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P30875 (SSR2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Somatostatin receptor type 2

Short name=SS-2-R
Short name=SS2-R
Short name=SS2R
Alternative name(s):
SRIF-1
Gene names
Name:Sstr2
Synonyms:Smstr2, Sst2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length369 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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. Ref.5 Ref.6

Subunit structure

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.

Subcellular location

Cell membrane; Multi-pass membrane protein. Cytoplasm By similarity. Note: Located mainly at the cell surface under basal conditions. Agonist stimulation results in internalization to the cytoplasm By similarity. Ref.5

Tissue specificity

Cerebrum and kidney.

Post-translational modification

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.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from mutant phenotype PubMed 7929134. Source: MGI

adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

Inferred from direct assay PubMed 9166719. Source: MGI

cellular response to estradiol stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to glucocorticoid stimulus

Inferred from electronic annotation. Source: Ensembl

cerebellum development

Inferred from electronic annotation. Source: Ensembl

forebrain development

Inferred from electronic annotation. Source: Ensembl

neuropeptide signaling pathway

Inferred from direct assay PubMed 9166719. Source: MGI

peristalsis

Inferred from electronic annotation. Source: Ensembl

regulation of muscle contraction

Inferred from electronic annotation. Source: Ensembl

response to starvation

Inferred from electronic annotation. Source: Ensembl

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from direct assay PubMed 7929134. Source: MGI

plasma membrane

Inferred from direct assay PubMed 9166719. Source: MGI

   Molecular_functionsomatostatin receptor activity

Inferred from direct assay Ref.1PubMed 7929134. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: P30875-1)

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.
Isoform B (identifier: P30875-2)

Also known as: SS2RB;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 369369Somatostatin receptor type 2
PRO_0000070121

Regions

Topological domain1 – 4343Extracellular Potential
Transmembrane44 – 6724Helical; Name=1; Potential
Topological domain68 – 7811Cytoplasmic Potential
Transmembrane79 – 10325Helical; Name=2; Potential
Topological domain104 – 11815Extracellular Potential
Transmembrane119 – 13820Helical; Name=3; Potential
Topological domain139 – 16123Cytoplasmic Potential
Transmembrane162 – 18120Helical; Name=4; Potential
Topological domain182 – 20726Extracellular Potential
Transmembrane208 – 22922Helical; Name=5; Potential
Topological domain230 – 25324Cytoplasmic Potential
Transmembrane254 – 27825Helical; Name=6; Potential
Topological domain279 – 28810Extracellular Potential
Transmembrane289 – 30315Helical; Name=7; Potential
Topological domain304 – 36966Cytoplasmic Potential

Amino acid modifications

Modified residue3411Phosphoserine By similarity
Modified residue3431Phosphoserine By similarity
Modified residue3481Phosphoserine By similarity
Modified residue3531Phosphothreonine By similarity
Modified residue3541Phosphothreonine By similarity
Lipidation3281S-palmitoyl cysteine Potential
Glycosylation91N-linked (GlcNAc...) Potential
Glycosylation221N-linked (GlcNAc...) Potential
Glycosylation291N-linked (GlcNAc...) Potential
Glycosylation321N-linked (GlcNAc...) Potential
Disulfide bond115 ↔ 193 By similarity

Natural variations

Alternative sequence332 – 36938VSGTE…LQTSI → ADNSQSGAEDIIAWV in isoform B.
VSP_001923

Experimental info

Sequence conflict1791I → L in CAA48766. Ref.2
Sequence conflict3051S → T in CAA48766. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform A (SS2RA) [UniParc].

Last modified July 1, 1993. Version 1.
Checksum: A78845AF74823039

FASTA36941,222
        10         20         30         40         50         60 
MEMSSEQLNG SQVWVSSPFD LNGSLGPSNG SNQTEPYYDM TSNAVLTFIY FVVCVVGLCG 

        70         80         90        100        110        120 
NTLVIYVILR YAKMKTITNI YILNLAIADE LFMLGLPFLA MQVALVHWPF GKAICRVVMT 

       130        140        150        160        170        180 
VDGINQFTSI FCLTVMSIDR YLAVVHPIKS AKWRRPRTAK MINVAVWCVS LLVILPIMIY 

       190        200        210        220        230        240 
AGLRSNQWGR SSCTINWPGE SGAWYTGFII YAFILGFLVP LTIICLCYLF IIIKVKSSGI 

       250        260        270        280        290        300 
RVGSSKRKKS EKKVTRMVSI VVAVFIFCWL PFYIFNVSSV SVAISPTPAL KGMFDFVVIL 

       310        320        330        340        350        360 
TYANSCANPI LYAFLSDNFK KSFQNVLCLV KVSGTEDGER SDSKQDKSRL NETTETQRTL 


LNGDLQTSI 

« Hide

Isoform B (SS2RB) [UniParc].

Checksum: D7A20AEC1371C400
Show »

FASTA34638,587

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS25598.1. [P30875-2]
CCDS59571.1. [P30875-1]
PIRD41795.
S29248.
RefSeqNP_001036071.1. NM_001042606.2. [P30875-1]
NP_033243.2. NM_009217.4. [P30875-2]

3D structure databases

ProteinModelPortalP30875.
SMRP30875. Positions 40-328.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP30875. 2 interactions.
MINTMINT-4590521.

Chemistry

BindingDBP30875.
ChEMBLCHEMBL3207.
GuidetoPHARMACOLOGY356.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP30875.

Proteomic databases

PRIDEP30875.

Protocols and materials databases

DNASU20606.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000067591; ENSMUSP00000068578; ENSMUSG00000047904. [P30875-2]
ENSMUST00000106630; ENSMUSP00000102241; ENSMUSG00000047904. [P30875-2]
ENSMUST00000146390; ENSMUSP00000138101; ENSMUSG00000047904. [P30875-1]
GeneID20606.
KEGGmmu:20606.
UCSCuc011yha.1. mouse. [P30875-1]

Organism-specific databases

CTD6752.
MGIMGI:98328. Sstr2.

Phylogenomic databases

eggNOGNOG274661.
GeneTreeENSGT00630000089736.
HOGENOMHOG000230485.
HOVERGENHBG106919.
InParanoidP30875.
KOK04218.
OMAVIMPIMI.
OrthoDBEOG7BKCVQ.
PhylomeDBP30875.
TreeFamTF315737.

Gene expression databases

BgeeP30875.
CleanExMM_SSTR2.
GenevestigatorP30875.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000586. Somatstn_rcpt.
IPR002074. Somatstn_rcpt_2.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR00246. SOMATOSTATNR.
PR00588. SOMATOSTTN2R.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio298949.
PROP30875.
SOURCESearch...

Entry information

Entry nameSSR2_MOUSE
AccessionPrimary (citable) accession number: P30875
Secondary accession number(s): P30934, Q91Y73
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: July 9, 2014
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries