Q02643 (GHRHR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	423 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	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 component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Dwarfism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of adenylate cyclase activity Inferred from electronic annotation. Source: Compara 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: Compara cellular response to insulin stimulus Inferred from electronic annotation. Source: Compara determination of adult lifespan Inferred from electronic annotation. Source: Compara growth hormone secretion Inferred from electronic annotation. Source: Compara hormone metabolic process Inferred from electronic annotation. Source: Compara lactation Inferred from electronic annotation. Source: Compara 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: Compara regulation of protein metabolic process Inferred from electronic annotation. Source: Compara response to estrogen stimulus Inferred from direct assay PubMed 9482665. Source: BHF-UCL response to glucocorticoid stimulus Inferred from direct assay PubMed 9482665. Source: BHF-UCL response to insulin stimulus Inferred from mutant phenotype PubMed 17356054. Source: BHF-UCL somatotropin secreting cell development Inferred from electronic annotation. Source: Compara water homeostasis Inferred from electronic annotation. Source: Compara
Cellular_component	cell surface Inferred from direct assay Ref.1. Source: BHF-UCL integral to 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_function	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
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Chain

23 – 423

401

Growth hormone-releasing hormone receptor

PRO_0000012828

Regions

Topological domain

23 – 132

110

Extracellular Potential

Transmembrane

133 – 152

20

Helical; Name=1; Potential

Topological domain

153 – 162

10

Cytoplasmic Potential

Transmembrane

163 – 181

19

Helical; Name=2; Potential

Topological domain

182 – 204

23

Extracellular Potential

Transmembrane

205 – 227

23

Helical; Name=3; Potential

Topological domain

228 – 240

13

Cytoplasmic Potential

Transmembrane

241 – 262

22

Helical; Name=4; Potential

Topological domain

263 – 280

18

Extracellular Potential

Transmembrane

281 – 304

24

Helical; Name=5; Potential

Topological domain

305 – 329

25

Cytoplasmic Potential

Transmembrane

330 – 348

19

Helical; Name=6; Potential

Topological domain

349 – 361

13

Extracellular Potential

Transmembrane

362 – 381

20

Helical; Name=7; Potential

Topological domain

382 – 423

42

Cytoplasmic Potential

Amino acid modifications

Glycosylation

50

1

N-linked (GlcNAc...) Potential

Disulfide bond

41 ↔ 64

Ref.7

Disulfide bond

55 ↔ 96

Ref.7

Disulfide bond

78 ↔ 112

Ref.7

Natural variations

Natural variant

45

1

A → T in a colorectal cancer sample; somatic mutation. Ref.11

VAR_036223

Natural variant

57

1

A → T.
Corresponds to variant rs4988496 [ dbSNP | Ensembl ].

VAR_033962

Natural variant

121

1

E → D.
Corresponds to variant rs4988498 [ dbSNP | Ensembl ].

VAR_033963

Natural variant

144

1

L → H in IGHD1B. Ref.8

VAR_015796

Natural variant

176

1

A → V in IGHD1B; reduced cAMP response to GHRH. Ref.10

VAR_015797

Natural variant

222

1

A → E in IGHD1B. Ref.8

VAR_015798

Natural variant

225

1

V → I.
Corresponds to variant rs28371560 [ dbSNP | Ensembl ].

VAR_033964

Natural variant

242

1

F → C in IGHD1B. Ref.8

VAR_015799

Natural variant

329

1

K → E in IGHD1B. Ref.9

VAR_015800

Natural variant

422

1

M → T.
Corresponds to variant rs2228078 [ dbSNP | Ensembl ].

VAR_033965

Experimental info

Sequence conflict

178

1

A → R in AAA35890. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

423

Helix Strand Turn

Details...

Helix

34 – 45

12

Beta strand

53 – 55

3

Beta strand

72 – 76

5

Helix

80 – 84

5

Beta strand

92 – 97

6

Helix

108 – 111

4

Helix

116 – 119

4

Sequences

	Sequence		Length	Mass (Da)
	Q02643 [UniParc]. Last modified July 15, 1998. Version 2. Checksum: C9C5E2E7D6649E06	FASTA	423	47,402
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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 , U42222, U42223, U42224 Genomic DNA. Translation: AAB37758.1.

IPI

IPI00295079.

PIR

A45363.

RefSeq

NP_000814.2. NM_000823.3.

UniGene

Hs.733003.
Hs.767.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2XDG	X-ray	1.95	A/B	34-123	[»]

ProteinModelPortal

Q02643.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000320180.

Protein family/group databases

GPCRDB

Search...

Polymorphism databases

DMDM

3041685.

Proteomic databases

PaxDb

Q02643.

PRIDE

Q02643.

Protocols and materials databases

DNASU

2692.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000326139; ENSP00000320180; ENSG00000106128.

GeneID

2692.

KEGG

hsa:2692.

UCSC

uc003tbx.3. human.

Organism-specific databases

CTD

2692.

GeneCards

GC07P030978.

HGNC

HGNC:4266. GHRHR.

HPA

CAB005620.

MIM

139191. gene.
612781. phenotype.

neXtProt

NX_Q02643.

Orphanet

231671. Isolated growth hormone deficiency type IB.

PharmGKB

PA28676.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG249002.

HOGENOM

HOG000008249.

HOVERGEN

HBG008318.

InParanoid

Q02643.

KO

K04584.

OMA

HFSSEPG.

OrthoDB

EOG4X0MSM.

PhylomeDB

Q02643.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q02643.

Bgee

Q02643.

CleanEx

HS_GHRHR.

Genevestigator

Q02643.

GermOnline

ENSG00000106128. Homo sapiens.

Family and domain databases

InterPro

IPR017981. 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]

PANTHER

PTHR12011:SF26. PTHR12011:SF26. 1 hit.

Pfam

PF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]

PRINTS

PR01352. GHRHRECEPTOR.
PR00249. GPCRSECRETIN.

SMART

SM00008. HormR. 1 hit.
[Graphical view]

PROSITE

PS00649. 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]

ProtoNet

Search...

Other

ChEMBL

CHEMBL2032.

DrugBank

DB00010. Sermorelin.

EvolutionaryTrace

Q02643.

GenomeRNAi

2692.

NextBio

10644.

SOURCE

Search...

Entry information

Entry name

GHRHR_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 124 of the entry and version 2 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.