SOMA_HUMAN
ID SOMA_HUMAN Reviewed; 217 AA.
AC P01241; A6NEF6; Q14405; Q16631; Q5EB53; Q9HBZ1; Q9UMJ7; Q9UNL5;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 2.
DT 03-AUG-2022, entry version 237.
DE RecName: Full=Somatotropin;
DE AltName: Full=Growth hormone;
DE Short=GH;
DE Short=GH-N;
DE AltName: Full=Growth hormone 1;
DE AltName: Full=Pituitary growth hormone;
DE Flags: Precursor;
GN Name=GH1;
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] (ISOFORM 1).
RX PubMed=386281; DOI=10.1093/nar/7.2.305;
RA Roskam W., Rougeon F.;
RT "Molecular cloning and nucleotide sequence of the human growth hormone
RT structural gene.";
RL Nucleic Acids Res. 7:305-320(1979).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=377496; DOI=10.1126/science.377496;
RA Martial J.A., Hallewell R.A., Baxter J.D., Goodman H.M.;
RT "Human growth hormone: complementary DNA cloning and expression in
RT bacteria.";
RL Science 205:602-607(1979).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND POSSIBLE ALTERNATIVE
RP SPLICING.
RX PubMed=6269091; DOI=10.1093/nar/9.15.3719;
RA Denoto F.M., Moore D.D., Goodman H.M.;
RT "Human growth hormone DNA sequence and mRNA structure: possible alternative
RT splicing.";
RL Nucleic Acids Res. 9:3719-3730(1981).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7169009; DOI=10.1089/dna.1.1982.1.239;
RA Seeburg P.H.;
RT "The human growth hormone gene family: nucleotide sequences show recent
RT divergence and predict a new polypeptide hormone.";
RL DNA 1:239-249(1982).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2744760; DOI=10.1016/0888-7543(89)90271-1;
RA Chen E.Y., Liao Y.C., Smith D.H., Barrera-Saldana H.A., Gelinas R.E.,
RA Seeburg P.H.;
RT "The human growth hormone locus: nucleotide sequence, biology, and
RT evolution.";
RL Genomics 4:479-497(1989).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Pituitary;
RA Gu J., Huang Q.-H., Li N., Xu S.-H., Han Z.-G., Fu G., Chen Z.;
RT "A novel gene expressed in human pituitary.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=18473352; DOI=10.1002/humu.20767;
RA Sedman L., Padhukasahasram B., Kelgo P., Laan M.;
RT "Complex signatures of locus-specific selective pressures and gene
RT conversion on human growth hormone/chorionic somatomammotropin genes.";
RL Hum. Mutat. 29:1181-1193(2008).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Pituitary;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 5).
RC TISSUE=Pituitary;
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 [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-26.
RX PubMed=3912261; DOI=10.1016/0378-1119(85)90319-1;
RA Gray G.L., Baldridge J.S., McKeown K.S., Heyneker H.L., Chang C.N.;
RT "Periplasmic production of correctly processed human growth hormone in
RT Escherichia coli: natural and bacterial signal sequences are
RT interchangeable.";
RL Gene 39:247-254(1985).
RN [13]
RP PROTEIN SEQUENCE OF 27-217.
RX PubMed=5810834; DOI=10.1016/0003-9861(69)90489-5;
RA Li C.H., Dixon J.S., Liu W.-K.;
RT "Human pituitary growth hormone. XIX. The primary structure of the
RT hormone.";
RL Arch. Biochem. Biophys. 133:70-91(1969).
RN [14]
RP PROTEIN SEQUENCE OF 27-217, AND SEQUENCE REVISION.
RX PubMed=5144027; DOI=10.1016/s0003-9861(71)80060-7;
RA Li C.H., Dixon J.S.;
RT "Human pituitary growth hormone. 32. The primary structure of the hormone:
RT revision.";
RL Arch. Biochem. Biophys. 146:233-236(1971).
RN [15]
RP SEQUENCE REVISION.
RX PubMed=4675454; DOI=10.1111/j.1399-3011.1972.tb03430.x;
RA Bewley T.A., Dixon J.S., Li C.H.;
RT "Sequence comparison of human pituitary growth hormone, human chorionic
RT somatomammotropin, and ovine pituitary growth and lactogenic hormones.";
RL Int. J. Pept. Protein Res. 4:281-287(1972).
