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Protein

Gonadotropin-releasing hormone receptor

Gene

GNRHR

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

Functioni

Receptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This receptor mediates its action by association with G-proteins that activate a phosphatidylinositol-calcium second messenger system. Isoform 2 may act as an inhibitor of GnRH-R signaling.

GO - Molecular functioni

  • gonadotropin-releasing hormone receptor activity Source: ProtInc
  • peptide binding Source: GO_Central

GO - Biological processi

  • G-protein coupled receptor signaling pathway Source: ProtInc
  • multicellular organism development Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109163-MONOMER.
ReactomeiR-HSA-375281. Hormone ligand-binding receptors.
R-HSA-416476. G alpha (q) signalling events.

Protein family/group databases

TCDBi9.A.14.10.1. the g-protein-coupled receptor (gpcr) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Gonadotropin-releasing hormone receptor
Short name:
GnRH receptor
Short name:
GnRH-R
Gene namesi
Name:GNRHR
Synonyms:GRHR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:4421. GNRHR.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 38ExtracellularSequence analysisAdd BLAST38
Transmembranei39 – 58Helical; Name=1Sequence analysisAdd BLAST20
Topological domaini59 – 77CytoplasmicSequence analysisAdd BLAST19
Transmembranei78 – 97Helical; Name=2Sequence analysisAdd BLAST20
Topological domaini98 – 115ExtracellularSequence analysisAdd BLAST18
Transmembranei116 – 137Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini138 – 164CytoplasmicSequence analysisAdd BLAST27
Transmembranei165 – 184Helical; Name=4Sequence analysisAdd BLAST20
Topological domaini185 – 212ExtracellularSequence analysisAdd BLAST28
Transmembranei213 – 232Helical; Name=5Sequence analysisAdd BLAST20
Topological domaini233 – 281CytoplasmicSequence analysisAdd BLAST49
Transmembranei282 – 300Helical; Name=6Sequence analysisAdd BLAST19
Topological domaini301 – 306ExtracellularSequence analysis6
Transmembranei307 – 326Helical; Name=7Sequence analysisAdd BLAST20
Topological domaini327 – 328CytoplasmicSequence analysis2

GO - Cellular componenti

  • integral component of plasma membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Hypogonadotropic hypogonadism 7 with or without anosmia (HH7)11 Publications
The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in GNRHR as well as in other HH-associated genes including FGFR1 (PubMed:23643382).1 Publication
Disease descriptionA disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
See also OMIM:146110
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01931110N → K in HH7; is able to bind GnRH but with a reduced affinity in vitro. 1 PublicationCorresponds to variant rs104893843dbSNPEnsembl.1
Natural variantiVAR_07297018N → S in HH7. 1 PublicationCorresponds to variant rs774317793dbSNPEnsembl.1
Natural variantiVAR_07297137I → S in HH7. 1 Publication1
Natural variantiVAR_06996083L → V in HH7; the patient also carries a mutation in FGFR1. 1 Publication1
Natural variantiVAR_07297290E → D in HH7. 1 Publication1
Natural variantiVAR_01931290E → K in HH7; virtual abolition of GnRH agonist binding and agonist-stimulated phosphoinositide turnover; impairs GnRHR-effector coupling. 2 PublicationsCorresponds to variant rs104893844dbSNPEnsembl.1
Natural variantiVAR_019313106Q → R in HH7; some patients also carry mutations in FGFR1; decreases but does not eliminate GnRH binding. 6 PublicationsCorresponds to variant rs104893836dbSNPEnsembl.1
Natural variantiVAR_019314129A → D in HH7; complete loss of function. 2 PublicationsCorresponds to variant rs104893838dbSNPEnsembl.1
Natural variantiVAR_019315139R → H in HH7; completely eliminates detectable GnRH-binding activity and prevents GnRH-induced stimulation of inositol phosphate accumulation in vitro. 2 PublicationsCorresponds to variant rs104893842dbSNPEnsembl.1
Natural variantiVAR_072973146P → S in HH7. 1 PublicationCorresponds to variant rs144900788dbSNPEnsembl.1
Natural variantiVAR_019316168S → R in HH7; complete loss of the receptor-mediated signaling response. 1 PublicationCorresponds to variant rs104893840dbSNPEnsembl.1
Natural variantiVAR_019317171A → T in HH7; complete loss of ligand binding and receptor activation; specific receptor binding of radioisotope-labeled GnRH ligand is undetectable in transfected cells. 1 PublicationCorresponds to variant rs74452732dbSNPEnsembl.1
Natural variantiVAR_019318217S → R in HH7; altered hormone binding. 1 PublicationCorresponds to variant rs104893839dbSNPEnsembl.1
Natural variantiVAR_019319262R → Q in HH7; unknown pathological significance; some patients also carry mutations in FGFR1; minimal effects upon receptor affinity but expression decreased; altered activation of phospholipase C. 6 PublicationsCorresponds to variant rs104893837dbSNPEnsembl.1
Natural variantiVAR_072974266L → R in HH7; unknown pathological significance. 1 PublicationCorresponds to variant rs148499544dbSNPEnsembl.1
Natural variantiVAR_019320284Y → C in HH7; minimal effects upon receptor affinity but receptor expression decreased. 1 PublicationCorresponds to variant rs28933074dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism

Organism-specific databases

DisGeNETi2798.
MalaCardsiGNRHR.
MIMi146110. phenotype.
OpenTargetsiENSG00000109163.
Orphaneti432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBiPA28800.

Chemistry databases

ChEMBLiCHEMBL1855.
DrugBankiDB00106. Abarelix.
DB06719. Buserelin.
DB00050. Cetrorelix.
DB01406. Danazol.
DB06699. Degarelix.
DB06785. Ganirelix.
DB00644. Gonadorelin.
DB00014. Goserelin.
DB00007. Leuprolide.
DB00666. Nafarelin.
DB06825. Triptorelin.
GuidetoPHARMACOLOGYi256.

Polymorphism and mutation databases

BioMutaiGNRHR.
DMDMi399777.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000694871 – 328Gonadotropin-releasing hormone receptorAdd BLAST328

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi18N-linked (GlcNAc...)Sequence analysis1
Glycosylationi102N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi114 ↔ 196PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP30968.
PaxDbiP30968.
PRIDEiP30968.

Expressioni

Tissue specificityi

Pituitary, ovary, testis, breast and prostate but not in liver and spleen.

Gene expression databases

BgeeiENSG00000109163.
CleanExiHS_GNRHR.
GenevisibleiP30968. HS.

Interactioni

Protein-protein interaction databases

BioGridi109060. 2 interactors.
STRINGi9606.ENSP00000226413.

Chemistry databases

BindingDBiP30968.

Structurei

3D structure databases

ProteinModelPortaliP30968.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000119156.
HOGENOMiHOG000251590.
HOVERGENiHBG009082.
InParanoidiP30968.
KOiK04280.
OMAiVAWIMAG.
OrthoDBiEOG091G0ZDG.
PhylomeDBiP30968.
TreeFamiTF106499.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001658. GphnRH_fam_rcpt.
IPR027982. GphnRH_rcpt.
[Graphical view]
PANTHERiPTHR24241:SF22. PTHR24241:SF22. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00529. GNADOTRPHINR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P30968-1) [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
MANSASPEQN QNHCSAINNS IPLMQGNLPT LTLSGKIRVT VTFFLFLLSA
60 70 80 90 100
TFNASFLLKL QKWTQKKEKG KKLSRMKLLL KHLTLANLLE TLIVMPLDGM
110 120 130 140 150
WNITVQWYAG ELLCKVLSYL KLFSMYAPAF MMVVISLDRS LAITRPLALK
160 170 180 190 200
SNSKVGQSMV GLAWILSSVF AGPQLYIFRM IHLADSSGQT KVFSQCVTHC
210 220 230 240 250
SFSQWWHQAF YNFFTFSCLF IIPLFIMLIC NAKIIFTLTR VLHQDPHELQ
260 270 280 290 300
LNQSKNNIPR ARLKTLKMTV AFATSFTVCW TPYYVLGIWY WFDPEMLNRL
310 320
SDPVNHFFFL FAFLNPCFDP LIYGYFSL
Length:328
Mass (Da):37,731
Last modified:July 1, 1993 - v1
Checksum:iD02B2EA2F4246D7B
GO
Isoform 2 (identifier: P30968-2) [UniParc]FASTAAdd to basket
Also known as: Truncated

The sequence of this isoform differs from the canonical sequence as follows:
     176-328: YIFRMIHLAD...DPLIYGYFSL → PLHHPSFHHA...LLCPRNLVLV

Show »
Length:249
Mass (Da):27,727
Checksum:i5801B1C5E5FBA64A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti247H → T in CAB17082 (PubMed:10366411).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01931110N → K in HH7; is able to bind GnRH but with a reduced affinity in vitro. 1 PublicationCorresponds to variant rs104893843dbSNPEnsembl.1
Natural variantiVAR_07297018N → S in HH7. 1 PublicationCorresponds to variant rs774317793dbSNPEnsembl.1
Natural variantiVAR_07297137I → S in HH7. 1 Publication1
Natural variantiVAR_06996083L → V in HH7; the patient also carries a mutation in FGFR1. 1 Publication1
Natural variantiVAR_07297290E → D in HH7. 1 Publication1
Natural variantiVAR_01931290E → K in HH7; virtual abolition of GnRH agonist binding and agonist-stimulated phosphoinositide turnover; impairs GnRHR-effector coupling. 2 PublicationsCorresponds to variant rs104893844dbSNPEnsembl.1
Natural variantiVAR_019313106Q → R in HH7; some patients also carry mutations in FGFR1; decreases but does not eliminate GnRH binding. 6 PublicationsCorresponds to variant rs104893836dbSNPEnsembl.1
Natural variantiVAR_019314129A → D in HH7; complete loss of function. 2 PublicationsCorresponds to variant rs104893838dbSNPEnsembl.1
Natural variantiVAR_019315139R → H in HH7; completely eliminates detectable GnRH-binding activity and prevents GnRH-induced stimulation of inositol phosphate accumulation in vitro. 2 PublicationsCorresponds to variant rs104893842dbSNPEnsembl.1
Natural variantiVAR_072973146P → S in HH7. 1 PublicationCorresponds to variant rs144900788dbSNPEnsembl.1
Natural variantiVAR_019316168S → R in HH7; complete loss of the receptor-mediated signaling response. 1 PublicationCorresponds to variant rs104893840dbSNPEnsembl.1
Natural variantiVAR_019317171A → T in HH7; complete loss of ligand binding and receptor activation; specific receptor binding of radioisotope-labeled GnRH ligand is undetectable in transfected cells. 1 PublicationCorresponds to variant rs74452732dbSNPEnsembl.1
Natural variantiVAR_019318217S → R in HH7; altered hormone binding. 1 PublicationCorresponds to variant rs104893839dbSNPEnsembl.1
Natural variantiVAR_019319262R → Q in HH7; unknown pathological significance; some patients also carry mutations in FGFR1; minimal effects upon receptor affinity but expression decreased; altered activation of phospholipase C. 6 PublicationsCorresponds to variant rs104893837dbSNPEnsembl.1
Natural variantiVAR_072974266L → R in HH7; unknown pathological significance. 1 PublicationCorresponds to variant rs148499544dbSNPEnsembl.1
Natural variantiVAR_019320284Y → C in HH7; minimal effects upon receptor affinity but receptor expression decreased. 1 PublicationCorresponds to variant rs28933074dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001914176 – 328YIFRM…GYFSL → PLHHPSFHHADLQCKNHLHP DTGPSSGPPRTTTESVQEQY TKSTAEDSKNDGCICHFIYC LLDSLLCPRNLVLV in isoform 2. 1 PublicationAdd BLAST153

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L03380 mRNA. Translation: AAA35918.1.
L07949 mRNA. Translation: AAA35917.1.
S60587 mRNA. Translation: AAB26287.1.
S77472 mRNA. Translation: AAB33884.1.
AF001952, AF001950, AF001951 Genomic DNA. Translation: AAB71348.1.
Z81148 mRNA. Translation: CAB03541.1.
AY392011 mRNA. Translation: AAR92228.1.
BC113546 mRNA. Translation: AAI13547.1.
Z99995 Genomic DNA. Translation: CAB17082.1.
CCDSiCCDS3517.1. [P30968-1]
CCDS47064.1. [P30968-2]
PIRiJC1353.
RefSeqiNP_000397.1. NM_000406.2. [P30968-1]
NP_001012781.1. NM_001012763.1. [P30968-2]
UniGeneiHs.407587.

Genome annotation databases

EnsembliENST00000226413; ENSP00000226413; ENSG00000109163. [P30968-1]
ENST00000420975; ENSP00000397561; ENSG00000109163. [P30968-2]
GeneIDi2798.
KEGGihsa:2798.
UCSCiuc003hdm.4. human. [P30968-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L03380 mRNA. Translation: AAA35918.1.
L07949 mRNA. Translation: AAA35917.1.
S60587 mRNA. Translation: AAB26287.1.
S77472 mRNA. Translation: AAB33884.1.
AF001952, AF001950, AF001951 Genomic DNA. Translation: AAB71348.1.
Z81148 mRNA. Translation: CAB03541.1.
AY392011 mRNA. Translation: AAR92228.1.
BC113546 mRNA. Translation: AAI13547.1.
Z99995 Genomic DNA. Translation: CAB17082.1.
CCDSiCCDS3517.1. [P30968-1]
CCDS47064.1. [P30968-2]
PIRiJC1353.
RefSeqiNP_000397.1. NM_000406.2. [P30968-1]
NP_001012781.1. NM_001012763.1. [P30968-2]
UniGeneiHs.407587.

3D structure databases

ProteinModelPortaliP30968.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109060. 2 interactors.
STRINGi9606.ENSP00000226413.

Chemistry databases

BindingDBiP30968.
ChEMBLiCHEMBL1855.
DrugBankiDB00106. Abarelix.
DB06719. Buserelin.
DB00050. Cetrorelix.
DB01406. Danazol.
DB06699. Degarelix.
DB06785. Ganirelix.
DB00644. Gonadorelin.
DB00014. Goserelin.
DB00007. Leuprolide.
DB00666. Nafarelin.
DB06825. Triptorelin.
GuidetoPHARMACOLOGYi256.

Protein family/group databases

TCDBi9.A.14.10.1. the g-protein-coupled receptor (gpcr) family.
GPCRDBiSearch...

Polymorphism and mutation databases

BioMutaiGNRHR.
DMDMi399777.

Proteomic databases

EPDiP30968.
PaxDbiP30968.
PRIDEiP30968.

Protocols and materials databases

DNASUi2798.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000226413; ENSP00000226413; ENSG00000109163. [P30968-1]
ENST00000420975; ENSP00000397561; ENSG00000109163. [P30968-2]
GeneIDi2798.
KEGGihsa:2798.
UCSCiuc003hdm.4. human. [P30968-1]

Organism-specific databases

CTDi2798.
DisGeNETi2798.
GeneCardsiGNRHR.
GeneReviewsiGNRHR.
HGNCiHGNC:4421. GNRHR.
MalaCardsiGNRHR.
MIMi138850. gene.
146110. phenotype.
neXtProtiNX_P30968.
OpenTargetsiENSG00000109163.
Orphaneti432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBiPA28800.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000119156.
HOGENOMiHOG000251590.
HOVERGENiHBG009082.
InParanoidiP30968.
KOiK04280.
OMAiVAWIMAG.
OrthoDBiEOG091G0ZDG.
PhylomeDBiP30968.
TreeFamiTF106499.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109163-MONOMER.
ReactomeiR-HSA-375281. Hormone ligand-binding receptors.
R-HSA-416476. G alpha (q) signalling events.

Miscellaneous databases

GeneWikiiGNRHR.
GenomeRNAii2798.
PROiP30968.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109163.
CleanExiHS_GNRHR.
GenevisibleiP30968. HS.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001658. GphnRH_fam_rcpt.
IPR027982. GphnRH_rcpt.
[Graphical view]
PANTHERiPTHR24241:SF22. PTHR24241:SF22. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00529. GNADOTRPHINR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGNRHR_HUMAN
AccessioniPrimary (citable) accession number: P30968
Secondary accession number(s): O75793, Q14D13, Q92644
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: November 2, 2016
This is version 164 of the entry and version 1 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

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 4
    Human chromosome 4: 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.