Details for: SSTR2

Gene ID: 6752

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SSTR2

Ensembl ID: ENSG00000180616

Description: somatostatin receptor 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • pancreatic A cell CL0000171
    CSI 11.58
    rCSI 12.13%
    PRS 97.62
  • progenitor cell CL0011026
    CSI 8.85
    rCSI 18.82%
    PRS 93.74
  • peripheral nervous system neuron CL2000032
    CSI 6.83
    rCSI 9.31%
    PRS 94.57
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 6.13
    rCSI 10.29%
    PRS 92.29
  • pancreatic D cell CL0000173
    CSI 6.1
    rCSI 6%
    PRS 97.47
  • microcirculation associated smooth muscle cell CL0008035
    CSI 5.8
    rCSI 16.8%
    PRS 96.97
  • vascular associated smooth muscle cell CL0000359
    CSI 4.79
    rCSI 15.53%
    PRS 97.06
  • enteroendocrine cell CL0000164
    CSI 4.68
    rCSI 6.39%
    PRS 95.82
  • pericyte CL0000669
    CSI 4.27
    rCSI 11.37%
    PRS 81.41
  • myofibroblast cell CL0000186
    CSI 4.21
    rCSI 5.83%
    PRS 95.94
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 4.09
    rCSI 9.95%
    PRS 90.72
  • glial cell CL0000125
    CSI 4.08
    rCSI 15.52%
    PRS 93.92
  • epithelial cell CL0000066
    CSI 3.87
    rCSI 5.94%
    PRS 90.06
  • L6b glutamatergic cortical neuron CL4023038
    CSI 3.62
    rCSI 11.3%
    PRS 92.68
  • cerebral cortex neuron CL0010012
    CSI 3.59
    rCSI 14.62%
    PRS 92.71
  • intestine goblet cell CL0019031
    CSI 3.51
    rCSI 3.11%
    PRS 96.2
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.49
    rCSI 4.17%
    PRS 92.13
  • OFF-bipolar cell CL0000750
    CSI 3.46
    rCSI 4.74%
    PRS 95.85
  • interneuron CL0000099
    CSI 3.42
    rCSI 6.87%
    PRS 95.07
  • pancreatic epsilon cell CL0005019
    CSI 3.4
    rCSI 15.84%
    PRS 97.47
  • GABAergic amacrine cell CL4030027
    CSI 2.8
    rCSI 9.6%
    PRS 90.14
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.38
    rCSI 3.81%
    PRS 98.17
  • forebrain radial glial cell CL0013000
    CSI 2.37
    rCSI 7.6%
    PRS 97.2
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.32
    rCSI 2.97%
    PRS 95.73
  • epithelial cell of proximal tubule CL0002306
    CSI 2.19
    rCSI 5.35%
    PRS 93.76
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 2.16
    rCSI 7.77%
    PRS 90.89
  • type L enteroendocrine cell CL0002279
    CSI 1.95
    rCSI 3.65%
    PRS 96.97
  • enteroendocrine cell of small intestine CL0009006
    CSI 1.83
    rCSI 4.03%
    PRS 97.37
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.71
    rCSI 3.03%
    PRS 92.05
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.4
    rCSI 3.36%
    PRS 91.72
  • type B pancreatic cell CL0000169
    CSI 1.34
    rCSI 2.97%
    PRS 97.02
  • smooth muscle cell of prostate CL1000487
    CSI 1.32
    rCSI 7.79%
    PRS 98.42
  • diffuse bipolar 3b cell CL4033030
    CSI 1.32
    rCSI 8.75%
    PRS 93.03
  • P/D1 enteroendocrine cell CL0002268
    CSI 1.21
    rCSI 6.61%
    PRS 96.91
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 1.18
    rCSI 3.86%
    PRS 90.8
  • diffuse bipolar 2 cell CL4033028
    CSI 1.14
    rCSI 8.84%
    PRS 92.19
  • enteroendocrine cell of colon CL0009042
    CSI 1.06
    rCSI 4.97%
    PRS 96.89
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.01
    rCSI 5.94%
    PRS 92.19
  • pancreatic stellate cell CL0002410
    CSI 0.98
    rCSI 5.71%
    PRS 97.57
  • blood vessel smooth muscle cell CL0019018
    CSI 0.59
    rCSI 4.76%
    PRS 96.91
  • direct pathway medium spiny neuron CL4023026
    CSI 0.45
    rCSI 10.72%
    PRS 89.94

