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Q02643

- GHRHR_HUMAN

UniProt

Q02643 - GHRHR_HUMAN

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Protein

Growth hormone-releasing hormone receptor

Gene

GHRHR

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: BHF-UCL
  2. growth factor binding Source: BHF-UCL
  3. growth hormone-releasing hormone receptor activity Source: BHF-UCL
  4. peptide hormone binding Source: BHF-UCL

GO - Biological processi

  1. activation of adenylate cyclase activity Source: Ensembl
  2. adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: BHF-UCL
  3. cAMP-mediated signaling Source: BHF-UCL
  4. cell maturation Source: Ensembl
  5. cellular response to insulin stimulus Source: Ensembl
  6. determination of adult lifespan Source: Ensembl
  7. growth hormone secretion Source: Ensembl
  8. hormone metabolic process Source: Ensembl
  9. lactation Source: Ensembl
  10. multicellular organismal reproductive process Source: BHF-UCL
  11. positive regulation of cAMP biosynthetic process Source: BHF-UCL
  12. positive regulation of cell proliferation Source: BHF-UCL
  13. positive regulation of growth hormone secretion Source: BHF-UCL
  14. positive regulation of insulin-like growth factor receptor signaling pathway Source: BHF-UCL
  15. positive regulation of multicellular organism growth Source: BHF-UCL
  16. regulation of intracellular steroid hormone receptor signaling pathway Source: Ensembl
  17. regulation of protein metabolic process Source: Ensembl
  18. response to estrogen Source: BHF-UCL
  19. response to glucocorticoid Source: BHF-UCL
  20. response to insulin Source: BHF-UCL
  21. somatotropin secreting cell development Source: Ensembl
  22. water homeostasis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_18377. Glucagon-type ligand receptors.
REACT_19327. G alpha (s) signalling events.

Protein family/group databases

TCDBi9.A.14.4.7. the g-protein-coupled receptor (gpcr) family.

Names & Taxonomyi

Protein namesi
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 namesi
Name:GHRHR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:4266. GHRHR.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 132110ExtracellularSequence AnalysisAdd
BLAST
Transmembranei133 – 15220Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini153 – 16210CytoplasmicSequence Analysis
Transmembranei163 – 18119Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini182 – 20423ExtracellularSequence AnalysisAdd
BLAST
Transmembranei205 – 22723Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini228 – 24013CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei241 – 26222Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini263 – 28018ExtracellularSequence AnalysisAdd
BLAST
Transmembranei281 – 30424Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini305 – 32925CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei330 – 34819Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini349 – 36113ExtracellularSequence AnalysisAdd
BLAST
Transmembranei362 – 38120Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini382 – 42342CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cell surface Source: BHF-UCL
  2. cytoplasm Source: BHF-UCL
  3. integral component of membrane Source: BHF-UCL
  4. nuclear inner membrane Source: BHF-UCL
  5. nuclear matrix Source: BHF-UCL
  6. nuclear outer membrane Source: BHF-UCL
  7. plasma membrane Source: BHF-UCL
  8. secretory granule Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

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.3 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti144 – 1441L → H in IGHD1B. 1 Publication
Corresponds to variant rs121918118 [ dbSNP | Ensembl ].
VAR_015796
Natural varianti176 – 1761A → V in IGHD1B; reduced cAMP response to GHRH. 1 Publication
VAR_015797
Natural varianti222 – 2221A → E in IGHD1B. 1 Publication
VAR_015798
Natural varianti242 – 2421F → C in IGHD1B. 1 Publication
VAR_015799
Natural varianti329 – 3291K → E in IGHD1B. 1 Publication
VAR_015800

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

MIMi612781. phenotype.
Orphaneti231671. Isolated growth hormone deficiency type IB.
PharmGKBiPA28676.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence AnalysisAdd
BLAST
Chaini23 – 423401Growth hormone-releasing hormone receptorPRO_0000012828Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi41 ↔ 641 Publication
Glycosylationi50 – 501N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi55 ↔ 961 Publication
Disulfide bondi78 ↔ 1121 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ02643.
PRIDEiQ02643.

Expressioni

Tissue specificityi

Pituitary gland.

Gene expression databases

BgeeiQ02643.
CleanExiHS_GHRHR.
ExpressionAtlasiQ02643. baseline.
GenevestigatoriQ02643.

Interactioni

Protein-protein interaction databases

BioGridi108959. 1 interaction.
STRINGi9606.ENSP00000320180.

Structurei

Secondary structure

1
423
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi34 – 4512Combined sources
Beta strandi53 – 553Combined sources
Beta strandi72 – 765Combined sources
Helixi80 – 845Combined sources
Beta strandi92 – 976Combined sources
Helixi108 – 1114Combined sources
Helixi116 – 1194Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2XDGX-ray1.95A/B34-123[»]
ProteinModelPortaliQ02643.
SMRiQ02643. Positions 34-386.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ02643.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG249002.
GeneTreeiENSGT00760000118800.
HOGENOMiHOG000008249.
HOVERGENiHBG008318.
InParanoidiQ02643.
KOiK04584.
OMAiIHYIIFN.
OrthoDBiEOG7TF78W.
PhylomeDBiQ02643.
TreeFamiTF315710.

Family and domain databases

InterProiIPR017981. 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]
PfamiPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSiPR01352. GHRHRECEPTOR.
PR00249. GPCRSECRETIN.
SMARTiSM00008. HormR. 1 hit.
[Graphical view]
PROSITEiPS00649. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q02643-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MDRRMWGAHV FCVLSPLPTV LGHMHPECDF ITQLREDESA CLQAAEEMPN
60 70 80 90 100
TTLGCPATWD GLLCWPTAGS GEWVTLPCPD FFSHFSSESG AVKRDCTITG
110 120 130 140 150
WSEPFPPYPV ACPVPLELLA EEESYFSTVK IIYTVGHSIS IVALFVAITI
160 170 180 190 200
LVALRRLHCP RNYVHTQLFT TFILKAGAVF LKDAALFHSD DTDHCSFSTV
210 220 230 240 250
LCKVSVAASH FATMTNFSWL LAEAVYLNCL LASTSPSSRR AFWWLVLAGW
260 270 280 290 300
GLPVLFTGTW VSCKLAFEDI ACWDLDDTSP YWWIIKGPIV LSVGVNFGLF
310 320 330 340 350
LNIIRILVRK LEPAQGSLHT QSQYWRLSKS TLFLIPLFGI HYIIFNFLPD
360 370 380 390 400
NAGLGIRLPL ELGLGSFQGF IVAILYCFLN QEVRTEISRK WHGHDPELLP
410 420
AWRTRAKWTT PSRSAAKVLT SMC
Length:423
Mass (Da):47,402
Last modified:July 15, 1998 - v2
Checksum:iC9C5E2E7D6649E06
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti178 – 1781A → R in AAA35890. (PubMed:1333056)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti45 – 451A → T in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036223
Natural varianti57 – 571A → T.
Corresponds to variant rs4988496 [ dbSNP | Ensembl ].
VAR_033962
Natural varianti121 – 1211E → D.
Corresponds to variant rs4988498 [ dbSNP | Ensembl ].
VAR_033963
Natural varianti144 – 1441L → H in IGHD1B. 1 Publication
Corresponds to variant rs121918118 [ dbSNP | Ensembl ].
VAR_015796
Natural varianti176 – 1761A → V in IGHD1B; reduced cAMP response to GHRH. 1 Publication
VAR_015797
Natural varianti222 – 2221A → E in IGHD1B. 1 Publication
VAR_015798
Natural varianti225 – 2251V → I.
Corresponds to variant rs28371560 [ dbSNP | Ensembl ].
VAR_033964
Natural varianti242 – 2421F → C in IGHD1B. 1 Publication
VAR_015799
Natural varianti329 – 3291K → E in IGHD1B. 1 Publication
VAR_015800
Natural varianti422 – 4221M → T.
Corresponds to variant rs2228078 [ dbSNP | Ensembl ].
VAR_033965

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5432.1.
PIRiA45363.
RefSeqiNP_000814.2. NM_000823.3.
UniGeneiHs.733003.
Hs.767.

Genome annotation databases

EnsembliENST00000326139; ENSP00000320180; ENSG00000106128.
GeneIDi2692.
KEGGihsa:2692.
UCSCiuc003tbx.3. human.

Polymorphism databases

DMDMi3041685.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS5432.1.
PIRi A45363.
RefSeqi NP_000814.2. NM_000823.3.
UniGenei Hs.733003.
Hs.767.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2XDG X-ray 1.95 A/B 34-123 [» ]
ProteinModelPortali Q02643.
SMRi Q02643. Positions 34-386.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108959. 1 interaction.
STRINGi 9606.ENSP00000320180.

Chemistry

BindingDBi Q02643.
ChEMBLi CHEMBL2032.
DrugBanki DB00010. Sermorelin.
DB08869. Tesamorelin.
GuidetoPHARMACOLOGYi 247.

Protein family/group databases

TCDBi 9.A.14.4.7. the g-protein-coupled receptor (gpcr) family.
GPCRDBi Search...

Polymorphism databases

DMDMi 3041685.

Proteomic databases

PaxDbi Q02643.
PRIDEi Q02643.

Protocols and materials databases

DNASUi 2692.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000326139 ; ENSP00000320180 ; ENSG00000106128 .
GeneIDi 2692.
KEGGi hsa:2692.
UCSCi uc003tbx.3. human.

Organism-specific databases

CTDi 2692.
GeneCardsi GC07P030978.
HGNCi HGNC:4266. GHRHR.
MIMi 139191. gene.
612781. phenotype.
neXtProti NX_Q02643.
Orphaneti 231671. Isolated growth hormone deficiency type IB.
PharmGKBi PA28676.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG249002.
GeneTreei ENSGT00760000118800.
HOGENOMi HOG000008249.
HOVERGENi HBG008318.
InParanoidi Q02643.
KOi K04584.
OMAi IHYIIFN.
OrthoDBi EOG7TF78W.
PhylomeDBi Q02643.
TreeFami TF315710.

Enzyme and pathway databases

Reactomei REACT_18377. Glucagon-type ligand receptors.
REACT_19327. G alpha (s) signalling events.

Miscellaneous databases

EvolutionaryTracei Q02643.
GeneWikii Growth-hormone-releasing_hormone_receptor.
Growth_hormone-releasing_hormone_receptor.
GenomeRNAii 2692.
NextBioi 10644.
PROi Q02643.
SOURCEi Search...

Gene expression databases

Bgeei Q02643.
CleanExi HS_GHRHR.
ExpressionAtlasi Q02643. baseline.
Genevestigatori Q02643.

Family and domain databases

InterProi 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 ]
Pfami PF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view ]
PRINTSi PR01352. GHRHRECEPTOR.
PR00249. GPCRSECRETIN.
SMARTi SM00008. HormR. 1 hit.
[Graphical view ]
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-45.

Entry informationi

Entry nameiGHRHR_HUMAN
AccessioniPrimary (citable) accession number: Q02643
Secondary accession number(s): Q99863
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: July 15, 1998
Last modified: November 26, 2014
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3