Q92847 (GHSR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Growth hormone secretagogue receptor type 1
Short name=GHS-R

Alternative name(s):
GH-releasing peptide receptor
Short name=GHRP
Ghrelin receptor

Gene names

Name:

GHSR

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	366 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for ghrelin, coupled to G-alpha-11 proteins. Stimulates growth hormone secretion. Binds also other growth hormone releasing peptides (GHRP) (e.g. Met-enkephalin and GHRP-6) as well as non-peptide, low molecular weight secretagogues (e.g. L-692,429, MK-0677, adenosine). Ref.6 Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Pituitary and hypothalamus.
Involvement in disease	Idiopathic short stature autosomal (ISSA) [MIM:604271]: Short stature is defined by a subnormal rate of growth. Note: The disease may be caused by mutations affecting the gene represented in this entry. Ref.8
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin polymerization or depolymerization Inferred from direct assay PubMed 15232612. Source: UniProtKB adult feeding behavior Inferred from sequence or structural similarity. Source: HGNC cellular response to insulin stimulus Inferred from electronic annotation. Source: Compara decidualization Inferred from direct assay PubMed 17494105. Source: UniProtKB growth hormone secretion Traceable author statement Ref.8. Source: HGNC hormone-mediated signaling pathway Inferred from direct assay Ref.1. Source: HGNC negative regulation of inflammatory response Inferred from direct assay PubMed 15232612. Source: UniProtKB negative regulation of insulin secretion Inferred from electronic annotation. Source: Compara negative regulation of interleukin-1 beta production Inferred from direct assay PubMed 15232612. Source: UniProtKB negative regulation of interleukin-6 biosynthetic process Inferred from direct assay PubMed 15232612. Source: UniProtKB negative regulation of tumor necrosis factor biosynthetic process Inferred from direct assay PubMed 15232612. Source: UniProtKB positive regulation of appetite Inferred from sequence or structural similarity. Source: HGNC positive regulation of fatty acid metabolic process Inferred from electronic annotation. Source: Compara positive regulation of insulin-like growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of multicellular organism growth Inferred from mutant phenotype Ref.8. Source: HGNC regulation of hindgut contraction Inferred from electronic annotation. Source: Compara regulation of synapse assembly Inferred from electronic annotation. Source: Compara response to food Inferred from electronic annotation. Source: Compara
Cellular_component	cell surface Inferred from direct assay Ref.1. Source: HGNC integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane raft Inferred from direct assay PubMed 15232612. Source: UniProtKB neuron projection Inferred from direct assay PubMed 12890514. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Molecular_function	growth hormone secretagogue receptor activity Inferred from direct assay Ref.1. Source: HGNC growth hormone-releasing hormone receptor activity Inferred from direct assay Ref.1. Source: HGNC peptide hormone binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1A (identifier: Q92847-1)

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.

Isoform 1B (identifier: Q92847-2)

The sequence of this isoform differs from the canonical sequence as follows:
     266-289: AVVVFAFILCWLPFHVGRYLFSKS → GGSQRALRLSLAGPILSLCLLPSL
     290-366: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 366	366	Growth hormone secretagogue receptor type 1		PRO_0000069479
Regions
	Topological domain	1 – 40	40	Extracellular Potential
	Transmembrane	41 – 66	26	Helical; Name=1; Potential
	Topological domain	67 – 72	6	Cytoplasmic Potential
	Transmembrane	73 – 96	24	Helical; Name=2; Potential
	Topological domain	97 – 117	21	Extracellular Potential
	Transmembrane	118 – 139	22	Helical; Name=3; Potential
	Topological domain	140 – 162	23	Cytoplasmic Potential
	Transmembrane	163 – 183	21	Helical; Name=4; Potential
	Topological domain	184 – 211	28	Extracellular Potential
	Transmembrane	212 – 235	24	Helical; Name=5; Potential
	Topological domain	236 – 263	28	Cytoplasmic Potential
	Transmembrane	264 – 285	22	Helical; Name=6; Potential
	Topological domain	286 – 302	17	Extracellular Potential
	Transmembrane	303 – 326	24	Helical; Name=7; Potential
	Topological domain	327 – 366	40	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	13	1	N-linked (GlcNAc...) Potential
	Glycosylation	27	1	N-linked (GlcNAc...) Potential
	Disulfide bond	116 ↔ 198		By similarity
Natural variations
	Alternative sequence	266 – 289	24	AVVVF…LFSKS → GGSQRALRLSLAGPILSLCL LPSL in isoform 1B.		VSP_001916
	Alternative sequence	290 – 366	77	Missing in isoform 1B.		VSP_001917
	Natural variant	5	1	T → I. Corresponds to variant rs2232165 [ dbSNP | Ensembl ].		VAR_049389
	Natural variant	204	1	A → E in ISSA; affects cell-surface expression; impairs constitutive activity but not the ability to respond to ghrelin. Ref.8		VAR_032705

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1A [UniParc]. Last modified February 1, 1997. Version 1. Checksum: D1B62710DA9DC0C6	FASTA	366	41,329
	10 20 30 40 50 60 MWNATPSEEP GFNLTLADLD WDASPGNDSL GDELLQLFPA PLLAGVTATC VALFVVGIAG 70 80 90 100 110 120 NLLTMLVVSR FRELRTTTNL YLSSMAFSDL LIFLCMPLDL VRLWQYRPWN FGDLLCKLFQ 130 140 150 160 170 180 FVSESCTYAT VLTITALSVE RYFAICFPLR AKVVVTKGRV KLVIFVIWAV AFCSAGPIFV 190 200 210 220 230 240 LVGVEHENGT DPWDTNECRP TEFAVRSGLL TVMVWVSSIF FFLPVFCLTV LYSLIGRKLW 250 260 270 280 290 300 RRRRGDAVVG ASLRDQNHKQ TVKMLAVVVF AFILCWLPFH VGRYLFSKSF EPGSLEIAQI 310 320 330 340 350 360 SQYCNLVSFV LFYLSAAINP ILYNIMSKKY RVAVFRLLGF EPFSQRKLST LKDESSRAWT ESSINT
	Isoform 1B [UniParc]. Checksum: 8032FDB4C6BDD42B	FASTA	289	32,153
	10 20 30 40 50 60 MWNATPSEEP GFNLTLADLD WDASPGNDSL GDELLQLFPA PLLAGVTATC VALFVVGIAG 70 80 90 100 110 120 NLLTMLVVSR FRELRTTTNL YLSSMAFSDL LIFLCMPLDL VRLWQYRPWN FGDLLCKLFQ 130 140 150 160 170 180 FVSESCTYAT VLTITALSVE RYFAICFPLR AKVVVTKGRV KLVIFVIWAV AFCSAGPIFV 190 200 210 220 230 240 LVGVEHENGT DPWDTNECRP TEFAVRSGLL TVMVWVSSIF FFLPVFCLTV LYSLIGRKLW 250 260 270 280 RRRRGDAVVG ASLRDQNHKQ TVKMLGGSQR ALRLSLAGPI LSLCLLPSL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A receptor in pituitary and hypothalamus that functions in growth hormone release." Howard A.D., Feighner S.D., Cully D.F., Arena J.P., Liberator P.A., Rosenblum C.I., Hamelin M., Hreniuk D.L., Palyha O.C., Anderson J., Paress P.S., Diaz C., Chou M., Liu K.K., McKee K.K., Pong S.-S., Chaung L.-Y., Elbrecht A. , Dashkevicz M., Heavens R., Rigby M., Sirinathsinghji D.J.S., Dean D.C., Melillo D.G., Patchett A.A., Nargund R., Griffin P.R., Demartino J.A., Gupta S.K., Schaeffer J.M., Smith R.G., van der Ploeg L.H.T. Science 273:974-977(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A AND 1B). Tissue: Pituitary.
[2]	"Genomic structure and transcriptional regulation of the human growth hormone secretagogue receptor." Petersenn S., Rasch A.C., Penshorn M., Beil F.U., Schulte H.M. Endocrinology 142:2649-2659(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1A AND 1B).
[3]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Kopatz S.A., Aronstam R.S., Sharma S.V. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1A AND 1B).
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORMS 1A AND 1B).
[6]	"Growth hormone secretagogue receptor family members and ligands." Smith R.G., Leonard R., Bailey A.R.T., Palyha O.C., Feighner S.D., Tan C.P., Mckee K.K., Pong S.-S., Griffin P.R., Howard A.D. Endocrine 14:9-14(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Ghrelin is a growth-hormone-releasing acylated peptide from stomach." Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H., Kangawa K. Nature 402:656-660(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature." Pantel J., Legendre M., Cabrol S., Hilal L., Hajaji Y., Morisset S., Nivot S., Vie-Luton M.-P., Grouselle D., de Kerdanet M., Kadiri A., Epelbaum J., Le Bouc Y., Amselem S. J. Clin. Invest. 116:760-768(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ISSA GLU-204, CHARACTERIZATION OF VARIANT ISSA GLU-204.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U60179 mRNA. Translation: AAC50653.1. U60181 mRNA. Translation: AAC50654.1. AF369786 Genomic DNA. Translation: AAK71539.1. AF369786 Genomic DNA. Translation: AAK71540.1. AY429112 mRNA. Translation: AAR07907.1. AY322544 Genomic DNA. Translation: AAP84357.1. CH471052 Genomic DNA. Translation: EAW78468.1. BC069068 mRNA. Translation: AAH69068.1. BC069374 mRNA. Translation: AAH69374.1. BC113547 mRNA. Translation: AAI13548.1.
IPI	IPI00023793. IPI00219687.
RefSeq	NP_004113.1. NM_004122.2. NP_940799.1. NM_198407.2.
UniGene	Hs.130212.
3D structure databases
ProteinModelPortal	Q92847.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000241256.
Protein family/group databases
GPCRDB	Search...
Polymorphism databases
DMDM	2494998.
Proteomic databases
PRIDE	Q92847.
Protocols and materials databases
DNASU	2693.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000241256; ENSP00000241256; ENSG00000121853. ENST00000427970; ENSP00000395344; ENSG00000121853.
GeneID	2693.
KEGG	hsa:2693.
UCSC	uc003fib.2. human. uc011bpv.2. human.
Organism-specific databases
CTD	2693.
GeneCards	GC03M172162.
HGNC	HGNC:4267. GHSR.
HPA	CAB012451.
MIM	601898. gene. 604271. phenotype.
neXtProt	NX_Q92847.
Orphanet	137693. Idiopathic short stature. 231671. Isolated growth hormone deficiency type IB.
PharmGKB	PA28677.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG303294.
HOGENOM	HOG000272571.
HOVERGEN	HBG006538.
InParanoid	Q92847.
KO	K04284.
OMA	MVWVSSV.
OrthoDB	EOG4FFD28.
PhylomeDB	Q92847.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q92847.
Bgee	Q92847.
CleanEx	HS_GHSR.
Genevestigator	Q92847.
GermOnline	ENSG00000121853. Homo sapiens.
Family and domain databases
InterPro	IPR003905. GHS-R. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR01417. GHSRECEPTOR. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q92847.
ChEMBL	CHEMBL4616.
GenomeRNAi	2693.
NextBio	10650.
SOURCE	Search...

Entry information

Entry name

GHSR_HUMAN

Accession

Primary (citable) accession number: Q92847
Secondary accession number(s): Q14D12 , Q6ISR8, Q92848, Q96RJ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	February 1, 1997
Last modified:	May 1, 2013
This is version 119 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.