ID   SSR2_MOUSE              Reviewed;         369 AA.
AC   P30875; P30934; Q91Y73;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   27-MAR-2024, entry version 193.
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; Synonyms=Smstr2, Sst2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A).
RX   PubMed=1346068; DOI=10.1073/pnas.89.1.251;
RA   Yamada Y., Post S.R., Wang K., Tager H.S., Bell G.I., Seino S.;
RT   "Cloning and functional characterization of a family of human and mouse
RT   somatostatin receptors expressed in brain, gastrointestinal tract, and
RT   kidney.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:251-255(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM B).
RX   PubMed=1397330; DOI=10.1016/0014-5793(92)81122-3;
RA   Vanetti M., Kouba M., Wang X., Vogt G., Hoellt V.;
RT   "Cloning and expression of a novel mouse somatostatin receptor (SSTR2B).";
RL   FEBS Lett. 311:290-294(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS A AND
RP   B).
RC   STRAIN=129; TISSUE=Liver;
RX   PubMed=11278805; DOI=10.1074/jbc.m010981200;
RA   Puente E., Saint-Laurent N., Torrisani J., Furet C., Schally A.V.,
RA   Vaysse N., Buscail L., Susini C.;
RT   "Transcriptional activation of mouse sst2 somatostatin receptor promoter by
RT   transforming growth factor-beta. Involvement of Smad4.";
RL   J. Biol. Chem. 276:13461-13468(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 99-309 (ISOFORMS A/B).
RX   PubMed=7913111;
RA   Elliott D.E., Metwali A., Blum A.M., Sandor M., Lynch R., Weinstock J.V.;
RT   "T lymphocytes isolated from the hepatic granulomas of schistosome-infected
RT   mice express somatostatin receptor subtype II (SSTR2) messenger RNA.";
RL   J. Immunol. 153:1180-1186(1994).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, AND ALTERNATIVE SPLICING (ISOFORMS A AND
RP   B).
RX   PubMed=8104154; DOI=10.1016/0014-5793(93)80349-y;
RA   Vanetti M., Hoellt V.;
RT   "The two isoforms of the mouse somatostatin receptor (mSSTR2A and mSSTR2B)
RT   differ in coupling efficiency to adenylate cyclase and in agonist-induced
RT   receptor desensitization.";
RL   FEBS Lett. 331:260-266(1993).
RN   [6]
RP   FUNCTION.
RX   PubMed=9507021; DOI=10.1074/jbc.273.12.7099;
RA   Bousquet C., Delesque N., Lopez F., Saint-Laurent N., Esteve J.P.,
RA   Bedecs K., Buscail L., Vaysse N., Susini C.;
RT   "sst2 somatostatin receptor mediates negative regulation of insulin
RT   receptor signaling through the tyrosine phosphatase SHP-1.";
RL   J. Biol. Chem. 273:7099-7106(1998).
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:8104154,
CC       ECO:0000269|PubMed:9507021}.
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) (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8104154};
CC       Multi-pass membrane protein {ECO:0000269|PubMed:8104154}. Cytoplasm
CC       {ECO:0000250}. Note=Located mainly at the cell surface under basal
CC       conditions. Agonist stimulation results in internalization to the
CC       cytoplasm (By similarity). {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=A; Synonyms=SS2RA;
CC         IsoId=P30875-1; Sequence=Displayed;
CC       Name=B; Synonyms=SS2RB;
CC         IsoId=P30875-2; Sequence=VSP_001923;
CC   -!- TISSUE SPECIFICITY: Cerebrum and kidney.
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 (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; M81832; AAA58256.1; -; Genomic_DNA.
DR   EMBL; X68951; CAA48766.1; -; mRNA.
DR   EMBL; AF008914; AAD01419.1; -; Genomic_DNA.
DR   EMBL; AF008914; AAD01420.1; -; Genomic_DNA.
DR   EMBL; S71756; AAP20804.1; -; mRNA.
DR   CCDS; CCDS25598.1; -. [P30875-2]
DR   CCDS; CCDS59571.1; -. [P30875-1]
DR   PIR; D41795; D41795.
DR   PIR; S29248; S29248.
DR   RefSeq; NP_001036071.1; NM_001042606.2. [P30875-1]
DR   RefSeq; NP_033243.2; NM_009217.4. [P30875-2]
DR   AlphaFoldDB; P30875; -.
DR   SMR; P30875; -.
DR   IntAct; P30875; 2.
DR   MINT; P30875; -.
DR   STRING; 10090.ENSMUSP00000138101; -.
DR   BindingDB; P30875; -.
DR   ChEMBL; CHEMBL3207; -.
DR   DrugCentral; P30875; -.
DR   GuidetoPHARMACOLOGY; 356; -.
DR   GlyCosmos; P30875; 4 sites, No reported glycans.
DR   GlyGen; P30875; 4 sites.
DR   iPTMnet; P30875; -.
DR   PhosphoSitePlus; P30875; -.
DR   SwissPalm; P30875; -.
DR   PaxDb; 10090-ENSMUSP00000138101; -.
DR   ProteomicsDB; 257419; -. [P30875-1]
DR   ProteomicsDB; 257420; -. [P30875-2]
DR   ABCD; P30875; 20 sequenced antibodies.
DR   Antibodypedia; 1548; 455 antibodies from 37 providers.
DR   DNASU; 20606; -.
DR   Ensembl; ENSMUST00000067591.3; ENSMUSP00000068578.3; ENSMUSG00000047904.7. [P30875-2]
DR   Ensembl; ENSMUST00000106630.2; ENSMUSP00000102241.2; ENSMUSG00000047904.7. [P30875-2]
DR   Ensembl; ENSMUST00000146390.3; ENSMUSP00000138101.2; ENSMUSG00000047904.7. [P30875-1]
DR   GeneID; 20606; -.
DR   KEGG; mmu:20606; -.
DR   UCSC; uc007mep.2; mouse. [P30875-2]
DR   UCSC; uc011yha.2; mouse. [P30875-1]
DR   AGR; MGI:98328; -.
DR   CTD; 6752; -.
DR   MGI; MGI:98328; Sstr2.
DR   VEuPathDB; HostDB:ENSMUSG00000047904; -.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT00940000156544; -.
DR   HOGENOM; CLU_009579_8_1_1; -.
DR   InParanoid; P30875; -.
DR   OMA; YYDQTSN; -.
DR   OrthoDB; 5393360at2759; -.
DR   PhylomeDB; P30875; -.
DR   TreeFam; TF315737; -.
DR   Reactome; R-MMU-375276; Peptide ligand-binding receptors.
DR   Reactome; R-MMU-418594; G alpha (i) signalling events.
DR   BioGRID-ORCS; 20606; 3 hits in 75 CRISPR screens.
DR   ChiTaRS; Sstr2; mouse.
DR   PRO; PR:P30875; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; P30875; Protein.
DR   Bgee; ENSMUSG00000047904; Expressed in skin of snout and 116 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0042923; F:neuropeptide binding; IBA:GO_Central.
DR   GO; GO:0030165; F:PDZ domain binding; ISO:MGI.
DR   GO; GO:0004994; F:somatostatin receptor activity; IDA:MGI.
DR   GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:MGI.
DR   GO; GO:0071392; P:cellular response to estradiol stimulus; IBA:GO_Central.
DR   GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IBA:GO_Central.
DR   GO; GO:0021549; P:cerebellum development; IEA:Ensembl.
DR   GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IMP:MGI.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IDA:MGI.
DR   GO; GO:0030432; P:peristalsis; ISO:MGI.
DR   GO; GO:0042594; P:response to starvation; IEA:Ensembl.
DR   GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR   CDD; cd15971; 7tmA_SSTR2; 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; IPR002074; Somatstn_rcpt_2.
DR   PANTHER; PTHR24229; NEUROPEPTIDES RECEPTOR; 1.
DR   PANTHER; PTHR24229:SF6; SOMATOSTATIN RECEPTOR TYPE 2; 1.
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   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; P30875; MM.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Cell membrane; Cytoplasm; Disulfide bond;
KW   G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Palmitate;
KW   Phosphoprotein; Receptor; Reference proteome; Transducer; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..369
FT                   /note="Somatostatin receptor type 2"
FT                   /id="PRO_0000070121"
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:0000250|UniProtKB:P30680"
FT   MOD_RES         343
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P30680"
FT   MOD_RES         348
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P30680"
FT   MOD_RES         353
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P30680"
FT   MOD_RES         354
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P30680"
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="VSGTEDGERSDSKQDKSRLNETTETQRTLLNGDLQTSI -> ADNSQSGAED
FT                   IIAWV (in isoform B)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001923"
FT   CONFLICT        179
FT                   /note="I -> L (in Ref. 2; CAA48766)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        305
FT                   /note="S -> T (in Ref. 2; CAA48766)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   369 AA;  41222 MW;  A78845AF74823039 CRC64;
     MEMSSEQLNG SQVWVSSPFD LNGSLGPSNG SNQTEPYYDM TSNAVLTFIY FVVCVVGLCG
     NTLVIYVILR YAKMKTITNI YILNLAIADE LFMLGLPFLA MQVALVHWPF GKAICRVVMT
     VDGINQFTSI FCLTVMSIDR YLAVVHPIKS AKWRRPRTAK MINVAVWCVS LLVILPIMIY
     AGLRSNQWGR SSCTINWPGE SGAWYTGFII YAFILGFLVP LTIICLCYLF IIIKVKSSGI
     RVGSSKRKKS EKKVTRMVSI VVAVFIFCWL PFYIFNVSSV SVAISPTPAL KGMFDFVVIL
     TYANSCANPI LYAFLSDNFK KSFQNVLCLV KVSGTEDGER SDSKQDKSRL NETTETQRTL
     LNGDLQTSI
//