Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P01148 (GON1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Progonadoliberin-1
Alternative name(s):
Progonadoliberin I

Cleaved into the following 2 chains:

  1. Gonadoliberin-1
    Alternative name(s):
    Gonadoliberin I
    Gonadorelin
    Gonadotropin-releasing hormone I
    Short name=GnRH-I
    Luliberin I
    Luteinizing hormone-releasing hormone I
    Short name=LH-RH I
  2. GnRH-associated peptide 1
    Alternative name(s):
    GnRH-associated peptide I
Gene names
Name:GNRH1
Synonyms:GNRH, GRH, LHRH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length92 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Stimulates the secretion of gonadotropins; it stimulates the secretion of both luteinizing and follicle-stimulating hormones.

Subcellular location

Secreted.

Involvement in disease

Hypogonadotropic hypogonadism 12 with or without anosmia (HH12) [MIM:614841]: A 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).
Note: 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 GNRH1 as well as in other HH-associated genes including PROKR2 and FGFR1 (Ref.9). Ref.6 Ref.9

Pharmaceutical use

Available under the names Factrel (Ayerst Labs), Lutrepulse or Lutrelef (Ferring Pharmaceuticals) and Relisorm (Serono). Used in evaluating hypothalamic-pituitary gonadotropic function.

Sequence similarities

Belongs to the GnRH family.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Hypogonadotropic hypogonadism
Kallmann syndrome
   DomainSignal
   Molecular functionHormone
   PTMAmidation
Cleavage on pair of basic residues
Pyrrolidone carboxylic acid
   Technical termComplete proteome
Direct protein sequencing
Pharmaceutical
Reference proteome
Gene Ontology (GO)
   Biological_processcell-cell signaling

Traceable author statement PubMed 1310542. Source: ProtInc

female pregnancy

Inferred from electronic annotation. Source: Ensembl

multicellular organismal development

Traceable author statement Ref.2. Source: ProtInc

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Traceable author statement PubMed 10832105. Source: ProtInc

negative regulation of neuron migration

Inferred from electronic annotation. Source: Ensembl

ovulation cycle

Inferred from electronic annotation. Source: Ensembl

regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

regulation of ovarian follicle development

Inferred from electronic annotation. Source: Ensembl

response to corticosteroid

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement PubMed 8692981. Source: ProtInc

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: Ensembl

   Molecular_functiongonadotropin hormone-releasing hormone activity

Traceable author statement PubMed 10832105. Source: ProtInc

hormone activity

Traceable author statement PubMed 2863757. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.5
Chain24 – 9269Progonadoliberin-1
PRO_0000012395
Peptide24 – 3310Gonadoliberin-1 Ref.5
PRO_0000012396
Peptide37 – 9256GnRH-associated peptide 1
PRO_0000012397

Sites

Site261Appears to be essential for biological activity

Amino acid modifications

Modified residue241Pyrrolidone carboxylic acid Ref.5
Modified residue331Glycine amide Ref.5

Natural variations

Natural variant161W → S. Ref.3 Ref.7
Corresponds to variant rs6185 [ dbSNP | Ensembl ].
VAR_013943
Natural variant311R → C in HH12; uncertain pathological significance; the patient also carries mutations in PROKR2 and FGFR1. Ref.9
VAR_069966

Sequences

Sequence LengthMass (Da)Tools
P01148 [UniParc].

Last modified April 1, 1988. Version 1.
Checksum: 30A72221B076FA79

FASTA9210,380
        10         20         30         40         50         60 
MKPIQKLLAG LILLTWCVEG CSSQHWSYGL RPGGKRDAEN LIDSFQEIVK EVGQLAETQR 

