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P30680 (SSR2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length369 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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.3 Ref.4 Ref.5 Ref.7

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). Ref.4 Ref.5

Subcellular location

Cell membrane; Multi-pass membrane protein. Cytoplasm. Note: Located mainly at the cell surface under basal conditions. Agonist stimulation results in internalization to the cytoplasm. Ref.4 Ref.5 Ref.7

Tissue specificity

Cortex, hippocampus, pituitary gland, colon, kidney, and adrenal gland. In the developing nervous system, expressed from E12 when it is restricted to postmitotic neuronal populations leaving the ventricular zone. From E12 on, expressed in migrating neuronal populations in numerous developing regions including the cerebral cortex, hippocampus and ganglionic eminences. Also detected in the deep part of the external granular layer of the cerebellum, the rostral migratory stream and a subset of axons and neurons. Expressed in the medial forebrain bundle, rostral migratory stream and cerebellum during development but not in adulthood. Ref.1 Ref.3 Ref.7

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. Ref.5 Ref.6

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
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

cellular response to estradiol stimulus

Inferred from expression pattern PubMed 9564833. Source: RGD

cellular response to glucocorticoid stimulus

Inferred from expression pattern PubMed 14512709. Source: RGD

cerebellum development

Inferred from expression pattern PubMed 9166718. Source: RGD

forebrain development

Inferred from expression pattern PubMed 10805921. Source: RGD

peristalsis

Inferred from mutant phenotype PubMed 12504886. Source: RGD

regulation of muscle contraction

Inferred from mutant phenotype PubMed 11897621. Source: RGD

response to starvation

Inferred from expression pattern PubMed 7956902. Source: RGD

somatostatin signaling pathway

Inferred from direct assay Ref.1. Source: GOC

spermatogenesis

Inferred from expression pattern PubMed 9421433. Source: RGD

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 9322965. Source: RGD

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from direct assay PubMed 9322965. Source: RGD

   Molecular_functionPDZ domain binding

Inferred from physical interaction PubMed 10551867. Source: UniProtKB

somatostatin receptor activity

Inferred from direct assay Ref.1. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: P30680-1)

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: P30680-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 369369Somatostatin receptor type 2
PRO_0000070123

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 Ref.6
Modified residue3431Phosphoserine Ref.6
Modified residue3481Phosphoserine Ref.6
Modified residue3531Phosphothreonine Ref.6
Modified residue3541Phosphothreonine Ref.6
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 – 36938VSGAE…LQTSI → ADNSKTGEEDTMAWV in isoform B.
VSP_001924

Sequences

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

Last modified April 1, 1993. Version 1.
Checksum: 4990E489E88D7D19

FASTA36941,200
        10         20         30         40         50         60 
MELTSEQFNG SQVWIPSPFD 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 MINVAVWGVS 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 KVSGAEDGER SDSKQDKSRL NETTETQRTL 


LNGDLQTSI 

« Hide

Isoform B [UniParc].

Checksum: 2D75370906A660E3
Show »

FASTA34638,673

References

[1]"Expression cloning of a rat brain somatostatin receptor cDNA."
Kluxen F.-W., Bruns C., Luebbert H.
Proc. Natl. Acad. Sci. U.S.A. 89:4618-4622(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), TISSUE SPECIFICITY.
Tissue: Brain.
[2]"Partial amino acid sequence of a somatostatin receptor isolated from GH4C1 pituitary cells."
Hulmes J.D., Corbett M., Zysk J.R., Boehlen P., Eppler C.M.
Biochem. Biophys. Res. Commun. 184:131-136(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 76-81; 179-189; 294-320 AND 350-358.
Tissue: Pituitary.
[3]"Multiple gene transcripts of the somatostatin receptor SSTR2: tissue selective distribution and cAMP regulation."
Patel Y.C., Greenwood M., Kent G., Panetta R., Srikant C.B.
Biochem. Biophys. Res. Commun. 192:288-294(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, ALTERNATIVE SPLICING (ISOFORMS A AND B).
[4]"Homo- and heterodimerization of somatostatin receptor subtypes. Inactivation of sst(3) receptor function by heterodimerization with sst(2A)."
Pfeiffer M., Koch T., Schroder H., Klutzny M., Kirscht S., Kreienkamp H.J., Hollt V., Schulz S.
J. Biol. Chem. 276:14027-14036(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
[5]"Distinct phosphorylation sites in the SST2A somatostatin receptor control internalization, desensitization, and arrestin binding."
Liu Q., Dewi D.A., Liu W., Bee M.S., Schonbrunn A.
Mol. Pharmacol. 73:292-304(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH BETA-ARRESTIN, SUBCELLULAR LOCATION, PHOSPHORYLATION.
[6]"Site specificity of agonist and second messenger-activated kinases for somatostatin receptor subtype 2A (Sst2A) phosphorylation."
Liu Q., Bee M.S., Schonbrunn A.
Mol. Pharmacol. 76:68-80(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-341; SER-343; SER-348; THR-353 AND THR-354.
[7]"The somatostatin 2A receptor is enriched in migrating neurons during rat and human brain development and stimulates migration and axonal outgrowth."
Le Verche V., Kaindl A.M., Verney C., Csaba Z., Peineau S., Olivier P., Adle-Biassette H., Leterrier C., Vitalis T., Renaud J., Dargent B., Gressens P., Dournaud P.
PLoS ONE 4:E5509-E5509(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M96817 mRNA. Translation: AAA42166.1.
M93273 mRNA. Translation: AAA42165.1.
PIRA45291.
RefSeqNP_062221.1. NM_019348.1. [P30680-1]
UniGeneRn.202974.
Rn.9929.

3D structure databases

ProteinModelPortalP30680.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid248525. 4 interactions.
IntActP30680. 1 interaction.
MINTMINT-151186.

Chemistry

BindingDBP30680.
ChEMBLCHEMBL2096977.
GuidetoPHARMACOLOGY356.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP30680.

Proteomic databases

PRIDEP30680.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000003734; ENSRNOP00000003734; ENSRNOG00000002793. [P30680-2]
ENSRNOT00000003735; ENSRNOP00000003735; ENSRNOG00000002793. [P30680-1]
GeneID54305.
KEGGrno:54305.

Organism-specific databases

CTD6752.
RGD3763. Sstr2.

Phylogenomic databases

eggNOGNOG274661.
GeneTreeENSGT00630000089736.
HOGENOMHOG000230485.
HOVERGENHBG106919.
InParanoidP30680.
KOK04218.
OMAVIMPIMI.
OrthoDBEOG7BKCVQ.
PhylomeDBP30680.
TreeFamTF315737.

Gene expression databases

GenevestigatorP30680.

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

NextBio610964.
PROP30680.

Entry information

Entry nameSSR2_RAT
AccessionPrimary (citable) accession number: P30680
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: June 11, 2014
This is version 115 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

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries