[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). TISSUE=Pituitary; DOI=10.1016/0006-291X(92)91556-6; PubMed=1333190 [NCBI, ExPASy, EBI, Israel, Japan] Kakar S.S., Musgrove L.C., Devor D.C., Sellers J.C., Neill J.D.; "Cloning, sequencing, and expression of human gonadotropin releasing hormone (GnRH) receptor."; Biochem. Biophys. Res. Commun. 189:289-295(1992).
[2]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). TISSUE=Pituitary; DOI=10.1016/0303-7207(93)90278-R; PubMed=8386108 [NCBI, ExPASy, EBI, Israel, Japan] Chi L., Zhou W., Prikhozhan A., Flanagan C.A., Davidson J.S., Golembo M., Illing N., Millar R.P., Sealfon S.C.; "Cloning and characterization of the human GnRH receptor."; Mol. Cell. Endocrinol. 91:R1-R6(1993).
[3]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). DOI=10.1016/0303-7207(94)90196-1; PubMed=7534732 [NCBI, ExPASy, EBI, Israel, Japan] Kakar S.S., Grizzle W.E., Neill J.D.; "The nucleotide sequences of human GnRH receptors in breast and ovarian tumors are identical with that found in pituitary."; Mol. Cell. Endocrinol. 106:145-149(1994).
[4]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). DOI=10.1530/eje.0.1370183; PubMed=9272108 [NCBI, ExPASy, EBI, Israel, Japan] Kakar S.S.; "Molecular structure of the human gonadotropin-releasing hormone receptor gene."; Eur. J. Endocrinol. 137:183-192(1997).
[5]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). TISSUE=Pituitary; DOI=10.1210/me.11.9.1305; PubMed=9259321 [NCBI, ExPASy, EBI, Israel, Japan] Grosse R., Schoneberg T., Schultz G., Gudermann T.; "Inhibition of gonadotropin-releasing hormone receptor signaling by expression of a splice variant of the human receptor."; Mol. Endocrinol. 11:1305-1318(1997).
[6]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). TISSUE=Testis; Kopatz S.A., Aronstam R.S., Sharma S.V.; "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."; Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
[7]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[8]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 247-328 (ISOFORM 1). PubMed=10366411 [NCBI, ExPASy, EBI, Israel, Japan] Kottler M.L., Bergametti F., Carre M.C., Morice S., Decoret E., Lagarde J.P., Starzec A., Counis R.; "Tissue-specific pattern of variant transcripts of the human gonadotropin-releasing hormone receptor gene."; Eur. J. Endocrinol. 140:561-569(1999).
[9]	VARIANTS HH ARG-106 AND GLN-262. DOI=10.1056/NEJM199711273372205; PubMed=9371856 [NCBI, ExPASy, EBI, Israel, Japan] de Roux N., Young J., Misrahi M., Genet R., Chanson P., Schaison G., Milgrom E.; "A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor."; N. Engl. J. Med. 337:1597-1602(1997).
[10]	VARIANTS HH GLN-262 AND CYS-284, AND CHARACTERIZATION OF VARIANTS HH GLN-262 AND CYS-284. DOI=10.1038/ng0198-14; PubMed=9425890 [NCBI, ExPASy, EBI, Israel, Japan] Layman L.C., Cohen D.P., Jin M., Xie J., Li Z., Reindollar R.H., Bolbolan S., Bick D.P., Sherins R.R., Duck L.W., Musgrove L.C., Sellers J.C., Neill J.D.; "Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism."; Nat. Genet. 18:14-15(1998).
[11]	VARIANTS HH ARG-106; ARG-217 AND GLN-262, AND CHARACTERIZATION OF VARIANTS HH ARG-106; ARG-217 AND GLN-262. DOI=10.1210/jc.84.2.567; PubMed=10022417 [NCBI, ExPASy, EBI, Israel, Japan] de Roux N., Young J., Brailly-Tabard S., Misrahi M., Milgrom E., Schaison G.; "The same molecular defects of the gonadotropin-releasing hormone receptor determine a variable degree of hypogonadism in affected kindred."; J. Clin. Endocrinol. Metab. 84:567-572(1999).
[12]	VARIANTS HH ASP-129 AND GLN-262, AND CHARACTERIZATION OF VARIANT HH ASP-129. DOI=10.1210/jc.84.3.990; PubMed=10084584 [NCBI, ExPASy, EBI, Israel, Japan] Caron P., Chauvin S., Christin-Maitre S., Bennet A., Lahlou N., Counis R., Bouchard P., Kottler M.-L.; "Resistance of hypogonadic patients with mutated GnRH receptor genes to pulsatile GnRH administration."; J. Clin. Endocrinol. Metab. 84:990-996(1999).
[13]	VARIANT HH ARG-168, AND CHARACTERIZATION OF VARIANT HH ARG-168. DOI=10.1210/jc.84.10.3811; PubMed=10523035 [NCBI, ExPASy, EBI, Israel, Japan] Pralong F.P., Gomez F., Castillo E., Cotecchia S., Abuin L., Aubert M.L., Portmann L., Gaillard R.C.; "Complete hypogonadotropic hypogonadism associated with a novel inactivating mutation of the gonadotropin-releasing hormone receptor."; J. Clin. Endocrinol. Metab. 84:3811-3816(1999).
[14]	VARIANT FERTILE EUNUCH SYNDROME ARG-106. DOI=10.1210/jc.86.6.2470; PubMed=11397842 [NCBI, ExPASy, EBI, Israel, Japan] Pitteloud N., Boepple P.A., DeCruz S., Valkenburgh S.B., Crowley W.F. Jr., Hayes F.J.; "The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor."; J. Clin. Endocrinol. Metab. 86:2470-2475(2001).
[15]	VARIANT HH LYS-90. PubMed=11318785 [NCBI, ExPASy, EBI, Israel, Japan] Soederlund D., Canto P., de la Chesnaye E., Ulloa-Aguirre A., Mendez J.P.; "A novel homozygous mutation in the second transmembrane domain of the gonadotrophin releasing hormone receptor gene."; Clin. Endocrinol. (Oxf.) 54:493-498(2001).
[16]	VARIANTS HH LYS-10; ARG-106 AND HIS-139, AND CHARACTERIZATION OF VARIANTS HH LYS-10; ARG-106 AND HIS-139. DOI=10.1210/jc.86.6.2680; PubMed=11397871 [NCBI, ExPASy, EBI, Israel, Japan] Costa E.M.F., Bedecarrats G.Y., Mendonca B.B., Arnhold I.J.P., Kaiser U.B., Latronico A.C.; "Two novel mutations in the gonadotropin-releasing hormone receptor gene in Brazilian patients with hypogonadotropic hypogonadism and normal olfaction."; J. Clin. Endocrinol. Metab. 86:2680-2686(2001).
[17]	CHARACTERIZATION OF VARIANT HH LYS-90. DOI=10.1210/jc.87.5.2144; PubMed=11994356 [NCBI, ExPASy, EBI, Israel, Japan] Maya-Nunez G., Janovick J.A., Ulloa-Aguirre A., Soederlund D., Conn P.M., Mendez J.P.; "Molecular basis of hypogonadotropic hypogonadism: restoration of mutant (E(90)K) GnRH receptor function by a deletion at a distant site."; J. Clin. Endocrinol. Metab. 87:2144-2149(2002).
[18]	VARIANT HH THR-171, AND CHARACTERIZATION OF VARIANT HH THR-171. DOI=10.1210/jc.2002-020005; PubMed=12679486 [NCBI, ExPASy, EBI, Israel, Japan] Karges B., Karges W., Mine M., Ludwig L., Kuehne R., Milgrom E., de Roux N.; "Mutation Ala(171)Thr stabilizes the gonadotropin-releasing hormone receptor in its inactive conformation, causing familial hypogonadotropic hypogonadism."; J. Clin. Endocrinol. Metab. 88:1873-1879(2003).

Comments

FUNCTION: Receptor for gonadotropin releasing hormone (GnRH) that mediate the action of GnRH to stimulate the secretion of the gonadotropic hormones (LH and FSH). This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Isoform 2 may act a an inhibitor of GnRH-R signaling.
SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.

ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.

Name	1
Isoform ID	P30968-1
This is the isoform sequence displayed in this entry.

Name	2
Synonyms	Truncated
Isoform ID	P30968-2
Features which should be applied to build the isoform sequence: VSP_001914.

TISSUE SPECIFICITY: Pituitary, ovary, testis, breast and prostate but not in liver and spleen.
DISEASE: Defects in GNRHR are a cause of hypogonadotropic hypogonadism (HH) [MIM:146110]. HH is a clinical disorder defined as the selective failure of the neuroendocrine components of the reproductive system in the absence of an anatomic or functional cause. The classical clinical and biochemical features of HH include the absence of pubertal development by age 18 years in males, prepubertal sex steroids, and low or inappropriately normal gonadotropin levels. In males, the presence of microphallus and/or cryptorchidism in hypogonadotropic hypogonadism subjects attests to an in utero deficiency of androgens. However, there is a wide clinical spectrum in both the time of onset and the completeness of this syndrome.
DISEASE: Defects in GNRHR are a cause of fertile eunuch syndrome [MIM:228300]. Fertile eunuch syndrome is a mild phenotypic form of HH going with the presence of normal testicular size and some degree of spermatogenesis.
SIMILARITY: Belongs to the G-protein coupled receptor 1 family [view classification].
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=GNRHR";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

L03380; AAA35918.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
L07949; AAA35917.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S60587; AAB26287.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S77472; AAB33884.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF001952; AAB71348.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF001950; AAB71348.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF001951; AAB71348.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
Z81148; CAB03541.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY392011; AAR92228.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC113546; AAI13547.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
Z99995; CAB17082.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

JC1353; JC1353.

RefSeq

NP_000397.1; -.
NP_001012781.1; -.

UniGene

Hs.407587

3D structure databases

ModBase

P30968.

Protein family/group databases

GPCRDB

P30968; GNRHR_HUMAN.

Organism-specific databases

HIX0031415; -.

HGNC:4421; GNRHR.

138850; gene. [NCBI / EBI]
146110; phenotype. [NCBI / EBI]
228300; phenotype. [NCBI / EBI]

Orphanet

432; Hypogonadism, hypogonadotropic, congenital, normosmic.
478; Kallmann syndrome.

PharmGKB

PA28800; -.

GeneCards

P30968.

Gene expression databases

ArrayExpress

P30968; -.

CleanEx

HS_GNRHR; -.

GermOnline

ENSG00000109163; Homo sapiens.

Ontologies

GO:0005887;	Cellular component: integral to plasma membrane (traceable author statement from UniProtKB).
GO:0004968;	Molecular function: gonadotropin-releasing hormone receptor activity (traceable author statement from ProtInc).
GO:0007186;	Biological process: G-protein coupled receptor protein signaling pathway (traceable author statement from ProtInc).
GO:0007275;	Biological process: multicellular organismal development (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR015693; GnRH_recept.
IPR000276; GPCR_Rhodpsn.
IPR017452; GPCR_Rhodpsn_supfam.
IPR001658; GphnRH_rcpt.
Graphical view of domain structure.

PANTHER

PTHR19264:SF53; GnRH_recept; 1.

Pfam

PF00001; 7tm_1; 1.
Pfam graphical view of domain structure.

PRINTS

PR00529; GNADOTRPHINR.
PR00237; GPCRRHODOPSN.

PROSITE

PS00237; G_PROTEIN_RECEP_F1_1; 1.
PS50262; G_PROTEIN_RECEP_F1_2; 1.
PROSITE graphical view of domain structure (profiles).

BLOCKS

P30968.

Genome annotation databases

Ensembl

ENSG00000109163; Homo sapiens. [Contig view]

GeneID

2798; -.

KEGG

hsa:2798; -.

Phylogenomic databases

HOGENOM

P30968; -.

HOVERGEN

P30968; -.

Other

DrugBank

DB00106; Abarelix.
DB00050; Cetrorelix.
DB01406; Danazol.
DB00644; Gonadorelin.
DB00007; Leuprolide.
DB00666; Nafarelin.

