SSR2_RAT
ID SSR2_RAT Reviewed; 369 AA.
AC P30680;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Somatostatin receptor type 2;
DE Short=SS-2-R;
DE Short=SS2-R;
DE Short=SS2R;
DE AltName: Full=SRIF-1;
GN Name=Sstr2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=1374909; DOI=10.1073/pnas.89.10.4618;
RA Kluxen F.-W., Bruns C., Luebbert H.;
RT "Expression cloning of a rat brain somatostatin receptor cDNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:4618-4622(1992).
RN [2]
RP PROTEIN SEQUENCE OF 76-81; 179-189; 294-320 AND 350-358.
RC TISSUE=Pituitary;
RX PubMed=1348934; DOI=10.1016/0006-291x(92)91168-p;
RA Hulmes J.D., Corbett M., Zysk J.R., Boehlen P., Eppler C.M.;
RT "Partial amino acid sequence of a somatostatin receptor isolated from GH4C1
RT pituitary cells.";
RL Biochem. Biophys. Res. Commun. 184:131-136(1992).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, AND ALTERNATIVE SPLICING (ISOFORMS A AND B).
RX PubMed=8386508; DOI=10.1006/bbrc.1993.1412;
RA Patel Y.C., Greenwood M., Kent G., Panetta R., Srikant C.B.;
RT "Multiple gene transcripts of the somatostatin receptor SSTR2: tissue
RT selective distribution and cAMP regulation.";
RL Biochem. Biophys. Res. Commun. 192:288-294(1993).
RN [4]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=11134004; DOI=10.1074/jbc.m006084200;
RA Pfeiffer M., Koch T., Schroder H., Klutzny M., Kirscht S., Kreienkamp H.J.,
RA Hollt V., Schulz S.;
RT "Homo- and heterodimerization of somatostatin receptor subtypes.
RT Inactivation of sst(3) receptor function by heterodimerization with
RT sst(2A).";
RL J. Biol. Chem. 276:14027-14036(2001).
RN [5]
RP FUNCTION, INTERACTION WITH BETA-ARRESTIN, SUBCELLULAR LOCATION, AND
RP PHOSPHORYLATION.
RX PubMed=17981995; DOI=10.1124/mol.107.038570;
RA Liu Q., Dewi D.A., Liu W., Bee M.S., Schonbrunn A.;
RT "Distinct phosphorylation sites in the SST2A somatostatin receptor control
RT internalization, desensitization, and arrestin binding.";
RL Mol. Pharmacol. 73:292-304(2008).
RN [6]
RP PHOSPHORYLATION AT SER-341; SER-343; SER-348; THR-353 AND THR-354.
RX PubMed=19389921; DOI=10.1124/mol.108.054262;
RA Liu Q., Bee M.S., Schonbrunn A.;
RT "Site specificity of agonist and second messenger-activated kinases for
RT somatostatin receptor subtype 2A (Sst2A) phosphorylation.";
RL Mol. Pharmacol. 76:68-80(2009).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19434240; DOI=10.1371/journal.pone.0005509;
RA Le Verche V., Kaindl A.M., Verney C., Csaba Z., Peineau S., Olivier P.,
RA Adle-Biassette H., Leterrier C., Vitalis T., Renaud J., Dargent B.,
RA Gressens P., Dournaud P.;
RT "The somatostatin 2A receptor is enriched in migrating neurons during rat
RT and human brain development and stimulates migration and axonal
RT outgrowth.";
RL PLoS ONE 4:E5509-E5509(2009).
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. In addition it stimulates phosphotyrosine phosphatase
CC and PLC via pertussis toxin insensitive as well as sensitive G
CC proteins. Inhibits calcium entry by suppressing voltage-dependent
CC calcium channels. Acts as the functionally dominant somatostatin
CC receptor in pancreatic alpha- and beta-cells where it mediates the
CC inhibitory effect of somatostatin-14 on hormone secretion. Inhibits
CC cell growth through enhancement of MAPK1 and MAPK2 phosphorylation and
CC subsequent up-regulation of CDKN1B. Stimulates neuronal migration and
CC axon outgrowth and may participate in neuron development and maturation
CC during brain development. Mediates negative regulation of insulin
CC receptor signaling through PTPN6. Inactivates SSTR3 receptor function
CC following heterodimerization. {ECO:0000269|PubMed:11134004,
CC ECO:0000269|PubMed:17981995, ECO:0000269|PubMed:19434240,
CC ECO:0000269|PubMed:8386508}.
CC -!- SUBUNIT: Homodimer and heterodimer with SSTR3 and SSTR5.
CC Heterodimerization with SSTR3 inactivates SSTR3 receptor function.
CC Heterodimerization with SSTR5 is enhanced by agonist stimulation of
CC SSTR2 and increases SSTR2 cell growth inhibition activity. Following
CC agonist stimulation, homodimers dissociate into monomers which is
CC required for receptor internalization. Interacts with beta-arrestin;
CC this interaction is necessary for receptor internalization and is
CC destabilized by heterodimerization with SSTR5 which results in
CC increased recycling of SSTR2 to the cell surface. Interacts (via C-
CC terminus) with SHANK1 (via PDZ domain). {ECO:0000269|PubMed:11134004,
CC ECO:0000269|PubMed:17981995}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC Cytoplasm. Note=Located mainly at the cell surface under basal
CC conditions. Agonist stimulation results in internalization to the
CC cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A;
CC IsoId=P30680-1; Sequence=Displayed;
CC Name=B;
CC IsoId=P30680-2; Sequence=VSP_001924;
CC -!- TISSUE SPECIFICITY: Cortex, hippocampus, pituitary gland, colon,
CC kidney, and adrenal gland. In the developing nervous system, expressed
CC from E12 when it is restricted to postmitotic neuronal populations
CC leaving the ventricular zone. From E12 on, expressed in migrating
CC neuronal populations in numerous developing regions including the
CC cerebral cortex, hippocampus and ganglionic eminences. Also detected in
CC the deep part of the external granular layer of the cerebellum, the
CC rostral migratory stream and a subset of axons and neurons. Expressed
CC in the medial forebrain bundle, rostral migratory stream and cerebellum
CC during development but not in adulthood. {ECO:0000269|PubMed:1374909,
CC ECO:0000269|PubMed:19434240, ECO:0000269|PubMed:8386508}.
