ID SSR3_HUMAN Reviewed; 418 AA. AC P32745; A8K550; Q53ZR7; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1993, sequence version 1. DT 24-JAN-2024, entry version 207. DE RecName: Full=Somatostatin receptor type 3; DE Short=SS-3-R; DE Short=SS3-R; DE Short=SS3R; DE Short=SST3; DE AltName: Full=SSR-28; GN Name=SSTR3; 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 [GENOMIC DNA], FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=1337145; DOI=10.1210/mend.6.12.1337145; RA Yamada Y., Reisine T., Law S.F., Ihara Y., Kubota A., Kagimoto S., RA Seino M., Seino Y., Bell G.I., Seino S.; RT "Somatostatin receptors, an expanding gene family: cloning and functional RT characterization of human SSTR3, a protein coupled to adenylyl cyclase."; RL Mol. Endocrinol. 6:2136-2142(1992). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8097479; DOI=10.1016/0014-5793(93)80124-d; RA Corness J.D., Demchyshyn L.L., Seeman P., van Tol H.H.M., Srikant C.B., RA Kent G., Patel Y.C., Niznik H.B.; RT "A human somatostatin receptor (SSTR3), located on chromosome 22, displays RT preferential affinity for somatostatin-14 like peptides."; RL FEBS Lett. 321:279-284(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Rasch A.C., Boehnke C., Petersenn S.; RT "The human somatostatin receptor subtype 3 contains an upstream exon in the RT 5'-untranslated region: functional promoter studies."; RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Kopatz S.A., Aronstam R.S., Sharma S.V.; RT "cDNA clones of human proteins involved in signal transduction sequenced by RT the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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). CC -!- FUNCTION: Receptor for somatostatin-14 and -28. This receptor is CC coupled via pertussis toxin sensitive G proteins to inhibition of CC adenylyl cyclase. {ECO:0000269|PubMed:1337145}. CC -!- SUBUNIT: Homodimer and heterodimer with SSTR2. Heterodimerization with CC SSTR2 inactivates SSTR3 receptor function (By similarity). CC {ECO:0000250}. CC -!- INTERACTION: CC P32745; P05067: APP; NbExp=3; IntAct=EBI-6266935, EBI-77613; CC P32745; O75970: MPDZ; NbExp=5; IntAct=EBI-6266935, EBI-821405; CC P32745; P30874: SSTR2; NbExp=3; IntAct=EBI-6266935, EBI-6266898; CC P32745; O55164: Mpdz; Xeno; NbExp=2; IntAct=EBI-6266935, EBI-7401093; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane CC protein {ECO:0000250}. Note=Internalized into endoplasmic vesicles upon CC somatostatin-stimulation. {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Brain, pituitary and pancreas. CC {ECO:0000269|PubMed:1337145}. CC -!- PTM: Phosphorylated. Phosphorylation increases upon somatostatin CC binding (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. 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; M96738; AAA60592.1; -; Genomic_DNA. DR EMBL; AY277678; AAP32288.1; -; Genomic_DNA. DR EMBL; AY322541; AAP84354.1; -; Genomic_DNA. DR EMBL; CR456585; CAG30471.1; -; mRNA. DR EMBL; AK291165; BAF83854.1; -; mRNA. DR EMBL; Z82188; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC096829; AAH96829.1; -; mRNA. DR CCDS; CCDS13944.1; -. DR PIR; A46226; A46226. DR RefSeq; NP_001042.1; NM_001051.4. DR RefSeq; NP_001265616.1; NM_001278687.2. DR RefSeq; XP_005261778.1; XM_005261721.4. DR RefSeq; XP_006724374.1; XM_006724311.2. DR RefSeq; XP_011528651.1; XM_011530349.2. DR RefSeq; XP_016884412.1; XM_017028923.1. DR RefSeq; XP_016884413.1; XM_017028924.1. DR AlphaFoldDB; P32745; -. DR EMDB; EMD-28907; -. DR EMDB; EMD-28908; -. DR SMR; P32745; -. DR BioGRID; 112631; 13. DR CORUM; P32745; -. DR IntAct; P32745; 12. DR MINT; P32745; -. DR STRING; 9606.ENSP00000480971; -. DR BindingDB; P32745; -. DR ChEMBL; CHEMBL2028; -. DR DrugBank; DB15494; Edotreotide gallium Ga-68. DR DrugBank; DB13985; Lutetium Lu 177 dotatate. DR DrugBank; DB06663; Pasireotide. DR DrugBank; DB09099; Somatostatin. DR DrugCentral; P32745; -. DR GuidetoPHARMACOLOGY; 357; -. DR TCDB; 9.A.14.13.23; the g-protein-coupled receptor (gpcr) family. DR GlyCosmos; P32745; 2 sites, No reported glycans. DR GlyGen; P32745; 2 sites. DR iPTMnet; P32745; -. DR PhosphoSitePlus; P32745; -. DR BioMuta; SSTR3; -. DR DMDM; 417815; -. DR MassIVE; P32745; -. DR PaxDb; 9606-ENSP00000480971; -. DR PeptideAtlas; P32745; -. DR ProteomicsDB; 54880; -. DR Antibodypedia; 74216; 221 antibodies from 32 providers. DR DNASU; 6753; -. DR Ensembl; ENST00000610913.2; ENSP00000480971.1; ENSG00000278195.2. DR Ensembl; ENST00000617123.1; ENSP00000481325.1; ENSG00000278195.2. DR GeneID; 6753; -. DR KEGG; hsa:6753; -. DR MANE-Select; ENST00000610913.2; ENSP00000480971.1; NM_001051.5; NP_001042.1. DR UCSC; uc021wos.3; human. DR AGR; HGNC:11332; -. DR CTD; 6753; -. DR DisGeNET; 6753; -. DR GeneCards; SSTR3; -. DR HGNC; HGNC:11332; SSTR3. DR HPA; ENSG00000278195; Tissue enhanced (brain, lymphoid tissue, testis). DR MIM; 182453; gene. DR neXtProt; NX_P32745; -. DR OpenTargets; ENSG00000278195; -. DR PharmGKB; PA36156; -. DR VEuPathDB; HostDB:ENSG00000278195; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT00940000162038; -. DR HOGENOM; CLU_009579_8_1_1; -. DR InParanoid; P32745; -. DR OMA; NTSSAWP; -. DR OrthoDB; 5393360at2759; -. DR PhylomeDB; P32745; -. DR TreeFam; TF315737; -. DR PathwayCommons; P32745; -. DR Reactome; R-HSA-375276; Peptide ligand-binding receptors. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR Reactome; R-HSA-5620922; BBSome-mediated cargo-targeting to cilium. DR SignaLink; P32745; -. DR SIGNOR; P32745; -. DR BioGRID-ORCS; 6753; 12 hits in 1144 CRISPR screens. DR GeneWiki; Somatostatin_receptor_3; -. DR GenomeRNAi; 6753; -. DR Pharos; P32745; Tclin. DR PRO; PR:P32745; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P32745; Protein. DR Bgee; ENSG00000278195; Expressed in buccal mucosa cell and 76 other cell types or tissues. DR GO; GO:0060170; C:ciliary membrane; TAS:Reactome. DR GO; GO:0005929; C:cilium; IDA:MGI. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. DR GO; GO:0097730; C:non-motile cilium; ISS:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central. DR GO; GO:0042923; F:neuropeptide binding; IBA:GO_Central. DR GO; GO:0005102; F:signaling receptor binding; IEA:Ensembl. DR GO; GO:0004994; F:somatostatin receptor activity; TAS:ProtInc. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEA:Ensembl. DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEA:Ensembl. DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl. DR GO; GO:0030900; P:forebrain development; IEA:Ensembl. DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; TAS:ProtInc. DR GO; GO:0008628; P:hormone-mediated apoptotic signaling pathway; TAS:ProtInc. DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc. DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central. DR GO; GO:0042594; P:response to starvation; IEA:Ensembl. DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR InterPro; IPR000586; Somatstn_rcpt. DR InterPro; IPR001856; Somatstn_rcpt_3. DR PANTHER; PTHR24229; NEUROPEPTIDES RECEPTOR; 1. DR PANTHER; PTHR24229:SF42; SOMATOSTATIN RECEPTOR TYPE 3; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00237; GPCRRHODOPSN. DR PRINTS; PR00246; SOMATOSTATNR. DR PRINTS; PR00589; SOMATOSTTN3R. DR SMART; SM01381; 7TM_GPCR_Srsx; 1. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; P32745; HS. PE 1: Evidence at protein level; KW Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein; KW Membrane; Phosphoprotein; Receptor; Reference proteome; Transducer; KW Transmembrane; Transmembrane helix. FT CHAIN 1..418 FT /note="Somatostatin receptor type 3" FT /id="PRO_0000070124" FT TOPO_DOM 1..43 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 44..69 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 70..79 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 80..101 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 102..116 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 117..138 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 139..161 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 162..181 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 182..205 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 206..231 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 232..257 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 258..279 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 280..293 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 294..316 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 317..418 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 1..21 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 335..418 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 346..360 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 372..418 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 332 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P30936" FT MOD_RES 337 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P30936" FT MOD_RES 348 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P30936" FT CARBOHYD 17 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 30 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 116..191 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT VARIANT 33 FT /note="A -> V (in dbSNP:rs4988466)" FT /id="VAR_029219" FT VARIANT 37 FT /note="P -> L (in dbSNP:rs34943557)" FT /id="VAR_049440" FT VARIANT 251 FT /note="S -> F (in dbSNP:rs6413537)" FT /id="VAR_020072" FT VARIANT 336 FT /note="R -> C (in dbSNP:rs4988469)" FT /id="VAR_029220" FT VARIANT 411 FT /note="S -> T (in dbSNP:rs229568)" FT /id="VAR_011853" FT VARIANT 414 FT /note="R -> H (in dbSNP:rs4988471)" FT /id="VAR_029221" SQ SEQUENCE 418 AA; 45847 MW; 1227095F801190C4 CRC64; MDMLHPSSVS TTSEPENASS AWPPDATLGN VSAGPSPAGL AVSGVLIPLV YLVVCVVGLL GNSLVIYVVL RHTASPSVTN VYILNLALAD ELFMLGLPFL AAQNALSYWP FGSLMCRLVM AVDGINQFTS IFCLTVMSVD RYLAVVHPTR SARWRTAPVA RTVSAAVWVA SAVVVLPVVV FSGVPRGMST CHMQWPEPAA AWRAGFIIYT AALGFFGPLL VICLCYLLIV VKVRSAGRRV WAPSCQRRRR SERRVTRMVV AVVALFVLCW MPFYVLNIVN VVCPLPEEPA FFGLYFLVVA LPYANSCANP ILYGFLSYRF KQGFRRVLLR PSRRVRSQEP TVGPPEKTEE EDEEEEDGEE SREGGKGKEM NGRVSQITQP GTSGQERPPS RVASKEQQLL PQEASTGEKS STMRISYL //