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P30875

- SSR2_MOUSE

UniProt

P30875 - SSR2_MOUSE

Protein

Somatostatin receptor type 2

Gene

Sstr2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 136 (01 Oct 2014)
      Sequence version 1 (01 Jul 1993)
      Previous versions | rss
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    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

    1. somatostatin receptor activity Source: MGI

    GO - Biological processi

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

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    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: 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

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. integral component of membrane Source: UniProtKB-KW
    3. membrane Source: MGI
    4. plasma membrane Source: MGI

    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.
    GenevestigatoriP30875.

    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.

    Structurei

    3D structure databases

    ProteinModelPortaliP30875.
    SMRiP30875. Positions 40-328.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 4343ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini68 – 7811CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini104 – 11815ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini139 – 16123CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini182 – 20726ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini230 – 25324CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini279 – 28810ExtracellularSequence Analysis
    Topological domaini304 – 36966CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei44 – 6724Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei79 – 10325Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei119 – 13820Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei162 – 18120Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei208 – 22922Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei254 – 27825Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei289 – 30315Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

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

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG274661.
    GeneTreeiENSGT00630000089736.
    HOGENOMiHOG000230485.
    HOVERGENiHBG106919.
    InParanoidiP30875.
    KOiK04218.
    OMAiVIMPIMI.
    OrthoDBiEOG7BKCVQ.
    PhylomeDBiP30875.
    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: 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

    MEMSSEQLNG SQVWVSSPFD LNGSLGPSNG SNQTEPYYDM TSNAVLTFIY    50
    FVVCVVGLCG NTLVIYVILR YAKMKTITNI YILNLAIADE LFMLGLPFLA 100
    MQVALVHWPF GKAICRVVMT VDGINQFTSI FCLTVMSIDR YLAVVHPIKS 150
    AKWRRPRTAK MINVAVWCVS LLVILPIMIY AGLRSNQWGR SSCTINWPGE 200
    SGAWYTGFII YAFILGFLVP LTIICLCYLF IIIKVKSSGI RVGSSKRKKS 250
    EKKVTRMVSI VVAVFIFCWL PFYIFNVSSV SVAISPTPAL KGMFDFVVIL 300
    TYANSCANPI LYAFLSDNFK KSFQNVLCLV KVSGTEDGER SDSKQDKSRL 350
    NETTETQRTL LNGDLQTSI 369
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS25598.1. [P30875-2 ]
    CCDS59571.1. [P30875-1 ]
    PIRi D41795.
    S29248.
    RefSeqi NP_001036071.1. NM_001042606.2. [P30875-1 ]
    NP_033243.2. NM_009217.4. [P30875-2 ]

    3D structure databases

    ProteinModelPortali P30875.
    SMRi P30875. Positions 40-328.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P30875. 2 interactions.
    MINTi MINT-4590521.

    Chemistry

    BindingDBi P30875.
    ChEMBLi CHEMBL3207.
    GuidetoPHARMACOLOGYi 356.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei P30875.

    Proteomic databases

    PRIDEi P30875.

    Protocols and materials databases

    DNASUi 20606.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000067591 ; ENSMUSP00000068578 ; ENSMUSG00000047904 . [P30875-2 ]
    ENSMUST00000106630 ; ENSMUSP00000102241 ; ENSMUSG00000047904 . [P30875-2 ]
    ENSMUST00000146390 ; ENSMUSP00000138101 ; ENSMUSG00000047904 . [P30875-1 ]
    GeneIDi 20606.
    KEGGi mmu:20606.
    UCSCi uc011yha.1. mouse. [P30875-1 ]

    Organism-specific databases

    CTDi 6752.
    MGIi MGI:98328. Sstr2.

    Phylogenomic databases

    eggNOGi NOG274661.
    GeneTreei ENSGT00630000089736.
    HOGENOMi HOG000230485.
    HOVERGENi HBG106919.
    InParanoidi P30875.
    KOi K04218.
    OMAi VIMPIMI.
    OrthoDBi EOG7BKCVQ.
    PhylomeDBi P30875.
    TreeFami TF315737.

    Miscellaneous databases

    NextBioi 298949.
    PROi P30875.
    SOURCEi Search...

    Gene expression databases

    Bgeei P30875.
    CleanExi MM_SSTR2.
    Genevestigatori P30875.

    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. "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: October 1, 2014
    This is version 136 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