RN [16]
RP PROTEIN SEQUENCE OF 27-61 AND 102-124.
RX PubMed=5279046; DOI=10.1038/newbio230090a0;
RA Niall H.D.;
RT "Revised primary structure for human growth hormone.";
RL Nature New Biol. 230:90-91(1971).
RN [17]
RP SEQUENCE REVISION TO 119-120 AND 157-159.
RX PubMed=5279528; DOI=10.1073/pnas.68.4.866;
RA Niall H.D., Hogan M.L., Sauer R., Rosenblum I.Y., Greenwood F.C.;
RT "Sequences of pituitary and placental lactogenic and growth hormones:
RT evolution from a primordial peptide by gene reduplication.";
RL Proc. Natl. Acad. Sci. U.S.A. 68:866-869(1971).
RN [18]
RP SEQUENCE REVISION.
RA Niall H.D.;
RT "The chemistry of the human lactogenic hormones.";
RL (In) Griffiths K. (eds.);
RL Prolactin and carcinogenesis, Proc. fourth tenovus workshop prolactin,
RL pp.13-20, Alpha Omega Alpha Press, Cardiff (1972).
RN [19]
RP PROTEIN SEQUENCE OF 27-79 (ISOFORM 2).
RX PubMed=7462247; DOI=10.1016/s0021-9258(19)69793-0;
RA Chapman G.E., Rogers K.M., Brittain T., Bradshaw R.A., Bates O.J.,
RA Turner C., Cary P.D., Crane-Robinson C.;
RT "The 20,000 molecular weight variant of human growth hormone. Preparation
RT and some physical and chemical properties.";
RL J. Biol. Chem. 256:2395-2401(1981).
RN [20]
RP PROTEIN SEQUENCE OF 46-80 (ISOFORM 2).
RX PubMed=7356479; DOI=10.1016/0006-291x(80)90363-0;
RA Lewis U.J., Bonewald L.F., Lewis L.J.;
RT "The 20,000-dalton variant of human growth hormone: location of the amino
RT acid deletions.";
RL Biochem. Biophys. Res. Commun. 92:511-516(1980).
RN [21]
RP DEAMIDATION AT GLN-163 AND ASN-178.
RX PubMed=7028740; DOI=10.1016/s0021-9258(19)68453-x;
RA Lewis U.J., Singh R.N., Bonewald L.F., Seavey B.K.;
RT "Altered proteolytic cleavage of human growth hormone as a result of
RT deamidation.";
RL J. Biol. Chem. 256:11645-11650(1981).
RN [22]
RP INVOLVEMENT IN IGHD1A.
RX PubMed=8364549; DOI=10.1093/hmg/2.7.1073;
RA Igarashi Y., Ogawa M., Kamijo T., Iwatani N., Nishi Y., Kohno H.,
RA Masumura T., Koga J.;
RT "A new mutation causing inherited growth hormone deficiency: a compound
RT heterozygote of a 6.7 kb deletion and a two base deletion in the third exon
RT of the GH-1 gene.";
RL Hum. Mol. Genet. 2:1073-1074(1993).
RN [23]
RP PHOSPHORYLATION AT SER-132 AND SER-176.
RC TISSUE=Pituitary;
RX PubMed=14997482; DOI=10.1002/pmic.200300584;
RA Giorgianni F., Beranova-Giorgianni S., Desiderio D.M.;
RT "Identification and characterization of phosphorylated proteins in the
RT human pituitary.";
RL Proteomics 4:587-598(2004).
RN [24]
RP REVIEW.
RX PubMed=10393484; DOI=10.1159/000053128;
RA Baumann G.;
RT "Growth hormone heterogeneity in human pituitary and plasma.";
RL Horm. Res. 51 Suppl. 1:2-6(1999).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pituitary;
RX PubMed=16807684; DOI=10.1007/s11102-006-8916-x;
RA Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.;
RT "Phosphoproteomic analysis of the human pituitary.";
RL Pituitary 9:109-120(2006).
RN [26]
RP 3D-STRUCTURE MODELING.
RX PubMed=3447173; DOI=10.1002/prot.340020209;
RA Cohen F.E., Kuntz I.D.;
RT "Prediction of the three-dimensional structure of human growth hormone.";
RL Proteins 2:162-166(1987).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=1549776; DOI=10.1126/science.1549776;
RA de Vos A.M., Ultsch M., Kossiakoff A.A.;
RT "Human growth hormone and extracellular domain of its receptor: crystal
RT structure of the complex.";
RL Science 255:306-312(1992).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
RX PubMed=7984244; DOI=10.1038/372478a0;
RA Somers W., Ultsch M., de Vos A.M., Kossiakoff A.A.;
RT "The X-ray structure of a growth hormone-prolactin receptor complex.";
RL Nature 372:478-481(1994).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RA Chantalat L., Chirgadze N.Y., Jones N., Korber F., Navaza J.,
RA Pavlovsk A.G., Wlodawer A.;
RT "The crystal-structure of wild-type growth-hormone at 2.5-A resolution.";
RL Protein Pept. Lett. 2:333-340(1995).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=8943276; DOI=10.1074/jbc.271.50.32197;
RA Sundstroem M., Lundqvist T., Roedin J., Giebel L.B., Milligan D.,
RA Norstedt G.;
RT "Crystal structure of an antagonist mutant of human growth hormone, G120R,
RT in complex with its receptor at 2.9-A resolution.";
RL J. Biol. Chem. 271:32197-32203(1996).
RN [31]
RP VARIANT KWKS CYS-103.
RX PubMed=8552145; DOI=10.1056/nejm199602153340704;
RA Takahashi Y., Kaji H., Okimura Y., Goji K., Abe H., Chihara K.;
RT "Short stature caused by a mutant growth hormone.";
RL N. Engl. J. Med. 334:432-436(1996).
RN [32]
RP ERRATUM OF PUBMED:8552145.
RA Takahashi Y., Kaji H., Okimura Y., Goji K., Abe H., Chihara K.;
RL N. Engl. J. Med. 334:1207-1207(1996).
RN [33]
RP VARIANT ALA-3, AND VARIANT IGHD2 HIS-209.
RX PubMed=9152628; DOI=10.1507/endocrj.44.149;
RA Miyata I., Cogan J.D., Prince M.A., Kamijo T., Ogawa M., Phillips J.A. III;
RT "Detection of growth hormone gene defects by dideoxy fingerprinting
RT (ddF).";
RL Endocr. J. 44:149-154(1997).
RN [34]
RP VARIANT KWKS GLY-138.
RX PubMed=9276733; DOI=10.1172/jci119627;
RA Takahashi Y., Shirono H., Arisaka O., Takahashi K., Yagi T., Koga J.,
RA Kaji H., Okimura Y., Abe H., Tanaka T., Chihara K.;
RT "Biologically inactive growth hormone caused by an amino acid
RT substitution.";
RL J. Clin. Invest. 100:1159-1165(1997).
RN [35]
RP VARIANT CYS-105.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [36]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [37]
RP VARIANT IGHD2 HIS-209.
RX PubMed=11502836; DOI=10.1210/jcem.86.8.7723;
RA Deladoey J., Stocker P., Mullis P.E.;
RT "Autosomal dominant GH deficiency due to an Arg183His GH-1 gene mutation:
RT clinical and molecular evidence of impaired regulated GH secretion.";
RL J. Clin. Endocrinol. Metab. 86:3941-3947(2001).
RN [38]
RP VARIANTS IGHD1B PRO-16; ASN-37; CYS-42; ILE-53; ARG-67; ASP-73; PHE-97;
RP LYS-100; LEU-117; CYS-134; ARG-134 AND ALA-201, AND VARIANTS ALA-3 AND
RP ILE-136.
RX PubMed=12655557; DOI=10.1002/humu.10168;
RA Millar D.S., Lewis M.D., Horan M., Newsway V., Easter T.E., Gregory J.W.,
RA Fryklund L., Norin M., Crowne E.C., Davies S.J., Edwards P., Kirk J.,
RA Waldron K., Smith P.J., Phillips J.A. III, Scanlon M.F., Krawczak M.,
RA Cooper D.N., Procter A.M.;
RT "Novel mutations of the growth hormone 1 (GH1) gene disclosed by modulation
RT of the clinical selection criteria for individuals with short stature.";
RL Hum. Mutat. 21:424-440(2003).
RN [39]
RP VARIANT SHORT STATURE MET-205, AND VARIANTS ALA-3 AND ILE-136.
