ID   SMS_HUMAN               Reviewed;         116 AA.
AC   P61278; B2R5G3; P01166;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   24-JAN-2024, entry version 148.
DE   RecName: Full=Somatostatin;
DE   AltName: Full=Growth hormone release-inhibiting factor;
DE   Contains:
DE     RecName: Full=Somatostatin-28;
DE   Contains:
DE     RecName: Full=Somatostatin-14;
DE              Short=SST-14 {ECO:0000303|PubMed:29615476};
DE   Contains:
DE     RecName: Full=Neuronostatin {ECO:0000303|PubMed:29615476};
DE              Short=NST {ECO:0000303|PubMed:29615476};
DE   Flags: Precursor;
GN   Name=SST;
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], STRUCTURE BY NMR OF 103-116, AND DISULFIDE
RP   BONDS.
RX   PubMed=6126875; DOI=10.1073/pnas.79.15.4575;
RA   Shen L.-P., Pictet R.L., Rutter W.J.;
RT   "Human somatostatin I: sequence of the cDNA.";
RL   Proc. Natl. Acad. Sci. U.S.A. 79:4575-4579(1982).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6142531; DOI=10.1126/science.6142531;
RA   Shen L.-P., Rutter W.J.;
RT   "Sequence of the human somatostatin I gene.";
RL   Science 224:168-171(1984).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Fetal brain;
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   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [7]
RP   FUNCTION (NEURONOSTATIN AND SOMATOSTATIN-14).
RX   PubMed=29615476; DOI=10.1530/joe-18-0135;
RA   Luque R.M., Kineman R.D.;
RT   "Neuronostatin exerts actions on pituitary that are unique from its sibling
RT   peptide somatostatin.";
RL   J. Endocrinol. 237:217-227(2018).
CC   -!- FUNCTION: [Somatostatin-14]: Inhibits the secretion of pituitary
CC       hormones, including that of growth hormone/somatotropin (GH1), PRL,
CC       ACTH, luteinizing hormone (LH) and TSH. Also impairs ghrelin- and GnRH-
CC       stimulated secretion of GH1 and LH; the inhibition of ghrelin-
CC       stimulated secretion of GH1 can be further increased by neuronostatin.
CC       {ECO:0000269|PubMed:29615476}.
CC   -!- FUNCTION: [Neuronostatin]: May enhance low-glucose-induced glucagon
CC       release by pancreatic alpha cells (By similarity). This effect may be
CC       mediated by binding to GPR107 and PKA activation (By similarity). May
CC       regulate cardiac contractile function (By similarity). May compromise
CC       cardiomyocyte viability (By similarity). In the central nervous system,
CC       may impair memory retention and may affect hippocampal excitability (By
CC       similarity). May also have anxiolytic and anorexigenic effects (By
CC       similarity). May play a role in arterial pressure regulation (By
CC       similarity). May inhibit basal, but not ghrelin- or GnRH-stimulated
CC       secretion of GH1 or LH, but does not affect the release of other
CC       pituitary hormones, including PRL, ACTH, FSH or TSH. Potentiates
CC       inhibitory action of somatostatin on ghrelin-stimulated secretion of
CC       GH1, but not that on GnRH-stimulated secretion of LH (PubMed:29615476).
CC       {ECO:0000250|UniProtKB:P60041, ECO:0000250|UniProtKB:P60042,
CC       ECO:0000269|PubMed:29615476}.
CC   -!- INTERACTION:
CC       P61278; P05067: APP; NbExp=3; IntAct=EBI-20823968, EBI-77613;
CC       PRO_0000033087; P05026: ATP1B1; NbExp=2; IntAct=EBI-26451163, EBI-714630;
CC       PRO_0000033088; PRO_0000000092 [P05067]: APP; NbExp=8; IntAct=EBI-20824010, EBI-821758;
CC       PRO_0000033088; PRO_0000033088 [P61278]: SST; NbExp=3; IntAct=EBI-20824010, EBI-20824010;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P60042}.
CC   -!- PTM: C-terminal amidation of the neuronostatin peptide is required for
CC       its biological activity, including for the regulation of mean arterial
CC       pressure. {ECO:0000250|UniProtKB:P60042}.