CC -!- PTM: Phosphorylated on serine and threonine residues in response to
CC agonist stimulation, leading to receptor desensitization and rapid
CC internalization. Phosphorylated to a greater extent on serine than
CC threonine residues. Threonine phosphorylation is required for arrestin
CC binding and receptor endocytosis but is not necessary for
CC desensitization. {ECO:0000269|PubMed:17981995,
CC ECO:0000269|PubMed:19389921}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; M96817; AAA42166.1; -; mRNA.
DR EMBL; M93273; AAA42165.1; -; mRNA.
DR PIR; A45291; A45291.
DR RefSeq; NP_062221.1; NM_019348.1. [P30680-1]
DR PDB; 6EXJ; X-ray; 1.80 A; B/D=364-369.
DR PDBsum; 6EXJ; -.
DR AlphaFoldDB; P30680; -.
DR SMR; P30680; -.
DR BioGRID; 248525; 6.
DR IntAct; P30680; 1.
DR MINT; P30680; -.
DR STRING; 10116.ENSRNOP00000003735; -.
DR BindingDB; P30680; -.
DR ChEMBL; CHEMBL2978; -.
DR DrugCentral; P30680; -.
DR GuidetoPHARMACOLOGY; 356; -.
DR GlyGen; P30680; 4 sites.
DR iPTMnet; P30680; -.
DR PhosphoSitePlus; P30680; -.
DR PaxDb; P30680; -.
DR Ensembl; ENSRNOT00000003735; ENSRNOP00000003735; ENSRNOG00000002793. [P30680-2]
DR Ensembl; ENSRNOT00000116317; ENSRNOP00000094133; ENSRNOG00000002793. [P30680-1]
DR GeneID; 54305; -.
DR KEGG; rno:54305; -.
DR CTD; 6752; -.
DR RGD; 3763; Sstr2.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000156544; -.
DR HOGENOM; CLU_009579_8_1_1; -.
DR InParanoid; P30680; -.
DR OMA; NGCFCTI; -.
DR OrthoDB; 1011272at2759; -.
DR PhylomeDB; P30680; -.
DR TreeFam; TF315737; -.
DR Reactome; R-RNO-375276; Peptide ligand-binding receptors.
DR Reactome; R-RNO-418594; G alpha (i) signalling events.
DR PRO; PR:P30680; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000002793; Expressed in Ammon's horn and 6 other tissues.
DR Genevisible; P30680; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
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:0030165; F:PDZ domain binding; IPI:UniProtKB.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0004994; F:somatostatin receptor activity; IDA:RGD.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEP:RGD.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEP:RGD.
DR GO; GO:0021549; P:cerebellum development; IEP:RGD.
DR GO; GO:0030900; P:forebrain development; IEP:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0007218; P:neuropeptide signaling pathway; ISO:RGD.
DR GO; GO:0030432; P:peristalsis; IMP:RGD.
DR GO; GO:0006937; P:regulation of muscle contraction; IMP:RGD.
DR GO; GO:0042594; P:response to starvation; IEP:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR000586; Somatstn_rcpt.
DR InterPro; IPR002074; Somatstn_rcpt_2.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR00246; SOMATOSTATNR.
DR PRINTS; PR00588; SOMATOSTTN2R.
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 3D-structure; Alternative splicing; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Lipoprotein; Membrane; Palmitate; Phosphoprotein; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..369
FT /note="Somatostatin receptor type 2"
FT /id="PRO_0000070123"
FT TOPO_DOM 1..43
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 44..67
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 68..78
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 79..103
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 104..118
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 119..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..207
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 208..229
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..253
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 254..278
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 279..288
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 289..303
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 304..369
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19389921"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19389921"
FT MOD_RES 348
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19389921"
FT MOD_RES 353
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:19389921"
FT MOD_RES 354
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:19389921"
FT LIPID 328
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 9
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 22
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 32
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 115..193
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 332..369
FT /note="VSGAEDGERSDSKQDKSRLNETTETQRTLLNGDLQTSI -> ADNSKTGEED
FT TMAWV (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_001924"
FT STRAND 365..368
FT /evidence="ECO:0007829|PDB:6EXJ"
SQ SEQUENCE 369 AA; 41200 MW; 4990E489E88D7D19 CRC64;
MELTSEQFNG SQVWIPSPFD LNGSLGPSNG SNQTEPYYDM TSNAVLTFIY FVVCVVGLCG
NTLVIYVILR YAKMKTITNI YILNLAIADE LFMLGLPFLA MQVALVHWPF GKAICRVVMT
VDGINQFTSI FCLTVMSIDR YLAVVHPIKS AKWRRPRTAK MINVAVWGVS LLVILPIMIY
AGLRSNQWGR SSCTINWPGE SGAWYTGFII YAFILGFLVP LTIICLCYLF IIIKVKSSGI
RVGSSKRKKS EKKVTRMVSI VVAVFIFCWL PFYIFNVSSV SVAISPTPAL KGMFDFVVIL
TYANSCANPI LYAFLSDNFK KSFQNVLCLV KVSGAEDGER SDSKQDKSRL NETTETQRTL
LNGDLQTSI
