P01148 (GON1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	92 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 the gene represented in this entry. Ref.6
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 component	Secreted
Coding sequence diversity	Polymorphism
Disease	Hypogonadotropic hypogonadism Kallmann syndrome
Domain	Signal
Molecular function	Hormone
PTM	Amidation Cleavage on pair of basic residues Pyrrolidone carboxylic acid
Technical term	Complete proteome Direct protein sequencing Pharmaceutical Reference proteome
Gene Ontology (GO)
Biological_process	cell-cell signaling Traceable author statement PubMed 1310542. Source: ProtInc female pregnancy Inferred from electronic annotation. Source: Compara multicellular organismal development Traceable author statement Ref.2. Source: ProtInc negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Traceable author statement PubMed 10832105. Source: ProtInc ovulation cycle Inferred from electronic annotation. Source: Compara regulation of gene expression Inferred from electronic annotation. Source: Compara response to corticosteroid stimulus Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement PubMed 8692981. Source: ProtInc
Cellular_component	extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: Compara
Molecular_function	gonadotropin hormone-releasing hormone activity Traceable author statement PubMed 10832105. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Ref.5
	Chain	24 – 92	69	Progonadoliberin-1		PRO_0000012395
	Peptide	24 – 33	10	Gonadoliberin-1 Ref.5		PRO_0000012396
	Peptide	37 – 92	56	GnRH-associated peptide 1		PRO_0000012397
Sites
	Site	26	1	Appears to be essential for biological activity
Amino acid modifications
	Modified residue	24	1	Pyrrolidone carboxylic acid Ref.5
	Modified residue	33	1	Glycine amide Ref.5
Natural variations
	Natural variant	16	1	W → S. Ref.3 Ref.7 Corresponds to variant rs6185 [ dbSNP | Ensembl ].		VAR_013943

Sequences

	Sequence		Length	Mass (Da)
	P01148 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: 30A72221B076FA79	FASTA	92	10,380
	10 20 30 40 50 60 MKPIQKLLAG LILLTWCVEG CSSQHWSYGL RPGGKRDAEN LIDSFQEIVK EVGQLAETQR 70 80 90 FECTTHQPRS PLRDLKGALE SLIEEETGQK KI

References

	« Hide 'large scale' referencesShow '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.
[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)
+	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.
IPI	IPI00000102.
PIR	RHHUG. S05308.
RefSeq	NP_001076580.1. NM_001083111.1.
UniGene	Hs.82963.
3D structure databases
ProteinModelPortal	P01148.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000276414.
Polymorphism databases
DMDM	121522.
Proteomic databases
PRIDE	P01148.
Protocols and materials databases
DNASU	2796.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000276414; ENSP00000276414; ENSG00000147437. ENST00000421054; ENSP00000391280; ENSG00000147437.
GeneID	2796.
KEGG	hsa:2796.
UCSC	uc003xem.4. human.
Organism-specific databases
CTD	2796.
GeneCards	GC08M025276.
HGNC	HGNC:4419. GNRH1.
HPA	HPA027532.
MIM	152760. gene. 614841. phenotype.
neXtProt	NX_P01148.
Orphanet	432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKB	PA28798.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG39107.
HOGENOM	HOG000033698.
HOVERGEN	HBG014746.
InParanoid	P01148.
KO	K05252.
OMA	GCSSQHW.
OrthoDB	EOG4MCX1W.
PhylomeDB	P01148.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	P01148.
CleanEx	HS_GNRH1.
Genevestigator	P01148.
GermOnline	ENSG00000147437. Homo sapiens.
Family and domain databases
InterPro	IPR002012. GnRH. IPR019792. Gonadoliberin_I. IPR004079. Gonadoliberin_I_precursor. [Graphical view]
PANTHER	PTHR10522. PTHR10522. 1 hit.
Pfam	PF00446. GnRH. 1 hit. [Graphical view]
PRINTS	PR01541. GONADOLIBRNI.
PROSITE	PS00473. GNRH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	2796.
NextBio	11013.
PMAP-CutDB	P01148.
SOURCE	Search...

Entry information

Entry name

GON1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 133 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.