        70         80         90 
FECTTHQPRS PLRDLKGALE SLIEEETGQK KI 

« Hide

References

« Hide 'large scale' references
[1]"The complete nucleotide sequence of the human gonadotropin-releasing hormone gene."
Hayflick J.S., Adelman J.P., Seeburg P.H.
Nucleic Acids Res. 17:6403-6403(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Isolation of the gene and hypothalamic cDNA for the common precursor of gonadotropin-releasing hormone and prolactin release-inhibiting factor in human and rat."
Adelman J.P., Mason A.J., Hayflick J.S., Seeburg P.H.
Proc. Natl. Acad. Sci. U.S.A. 83:179-183(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Characterization of cDNA for precursor of human luteinizing hormone releasing hormone."
Seeburg P.H., Adelman J.P.
Nature 311:666-668(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-16.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"The chemical identity of the immunoreactive LHRH-like peptide biosynthesized in the human placenta."
Tan L., Rousseau P.
Biochem. Biophys. Res. Commun. 109:1061-1071(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-33, PYROGLUTAMATE FORMATION AT GLN-24, AMIDATION AT GLY-33.
[6]"Isolated familial hypogonadotropic hypogonadism and a GNRH1 mutation."
Bouligand J., Ghervan C., Tello J.A., Brailly-Tabard S., Salenave S., Chanson P., Lombes M., Millar R.P., Guiochon-Mantel A., Young J.
N. Engl. J. Med. 360:2742-2748(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN HH12.
[7]"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SER-16.
[8]Erratum
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 23:373-373(1999)
[9]"Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism."
Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B., Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K., Niedziela M., Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R., Hughes V.A., Kumanov P. expand/collapse author list , Young J., Yialamas M.A., Hall J.E., Van Vliet G., Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S., Sidis Y., Lage K., Pitteloud N.
Am. J. Hum. Genet. 92:725-743(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HH12 CYS-31.
+Additional computationally mapped references.

Web resources

Wikipedia

Gonadotropin-releasing hormone entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X01059 mRNA. Translation: CAA25526.1.
M12578 mRNA. Translation: AAA35916.1.
X15215 Genomic DNA. Translation: CAA33285.1.
BC126437 mRNA. Translation: AAI26438.1.
BC126463 mRNA. Translation: AAI26464.1.
CCDSCCDS43725.1.
PIRRHHUG. S05308.
RefSeqNP_001076580.1. NM_001083111.1.
UniGeneHs.82963.

3D structure databases

ProteinModelPortalP01148.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109058. 1 interaction.
STRING9606.ENSP00000276414.

Polymorphism databases

DMDM121522.

Proteomic databases

PRIDEP01148.

Protocols and materials databases

DNASU2796.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000276414; ENSP00000276414; ENSG00000147437.
ENST00000421054; ENSP00000391280; ENSG00000147437.
GeneID2796.
KEGGhsa:2796.
UCSCuc003xem.4. human.

Organism-specific databases

CTD2796.
GeneCardsGC08M025276.
GeneReviewsGNRH1.
HGNCHGNC:4419. GNRH1.
HPAHPA027532.
MIM152760. gene.
614841. phenotype.
neXtProtNX_P01148.
Orphanet432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBPA28798.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39107.
HOGENOMHOG000033698.
HOVERGENHBG014746.
InParanoidP01148.
KOK05252.
OMATRIIFEL.
OrthoDBEOG7JX36N.
PhylomeDBP01148.
TreeFamTF330934.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeP01148.
CleanExHS_GNRH1.
GenevestigatorP01148.

Family and domain databases

InterProIPR002012. GnRH.
IPR019792. Gonadoliberin_I.
IPR004079. Gonadoliberin_I_precursor.
[Graphical view]
PANTHERPTHR10522. PTHR10522. 1 hit.
PfamPF00446. GnRH. 1 hit.
[Graphical view]
PRINTSPR01541. GONADOLIBRNI.
PROSITEPS00473. GNRH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGonadotropin-releasing_hormone.
GenomeRNAi2796.
NextBio11013.
PMAP-CutDBP01148.
PROP01148.
SOURCESearch...

Entry information

Entry nameGON1_HUMAN
AccessionPrimary (citable) accession number: P01148
Secondary accession number(s): A0AVP0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: April 1, 1988
Last modified: July 9, 2014
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM