]  male gonad development
GO	male genitalia development [Amigo]  male genitalia development
KEGG	Calcium signaling pathway
KEGG	Neuroactive ligand-receptor interaction
PubGene	LHCGR
TreeFam	LHCGR
CTD	3973 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	LHCGR Related clones (RZPD - Berlin)
	PubMed
PubMed	97 Pubmed reference(s) in Entrez

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Contributor(s)

Written	08-2004	Chon-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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Thu Nov 27 13:24:55 2008