CC   -!- PHARMACEUTICAL: A synthetic analog known as octreotide or SMS 201-995
CC       is available under the name Sandostatin (Novartis). It is used for the
CC       treatment of a variety of disorders including acromegaly and the
CC       symptomatic treatment of carcinoid tumors and vasoactive intestinal
CC       peptide tumors.
CC   -!- SIMILARITY: Belongs to the somatostatin family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Somatostatin entry;
CC       URL="https://en.wikipedia.org/wiki/Somatostatin";
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DR   EMBL; J00306; AAA60566.1; -; Genomic_DNA.
DR   EMBL; AK312177; BAG35110.1; -; mRNA.
DR   EMBL; CH471052; EAW78145.1; -; Genomic_DNA.
DR   EMBL; BC032625; AAH32625.1; -; mRNA.
DR   CCDS; CCDS3288.1; -.
DR   PIR; A43614; RIHUS1.
DR   RefSeq; NP_001039.1; NM_001048.3.
DR   PDB; 2MI1; NMR; -; A=103-116.
DR   PDB; 7T10; EM; 2.50 A; P=103-116.
DR   PDB; 7WIC; EM; 2.80 A; L=103-116.
DR   PDB; 7WJ5; EM; 3.72 A; S=103-116.
DR   PDB; 7XAT; EM; 2.85 A; F=103-116.
DR   PDB; 7XMR; EM; 3.10 A; L=103-116.
DR   PDB; 7XMS; EM; 2.90 A; L=103-116.
DR   PDB; 7Y27; EM; 3.48 A; C=105-116.
DR   PDBsum; 2MI1; -.
DR   PDBsum; 7T10; -.
DR   PDBsum; 7WIC; -.
DR   PDBsum; 7WJ5; -.
DR   PDBsum; 7XAT; -.
DR   PDBsum; 7XMR; -.
DR   PDBsum; 7XMS; -.
DR   PDBsum; 7Y27; -.
DR   AlphaFoldDB; P61278; -.
DR   EMDB; EMD-25586; -.
DR   EMDB; EMD-32528; -.
DR   EMDB; EMD-33098; -.
DR   EMDB; EMD-33302; -.
DR   EMDB; EMD-33303; -.
DR   SMR; P61278; -.
DR   BioGRID; 112628; 4.
DR   IntAct; P61278; 33.
DR   STRING; 9606.ENSP00000287641; -.
DR   BindingDB; P61278; -.
DR   PhosphoSitePlus; P61278; -.
DR   BioMuta; SST; -.
DR   DMDM; 47117741; -.
DR   MassIVE; P61278; -.
DR   PaxDb; 9606-ENSP00000287641; -.
DR   PeptideAtlas; P61278; -.
DR   ProteomicsDB; 57289; -.
DR   ABCD; P61278; 1 sequenced antibody.
DR   Antibodypedia; 3518; 634 antibodies from 41 providers.
DR   DNASU; 6750; -.
DR   Ensembl; ENST00000287641.4; ENSP00000287641.3; ENSG00000157005.4.
DR   GeneID; 6750; -.
DR   KEGG; hsa:6750; -.
DR   MANE-Select; ENST00000287641.4; ENSP00000287641.3; NM_001048.4; NP_001039.1.
DR   UCSC; uc003frn.4; human.
DR   AGR; HGNC:11329; -.
DR   CTD; 6750; -.
DR   DisGeNET; 6750; -.
DR   GeneCards; SST; -.
DR   HGNC; HGNC:11329; SST.
DR   HPA; ENSG00000157005; Group enriched (brain, intestine, pancreas, stomach).
DR   MIM; 182450; gene.
DR   neXtProt; NX_P61278; -.
DR   OpenTargets; ENSG00000157005; -.
DR   PharmGKB; PA36153; -.
DR   VEuPathDB; HostDB:ENSG00000157005; -.
DR   eggNOG; ENOG502S11K; Eukaryota.
DR   GeneTree; ENSGT00510000047914; -.
DR   HOGENOM; CLU_124515_1_1_1; -.
DR   InParanoid; P61278; -.
DR   OMA; AEQDDMR; -.
DR   OrthoDB; 5358664at2759; -.
DR   PhylomeDB; P61278; -.
DR   TreeFam; TF333185; -.
DR   PathwayCommons; P61278; -.
DR   Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   Reactome; R-HSA-9022702; MECP2 regulates transcription of neuronal ligands.
DR   SignaLink; P61278; -.
DR   SIGNOR; P61278; -.
DR   BioGRID-ORCS; 6750; 8 hits in 1144 CRISPR screens.
DR   ChiTaRS; SST; human.
DR   GeneWiki; Somatostatin; -.
DR   GenomeRNAi; 6750; -.
DR   Pharos; P61278; Tbio.
DR   PRO; PR:P61278; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; P61278; Protein.
DR   Bgee; ENSG00000157005; Expressed in type B pancreatic cell and 142 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR   GO; GO:0098992; C:neuronal dense core vesicle; IEA:Ensembl.
DR   GO; GO:0005179; F:hormone activity; TAS:UniProtKB.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:UniProtKB.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:UniProtKB.
DR   GO; GO:0007268; P:chemical synaptic transmission; TAS:UniProtKB.
DR   GO; GO:0007586; P:digestion; TAS:UniProtKB.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:UniProtKB.
DR   GO; GO:0008628; P:hormone-mediated apoptotic signaling pathway; TAS:UniProtKB.
DR   GO; GO:0006972; P:hyperosmotic response; IEA:Ensembl.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:UniProtKB.
DR   GO; GO:0030334; P:regulation of cell migration; IBA:GO_Central.
DR   GO; GO:0099072; P:regulation of postsynaptic membrane neurotransmitter receptor levels; IEA:Ensembl.
DR   GO; GO:0010447; P:response to acidic pH; IEA:Ensembl.
DR   GO; GO:0043200; P:response to amino acid; IEA:Ensembl.
DR   GO; GO:0007584; P:response to nutrient; TAS:UniProtKB.
DR   GO; GO:0048545; P:response to steroid hormone; IEA:Ensembl.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR   GO; GO:0038170; P:somatostatin signaling pathway; IEA:Ensembl.
DR   InterPro; IPR004250; Somatostatin.
DR   InterPro; IPR018142; Somatostatin/Cortistatin_C.
DR   PANTHER; PTHR10558; SOMATOSTATIN; 1.
DR   PANTHER; PTHR10558:SF2; SOMATOSTATIN; 1.
DR   Pfam; PF03002; Somatostatin; 1.
DR   PIRSF; PIRSF001814; Somatostatin; 1.
DR   Genevisible; P61278; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Cleavage on pair of basic residues;
KW   Disulfide bond; Hormone; Pharmaceutical; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..24
FT   PROPEP          25..88
FT                   /id="PRO_0000033086"
FT   PEPTIDE         31..43
FT                   /note="Neuronostatin"
FT                   /id="PRO_0000447375"
FT   PEPTIDE         89..116
FT                   /note="Somatostatin-28"
FT                   /id="PRO_0000033087"
FT   PEPTIDE         103..116
FT                   /note="Somatostatin-14"
FT                   /id="PRO_0000033088"
FT   REGION          62..82
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         43
FT                   /note="Alanine amide"
FT                   /evidence="ECO:0000250|UniProtKB:P01168"
FT   DISULFID        105..116
FT                   /evidence="ECO:0007744|PDB:2MI1"
FT   VARIANT         11
FT                   /note="A -> V (in dbSNP:rs35603672)"
FT                   /id="VAR_034499"
FT   VARIANT         61
FT                   /note="N -> T (in dbSNP:rs33934967)"
FT                   /id="VAR_034500"
FT   STRAND          107..109
FT                   /evidence="ECO:0007829|PDB:7T10"
FT   STRAND          110..112
FT                   /evidence="ECO:0007829|PDB:7XMS"
SQ   SEQUENCE   116 AA;  12736 MW;  AB49BB89DC9DD8DA CRC64;
     MLSCRLQCAL AALSIVLALG CVTGAPSDPR LRQFLQKSLA AAAGKQELAK YFLAELLSEP
     NQTENDALEP EDLSQAAEQD EMRLELQRSA NSNPAMAPRE RKAGCKNFFW KTFTSC
//