RX PubMed=15001589; DOI=10.1210/jc.2003-030652;
RA Lewis M.D., Horan M., Millar D.S., Newsway V., Easter T.E., Fryklund L.,
RA Gregory J.W., Norin M., Del Valle C.-J., Lopez-Siguero J.P., Canete R.,
RA Lopez-Canti L.F., Diaz-Torrado N., Espino R., Ulied A., Scanlon M.F.,
RA Procter A.M., Cooper D.N.;
RT "A novel dysfunctional growth hormone variant (Ile179Met) exhibits a
RT decreased ability to activate the extracellular signal-regulated kinase
RT pathway.";
RL J. Clin. Endocrinol. Metab. 89:1068-1075(2004).
RN [40]
RP VARIANT SHORT STATURE SER-79, AND CHARACTERIZATION OF VARIANT SHORT STATURE
RP SER-79.
RX PubMed=15713716; DOI=10.1210/jc.2004-1838;
RA Besson A., Salemi S., Deladoeey J., Vuissoz J.-M., Eble A.,
RA Bidlingmaier M., Buergi S., Honegger U., Flueck C., Mullis P.E.;
RT "Short stature caused by a biologically inactive mutant growth hormone (GH-
RT C53S).";
RL J. Clin. Endocrinol. Metab. 90:2493-2499(2005).
RN [41]
RP CHARACTERIZATION OF VARIANT KWKS CYS-103.
RX PubMed=17519310; DOI=10.1210/jc.2006-2238;
RA Petkovic V., Besson A., Thevis M., Lochmatter D., Eble A., Fluck C.E.,
RA Mullis P.E.;
RT "Evaluation of the biological activity of a growth hormone (GH) mutant
RT (R77C) and its impact on GH responsiveness and stature.";
RL J. Clin. Endocrinol. Metab. 92:2893-2901(2007).
CC -!- FUNCTION: Plays an important role in growth control. Its major role in
CC stimulating body growth is to stimulate the liver and other tissues to
CC secrete IGF-1. It stimulates both the differentiation and proliferation
CC of myoblasts. It also stimulates amino acid uptake and protein
CC synthesis in muscle and other tissues.
CC -!- SUBUNIT: Monomer, dimer, trimer, tetramer and pentamer, disulfide-
CC linked or non-covalently associated, in homomeric and heteromeric
CC combinations. Can also form a complex either with GHBP or with the
CC alpha2-macroglobulin complex.
CC -!- INTERACTION:
CC P01241; P10912: GHR; NbExp=4; IntAct=EBI-1026046, EBI-286316;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=22 kDa;
CC IsoId=P01241-1; Sequence=Displayed;
CC Name=2; Synonyms=20 kDa variant;
CC IsoId=P01241-2; Sequence=VSP_006200;
CC Name=3;
CC IsoId=P01241-3; Sequence=VSP_006201;
CC Name=4;
CC IsoId=P01241-4; Sequence=VSP_006202;
CC Name=5;
CC IsoId=P01241-5; Sequence=VSP_045642;
CC -!- DISEASE: Growth hormone deficiency, isolated, 1A (IGHD1A) [MIM:262400]:
CC An autosomal recessive, severe deficiency of growth hormone leading to
CC dwarfism. Patients often develop antibodies to administered growth
CC hormone. {ECO:0000269|PubMed:8364549}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Growth hormone deficiency, isolated, 1B (IGHD1B) [MIM:612781]:
CC An autosomal recessive deficiency of growth hormone leading to short
CC stature. Patients have low but detectable levels of growth hormone,
CC significantly retarded bone age, and a positive response and
CC immunologic tolerance to growth hormone therapy.
CC {ECO:0000269|PubMed:12655557}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Kowarski syndrome (KWKS) [MIM:262650]: A syndrome clinically
CC characterized by short stature associated with bioinactive growth
CC hormone, normal or slightly increased growth hormone secretion,
CC pathologically low insulin-like growth factor 1 levels, and normal
CC catch-up growth on growth hormone replacement therapy.
CC {ECO:0000269|PubMed:17519310, ECO:0000269|PubMed:8552145,
CC ECO:0000269|PubMed:9276733}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Growth hormone deficiency, isolated, 2 (IGHD2) [MIM:173100]:
CC An autosomal dominant deficiency of growth hormone leading to short
CC stature. Clinical severity is variable. Patients have a positive
CC response and immunologic tolerance to growth hormone therapy.
CC {ECO:0000269|PubMed:11502836, ECO:0000269|PubMed:9152628}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- PHARMACEUTICAL: Available under the names Nutropin or Protropin
CC (Genentech), Norditropin (Novo Nordisk), Genotropin (Pharmacia Upjohn),
CC Humatrope (Eli Lilly) and Saizen or Serostim (Serono). Used for the
CC treatment of growth hormone deficiency and for Turner's syndrome.
CC -!- MISCELLANEOUS: Circulating GH shows a great heterogeneity due to
CC alternative splicing, differential post-translational modifications of
CC monomeric forms, oligomerization, optional binding to 2 different GH-
CC binding proteins, and potentially proteolytic processing.
CC -!- SIMILARITY: Belongs to the somatotropin/prolactin family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Growth hormone entry;
CC URL="https://en.wikipedia.org/wiki/Growth_hormone";
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DR EMBL; V00519; CAA23778.1; -; mRNA.
DR EMBL; V00520; CAA23779.1; -; Genomic_DNA.
DR EMBL; M13438; AAA98618.1; -; Genomic_DNA.
DR EMBL; J03071; AAA52549.1; -; Genomic_DNA.
DR EMBL; AF185611; AAG09699.1; -; mRNA.
DR EMBL; AF110644; AAD48584.1; -; mRNA.
DR EMBL; EU421712; ABZ88713.1; -; Genomic_DNA.
DR EMBL; AC127029; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471109; EAW94233.1; -; Genomic_DNA.
DR EMBL; BC062475; AAH62475.1; -; mRNA.
DR EMBL; BC075012; AAH75012.1; -; mRNA.
DR EMBL; BC075013; AAH75013.1; -; mRNA.
DR EMBL; BC090045; AAH90045.1; -; mRNA.
DR EMBL; CD106566; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; M14398; AAA52554.1; -; mRNA.
DR CCDS; CCDS11653.1; -. [P01241-1]
DR CCDS; CCDS11654.1; -. [P01241-5]
DR CCDS; CCDS45760.1; -. [P01241-2]
DR PIR; A93731; STHU.
DR RefSeq; NP_000506.2; NM_000515.4. [P01241-1]
DR RefSeq; NP_072053.1; NM_022559.3. [P01241-2]
DR RefSeq; NP_072054.1; NM_022560.3. [P01241-5]
DR PDB; 1A22; X-ray; 2.60 A; A=27-217.
DR PDB; 1AXI; X-ray; 2.10 A; A=27-217.
DR PDB; 1BP3; X-ray; 2.90 A; A=27-217.
DR PDB; 1HGU; X-ray; 2.50 A; A=27-217.
DR PDB; 1HUW; X-ray; 2.00 A; A=27-217.
DR PDB; 1HWG; X-ray; 2.50 A; A=27-217.
DR PDB; 1HWH; X-ray; 2.90 A; A=27-217.
DR PDB; 1KF9; X-ray; 2.60 A; A/D=27-217.
DR PDB; 3HHR; X-ray; 2.80 A; A=27-216.
DR PDB; 6QIO; X-ray; 1.95 A; D=27-217.
DR PDBsum; 1A22; -.
DR PDBsum; 1AXI; -.
DR PDBsum; 1BP3; -.
DR PDBsum; 1HGU; -.
DR PDBsum; 1HUW; -.
DR PDBsum; 1HWG; -.
DR PDBsum; 1HWH; -.
DR PDBsum; 1KF9; -.
DR PDBsum; 3HHR; -.
DR PDBsum; 6QIO; -.
DR AlphaFoldDB; P01241; -.
DR BMRB; P01241; -.
DR SASBDB; P01241; -.
DR SMR; P01241; -.
DR BioGRID; 108955; 11.
DR DIP; DIP-1022N; -.
DR IntAct; P01241; 5.
DR STRING; 9606.ENSP00000312673; -.
DR iPTMnet; P01241; -.
DR MetOSite; P01241; -.
DR PhosphoSitePlus; P01241; -.
DR BioMuta; GH1; -.
DR MassIVE; P01241; -.
DR PaxDb; P01241; -.
DR PeptideAtlas; P01241; -.
DR PRIDE; P01241; -.
DR ProteomicsDB; 51353; -. [P01241-1]
DR ProteomicsDB; 51354; -. [P01241-2]
DR ProteomicsDB; 51355; -. [P01241-3]
DR ProteomicsDB; 51356; -. [P01241-4]
DR ProteomicsDB; 982; -.
DR Antibodypedia; 52672; 1368 antibodies from 38 providers.
DR DNASU; 2688; -.
DR Ensembl; ENST00000323322.10; ENSP00000312673.5; ENSG00000259384.7. [P01241-1]
DR Ensembl; ENST00000351388.8; ENSP00000343791.4; ENSG00000259384.7. [P01241-5]
DR Ensembl; ENST00000458650.6; ENSP00000408486.2; ENSG00000259384.7. [P01241-2]
DR GeneID; 2688; -.
DR KEGG; hsa:2688; -.
DR MANE-Select; ENST00000323322.10; ENSP00000312673.5; NM_000515.5; NP_000506.2.
DR UCSC; uc002jdi.4; human. [P01241-1]
DR CTD; 2688; -.
DR DisGeNET; 2688; -.
DR GeneCards; GH1; -.
DR HGNC; HGNC:4261; GH1.
DR HPA; ENSG00000259384; Tissue enriched (pituitary).
DR MalaCards; GH1; -.
DR MIM; 139250; gene.
DR MIM; 173100; phenotype.
DR MIM; 262400; phenotype.
DR MIM; 262650; phenotype.
DR MIM; 612781; phenotype.
DR neXtProt; NX_P01241; -.
DR OpenTargets; ENSG00000259384; -.
DR Orphanet; 231662; Isolated growth hormone deficiency type IA.
DR Orphanet; 231671; Isolated growth hormone deficiency type IB.
DR Orphanet; 231679; Isolated growth hormone deficiency type II.
DR Orphanet; 629; Short stature due to growth hormone qualitative anomaly.
DR PharmGKB; PA171; -.
DR VEuPathDB; HostDB:ENSG00000259384; -.
DR eggNOG; ENOG502R5GJ; Eukaryota.
DR GeneTree; ENSGT00950000182818; -.
DR HOGENOM; CLU_088274_2_1_1; -.
DR InParanoid; P01241; -.
DR OMA; NSQVAFC; -.
DR PhylomeDB; P01241; -.
DR TreeFam; TF332592; -.
DR PathwayCommons; P01241; -.
DR Reactome; R-HSA-1170546; Prolactin receptor signaling.
DR Reactome; R-HSA-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR Reactome; R-HSA-982772; Growth hormone receptor signaling.
DR SABIO-RK; P01241; -.
DR SignaLink; P01241; -.
DR SIGNOR; P01241; -.
DR BioGRID-ORCS; 2688; 8 hits in 1036 CRISPR screens.
DR ChiTaRS; GH1; human.
DR EvolutionaryTrace; P01241; -.
DR GenomeRNAi; 2688; -.
DR Pharos; P01241; Tbio.
DR PRO; PR:P01241; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P01241; protein.
DR Bgee; ENSG00000259384; Expressed in pituitary gland and 79 other tissues.
DR ExpressionAtlas; P01241; baseline and differential.
DR Genevisible; P01241; HS.
DR GO; GO:0031904; C:endosome lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0070195; C:growth hormone receptor complex; IDA:CAFA.
DR GO; GO:0008083; F:growth factor activity; IPI:BHF-UCL.
DR GO; GO:0005131; F:growth hormone receptor binding; IDA:MGI.
DR GO; GO:0005179; F:hormone activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005148; F:prolactin receptor binding; IDA:AgBase.
DR GO; GO:0048513; P:animal organ development; IBA:GO_Central.
DR GO; GO:0070977; P:bone maturation; IDA:BHF-UCL.
DR GO; GO:0060396; P:growth hormone receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0010536; P:positive regulation of activation of Janus kinase activity; IDA:BHF-UCL.
DR GO; GO:0010828; P:positive regulation of glucose transmembrane transport; IDA:MGI.
DR GO; GO:0045927; P:positive regulation of growth; IBA:GO_Central.
DR GO; GO:0043568; P:positive regulation of insulin-like growth factor receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; TAS:BHF-UCL.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IDA:BHF-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IDA:BHF-UCL.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IDA:BHF-UCL.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:BHF-UCL.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IDA:BHF-UCL.
DR GO; GO:0032355; P:response to estradiol; IDA:BHF-UCL.
DR GO; GO:0031667; P:response to nutrient levels; IBA:GO_Central.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR001400; Somatotropin/Prolactin.
DR InterPro; IPR018116; Somatotropin_CS.
DR PANTHER; PTHR11417; PTHR11417; 1.
DR Pfam; PF00103; Hormone_1; 1.
DR PRINTS; PR00836; SOMATOTROPIN.
DR SUPFAM; SSF47266; SSF47266; 1.
DR PROSITE; PS00266; SOMATOTROPIN_1; 1.
DR PROSITE; PS00338; SOMATOTROPIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Disease variant; Disulfide bond; Dwarfism; Hormone; Metal-binding;
KW Pharmaceutical; Phosphoprotein; Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..26
FT /evidence="ECO:0000269|PubMed:5144027,
FT ECO:0000269|PubMed:5279046, ECO:0000269|PubMed:5810834"
FT CHAIN 27..217
FT /note="Somatotropin"
FT /id="PRO_0000032988"
FT BINDING 44
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 200
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 132
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:14997482"
FT MOD_RES 163
FT /note="Deamidated glutamine; by deterioration"
FT /evidence="ECO:0000269|PubMed:7028740"
FT MOD_RES 176
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:14997482"
FT MOD_RES 178
FT /note="Deamidated asparagine; by deterioration"
FT /evidence="ECO:0000269|PubMed:7028740"
FT DISULFID 79..191
FT /evidence="ECO:0000269|PubMed:5144027"
FT DISULFID 208..215
FT VAR_SEQ 58..97
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045642"
FT VAR_SEQ 58..72
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_006200"
FT VAR_SEQ 111..148
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_006201"
FT VAR_SEQ 117..162
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10931946"
FT /id="VSP_006202"
FT VARIANT 3
FT /note="T -> A (found in patients with isolated growth
FT hormone deficiency; dbSNP:rs2001345)"
FT /evidence="ECO:0000269|PubMed:12655557,
FT ECO:0000269|PubMed:15001589, ECO:0000269|PubMed:9152628"
FT /id="VAR_011917"
FT VARIANT 16
FT /note="L -> P (in IGHD1B; suppresses secretion)"
FT /evidence="ECO:0000269|PubMed:12655557"
FT /id="VAR_015801"
FT VARIANT 37
FT /note="D -> N (in IGHD1B)"
FT /evidence="ECO:0000269|PubMed:12655557"
FT /id="VAR_015802"
FT VARIANT 42
FT /note="R -> C (in IGHD1B; reduced secretion;
FT dbSNP:rs71640273)"
FT /evidence="ECO:0000269|PubMed:12655557"
FT /id="VAR_015803"
FT VARIANT 53
FT /note="T -> I (in IGHD1B; reduced ability to activate the
FT JAK/STAT pathway)"
FT /evidence="ECO:0000269|PubMed:12655557"
FT /id="VAR_015804"
FT VARIANT 67
FT /note="K -> R (in IGHD1B; reduced ability to activate the
FT JAK/STAT pathway)"
FT /evidence="ECO:0000269|PubMed:12655557"
FT /id="VAR_015805"
FT VARIANT 73
FT /note="N -> D (in IGHD1B; reduced ability to activate the
FT JAK/STAT pathway; dbSNP:rs71640276)"
FT /evidence="ECO:0000269|PubMed:12655557"
FT /id="VAR_015806"
FT VARIANT 79
FT /note="C -> S (in short stature; idiopathic autosomal;
FT affects binding affinity of GH for GHR and the potency of
FT GH to activate the JAK2/STAT5 signaling pathway;
FT dbSNP:rs137853222)"
FT /evidence="ECO:0000269|PubMed:15713716"
FT /id="VAR_032702"
FT VARIANT 97
FT /note="S -> F (in IGHD1B; reduced ability to activate the
FT JAK/STAT pathway)"
FT /evidence="ECO:0000269|PubMed:12655557"
FT /id="VAR_015807"
FT VARIANT 100
FT /note="E -> K (in IGHD1B)"
FT /evidence="ECO:0000269|PubMed:12655557"
FT /id="VAR_015808"
FT VARIANT 103
FT /note="R -> C (in KWKS; no effect on GHR signaling pathway;
FT does not affect interaction with GHR; results in a stronger
FT interaction with GHBP; does not affect subcellular
FT location; dbSNP:rs137853220)"
FT /evidence="ECO:0000269|PubMed:17519310,
FT ECO:0000269|PubMed:8552145"
FT /id="VAR_015809"
FT VARIANT 105
FT /note="S -> C (in dbSNP:rs6174)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_011918"
FT VARIANT 117
FT /note="Q -> L (in IGHD1B; reduced secretion)"
FT /evidence="ECO:0000269|PubMed:12655557"
FT /id="VAR_015810"
FT VARIANT 134
FT /note="S -> C (in IGHD1B)"
FT /evidence="ECO:0000269|PubMed:12655557"
FT /id="VAR_015811"
FT VARIANT 134
FT /note="S -> R (in IGHD1B; reduced ability to activate the
FT JAK/STAT pathway)"
FT /evidence="ECO:0000269|PubMed:12655557"
FT /id="VAR_015812"
FT VARIANT 136
FT /note="V -> I (in dbSNP:rs5388)"
FT /evidence="ECO:0000269|PubMed:12655557,
FT ECO:0000269|PubMed:15001589"
FT /id="VAR_011919"
FT VARIANT 138
FT /note="D -> G (in KWKS; loss of activity;
FT dbSNP:rs137853221)"
FT /evidence="ECO:0000269|PubMed:9276733"
FT /id="VAR_015813"
FT VARIANT 201
FT /note="T -> A (in IGHD1B; reduced ability to activate the
FT JAK/STAT pathway)"
FT /evidence="ECO:0000269|PubMed:12655557"
FT /id="VAR_015814"
FT VARIANT 205
FT /note="I -> M (in short stature; idiopathic autosomal;
FT dbSNP:rs148474991)"
FT /evidence="ECO:0000269|PubMed:15001589"
FT /id="VAR_032703"
FT VARIANT 209
FT /note="R -> H (in IGHD2; dbSNP:rs137853223)"
FT /evidence="ECO:0000269|PubMed:11502836,
FT ECO:0000269|PubMed:9152628"
FT /id="VAR_015815"
FT CONFLICT 35
FT /note="L -> P (in Ref. 1; CAA23778)"
FT /evidence="ECO:0000305"
FT CONFLICT 40
FT /note="M -> S (in Ref. 3; CAA23779)"
FT /evidence="ECO:0000305"
FT HELIX 32..61
FT /evidence="ECO:0007829|PDB:1HUW"
FT HELIX 64..72
FT /evidence="ECO:0007829|PDB:1HUW"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:1HGU"
FT TURN 80..83
FT /evidence="ECO:0007829|PDB:1HUW"
FT HELIX 90..94
FT /evidence="ECO:0007829|PDB:1HUW"
FT HELIX 98..110
FT /evidence="ECO:0007829|PDB:1HUW"
FT TURN 111..114
FT /evidence="ECO:0007829|PDB:1HUW"
FT HELIX 115..119
FT /evidence="ECO:0007829|PDB:1HUW"
FT HELIX 120..125
FT /evidence="ECO:0007829|PDB:1HUW"
FT TURN 129..133
FT /evidence="ECO:0007829|PDB:1HUW"
FT HELIX 136..154
FT /evidence="ECO:0007829|PDB:1HUW"
FT HELIX 163..166
FT /evidence="ECO:0007829|PDB:1AXI"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:1HGU"
FT HELIX 182..209
FT /evidence="ECO:0007829|PDB:1HUW"
FT TURN 212..216
FT /evidence="ECO:0007829|PDB:1AXI"
SQ SEQUENCE 217 AA; 24847 MW; 72CC15AF4ED1C51A CRC64;
MATGSRTSLL LAFGLLCLPW LQEGSAFPTI PLSRLFDNAM LRAHRLHQLA FDTYQEFEEA
YIPKEQKYSF LQNPQTSLCF SESIPTPSNR EETQQKSNLE LLRISLLLIQ SWLEPVQFLR
SVFANSLVYG ASDSNVYDLL KDLEEGIQTL MGRLEDGSPR TGQIFKQTYS KFDTNSHNDD
ALLKNYGLLY CFRKDMDKVE TFLRIVQCRS VEGSCGF
