SSR4_HUMAN
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 03-AUG-2022, entry version 192.
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 AlphaFoldDB; P31391; -.
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 GlyGen; P31391; 1 site.
DR iPTMnet; P31391; -.
DR PhosphoSitePlus; P31391; -.
DR BioMuta; SSTR4; -.
DR DMDM; 206729897; -.
DR MassIVE; P31391; -.
DR PaxDb; P31391; -.
DR PeptideAtlas; P31391; -.
DR PRIDE; P31391; -.
DR Antibodypedia; 20974; 241 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 CTD; 6754; -.
DR DisGeNET; 6754; -.
DR GeneCards; SSTR4; -.
DR HGNC; HGNC:11333; SSTR4.
DR HPA; ENSG00000132671; Tissue enriched (brain).
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; WPHPAWS; -.
DR OrthoDB; 1011272at2759; -.
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; 14 hits in 1062 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 tissues.
DR Genevisible; P31391; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
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:0042277; F:peptide 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 InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR000586; Somatstn_rcpt.
DR InterPro; IPR001512; Somatstn_rcpt_4.
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 PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Lipoprotein; Membrane; Palmitate; Receptor; Reference proteome; Transducer;
KW 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"
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
