ID   SLIB_HUMAN              Reviewed;         108 AA.
AC   P01286; Q4KN10; Q5JYR1;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   24-JAN-2024, entry version 197.
DE   RecName: Full=Somatoliberin;
DE   AltName: Full=Growth hormone-releasing factor;
DE            Short=GRF;
DE   AltName: Full=Growth hormone-releasing hormone;
DE            Short=GHRH;
DE   AltName: Full=Somatocrinin;
DE   AltName: Full=Somatorelin;
DE   AltName: INN=Sermorelin;
DE   Flags: Precursor;
GN   Name=GHRH; Synonyms=GHRF;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX   PubMed=6192430; DOI=10.1073/pnas.80.14.4311;
RA   Gubler U., Monahan J.J., Lomedico P.T., Bhatt R.S., Collier K.J.,
RA   Hoffman B.J., Boehlen P., Esch F., Ling N., Zeytin F., Brazeau P.,
RA   Poonian M.S., Gage L.P.;
RT   "Cloning and sequence analysis of cDNA for the precursor of human growth
RT   hormone-releasing factor, somatocrinin.";
RL   Proc. Natl. Acad. Sci. U.S.A. 80:4311-4314(1983).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3918305; DOI=10.1073/pnas.82.1.63;
RA   Mayo K.E., Cerelli G.M., Lebo R.V., Bruce B.D., Rosenfeld M.G., Evans R.M.;
RT   "Gene encoding human growth hormone-releasing factor precursor: structure,
RT   sequence, and chromosomal assignment.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:63-67(1985).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA   Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA   Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA   Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA   Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA   Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA   Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA   Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA   Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA   Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA   Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA   Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 6-101.
RX   PubMed=6415488; DOI=10.1038/306086a0;
RA   Mayo K.E., Vale W., Rivier J., Rosenfeld M.G., Evans R.M.;
RT   "Expression-cloning and sequence of a cDNA encoding human growth hormone-
RT   releasing factor.";
RL   Nature 306:86-88(1983).
RN   [6]
RP   PROTEIN SEQUENCE OF 32-75, AND AMIDATION AT LEU-75.
RX   PubMed=6812220; DOI=10.1126/science.6812220;
RA   Guillemin R., Brazeau P., Boehlen P., Esch F., Ling N., Wehrenberg W.B.;
RT   "Growth hormone-releasing factor from a human pancreatic tumor that caused
RT   acromegaly.";
RL   Science 218:585-587(1982).
RN   [7]
RP   BIOTECHNOLOGY.
RX   PubMed=24029240; DOI=10.1210/en.2013-1427;
RA   Somm E., Bonnet N., Zizzari P., Tolle V., Toulotte A., Jones R.,
RA   Epelbaum J., Martinez A., Hueppi P.S., Aubert M.L.;
RT   "Comparative inhibition of the GH/IGF-I axis obtained with either the
RT   targeted secretion inhibitor SXN101959 or the somatostatin analog
RT   octreotide in growing male rats.";
RL   Endocrinology 154:4237-4248(2013).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
RN   [9]
RP   STRUCTURE BY NMR OF 32-60.
RX   PubMed=2854259; DOI=10.1093/protein/1.5.399;
RA   Bruenger A.T., Clore G.M., Gronenborn A.M., Karplus M.;
RT   "Solution conformations of human growth hormone releasing factor:
RT   comparison of the restrained molecular dynamics and distance geometry
RT   methods for a system without long-range distance data.";
RL   Protein Eng. 1:399-406(1987).
RN   [10]
RP   STRUCTURE BY NMR OF 32-60.
RX   PubMed=3029387; DOI=10.1016/0022-2836(86)90147-6;
RA   Clore G.M., Martin S.R., Gronenborn A.M.;
RT   "Solution structure of human growth hormone releasing factor. Combined use
RT   of circular dichroism and nuclear magnetic resonance spectroscopy.";
RL   J. Mol. Biol. 191:553-561(1986).
RN   [11] {ECO:0007744|PDB:5BQM}
RP   X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 32-73, AND BIOTECHNOLOGY.
RX   PubMed=26324071; DOI=10.1038/srep13397;
RA   Masuyer G., Davies J.R., Moore K., Chaddock J.A., Ravi Acharya K.;
RT   "Structural analysis of Clostridium botulinum neurotoxin type D as a
RT   platform for the development of targeted secretion inhibitors.";
RL   Sci. Rep. 5:13397-13397(2015).
