SMS_HUMAN
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 03-AUG-2022, entry version 140.
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 PDBsum; 2MI1; -.
DR PDBsum; 7T10; -.
DR AlphaFoldDB; P61278; -.
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; P61278; -.
DR PeptideAtlas; P61278; -.
DR PRIDE; P61278; -.
DR ProteomicsDB; 57289; -.
DR ABCD; P61278; 1 sequenced antibody.
DR Antibodypedia; 3518; 543 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 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; PDEMRME; -.
DR OrthoDB; 1561305at2759; -.
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; 7 hits in 1068 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 141 other tissues.
DR Genevisible; P61278; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0005179; F:hormone activity; TAS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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:0010447; P:response to acidic pH; IEA:Ensembl.
DR GO; GO:0043200; P:response to amino acid; IEA:Ensembl.
DR GO; GO:0009408; P:response to heat; 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 InterPro; IPR004250; Somatostatin.
DR InterPro; IPR018142; Somatostatin/Cortistatin_C.
DR PANTHER; PTHR10558; PTHR10558; 1.
DR Pfam; PF03002; Somatostatin; 1.
DR PIRSF; PIRSF001814; Somatostatin; 1.
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..114
FT /evidence="ECO:0007829|PDB:2MI1"
SQ SEQUENCE 116 AA; 12736 MW; AB49BB89DC9DD8DA CRC64;
MLSCRLQCAL AALSIVLALG CVTGAPSDPR LRQFLQKSLA AAAGKQELAK YFLAELLSEP
NQTENDALEP EDLSQAAEQD EMRLELQRSA NSNPAMAPRE RKAGCKNFFW KTFTSC
