SSR2_MOUSE
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 03-AUG-2022, entry version 184.
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 GlyGen; P30875; 4 sites.
DR iPTMnet; P30875; -.
DR PhosphoSitePlus; P30875; -.
DR SwissPalm; P30875; -.
DR PaxDb; P30875; -.
DR PRIDE; P30875; -.
DR ProteomicsDB; 257419; -. [P30875-1]
DR ProteomicsDB; 257420; -. [P30875-2]
DR ABCD; P30875; 21 sequenced antibodies.
DR Antibodypedia; 1548; 389 antibodies from 36 providers.
DR DNASU; 20606; -.
DR Ensembl; ENSMUST00000067591; ENSMUSP00000068578; ENSMUSG00000047904. [P30875-2]
DR Ensembl; ENSMUST00000106630; ENSMUSP00000102241; ENSMUSG00000047904. [P30875-2]
DR Ensembl; ENSMUST00000146390; ENSMUSP00000138101; ENSMUSG00000047904. [P30875-1]
DR GeneID; 20606; -.
DR KEGG; mmu:20606; -.
DR UCSC; uc007mep.2; mouse. [P30875-2]
DR UCSC; uc011yha.2; mouse. [P30875-1]
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; NGCFCTI; -.
DR OrthoDB; 1011272at2759; -.
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 70 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 114 other tissues.
DR Genevisible; P30875; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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: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; ISO:MGI.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
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:0006937; P:regulation of muscle contraction; ISO:MGI.
DR GO; GO:0042594; P:response to starvation; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
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 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