CC   -!- FUNCTION: GRF is released by the hypothalamus and acts on the
CC       adenohypophyse to stimulate the secretion of growth hormone.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P01286-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P01286-2; Sequence=VSP_023146;
CC   -!- BIOTECHNOLOGY: Can be used for targeted secretion inhibition. A
CC       construct with this protein's ligand domain inserted between the
CC       C.botulinum neurotoxin type D (BoNT/D, botD) light chain and
CC       translocation domains, when injected into rats, leads to decreased
CC       growth hormone production. The GHRH ligand domain binds to the GHRH
CC       receptor on somatotrophs where it is taken up into endosomes. There the
CC       translocation domain inserts into the membrane, releasing the light
CC       chain which cleaves synaptobrevin and inhibits growth hormone
CC       exocytosis (PubMed:24029240, PubMed:26324071).
CC       {ECO:0000269|PubMed:24029240, ECO:0000305|PubMed:26324071}.
CC   -!- PHARMACEUTICAL: Available under the names Groliberin (Pharmacia) or
CC       Somatrel (Ferring). Also available under the name Geref (Serono). Geref
CC       is a synthetic acetylated form of residues 1 to 29 of GHRH. Used for
CC       the treatment of growth hormone deficiency.
CC   -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Growth hormone releasing hormone
CC       entry;
CC       URL="https://en.wikipedia.org/wiki/Growth_hormone_releasing_hormone";
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DR   EMBL; L29177; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; L00137; AAA52608.1; -; Genomic_DNA.
DR   EMBL; L00134; AAA52608.1; JOINED; Genomic_DNA.
DR   EMBL; L00135; AAA52608.1; JOINED; Genomic_DNA.
DR   EMBL; L00136; AAA52608.1; JOINED; Genomic_DNA.
DR   EMBL; L00137; AAA52609.1; -; Genomic_DNA.
DR   EMBL; L00134; AAA52609.1; JOINED; Genomic_DNA.
DR   EMBL; L00135; AAA52609.1; JOINED; Genomic_DNA.
DR   EMBL; L00136; AAA52609.1; JOINED; Genomic_DNA.
DR   EMBL; AL031659; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC098109; AAH98109.1; -; mRNA.
DR   EMBL; BC098161; AAH98161.1; -; mRNA.
DR   EMBL; BC099727; AAH99727.1; -; mRNA.
DR   EMBL; X00094; CAA24955.1; -; mRNA.
DR   EMBL; X00094; CAA24956.1; -; mRNA.
DR   CCDS; CCDS13292.1; -. [P01286-1]
DR   CCDS; CCDS54460.1; -. [P01286-2]
DR   PIR; A21902; RHHUS.
DR   RefSeq; NP_001171660.1; NM_001184731.2. [P01286-2]
DR   RefSeq; NP_066567.1; NM_021081.5. [P01286-1]
DR   RefSeq; XP_011527086.1; XM_011528784.2.
DR   RefSeq; XP_011527090.1; XM_011528788.2.
DR   PDB; 5BQM; X-ray; 3.10 A; B/D=34-73.
DR   PDB; 7CZ5; EM; 2.60 A; P=32-75.
DR   PDB; 7V9M; EM; 3.29 A; P=32-75.
DR   PDBsum; 5BQM; -.
DR   PDBsum; 7CZ5; -.
DR   PDBsum; 7V9M; -.
DR   AlphaFoldDB; P01286; -.
DR   BMRB; P01286; -.
DR   EMDB; EMD-30505; -.
DR   EMDB; EMD-31825; -.
DR   SMR; P01286; -.
DR   BioGRID; 108958; 5.
DR   IntAct; P01286; 2.
DR   MINT; P01286; -.
DR   STRING; 9606.ENSP00000362716; -.
DR   BioMuta; GHRH; -.
DR   DMDM; 134521; -.
DR   MassIVE; P01286; -.
DR   PaxDb; 9606-ENSP00000362716; -.
DR   PeptideAtlas; P01286; -.
DR   Antibodypedia; 11938; 314 antibodies from 25 providers.
DR   DNASU; 2691; -.
DR   Ensembl; ENST00000237527.8; ENSP00000237527.4; ENSG00000118702.11. [P01286-2]
DR   Ensembl; ENST00000373614.7; ENSP00000362716.2; ENSG00000118702.11. [P01286-1]
DR   Ensembl; ENST00000709405.1; ENSP00000517673.1; ENSG00000291972.1. [P01286-1]
DR   Ensembl; ENST00000709406.1; ENSP00000517674.1; ENSG00000291972.1. [P01286-2]
DR   GeneID; 2691; -.
DR   KEGG; hsa:2691; -.
DR   MANE-Select; ENST00000373614.7; ENSP00000362716.2; NM_021081.6; NP_066567.1.
DR   UCSC; uc002xgr.5; human. [P01286-1]
DR   AGR; HGNC:4265; -.
DR   CTD; 2691; -.
DR   DisGeNET; 2691; -.
DR   GeneCards; GHRH; -.
DR   HGNC; HGNC:4265; GHRH.
DR   HPA; ENSG00000118702; Tissue enriched (brain).
DR   MIM; 139190; gene.
DR   neXtProt; NX_P01286; -.
DR   OpenTargets; ENSG00000118702; -.
DR   PharmGKB; PA28675; -.
DR   VEuPathDB; HostDB:ENSG00000118702; -.
DR   eggNOG; ENOG502S2N6; Eukaryota.
DR   GeneTree; ENSGT00950000183154; -.
DR   HOGENOM; CLU_174932_0_0_1; -.
DR   InParanoid; P01286; -.
DR   OMA; DSVWTDQ; -.
DR   OrthoDB; 4097249at2759; -.
DR   PhylomeDB; P01286; -.
DR   TreeFam; TF353187; -.
DR   PathwayCommons; P01286; -.
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   Reactome; R-HSA-420092; Glucagon-type ligand receptors.
DR   SignaLink; P01286; -.
DR   BioGRID-ORCS; 2691; 11 hits in 1147 CRISPR screens.
DR   GenomeRNAi; 2691; -.
DR   Pharos; P01286; Tbio.
DR   PRO; PR:P01286; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   RNAct; P01286; Protein.
DR   Bgee; ENSG00000118702; Expressed in primordial germ cell in gonad and 76 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; ISS:BHF-UCL.
DR   GO; GO:0043204; C:perikaryon; IBA:GO_Central.
DR   GO; GO:0043195; C:terminal bouton; ISS:BHF-UCL.
DR   GO; GO:0016608; F:growth hormone-releasing hormone activity; IDA:BHF-UCL.
DR   GO; GO:0031770; F:growth hormone-releasing hormone receptor binding; IPI:BHF-UCL.
DR   GO; GO:0005184; F:neuropeptide hormone activity; IBA:GO_Central.
DR   GO; GO:0051428; F:peptide hormone receptor binding; IBA:GO_Central.
DR   GO; GO:0021984; P:adenohypophysis development; ISS:BHF-UCL.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR   GO; GO:0030252; P:growth hormone secretion; IDA:MGI.
DR   GO; GO:0035264; P:multicellular organism growth; IMP:BHF-UCL.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR   GO; GO:0046005; P:positive regulation of circadian sleep/wake cycle, REM sleep; NAS:BHF-UCL.
DR   GO; GO:0060124; P:positive regulation of growth hormone secretion; IDA:BHF-UCL.
DR   GO; GO:0043568; P:positive regulation of insulin-like growth factor receptor signaling pathway; NAS:BHF-UCL.
DR   GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:MGI.
DR   GO; GO:0032094; P:response to food; ISS:BHF-UCL.
DR   InterPro; IPR000532; Glucagon_GIP_secretin_VIP.
DR   InterPro; IPR046963; VIP/GHRH-like.
DR   PANTHER; PTHR11213; GLUCAGON-FAMILY NEUROPEPTIDE; 1.
DR   PANTHER; PTHR11213:SF6; SOMATOLIBERIN; 1.
DR   Pfam; PF00123; Hormone_2; 1.
DR   SMART; SM00070; GLUCA; 1.
DR   PROSITE; PS00260; GLUCAGON; 1.
DR   Genevisible; P01286; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Amidation;
KW   Cleavage on pair of basic residues; Direct protein sequencing;
KW   Pharmaceutical; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..31
FT                   /evidence="ECO:0000269|PubMed:6812220"
FT                   /id="PRO_0000011438"
FT   PEPTIDE         32..75
FT                   /note="Somatoliberin"
FT                   /id="PRO_0000011439"
FT   PROPEP          78..108
FT                   /id="PRO_0000011440"
FT   MOD_RES         75
FT                   /note="Leucine amide"
FT                   /evidence="ECO:0000269|PubMed:6812220"
FT   VAR_SEQ         103
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:6192430"
FT                   /id="VSP_023146"
FT   VARIANT         32
FT                   /note="Y -> C (in dbSNP:rs17787698)"
FT                   /id="VAR_049185"
FT   VARIANT         75
FT                   /note="L -> F (in dbSNP:rs4988492)"
FT                   /id="VAR_024328"
FT   CONFLICT        92
FT                   /note="E -> D (in Ref. 5; CAA24955)"
FT                   /evidence="ECO:0000305"
FT   HELIX           34..58
FT                   /evidence="ECO:0007829|PDB:7CZ5"
SQ   SEQUENCE   108 AA;  12447 MW;  366AE05383488C53 CRC64;
     MPLWVFFFVI LTLSNSSHCS PPPPLTLRMR RYADAIFTNS YRKVLGQLSA RKLLQDIMSR
     QQGESNQERG ARARLGRQVD SMWAEQKQME LESILVALLQ KHSRNSQG
//