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SSTR2](/details-gene/6752) encodes the somatostatin receptor type 2, a member of the G protein-coupled receptor (GPCR) superfamily. As a primary receptor for the neuropeptide somatostatin, [SSTR2](/details-gene/6752) plays a crucial role in regulating endocrine and nervous system function by inhibiting cellular activity. Expression data shows that [SSTR2](/details-gene/6752) is a highly significant marker for specialized cell types, most notably [pancreatic A cell](/details-cell/CL0000171)s and various neuronal populations. Its function is primarily mediated through G alpha (i) signaling pathways, leading to the inhibition of adenylate cyclase and a subsequent reduction in intracellular cAMP levels, which in turn negatively regulates cell proliferation and secretory processes. This gene is clinically significant and is associated with certain developmental and endocrine disorders ([OMIM: 182452](https://omim.org/entry/182452)). ## Cellular Roles and Expression Landscape The expression profile of [SSTR2](/details-gene/6752) highlights its specialized role in neuroendocrine and neural tissues. **Overall**, the gene shows the highest significance in [pancreatic A cell](/details-cell/CL0000171)s (CSI: 11.58), which is consistent with its established function as the dominant somatostatin receptor modulating glucagon secretion in the pancreas ([Link](https://doi.org/10.1152/ajpendo.00207.2012)). High significance is also observed in [pancreatic D cell](/details-cell/CL0000173)s, the source of somatostatin, suggesting potential autocrine or paracrine feedback loops. Beyond the pancreas, [SSTR2](/details-gene/6752) is a key marker across the nervous system. It is highly significant in [peripheral nervous system neuron](/details-cell/CL2000032)s and specific cortical interneurons like the [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011). This broad neuronal expression aligns with its role in neuropeptide signaling and brain development, where it has been shown to influence neuronal migration and axonal outgrowth ([Link](https://doi.org/10.1371/journal.pone.0005509)). Furthermore, its notable significance in [progenitor cell](/details-cell/CL0011026)s suggests a potential role in regulating cell fate decisions and maintaining quiescence. The gene also shows relevance in the vasculature, with significant expression in [microcirculation associated smooth muscle cell](/details-cell/CL0008035)s and [pericyte](/details-cell/CL0000669)s, indicating a role in regulating blood flow and vessel tone. ## Pathways and Molecular Function The molecular function of [SSTR2](/details-gene/6752) is centered on its activity as a somatostatin receptor ([GO:0004994](https://www.ebi.ac.uk/QuickGO/term/GO:0004994)) located on the [plasma membrane](/details-cell/GO:0005886). Upon binding somatostatin, it initiates a signaling cascade characteristic of Class A/1 rhodopsin-like receptors ([R-HSA-373076](https://reactome.org/content/detail/R-HSA-373076)). The primary pathway engaged is the [adenylate cyclase-inhibiting g protein-coupled receptor signaling pathway](/details-cell/GO:0007193), which is driven by its coupling to inhibitory G proteins, as detailed in the [G alpha (i) signalling events](/details-cell/R-HSA-418594) pathway. This inhibitory signaling has broad physiological consequences, including the [negative regulation of cell population proliferation](/details-cell/GO:0008285), which is a key mechanism for its tumor-suppressive effects in certain contexts. Its involvement in the [neuropeptide signaling pathway](/details-cell/GO:0007218) underscores its high expression in neurons. Furthermore, its role in developmental processes such as [cerebellum development](/details-cell/GO:0021549) and [forebrain development](/details-cell/GO:0030900) is consistent with its expression in progenitor and neuronal cell populations during brain formation ([Link](https://doi.org/10.1371/journal.pone.0005509)). ## Research Directions The specific and high-level expression of [SSTR2](/details-gene/6752) in distinct cell populations, combined with its potent inhibitory function, presents several avenues for further investigation. **Testable Hypotheses:** 1. Given its high significance in [progenitor cell](/details-cell/CL0011026)s and its function in negatively regulating proliferation, [SSTR2](/details-gene/6752) signaling may act as a crucial brake to maintain stemness or quiescence. Dysregulation or downregulation of [SSTR2](/details-gene/6752) in these cells could be a prerequisite for their entry into the cell cycle during tissue repair or oncogenesis. 2. The expression of [SSTR2](/details-gene/6752) in vascular cells like [pericyte](/details-cell/CL0000669)s and smooth muscle cells suggests it may directly mediate the vasoactive effects of somatostatin. [SSTR2](/details-gene/6752) activation on these cells likely contributes to the regulation of microcirculatory blood flow and blood-brain barrier integrity, particularly under conditions of stress or inflammation. **Proposed Experiment:** To test the hypothesis that [SSTR2](/details-gene/6752) maintains progenitor cell quiescence (Hypothesis 1), one could utilize organoid models derived from human induced pluripotent stem cells (iPSCs) that generate [progenitor cell](/details-cell/CL0011026)s known to express this receptor (e.g., neural progenitor organoids). Using a CRISPR-Cas9 knockout system to ablate [SSTR2](/details-gene/6752), the proliferation rate of progenitor cells could be quantified using EdU incorporation assays and single-cell RNA sequencing. It would be expected that [SSTR2](/details-gene/6752)-knockout organoids would exhibit a higher proportion of cycling progenitor cells and potentially display signs of abnormal or accelerated differentiation compared to isogenic wild-type controls. **Therapeutic Potential:** [SSTR2](/details-gene/6752) is already a validated and highly valuable therapeutic target, particularly in oncology. Its high expression on the surface of many neuroendocrine tumors allows it to be targeted for both imaging (e.g., Gallium-68 DOTATATE PET/CT) and therapy. The primary strategy involves the use of synthetic somatostatin analogues (e.g., octreotide, lanreotide) which act as agonists to suppress hormone secretion and cell proliferation. Furthermore, these analogues can be coupled to radioisotopes (Peptide Receptor Radionuclide Therapy, PRRT) to deliver targeted radiation to [SSTR2](/details-gene/6752)-positive cancer cells. Its specific expression profile makes it a prime candidate for targeted activation or for use as a "delivery address" for cytotoxic payloads, minimizing off-target effects.

Genular Protein ID: 3212727138

Symbol: SSR2_HUMAN

Name: Somatostatin receptor type 2

UniProtKB Accession Codes:

P30874 A8K3Y0 B2R9P7 Q4VBP0 Q96GE0 Q96TF2 Q9BWH1

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 8 DrugCentral 1 EMBL 12 EMDB 12 Ensembl 1 GO 17 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 15 PDBsum 15 PIR 1 PRINTS 3 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 2 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 1346068

Title: Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney.

PubMed ID: 1346068

DOI: 10.1073/pnas.89.1.251

PubMed ID: 10619399

Title: Genomic structure and transcriptional regulation of the human somatostatin receptor type 2.

PubMed ID: 10619399

DOI: 10.1016/s0303-7207(99)00161-6

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8386508

Title: Multiple gene transcripts of the somatostatin receptor SSTR2: tissue selective distribution and cAMP regulation.

PubMed ID: 8386508

DOI: 10.1006/bbrc.1993.1412

PubMed ID: 10551867

Title: Somatostatin receptor interacting protein defines a novel family of multidomain proteins present in human and rodent brain.

PubMed ID: 10551867

DOI: 10.1074/jbc.274.46.32997

PubMed ID: 15231824

Title: Agonist-dependent dissociation of human somatostatin receptor 2 dimers: a role in receptor trafficking.

PubMed ID: 15231824

DOI: 10.1074/jbc.m407310200

PubMed ID: 18653781

Title: Cell growth inhibition and functioning of human somatostatin receptor type 2 are modulated by receptor heterodimerization.

PubMed ID: 18653781

DOI: 10.1210/me.2007-0334

PubMed ID: 19434240

Title: The somatostatin 2A receptor is enriched in migrating neurons during rat and human brain development and stimulates migration and axonal outgrowth.

PubMed ID: 19434240

DOI: 10.1371/journal.pone.0005509

PubMed ID: 22932785

Title: SSTR2 is the functionally dominant somatostatin receptor in human pancreatic beta- and alpha-cells.

PubMed ID: 22932785

DOI: 10.1152/ajpendo.00207.2012

PubMed ID: 22495673

Title: Identification of critical residues involved in ligand binding and G protein signaling in human somatostatin receptor subtype 2.

PubMed ID: 22495673

DOI: 10.1210/en.2011-1662

Sequence Information:

  • Length: 369
  • Mass: 41333
  • Checksum: 3B5D7D8A9AC246C6
  • Sequence:
    • MDMADEPLNG SHTWLSIPFD LNGSVVSTNT SNQTEPYYDL TSNAVLTFIY FVVCIIGLCG 
NTLVIYVILR YAKMKTITNI YILNLAIADE LFMLGLPFLA MQVALVHWPF GKAICRVVMT 
VDGINQFTSI FCLTVMSIDR YLAVVHPIKS AKWRRPRTAK MITMAVWGVS LLVILPIMIY 
AGLRSNQWGR SSCTINWPGE SGAWYTGFII YTFILGFLVP LTIICLCYLF IIIKVKSSGI 
RVGSSKRKKS EKKVTRMVSI VVAVFIFCWL PFYIFNVSSV SMAISPTPAL KGMFDFVVVL 
TYANSCANPI LYAFLSDNFK KSFQNVLCLV KVSGTDDGER SDSKQDKSRL NETTETQRTL 
LNGDLQTSI