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Protein

Somatostatin receptor type 2

Gene

Sstr2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and PLC via pertussis toxin insensitive as well as sensitive G proteins. Inhibits calcium entry by suppressing voltage-dependent calcium channels. Acts as the functionally dominant somatostatin receptor in pancreatic alpha- and beta-cells where it mediates the inhibitory effect of somatostatin-14 on hormone secretion. Inhibits cell growth through enhancement of MAPK1 and MAPK2 phosphorylation and subsequent up-regulation of CDKN1B. Stimulates neuronal migration and axon outgrowth and may participate in neuron development and maturation during brain development. Mediates negative regulation of insulin receptor signaling through PTPN6. Inactivates SSTR3 receptor function following heterodimerization.2 Publications

GO - Molecular functioni

  • neuropeptide binding Source: GO_Central
  • PDZ domain binding Source: MGI
  • somatostatin receptor activity Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_319210. Peptide ligand-binding receptors.
REACT_331048. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Somatostatin receptor type 2
Short name:
SS-2-R
Short name:
SS2-R
Short name:
SS2R
Alternative name(s):
SRIF-1
Gene namesi
Name:Sstr2
Synonyms:Smstr2, Sst2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:98328. Sstr2.

Subcellular locationi

  • Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
  • Cytoplasm By similarity

  • Note: Located mainly at the cell surface under basal conditions. Agonist stimulation results in internalization to the cytoplasm (By similarity).By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4343ExtracellularSequence AnalysisAdd
BLAST
Transmembranei44 – 6724Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini68 – 7811CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei79 – 10325Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini104 – 11815ExtracellularSequence AnalysisAdd
BLAST
Transmembranei119 – 13820Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini139 – 16123CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei162 – 18120Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini182 – 20726ExtracellularSequence AnalysisAdd
BLAST
Transmembranei208 – 22922Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini230 – 25324CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei254 – 27825Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini279 – 28810ExtracellularSequence Analysis
Transmembranei289 – 30315Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini304 – 36966CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: GO_Central
  • membrane Source: MGI
  • neuron projection Source: GO_Central
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 369369Somatostatin receptor type 2PRO_0000070121Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi9 – 91N-linked (GlcNAc...)Sequence Analysis
Glycosylationi22 – 221N-linked (GlcNAc...)Sequence Analysis
Glycosylationi29 – 291N-linked (GlcNAc...)Sequence Analysis
Glycosylationi32 – 321N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi115 ↔ 193PROSITE-ProRule annotation
Lipidationi328 – 3281S-palmitoyl cysteineSequence Analysis
Modified residuei341 – 3411PhosphoserineBy similarity
Modified residuei343 – 3431PhosphoserineBy similarity
Modified residuei348 – 3481PhosphoserineBy similarity
Modified residuei353 – 3531PhosphothreonineBy similarity
Modified residuei354 – 3541PhosphothreonineBy similarity

Post-translational modificationi

Phosphorylated on serine and threonine residues in response to agonist stimulation, leading to receptor desensitization and rapid internalization. Phosphorylated to a greater extent on serine than threonine residues. Threonine phosphorylation is required for arrestin binding and receptor endocytosis but is not necessary for desensitization (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PRIDEiP30875.

PTM databases

PhosphoSiteiP30875.

Expressioni

Tissue specificityi

Cerebrum and kidney.

Gene expression databases

BgeeiP30875.
CleanExiMM_SSTR2.
GenevisibleiP30875. MM.

Interactioni

Subunit structurei

Homodimer and heterodimer with SSTR3 and SSTR5. Heterodimerization with SSTR3 inactivates SSTR3 receptor function. Heterodimerization with SSTR5 is enhanced by agonist stimulation of SSTR2 and increases SSTR2 cell growth inhibition activity. Following agonist stimulation, homodimers dissociate into monomers which is required for receptor internalization. Interacts with beta-arrestin; this interaction is necessary for receptor internalization and is destabilized by heterodimerization with SSTR5 which results in increased recycling of SSTR2 to the cell surface. Interacts (via C-terminus) with SHANK1 (via PDZ domain) (By similarity).By similarity

Protein-protein interaction databases

IntActiP30875. 2 interactions.
MINTiMINT-4590521.
STRINGi10090.ENSMUSP00000068578.

Structurei

3D structure databases

ProteinModelPortaliP30875.
SMRiP30875. Positions 40-350.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG274661.
GeneTreeiENSGT00760000118797.
HOGENOMiHOG000230485.
HOVERGENiHBG106919.
InParanoidiP30875.
KOiK04218.
OMAiVIMPIMI.
OrthoDBiEOG7BKCVQ.
PhylomeDBiP30875.
TreeFamiTF315737.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000586. Somatstn_rcpt.
IPR002074. Somatstn_rcpt_2.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00246. SOMATOSTATNR.
PR00588. SOMATOSTTN2R.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform A (identifier: P30875-1) [UniParc]FASTAAdd to basket

Also known as: SS2RA

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEMSSEQLNG SQVWVSSPFD LNGSLGPSNG SNQTEPYYDM TSNAVLTFIY
60 70 80 90 100
FVVCVVGLCG NTLVIYVILR YAKMKTITNI YILNLAIADE LFMLGLPFLA
110 120 130 140 150
MQVALVHWPF GKAICRVVMT VDGINQFTSI FCLTVMSIDR YLAVVHPIKS
160 170 180 190 200
AKWRRPRTAK MINVAVWCVS LLVILPIMIY AGLRSNQWGR SSCTINWPGE
210 220 230 240 250
SGAWYTGFII YAFILGFLVP LTIICLCYLF IIIKVKSSGI RVGSSKRKKS
260 270 280 290 300
EKKVTRMVSI VVAVFIFCWL PFYIFNVSSV SVAISPTPAL KGMFDFVVIL
310 320 330 340 350
TYANSCANPI LYAFLSDNFK KSFQNVLCLV KVSGTEDGER SDSKQDKSRL
360
NETTETQRTL LNGDLQTSI
Length:369
Mass (Da):41,222
Last modified:July 1, 1993 - v1
Checksum:iA78845AF74823039
GO
Isoform B (identifier: P30875-2) [UniParc]FASTAAdd to basket

Also known as: SS2RB

The sequence of this isoform differs from the canonical sequence as follows:
     332-369: VSGTEDGERSDSKQDKSRLNETTETQRTLLNGDLQTSI → ADNSQSGAEDIIAWV

Show »
Length:346
Mass (Da):38,587
Checksum:iD7A20AEC1371C400
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti179 – 1791I → L in CAA48766 (PubMed:1397330).Curated
Sequence conflicti305 – 3051S → T in CAA48766 (PubMed:1397330).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei332 – 36938VSGTE…LQTSI → ADNSQSGAEDIIAWV in isoform B. CuratedVSP_001923Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81832 Genomic DNA. Translation: AAA58256.1.
X68951 mRNA. Translation: CAA48766.1.
AF008914 Genomic DNA. Translation: AAD01419.1.
AF008914 Genomic DNA. Translation: AAD01420.1.
S71756 mRNA. Translation: AAP20804.1.
CCDSiCCDS25598.1. [P30875-2]
CCDS59571.1. [P30875-1]
PIRiD41795.
S29248.
RefSeqiNP_001036071.1. NM_001042606.2. [P30875-1]
NP_033243.2. NM_009217.4. [P30875-2]

Genome annotation databases

EnsembliENSMUST00000067591; ENSMUSP00000068578; ENSMUSG00000047904. [P30875-2]
ENSMUST00000106630; ENSMUSP00000102241; ENSMUSG00000047904. [P30875-2]
ENSMUST00000146390; ENSMUSP00000138101; ENSMUSG00000047904. [P30875-1]
GeneIDi20606.
KEGGimmu:20606.
UCSCiuc011yha.1. mouse. [P30875-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81832 Genomic DNA. Translation: AAA58256.1.
X68951 mRNA. Translation: CAA48766.1.
AF008914 Genomic DNA. Translation: AAD01419.1.
AF008914 Genomic DNA. Translation: AAD01420.1.
S71756 mRNA. Translation: AAP20804.1.
CCDSiCCDS25598.1. [P30875-2]
CCDS59571.1. [P30875-1]
PIRiD41795.
S29248.
RefSeqiNP_001036071.1. NM_001042606.2. [P30875-1]
NP_033243.2. NM_009217.4. [P30875-2]

3D structure databases

ProteinModelPortaliP30875.
SMRiP30875. Positions 40-350.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP30875. 2 interactions.
MINTiMINT-4590521.
STRINGi10090.ENSMUSP00000068578.

Chemistry

BindingDBiP30875.
ChEMBLiCHEMBL3207.
GuidetoPHARMACOLOGYi356.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiP30875.

Proteomic databases

PRIDEiP30875.

Protocols and materials databases

DNASUi20606.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000067591; ENSMUSP00000068578; ENSMUSG00000047904. [P30875-2]
ENSMUST00000106630; ENSMUSP00000102241; ENSMUSG00000047904. [P30875-2]
ENSMUST00000146390; ENSMUSP00000138101; ENSMUSG00000047904. [P30875-1]
GeneIDi20606.
KEGGimmu:20606.
UCSCiuc011yha.1. mouse. [P30875-1]

Organism-specific databases

CTDi6752.
MGIiMGI:98328. Sstr2.

Phylogenomic databases

eggNOGiNOG274661.
GeneTreeiENSGT00760000118797.
HOGENOMiHOG000230485.
HOVERGENiHBG106919.
InParanoidiP30875.
KOiK04218.
OMAiVIMPIMI.
OrthoDBiEOG7BKCVQ.
PhylomeDBiP30875.
TreeFamiTF315737.

Enzyme and pathway databases

ReactomeiREACT_319210. Peptide ligand-binding receptors.
REACT_331048. G alpha (i) signalling events.

Miscellaneous databases

NextBioi298949.
PROiP30875.
SOURCEiSearch...

Gene expression databases

BgeeiP30875.
CleanExiMM_SSTR2.
GenevisibleiP30875. MM.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000586. Somatstn_rcpt.
IPR002074. Somatstn_rcpt_2.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00246. SOMATOSTATNR.
PR00588. SOMATOSTTN2R.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney."
    Yamada Y., Post S.R., Wang K., Tager H.S., Bell G.I., Seino S.
    Proc. Natl. Acad. Sci. U.S.A. 89:251-255(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A).
  2. "Cloning and expression of a novel mouse somatostatin receptor (SSTR2B)."
    Vanetti M., Kouba M., Wang X., Vogt G., Hoellt V.
    FEBS Lett. 311:290-294(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM B).
  3. "Transcriptional activation of mouse sst2 somatostatin receptor promoter by transforming growth factor-beta. Involvement of Smad4."
    Puente E., Saint-Laurent N., Torrisani J., Furet C., Schally A.V., Vaysse N., Buscail L., Susini C.
    J. Biol. Chem. 276:13461-13468(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS A AND B).
    Strain: 129.
    Tissue: Liver.
  4. "T lymphocytes isolated from the hepatic granulomas of schistosome-infected mice express somatostatin receptor subtype II (SSTR2) messenger RNA."
    Elliott D.E., Metwali A., Blum A.M., Sandor M., Lynch R., Weinstock J.V.
    J. Immunol. 153:1180-1186(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 99-309 (ISOFORMS A/B).
  5. "The two isoforms of the mouse somatostatin receptor (mSSTR2A and mSSTR2B) differ in coupling efficiency to adenylate cyclase and in agonist-induced receptor desensitization."
    Vanetti M., Hoellt V.
    FEBS Lett. 331:260-266(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING (ISOFORMS A AND B).
  6. "sst2 somatostatin receptor mediates negative regulation of insulin receptor signaling through the tyrosine phosphatase SHP-1."
    Bousquet C., Delesque N., Lopez F., Saint-Laurent N., Esteve J.P., Bedecs K., Buscail L., Vaysse N., Susini C.
    J. Biol. Chem. 273:7099-7106(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiSSR2_MOUSE
AccessioniPrimary (citable) accession number: P30875
Secondary accession number(s): P30934, Q91Y73
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: June 24, 2015
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.