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P30680

- SSR2_RAT

UniProt

P30680 - SSR2_RAT

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Protein

Somatostatin receptor type 2

Gene

Sstr2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein 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.4 Publications

GO - Molecular functioni

  1. PDZ domain binding Source: UniProtKB
  2. somatostatin receptor activity Source: RGD

GO - Biological processi

  1. adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: Ensembl
  2. cellular response to estradiol stimulus Source: RGD
  3. cellular response to glucocorticoid stimulus Source: RGD
  4. cerebellum development Source: RGD
  5. forebrain development Source: RGD
  6. peristalsis Source: RGD
  7. regulation of muscle contraction Source: RGD
  8. response to starvation Source: RGD
  9. somatostatin signaling pathway Source: GOC
  10. spermatogenesis Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_233455. G alpha (i) signalling events.
REACT_250028. Peptide ligand-binding receptors.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 10

Organism-specific databases

RGDi3763. Sstr2.

Subcellular locationi

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.

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

  1. cytoplasm Source: RGD
  2. integral component of membrane Source: UniProtKB-KW
  3. plasma membrane Source: RGD
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_0000070123Add
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 – 3411Phosphoserine1 Publication
Modified residuei343 – 3431Phosphoserine1 Publication
Modified residuei348 – 3481Phosphoserine1 Publication
Modified residuei353 – 3531Phosphothreonine1 Publication
Modified residuei354 – 3541Phosphothreonine1 Publication

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.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PRIDEiP30680.

PTM databases

PhosphoSiteiP30680.

Expressioni

Tissue specificityi

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.3 Publications

Gene expression databases

ExpressionAtlasiP30680. baseline.
GenevestigatoriP30680.

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).2 Publications

Protein-protein interaction databases

BioGridi248525. 4 interactions.
IntActiP30680. 1 interaction.
MINTiMINT-151186.

Structurei

3D structure databases

ProteinModelPortaliP30680.
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.
InParanoidiP30680.
KOiK04218.
OMAiVIMPIMI.
OrthoDBiEOG7BKCVQ.
PhylomeDBiP30680.
TreeFamiTF315737.

Family and domain databases

Gene3Di1.20.1070.10. 1 hit.
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. Align

Isoform A (identifier: P30680-1) [UniParc]FASTAAdd to Basket

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
MELTSEQFNG SQVWIPSPFD 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 MINVAVWGVS 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 KVSGAEDGER SDSKQDKSRL
360
NETTETQRTL LNGDLQTSI
Length:369
Mass (Da):41,200
Last modified:April 1, 1993 - v1
Checksum:i4990E489E88D7D19
GO
Isoform B (identifier: P30680-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:346
Mass (Da):38,673
Checksum:i2D75370906A660E3
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei332 – 36938VSGAE…LQTSI → ADNSKTGEEDTMAWV in isoform B. CuratedVSP_001924Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M96817 mRNA. Translation: AAA42166.1.
M93273 mRNA. Translation: AAA42165.1.
PIRiA45291.
RefSeqiNP_062221.1. NM_019348.1. [P30680-1]
UniGeneiRn.202974.
Rn.9929.

Genome annotation databases

EnsembliENSRNOT00000003734; ENSRNOP00000003734; ENSRNOG00000002793. [P30680-2]
ENSRNOT00000003735; ENSRNOP00000003735; ENSRNOG00000002793. [P30680-1]
GeneIDi54305.
KEGGirno:54305.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M96817 mRNA. Translation: AAA42166.1 .
M93273 mRNA. Translation: AAA42165.1 .
PIRi A45291.
RefSeqi NP_062221.1. NM_019348.1. [P30680-1 ]
UniGenei Rn.202974.
Rn.9929.

3D structure databases

ProteinModelPortali P30680.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 248525. 4 interactions.
IntActi P30680. 1 interaction.
MINTi MINT-151186.

Chemistry

BindingDBi P30680.
ChEMBLi CHEMBL2978.
GuidetoPHARMACOLOGYi 356.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei P30680.

Proteomic databases

PRIDEi P30680.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000003734 ; ENSRNOP00000003734 ; ENSRNOG00000002793 . [P30680-2 ]
ENSRNOT00000003735 ; ENSRNOP00000003735 ; ENSRNOG00000002793 . [P30680-1 ]
GeneIDi 54305.
KEGGi rno:54305.

Organism-specific databases

CTDi 6752.
RGDi 3763. Sstr2.

Phylogenomic databases

eggNOGi NOG274661.
GeneTreei ENSGT00760000118797.
HOGENOMi HOG000230485.
HOVERGENi HBG106919.
InParanoidi P30680.
KOi K04218.
OMAi VIMPIMI.
OrthoDBi EOG7BKCVQ.
PhylomeDBi P30680.
TreeFami TF315737.

Enzyme and pathway databases

Reactomei REACT_233455. G alpha (i) signalling events.
REACT_250028. Peptide ligand-binding receptors.

Miscellaneous databases

NextBioi 610964.
PROi P30680.

Gene expression databases

ExpressionAtlasi P30680. baseline.
Genevestigatori P30680.

Family and domain databases

Gene3Di 1.20.1070.10. 1 hit.
InterProi IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000586. Somatstn_rcpt.
IPR002074. Somatstn_rcpt_2.
[Graphical view ]
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR00237. GPCRRHODOPSN.
PR00246. SOMATOSTATNR.
PR00588. SOMATOSTTN2R.
PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiSSR2_RAT
AccessioniPrimary (citable) accession number: P30680
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: November 26, 2014
This is version 118 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, Direct protein sequencing, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3