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Q02643 (GHRHR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Growth hormone-releasing hormone receptor

Short name=GHRH receptor
Alternative name(s):
Growth hormone-releasing factor receptor
Short name=GRF receptor
Short name=GRFR
Gene names
Name:GHRHR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length423 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for GRF, coupled to G proteins which activate adenylyl cyclase. Stimulates somatotroph cell growth, growth hormone gene transcription and growth hormone secretion.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Pituitary gland.

Involvement in disease

Growth hormone deficiency, isolated, 1B (IGHD1B) [MIM:612781]: An autosomal recessive deficiency of growth hormone leading to short stature. Patients have low but detectable levels of growth hormone, significantly retarded bone age, and a positive response and immunologic tolerance to growth hormone therapy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.10

Sequence similarities

Belongs to the G-protein coupled receptor 2 family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Dwarfism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of adenylate cyclase activity

Inferred from electronic annotation. Source: Ensembl

adenylate cyclase-activating G-protein coupled receptor signaling pathway

Inferred from direct assay Ref.1. Source: BHF-UCL

cAMP-mediated signaling

Inferred from mutant phenotype Ref.2. Source: BHF-UCL

cell maturation

Inferred from electronic annotation. Source: Ensembl

cellular response to insulin stimulus

Inferred from electronic annotation. Source: Ensembl

determination of adult lifespan

Inferred from electronic annotation. Source: Ensembl

growth hormone secretion

Inferred from electronic annotation. Source: Ensembl

hormone metabolic process

Inferred from electronic annotation. Source: Ensembl

lactation

Inferred from electronic annotation. Source: Ensembl

multicellular organismal reproductive process

Non-traceable author statement PubMed 15944917. Source: BHF-UCL

positive regulation of cAMP biosynthetic process

Inferred from direct assay Ref.1Ref.2. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from direct assay PubMed 12867592. Source: BHF-UCL

positive regulation of growth hormone secretion

Non-traceable author statement PubMed 11773624. Source: BHF-UCL

positive regulation of insulin-like growth factor receptor signaling pathway

Non-traceable author statement PubMed 11773624. Source: BHF-UCL

positive regulation of multicellular organism growth

Inferred from mutant phenotype PubMed 8528260. Source: BHF-UCL

regulation of intracellular steroid hormone receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

regulation of protein metabolic process

Inferred from electronic annotation. Source: Ensembl

response to estrogen

Inferred from direct assay PubMed 9482665. Source: BHF-UCL

response to glucocorticoid

Inferred from direct assay PubMed 9482665. Source: BHF-UCL

response to insulin

Inferred from mutant phenotype PubMed 17356054. Source: BHF-UCL

somatotropin secreting cell development

Inferred from electronic annotation. Source: Ensembl

water homeostasis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell surface

Inferred from direct assay Ref.1. Source: BHF-UCL

cytoplasm

Inferred from direct assay PubMed 10461027. Source: BHF-UCL

integral component of membrane

Inferred from direct assay Ref.1. Source: BHF-UCL

nuclear inner membrane

Inferred from direct assay PubMed 10461027. Source: BHF-UCL

nuclear matrix

Inferred from direct assay PubMed 10461027. Source: BHF-UCL

nuclear outer membrane

Inferred from direct assay PubMed 10461027. Source: BHF-UCL

plasma membrane

Inferred from direct assay PubMed 10461027. Source: BHF-UCL

secretory granule

Inferred from direct assay PubMed 10461027. Source: BHF-UCL

   Molecular_functionG-protein coupled receptor activity

Inferred by curator Ref.1. Source: BHF-UCL

growth factor binding

Inferred from physical interaction Ref.2. Source: BHF-UCL

growth hormone-releasing hormone receptor activity

Inferred from mutant phenotype Ref.2. Source: BHF-UCL

peptide hormone binding

Inferred from physical interaction Ref.2. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.1Ref.2. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 423401Growth hormone-releasing hormone receptor
PRO_0000012828

Regions

Topological domain23 – 132110Extracellular Potential
Transmembrane133 – 15220Helical; Name=1; Potential
Topological domain153 – 16210Cytoplasmic Potential
Transmembrane163 – 18119Helical; Name=2; Potential
Topological domain182 – 20423Extracellular Potential
Transmembrane205 – 22723Helical; Name=3; Potential
Topological domain228 – 24013Cytoplasmic Potential
Transmembrane241 – 26222Helical; Name=4; Potential
Topological domain263 – 28018Extracellular Potential
Transmembrane281 – 30424Helical; Name=5; Potential
Topological domain305 – 32925Cytoplasmic Potential
Transmembrane330 – 34819Helical; Name=6; Potential
Topological domain349 – 36113Extracellular Potential
Transmembrane362 – 38120Helical; Name=7; Potential
Topological domain382 – 42342Cytoplasmic Potential

Amino acid modifications

Glycosylation501N-linked (GlcNAc...) Potential
Disulfide bond41 ↔ 64 Ref.7
Disulfide bond55 ↔ 96 Ref.7
Disulfide bond78 ↔ 112 Ref.7

Natural variations

Natural variant451A → T in a colorectal cancer sample; somatic mutation. Ref.11
VAR_036223
Natural variant571A → T.
Corresponds to variant rs4988496 [ dbSNP | Ensembl ].
VAR_033962
Natural variant1211E → D.
Corresponds to variant rs4988498 [ dbSNP | Ensembl ].
VAR_033963
Natural variant1441L → H in IGHD1B. Ref.8
Corresponds to variant rs121918118 [ dbSNP | Ensembl ].
VAR_015796
Natural variant1761A → V in IGHD1B; reduced cAMP response to GHRH. Ref.10
VAR_015797
Natural variant2221A → E in IGHD1B. Ref.8
VAR_015798
Natural variant2251V → I.
Corresponds to variant rs28371560 [ dbSNP | Ensembl ].
VAR_033964
Natural variant2421F → C in IGHD1B. Ref.8
VAR_015799
Natural variant3291K → E in IGHD1B. Ref.9
VAR_015800
Natural variant4221M → T.
Corresponds to variant rs2228078 [ dbSNP | Ensembl ].
VAR_033965

Experimental info

Sequence conflict1781A → R in AAA35890. Ref.1

Secondary structure

............... 423
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q02643 [UniParc].

Last modified July 15, 1998. Version 2.
Checksum: C9C5E2E7D6649E06

FASTA42347,402
        10         20         30         40         50         60 
MDRRMWGAHV FCVLSPLPTV LGHMHPECDF ITQLREDESA CLQAAEEMPN TTLGCPATWD 

        70         80         90        100        110        120 
GLLCWPTAGS GEWVTLPCPD FFSHFSSESG AVKRDCTITG WSEPFPPYPV ACPVPLELLA 

       130        140        150        160        170        180 
EEESYFSTVK IIYTVGHSIS IVALFVAITI LVALRRLHCP RNYVHTQLFT TFILKAGAVF 

       190        200        210        220        230        240 
LKDAALFHSD DTDHCSFSTV LCKVSVAASH FATMTNFSWL LAEAVYLNCL LASTSPSSRR 

       250        260        270        280        290        300 
AFWWLVLAGW GLPVLFTGTW VSCKLAFEDI ACWDLDDTSP YWWIIKGPIV LSVGVNFGLF 

       310        320        330        340        350        360 
LNIIRILVRK LEPAQGSLHT QSQYWRLSKS TLFLIPLFGI HYIIFNFLPD NAGLGIRLPL 

       370        380        390        400        410        420 
ELGLGSFQGF IVAILYCFLN QEVRTEISRK WHGHDPELLP AWRTRAKWTT PSRSAAKVLT 


SMC 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone."
Mayo K.E.
Mol. Endocrinol. 6:1734-1744(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Pituitary.
[2]"Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone."
Gaylinn B.D., Harrison J.K., Zysk J.R., Lyons C.E. Jr., Lynch K.R., Thorner M.O.
Mol. Endocrinol. 7:77-84(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Pituitary.
[3]"Genome-wide discovery and analysis of human seven transmembrane helix receptor genes."
Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., Tsutsumi S., Aburatani H., Asai K., Akiyama Y.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
King M.M., Aronstam R.S., Sharma S.V.
Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pituitary.
[5]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The structure of the gene coding for human growth hormone releasing hormone."
Tang J., Collu R.
Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 37-271.
[7]"Crystal structure of the extracellular domain of human growth hormone releasing hormone receptor."
Structural genomics consortium (SGC)
Submitted (JUN-2010) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 34-123, DISULFIDE BONDS.
[8]"Three new mutations in the gene for the growth hormone (GH)-releasing hormone receptor in familial isolated GH deficiency type IB."
Salvatori R., Fan X., Phillips J.A. III, Espigares-Martin R., Martin De Lara I., Freeman K.L., Plotnick L., Al-Ashwal A., Levine M.A.
J. Clin. Endocrinol. Metab. 86:273-279(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IGHD1B HIS-144; GLU-222 AND CYS-242.
[9]"Familial dwarfism due to a novel mutation of the growth hormone-releasing hormone receptor gene."
Salvatori R., Hayashida C.Y., Aguiar-Oliveira M.H., Phillips J.A. III, Souza A.H., Gondo R.G., Toledo S.P., Conceicao M.M., Prince M., Maheshwari H.G., Baumann G., Levine M.A.
J. Clin. Endocrinol. Metab. 84:917-923(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT IGHD1B GLU-329.
[10]"A new missense mutation in the growth hormone-releasing hormone receptor gene in familial isolated GH deficiency."
Carakushansky M., Whatmore A.J., Clayton P.E., Shalet S.M., Gleeson H.K., Price D.A., Levine M.A., Salvatori R.
Eur. J. Endocrinol. 148:25-30(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT IGHD1B VAL-176.
[11]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-45.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L01406 mRNA. Translation: AAA35890.1.
L09237 mRNA. Translation: AAA58619.1.
AB065701 Genomic DNA. Translation: BAC05924.1.
AY557192 mRNA. Translation: AAS59864.1.
AC005155 Genomic DNA. Translation: AAC23789.1.
U42225 expand/collapse EMBL AC list , U42222, U42223, U42224 Genomic DNA. Translation: AAB37758.1.
CCDSCCDS5432.1.
PIRA45363.
RefSeqNP_000814.2. NM_000823.3.
UniGeneHs.733003.
Hs.767.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2XDGX-ray1.95A/B34-123[»]
ProteinModelPortalQ02643.
SMRQ02643. Positions 34-386.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108959. 1 interaction.
STRING9606.ENSP00000320180.

Chemistry

ChEMBLCHEMBL2032.
DrugBankDB00010. Sermorelin.
GuidetoPHARMACOLOGY247.

Protein family/group databases

TCDB9.A.14.4.7. the g-protein-coupled receptor (gpcr) family.
GPCRDBSearch...

Polymorphism databases

DMDM3041685.

Proteomic databases

PaxDbQ02643.
PRIDEQ02643.

Protocols and materials databases

DNASU2692.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000326139; ENSP00000320180; ENSG00000106128.
GeneID2692.
KEGGhsa:2692.
UCSCuc003tbx.3. human.

Organism-specific databases

CTD2692.
GeneCardsGC07P030978.
HGNCHGNC:4266. GHRHR.
MIM139191. gene.
612781. phenotype.
neXtProtNX_Q02643.
Orphanet231671. Isolated growth hormone deficiency type IB.
PharmGKBPA28676.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG249002.
HOGENOMHOG000008249.
HOVERGENHBG008318.
InParanoidQ02643.
KOK04584.
OMAIHYIIFN.
OrthoDBEOG7TF78W.
PhylomeDBQ02643.
TreeFamTF315710.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressQ02643.
BgeeQ02643.
CleanExHS_GHRHR.
GenevestigatorQ02643.

Family and domain databases

InterProIPR017981. GPCR_2-like.
IPR001879. GPCR_2_extracellular_dom.
IPR003288. GPCR_2_GHRH_rcpt.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
[Graphical view]
PfamPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSPR01352. GHRHRECEPTOR.
PR00249. GPCRSECRETIN.
SMARTSM00008. HormR. 1 hit.
[Graphical view]
PROSITEPS00649. G_PROTEIN_RECEP_F2_1. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50227. G_PROTEIN_RECEP_F2_3. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ02643.
GeneWikiGrowth-hormone-releasing_hormone_receptor.
Growth_hormone-releasing_hormone_receptor.
GenomeRNAi2692.
NextBio10644.
PROQ02643.
SOURCESearch...

Entry information

Entry nameGHRHR_HUMAN
AccessionPrimary (citable) accession number: Q02643
Secondary accession number(s): Q99863
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: July 15, 1998
Last modified: July 9, 2014
This is version 135 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 7

Human chromosome 7: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries