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 13-FEB-2019, entry version 170. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT growth 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., RA Evans R.M.; RT "Gene encoding human growth hormone-releasing factor precursor: RT structure, 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., RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., RA 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., RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., RA 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 RT project: 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 RT hormone-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., RA Wehrenberg W.B.; RT "Growth hormone-releasing factor from a human pancreatic tumor that RT caused 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., RA Ayoub D., 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 RT use of circular dichroism and nuclear magnetic resonance RT spectroscopy."; RL J. Mol. Biol. 191:553-561(1986). RN [11] {ECO:0000244|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 CC GHRH receptor on somatotrophs where it is taken up into endosomes. CC There the translocation domain inserts into the membrane, CC releasing the light chain which cleaves synaptobrevin and inhibits CC growth hormone exocytosis (PubMed:24029240, PubMed:26324071). CC {ECO:0000269|PubMed:24029240, ECO:0000305|PubMed:26324071}. CC -!- PHARMACEUTICAL: Available under the names Groliberin (Pharmacia) CC or Somatrel (Ferring). Also available under the name Geref CC (Serono). Geref is a synthetic acetylated form of residues 1 to 29 CC of GHRH. Used for the treatment of growth hormone deficiency. CC -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Growth hormone releasing CC hormone entry; CC URL="https://en.wikipedia.org/wiki/Growth_hormone_releasing_hormone"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- 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. [P01286-1] DR RefSeq; XP_011527090.1; XM_011528788.2. [P01286-2] DR UniGene; Hs.37023; -. DR PDB; 5BQM; X-ray; 3.10 A; B/D=34-73. DR PDBsum; 5BQM; -. DR ProteinModelPortal; P01286; -. DR BioGrid; 108958; 3. DR IntAct; P01286; 2. DR MINT; P01286; -. DR STRING; 9606.ENSP00000237527; -. DR BioMuta; GHRH; -. DR DMDM; 134521; -. DR PaxDb; P01286; -. DR PRIDE; P01286; -. DR ProteomicsDB; 51370; -. DR ProteomicsDB; 51371; -. [P01286-2] DR Ensembl; ENST00000237527; ENSP00000237527; ENSG00000118702. [P01286-1] DR Ensembl; ENST00000373611; ENSP00000362713; ENSG00000118702. [P01286-2] DR Ensembl; ENST00000373614; ENSP00000362716; ENSG00000118702. [P01286-1] DR GeneID; 2691; -. DR KEGG; hsa:2691; -. DR UCSC; uc002xgr.5; human. [P01286-1] DR CTD; 2691; -. DR DisGeNET; 2691; -. DR EuPathDB; HostDB:ENSG00000118702.9; -. DR GeneCards; GHRH; -. DR HGNC; HGNC:4265; GHRH. DR MIM; 139190; gene. DR neXtProt; NX_P01286; -. DR OpenTargets; ENSG00000118702; -. DR PharmGKB; PA28675; -. DR eggNOG; ENOG410J1XI; Eukaryota. DR eggNOG; ENOG410ZCJQ; LUCA. DR GeneTree; ENSGT00940000154183; -. DR HOGENOM; HOG000115417; -. DR HOVERGEN; HBG004478; -. DR InParanoid; P01286; -. DR KO; K05260; -. DR OMA; RQVDSVW; -. DR OrthoDB; 1445692at2759; -. DR PhylomeDB; P01286; -. DR TreeFam; TF353187; -. DR Reactome; R-HSA-418555; G alpha (s) signalling events. DR Reactome; R-HSA-420092; Glucagon-type ligand receptors. DR GenomeRNAi; 2691; -. DR PRO; PR:P01286; -. DR Proteomes; UP000005640; Chromosome 20. DR Bgee; ENSG00000118702; Expressed in 42 organ(s), highest expression level in right atrium auricular region. DR Genevisible; P01286; HS. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; ISS:BHF-UCL. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. 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:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome. DR GO; GO:0030252; P:growth hormone secretion; IDA:MGI. 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:BHF-UCL. DR GO; GO:0032094; P:response to food; ISS:BHF-UCL. DR InterPro; IPR000532; Glucagon_GIP_secretin_VIP. DR Pfam; PF00123; Hormone_2; 1. DR SMART; SM00070; GLUCA; 1. DR PROSITE; PS00260; GLUCAGON; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Amidation; KW Cleavage on pair of basic residues; Complete proteome; KW Direct protein sequencing; Pharmaceutical; Polymorphism; KW Reference proteome; Secreted; Signal. FT SIGNAL 1 20 {ECO:0000255}. FT PROPEP 21 31 {ECO:0000269|PubMed:6812220}. FT /FTId=PRO_0000011438. FT PEPTIDE 32 75 Somatoliberin. FT /FTId=PRO_0000011439. FT PROPEP 78 108 FT /FTId=PRO_0000011440. FT MOD_RES 75 75 Leucine amide. FT {ECO:0000269|PubMed:6812220}. FT VAR_SEQ 103 103 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:6192430}. FT /FTId=VSP_023146. FT VARIANT 32 32 Y -> C (in dbSNP:rs17787698). FT /FTId=VAR_049185. FT VARIANT 75 75 L -> F (in dbSNP:rs4988492). FT /FTId=VAR_024328. FT CONFLICT 92 92 E -> D (in Ref. 5; CAA24955). FT {ECO:0000305}. SQ SEQUENCE 108 AA; 12447 MW; 366AE05383488C53 CRC64; MPLWVFFFVI LTLSNSSHCS PPPPLTLRMR RYADAIFTNS YRKVLGQLSA RKLLQDIMSR QQGESNQERG ARARLGRQVD SMWAEQKQME LESILVALLQ KHSRNSQG //