ID   SSR4_HUMAN              Reviewed;         388 AA.
AC   P31391; Q17RM1; Q17RM3; Q9UIY1;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   23-SEP-2008, sequence version 2.
DT   24-JAN-2024, entry version 200.
DE   RecName: Full=Somatostatin receptor type 4;
DE            Short=SS-4-R;
DE            Short=SS4-R;
DE            Short=SS4R;
DE            Short=SST4;
GN   Name=SSTR4;
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], AND VARIANTS VAL-284 AND SER-321.
RX   PubMed=8512564; DOI=10.1006/bbrc.1993.1673;
RA   Xu Y., Song J., Bruno J.F., Berelowitz M.;
RT   "Molecular cloning and sequencing of a human somatostatin receptor,
RT   hSSTR4.";
RL   Biochem. Biophys. Res. Commun. 193:648-652(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-83; VAL-284 AND
RP   SER-321.
RX   PubMed=8483934; DOI=10.1073/pnas.90.9.4196;
RA   Rohrer L., Raulf F., Bruns C., Buettner R., Hofstaedter F., Schuele R.;
RT   "Cloning and characterization of a fourth human somatostatin receptor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:4196-4200(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8373420; DOI=10.1006/bbrc.1993.2122;
RA   Yamada Y., Kagimoto S., Kubota A., Yasuda K., Masuda K., Someya Y.,
RA   Ihara Y., Li Q., Imura H., Seino S., Seino Y.;
RT   "Cloning, functional expression and pharmacological characterization of a
RT   fourth (hSSTR4) and a fifth (hSSTR5) human somatostatin receptor subtype.";
RL   Biochem. Biophys. Res. Commun. 195:844-852(1993).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8100352;
RA   Demchyshyn L.L., Srikant C.B., Sunahara R.K., Kent G., Seeman P.,
RA   van Tol H.H.M., Panetta R., Patel Y.C., Niznik H.B.;
RT   "Cloning and expression of a human somatostatin-14-selective receptor
RT   variant (somatostatin receptor 4) located on chromosome 20.";
RL   Mol. Pharmacol. 43:894-901(1993).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-284 AND SER-321.
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 (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN   [6]
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., Beasley O.P.,
RA   Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA   Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA   Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA   Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA   Dunn M., 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., Rice C.M.,
RA   Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA   Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA   Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA   Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA   Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA   Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [7]
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   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-284 AND SER-321.
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. The activity of this receptor
CC       is mediated by G proteins which inhibits adenylyl cyclase. It is
CC       functionally coupled not only to inhibition of adenylate cyclase, but
CC       also to activation of both arachidonate release and mitogen-activated
CC       protein (MAP) kinase cascade. Mediates antiproliferative action of
CC       somatostatin in tumor cells.
CC   -!- INTERACTION:
CC       P31391; P35346: SSTR5; NbExp=3; IntAct=EBI-21274002, EBI-27053622;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Specifically expressed in fetal and adult brain,
CC       lung tissue, stomach, and in lesser quantities in the kidney, pituitary
CC       and adrenals.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; D16826; BAA04106.1; -; Genomic_DNA.
DR   EMBL; L14856; AAA36623.1; -; Genomic_DNA.
DR   EMBL; L07833; AAA60565.1; -; Genomic_DNA.
DR   EMBL; L07061; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AY548169; AAS55648.1; -; Genomic_DNA.
DR   EMBL; AL049651; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471133; EAX10170.1; -; Genomic_DNA.
DR   EMBL; BC069063; AAH69063.1; -; mRNA.
DR   EMBL; BC117270; AAI17271.1; -; mRNA.
DR   EMBL; BC117272; AAI17273.1; -; mRNA.
DR   CCDS; CCDS42856.1; -.
DR   PIR; JN0605; JN0605.
DR   RefSeq; NP_001043.2; NM_001052.2.
DR   PDB; 7XMS; EM; 2.90 A; R=2-328.
DR   PDB; 7XMT; EM; 2.80 A; R=2-328.
DR   PDBsum; 7XMS; -.
DR   PDBsum; 7XMT; -.
DR   AlphaFoldDB; P31391; -.
DR   EMDB; EMD-33303; -.
DR   EMDB; EMD-33304; -.
DR   SMR; P31391; -.
DR   BioGRID; 112632; 5.
DR   CORUM; P31391; -.
DR   IntAct; P31391; 4.
DR   STRING; 9606.ENSP00000255008; -.
DR   BindingDB; P31391; -.
DR   ChEMBL; CHEMBL1853; -.
DR   DrugBank; DB13985; Lutetium Lu 177 dotatate.
DR   DrugBank; DB09099; Somatostatin.
DR   DrugCentral; P31391; -.
DR   GuidetoPHARMACOLOGY; 358; -.
DR   GlyCosmos; P31391; 1 site, No reported glycans.
DR   GlyGen; P31391; 1 site.
DR   iPTMnet; P31391; -.
DR   PhosphoSitePlus; P31391; -.
DR   BioMuta; SSTR4; -.
DR   DMDM; 206729897; -.
DR   MassIVE; P31391; -.
DR   PaxDb; 9606-ENSP00000255008; -.
DR   PeptideAtlas; P31391; -.
DR   Antibodypedia; 20974; 279 antibodies from 33 providers.
DR   DNASU; 6754; -.
DR   Ensembl; ENST00000255008.5; ENSP00000255008.3; ENSG00000132671.6.
DR   GeneID; 6754; -.
DR   KEGG; hsa:6754; -.
DR   MANE-Select; ENST00000255008.5; ENSP00000255008.3; NM_001052.4; NP_001043.2.
DR   UCSC; uc002wsr.3; human.
DR   AGR; HGNC:11333; -.
DR   CTD; 6754; -.
DR   DisGeNET; 6754; -.
DR   GeneCards; SSTR4; -.
DR   HGNC; HGNC:11333; SSTR4.
DR   HPA; ENSG00000132671; Not detected.
DR   MIM; 182454; gene.
DR   neXtProt; NX_P31391; -.
DR   OpenTargets; ENSG00000132671; -.
DR   PharmGKB; PA36157; -.
DR   VEuPathDB; HostDB:ENSG00000132671; -.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT00940000156819; -.
DR   HOGENOM; CLU_009579_8_1_1; -.
DR   InParanoid; P31391; -.
DR   OMA; AIQCIYA; -.
DR   OrthoDB; 5393360at2759; -.
DR   PhylomeDB; P31391; -.
DR   TreeFam; TF315737; -.
DR   PathwayCommons; P31391; -.
DR   Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   SignaLink; P31391; -.
DR   SIGNOR; P31391; -.
DR   BioGRID-ORCS; 6754; 15 hits in 1140 CRISPR screens.
DR   GeneWiki; Somatostatin_receptor_4; -.
DR   GenomeRNAi; 6754; -.
DR   Pharos; P31391; Tclin.
DR   PRO; PR:P31391; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   RNAct; P31391; Protein.
DR   Bgee; ENSG00000132671; Expressed in prefrontal cortex and 20 other cell types or tissues.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0042923; F:neuropeptide binding; IBA:GO_Central.
DR   GO; GO:0004994; F:somatostatin receptor activity; IBA:GO_Central.
DR   GO; GO:0016477; P:cell migration; IEA:Ensembl.
DR   GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IBA:GO_Central.
DR   GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; TAS:ProtInc.
DR   GO; GO:0106072; P:negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; IEA:Ensembl.
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:0090238; P:positive regulation of arachidonic acid secretion; IEA:Ensembl.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR   CDD; cd15973; 7tmA_SSTR4; 1.
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; IPR001512; Somatstn_rcpt_4.
DR   PANTHER; PTHR24229; NEUROPEPTIDES RECEPTOR; 1.
DR   PANTHER; PTHR24229:SF35; SOMATOSTATIN RECEPTOR TYPE 4; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR00246; SOMATOSTATNR.
DR   PRINTS; PR00590; SOMATOSTTN4R.
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; P31391; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor;
KW   Glycoprotein; Lipoprotein; Membrane; Palmitate; Receptor;
KW   Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT   CHAIN           1..388
FT                   /note="Somatostatin receptor type 4"
FT                   /id="PRO_0000070127"
FT   TOPO_DOM        1..46
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        47..73
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        74..83
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        84..104
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        105..120
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        121..142
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        143..161
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        162..185
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        186..208
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        209..232
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        233..260
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        261..280
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        281..291
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        292..314
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        315..388
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   LIPID           327
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        24
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        119..198
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT   VARIANT         83
FT                   /note="N -> T (in dbSNP:rs1065191)"
FT                   /evidence="ECO:0000269|PubMed:8483934"
FT                   /id="VAR_011703"
FT   VARIANT         236
FT                   /note="G -> D (in dbSNP:rs35601930)"
FT                   /id="VAR_049441"
FT   VARIANT         284
FT                   /note="F -> V (in dbSNP:rs3746726)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:8483934, ECO:0000269|PubMed:8512564,
FT                   ECO:0000269|Ref.5"
FT                   /id="VAR_021560"
FT   VARIANT         321
FT                   /note="F -> S (in dbSNP:rs2567608)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:8483934, ECO:0000269|PubMed:8512564,
FT                   ECO:0000269|Ref.5"
FT                   /id="VAR_021561"
FT   CONFLICT        365
FT                   /note="P -> K (in Ref. 2; AAA60565)"
FT                   /evidence="ECO:0000305"
FT   HELIX           47..73
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   TURN            74..76
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   HELIX           81..96
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   TURN            97..99
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   HELIX           100..108
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   HELIX           119..149
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   HELIX           151..154
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   TURN            155..157
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   HELIX           160..178
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   HELIX           180..183
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   STRAND          184..187
FT                   /evidence="ECO:0007829|PDB:7XMS"
FT   STRAND          191..194
FT                   /evidence="ECO:0007829|PDB:7XMS"
FT   STRAND          198..200
FT                   /evidence="ECO:0007829|PDB:7XMS"
FT   HELIX           205..217
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   TURN            218..220
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   HELIX           221..244
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   HELIX           252..283
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   TURN            287..290
FT                   /evidence="ECO:0007829|PDB:7XMS"
FT   HELIX           294..306
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   HELIX           308..311
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   STRAND          313..315
FT                   /evidence="ECO:0007829|PDB:7XMT"
FT   HELIX           316..319
FT                   /evidence="ECO:0007829|PDB:7XMT"
SQ   SEQUENCE   388 AA;  42003 MW;  DFCD9393620EDFC9 CRC64;
     MSAPSTLPPG GEEGLGTAWP SAANASSAPA EAEEAVAGPG DARAAGMVAI QCIYALVCLV
     GLVGNALVIF VILRYAKMKT ATNIYLLNLA VADELFMLSV PFVASSAALR HWPFGSVLCR
     AVLSVDGLNM FTSVFCLTVL SVDRYVAVVH PLRAATYRRP SVAKLINLGV WLASLLVTLP
     IAIFADTRPA RGGQAVACNL QWPHPAWSAV FVVYTFLLGF LLPVLAIGLC YLLIVGKMRA
     VALRAGWQQR RRSEKKITRL VLMVVVVFVL CWMPFYVVQL LNLFVTSLDA TVNHVSLILS
     YANSCANPIL YGFLSDNFRR FFQRVLCLRC CLLEGAGGAE EEPLDYYATA LKSKGGAGCM
     CPPLPCQQEA LQPEPGRKRI PLTRTTTF
//