GNRHR; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Alternative splicing; Cell membrane; Disease mutation; G-protein coupled receptor; Glycoprotein; Membrane; Receptor; Transducer; Transmembrane.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 328`	`328`	`Gonadotropin-releasing hormone receptor.`	`PRO_0000069487`
`TOPO_DOM`	`1 38`	`38`	`Extracellular (Potential).`
`TRANSMEM`	`39 58`	`20`	`1 (Potential).`
`TOPO_DOM`	`59 77`	`19`	`Cytoplasmic (Potential).`
`TRANSMEM`	`78 97`	`20`	`2 (Potential).`
`TOPO_DOM`	`98 115`	`18`	`Extracellular (Potential).`
`TRANSMEM`	`116 137`	`22`	`3 (Potential).`
`TOPO_DOM`	`138 164`	`27`	`Cytoplasmic (Potential).`
`TRANSMEM`	`165 184`	`20`	`4 (Potential).`
`TOPO_DOM`	`185 212`	`28`	`Extracellular (Potential).`
`TRANSMEM`	`213 232`	`20`	`5 (Potential).`
`TOPO_DOM`	`233 281`	`49`	`Cytoplasmic (Potential).`
`TRANSMEM`	`282 300`	`19`	`6 (Potential).`
`TOPO_DOM`	`301 306`	`6`	`Extracellular (Potential).`
`TRANSMEM`	`307 326`	`20`	`7 (Potential).`
`TOPO_DOM`	`327 328`	`2`	`Cytoplasmic (Potential).`
`CARBOHYD`	`18 18`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`102 102`		`N-linked (GlcNAc...) (Potential).`
`DISULFID`	`114 196`		`By similarity.`
`VAR_SEQ`	`176 328`		`YIFRMIHLADSSGQTKVFSQCVTHCSFSQWWHQAFYNFFT` `FSCLFIIPLFIMLICNAKIIFTLTRVLHQDPHELQLNQSK` `NNIPRARLKTLKMTVAFATSFTVCWTPYYVLGIWYWFDPE` `MLNRLSDPVNHFFFLFAFLNPCFDPLIYGYFSL -> PLHHPSFHHADLQCKNHLHPDTGPSSGPPRTTTESVQEQY` `TKSTAEDSKNDGCICHFIYCLLDSLLCPRNLVLV (in isoform 2).`	`VSP_001914`
`VARIANT`	`10 10`	`1`	`N -> K (in HH; is able to bind GnRH but with a reduced affinity in vitro).`	`VAR_019311`
`VARIANT`	`90 90`	`1`	`E -> K (in HH; virtual abolition of GnRH agonist binding and agonist-stimulated phosphoinositide turnover; impairs GnRHR-effector coupling).`	`VAR_019312`
`VARIANT`	`106 106`	`1`	`Q -> R (in HH and fertile eunuch syndrome; decreases but does not eliminate GnRH binding).`	`VAR_019313`
`VARIANT`	`129 129`	`1`	`A -> D (in HH; complete loss of function).`	`VAR_019314`
`VARIANT`	`139 139`	`1`	`R -> H (in HH; completely eliminates detectable GnRH-binding activity and prevents GnRH-induced stimulation of inositol phosphate accumulation in vitro).`	`VAR_019315`
`VARIANT`	`168 168`	`1`	`S -> R (in HH; complete loss of the receptor-mediated signaling response).`	`VAR_019316`
`VARIANT`	`171 171`	`1`	`A -> T (in HH; complete loss of ligand binding and receptor activation; specific receptor binding of radioisotope-labeled GnRH ligand is undetectable in transfected cells).`	`VAR_019317`
`VARIANT`	`217 217`	`1`	`S -> R (in HH; altered hormone binding).`	`VAR_019318`
`VARIANT`	`262 262`	`1`	`R -> Q (in HH; minimal effects upon receptor affinity but expression decreased; altered activation of phospholipase C).`	`VAR_019319`
`VARIANT`	`284 284`	`1`	`Y -> C (in HH; minimal effects upon receptor affinity but receptor expression decreased).`	`VAR_019320`
`CONFLICT`	`247 247`		`H -> T (in Ref. 8).`

Sequence information

Length: 328 AA [This is the length of the unprocessed precursor]

Molecular weight: 37731 Da [This is the MW of the unprocessed precursor]

CRC64: D02B2EA2F4246D7B [This is a checksum on the sequence]

        10         20         30         40         50         60 
MANSASPEQN QNHCSAINNS IPLMQGNLPT LTLSGKIRVT VTFFLFLLSA TFNASFLLKL 

        70         80         90        100        110        120 
QKWTQKKEKG KKLSRMKLLL KHLTLANLLE TLIVMPLDGM WNITVQWYAG ELLCKVLSYL 

       130        140        150        160        170        180 
KLFSMYAPAF MMVVISLDRS LAITRPLALK SNSKVGQSMV GLAWILSSVF AGPQLYIFRM 

       190        200        210        220        230        240 
IHLADSSGQT KVFSQCVTHC SFSQWWHQAF YNFFTFSCLF IIPLFIMLIC NAKIIFTLTR 

       250        260        270        280        290        300 
VLHQDPHELQ LNQSKNNIPR ARLKTLKMTV AFATSFTVCW TPYYVLGIWY WFDPEMLNRL 

       310        320 
SDPVNHFFFL FAFLNPCFDP LIYGYFSL

P30968 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools