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Protein

Somatostatin receptor type 2

Gene

SSTR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei89Important for ligand binding1

GO - Molecular functioni

  • neuropeptide binding Source: GO_Central
  • PDZ domain binding Source: UniProtKB
  • somatostatin receptor activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000180616-MONOMER.
ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
R-HSA-418594. G alpha (i) signalling events.
SignaLinkiP30874.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:11331. SSTR2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 43ExtracellularSequence analysisAdd BLAST43
Transmembranei44 – 67Helical; Name=1Sequence analysisAdd BLAST24
Topological domaini68 – 78CytoplasmicSequence analysisAdd BLAST11
Transmembranei79 – 103Helical; Name=2Sequence analysisAdd BLAST25
Topological domaini104 – 118ExtracellularSequence analysisAdd BLAST15
Transmembranei119 – 138Helical; Name=3Sequence analysisAdd BLAST20
Topological domaini139 – 161CytoplasmicSequence analysisAdd BLAST23
Transmembranei162 – 181Helical; Name=4Sequence analysisAdd BLAST20
Topological domaini182 – 207ExtracellularSequence analysisAdd BLAST26
Transmembranei208 – 229Helical; Name=5Sequence analysisAdd BLAST22
Topological domaini230 – 253CytoplasmicSequence analysisAdd BLAST24
Transmembranei254 – 278Helical; Name=6Sequence analysisAdd BLAST25
Topological domaini279 – 288ExtracellularSequence analysis10
Transmembranei289 – 303Helical; Name=7Sequence analysisAdd BLAST15
Topological domaini304 – 369CytoplasmicSequence analysisAdd BLAST66

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi89D → A: Expression levels reduced by 60%. 1 Publication1
Mutagenesisi89D → L: Expression levels reduced by 80%. 1 Publication1
Mutagenesisi89D → R: Slightly reduced expression levels. Remains localized in membrane. Abolishes ligand binding and G protein-mediated calcium release. 1 Publication1
Mutagenesisi139D → A: Expression levels reduced by 50%. Significantly reduced ligand binding capacity but increased affinity. Reduced G protein-mediated cAMP release but no effect on G-protein mediated calcium release. 1 Publication1
Mutagenesisi139D → N: Expression levels reduced by 40%. No significant change in ligand binding capacity or affinity. Reduced G protein-mediated cAMP signaling but no effect on G protein-mediated calcium release. 1 Publication1
Mutagenesisi140R → A: Slightly reduced expression levels. No significant change in ligand binding capacity or affinity. No significant change in G protein-mediated cAMP or calcium release. 1 Publication1
Mutagenesisi140R → E: Almost abolishes expression. Abolishes membrane localization. 1 Publication1
Mutagenesisi140R → L: Slightly reduced expression levels. Significantly reduced ligand binding capacity but increased affinity. Reduced G protein-mediated cAMP release but no effect on G protein-mediated calcium release. 1 Publication1

Organism-specific databases

DisGeNETi6752.
OpenTargetsiENSG00000180616.
PharmGKBiPA36155.

Chemistry databases

ChEMBLiCHEMBL1804.
DrugBankiDB06791. Lanreotide.
DB00104. Octreotide.
DB06663. Pasireotide.
DB04894. Vapreotide.
GuidetoPHARMACOLOGYi356.

Polymorphism and mutation databases

BioMutaiSSTR2.
DMDMi401126.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000701201 – 369Somatostatin receptor type 2Add BLAST369

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi9N-linked (GlcNAc...)Sequence analysis1
Glycosylationi22N-linked (GlcNAc...)Sequence analysis1
Glycosylationi29N-linked (GlcNAc...)Sequence analysis1
Glycosylationi32N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi115 ↔ 193PROSITE-ProRule annotation
Lipidationi328S-palmitoyl cysteineSequence analysis1
Modified residuei341PhosphoserineBy similarity1
Modified residuei343PhosphoserineBy similarity1
Modified residuei348PhosphoserineBy similarity1
Modified residuei353PhosphothreonineBy similarity1
Modified residuei354PhosphothreonineBy similarity1

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

PaxDbiP30874.
PeptideAtlasiP30874.
PRIDEiP30874.

PTM databases

iPTMnetiP30874.
PhosphoSitePlusiP30874.

Expressioni

Tissue specificityi

Expressed in both pancreatic alpha- and beta-cells (at protein level). Expressed at higher levels in the pancreas than other somatostatin receptors. Also expressed in the cerebrum and kidney and, in lesser amounts, in the jejunum, colon and liver. In the developing nervous system, expressed in the cortex where it is located in the preplate at early stages and is enriched in the outer part of the germinal zone at later stages. In the cerebellum, expressed in the deep part of the external granular layer at gestational week 19. This pattern persists until birth but disappears at adulthood.2 Publications

Gene expression databases

BgeeiENSG00000180616.
CleanExiHS_SSTR2.
GenevisibleiP30874. HS.

Organism-specific databases

HPAiHPA007264.

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).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PIK3R1P279865EBI-6266898,EBI-79464
SSTR3P327453EBI-6266898,EBI-6266935

GO - Molecular functioni

  • PDZ domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112630. 5 interactors.
IntActiP30874. 2 interactors.
MINTiMINT-3340293.
STRINGi9606.ENSP00000350198.

Chemistry databases

BindingDBiP30874.

Structurei

3D structure databases

ProteinModelPortaliP30874.
SMRiP30874.
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

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118797.
HOGENOMiHOG000230485.
HOVERGENiHBG106919.
InParanoidiP30874.
KOiK04218.
OMAiSTVVITC.
OrthoDBiEOG091G0HEN.
PhylomeDBiP30874.
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.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
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: P30874-1) [UniParc]FASTAAdd to basket
Also known as: SSTR2A

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
MDMADEPLNG SHTWLSIPFD LNGSVVSTNT SNQTEPYYDL TSNAVLTFIY
60 70 80 90 100
FVVCIIGLCG NTLVIYVILR YAKMKTITNI YILNLAIADE LFMLGLPFLA
110 120 130 140 150
MQVALVHWPF GKAICRVVMT VDGINQFTSI FCLTVMSIDR YLAVVHPIKS
160 170 180 190 200
AKWRRPRTAK MITMAVWGVS LLVILPIMIY AGLRSNQWGR SSCTINWPGE
210 220 230 240 250
SGAWYTGFII YTFILGFLVP LTIICLCYLF IIIKVKSSGI RVGSSKRKKS
260 270 280 290 300
EKKVTRMVSI VVAVFIFCWL PFYIFNVSSV SMAISPTPAL KGMFDFVVVL
310 320 330 340 350
TYANSCANPI LYAFLSDNFK KSFQNVLCLV KVSGTDDGER SDSKQDKSRL
360
NETTETQRTL LNGDLQTSI
Length:369
Mass (Da):41,333
Last modified:July 1, 1993 - v1
Checksum:i3B5D7D8A9AC246C6
GO
Isoform B (identifier: P30874-2) [UniParc]FASTAAdd to basket
Also known as: SSTR2B

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

Show »
Length:356
Mass (Da):40,007
Checksum:iD10FA237FAED61F3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti77I → T in BAG36594 (PubMed:14702039).Curated1
Sequence conflicti122D → N in BAG36594 (PubMed:14702039).Curated1
Sequence conflicti356T → A in BAG36594 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001922332 – 369VSGTD…LQTSI → VDNSKSGEEGSCLDMIFRNN KNRKK in isoform B. CuratedAdd BLAST38

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81830 Genomic DNA. Translation: AAA58248.1.
AY236542 Genomic DNA. Translation: AAO92064.1.
AF184174 Genomic DNA. Translation: AAF42809.1.
AF184174 Genomic DNA. Translation: AAF42810.1.
AB065911 Genomic DNA. Translation: BAC06126.1.
AK290745 mRNA. Translation: BAF83434.1.
AK313866 mRNA. Translation: BAG36594.1.
BT019926 mRNA. Translation: AAV38729.1.
BC000256 mRNA. Translation: AAH00256.1.
BC009522 mRNA. Translation: AAH09522.1.
BC019610 mRNA. Translation: AAH19610.1.
BC095495 mRNA. Translation: AAH95495.1.
CCDSiCCDS11691.1. [P30874-1]
PIRiB41795.
RefSeqiNP_001041.1. NM_001050.2. [P30874-1]
UniGeneiHs.514451.

Genome annotation databases

EnsembliENST00000357585; ENSP00000350198; ENSG00000180616. [P30874-1]
GeneIDi6752.
KEGGihsa:6752.
UCSCiuc002jje.4. human. [P30874-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81830 Genomic DNA. Translation: AAA58248.1.
AY236542 Genomic DNA. Translation: AAO92064.1.
AF184174 Genomic DNA. Translation: AAF42809.1.
AF184174 Genomic DNA. Translation: AAF42810.1.
AB065911 Genomic DNA. Translation: BAC06126.1.
AK290745 mRNA. Translation: BAF83434.1.
AK313866 mRNA. Translation: BAG36594.1.
BT019926 mRNA. Translation: AAV38729.1.
BC000256 mRNA. Translation: AAH00256.1.
BC009522 mRNA. Translation: AAH09522.1.
BC019610 mRNA. Translation: AAH19610.1.
BC095495 mRNA. Translation: AAH95495.1.
CCDSiCCDS11691.1. [P30874-1]
PIRiB41795.
RefSeqiNP_001041.1. NM_001050.2. [P30874-1]
UniGeneiHs.514451.

3D structure databases

ProteinModelPortaliP30874.
SMRiP30874.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112630. 5 interactors.
IntActiP30874. 2 interactors.
MINTiMINT-3340293.
STRINGi9606.ENSP00000350198.

Chemistry databases

BindingDBiP30874.
ChEMBLiCHEMBL1804.
DrugBankiDB06791. Lanreotide.
DB00104. Octreotide.
DB06663. Pasireotide.
DB04894. Vapreotide.
GuidetoPHARMACOLOGYi356.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP30874.
PhosphoSitePlusiP30874.

Polymorphism and mutation databases

BioMutaiSSTR2.
DMDMi401126.

Proteomic databases

PaxDbiP30874.
PeptideAtlasiP30874.
PRIDEiP30874.

Protocols and materials databases

DNASUi6752.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357585; ENSP00000350198; ENSG00000180616. [P30874-1]
GeneIDi6752.
KEGGihsa:6752.
UCSCiuc002jje.4. human. [P30874-1]

Organism-specific databases

CTDi6752.
DisGeNETi6752.
GeneCardsiSSTR2.
HGNCiHGNC:11331. SSTR2.
HPAiHPA007264.
MIMi182452. gene.
neXtProtiNX_P30874.
OpenTargetsiENSG00000180616.
PharmGKBiPA36155.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118797.
HOGENOMiHOG000230485.
HOVERGENiHBG106919.
InParanoidiP30874.
KOiK04218.
OMAiSTVVITC.
OrthoDBiEOG091G0HEN.
PhylomeDBiP30874.
TreeFamiTF315737.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000180616-MONOMER.
ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
R-HSA-418594. G alpha (i) signalling events.
SignaLinkiP30874.

Miscellaneous databases

GeneWikiiSomatostatin_receptor_2.
GenomeRNAii6752.
PROiP30874.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000180616.
CleanExiHS_SSTR2.
GenevisibleiP30874. HS.

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.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSSR2_HUMAN
AccessioniPrimary (citable) accession number: P30874
Secondary accession number(s): A8K3Y0
, B2R9P7, Q4VBP0, Q96GE0, Q96TF2, Q9BWH1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: November 2, 2016
This is version 159 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. SIMILARITY comments
    Index of protein domains and families

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 one 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.