SSTR2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004930 G protein-coupled receptor activity	IEA GO_REF:0000002	MODIFY	Summary: Generic GPCR activity from the InterPro 7TM rhodopsin-family signature. Reason: Correct but less specific than the well-supported somatostatin receptor activity (GO:0004994), which the gene already carries by IBA, IEA and TAS. Proposed replacements: somatostatin receptor activity Supporting Evidence: file:human/SSTR2/SSTR2-uniprot.txt Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase.
GO:0004994 somatostatin receptor activity	IBA GO_REF:0000033	ACCEPT	Summary: Somatostatin receptor activity inherited within the SSTR clade. Reason: Core function; consistent with direct human SSTR2 coupling studies. Supporting Evidence: PMID:7914078 somatostatin-14 inhibits the adenylyl cyclase in a dose dependent and pertussis toxin-sensitive manner when human SSTR2 is co-expressed with Gi alpha 1 in CHO cells
GO:0004994 somatostatin receptor activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated annotation of somatostatin receptor activity. Reason: Agrees with experimental evidence for this core activity. Supporting Evidence: file:human/SSTR2/SSTR2-uniprot.txt Receptor for somatostatin-14 and -28.
GO:0004994 somatostatin receptor activity	TAS PMID:7914078 Human somatostatin receptor, SSTR2, is coupled to adenylyl c...	ACCEPT	Summary: Human SSTR2 expressed in CHO cells mediates somatostatin-14 inhibition of adenylyl cyclase via Gi alpha 1. Reason: Direct functional demonstration of ligand-activated receptor signaling. Supporting Evidence: PMID:7914078 These results indicate that human SSTR2 is functionally coupled to Gi alpha 1 protein
GO:0005515 protein binding	IPI PMID:10551867 Somatostatin receptor interacting protein defines a novel fa...	MODIFY	Summary: SSTR2 C-terminus binds the PDZ domain of SHANK1 (somatostatin receptor interacting protein). Reason: Generic protein binding is uninformative; the paper supports PDZ domain binding, already annotated from the same study. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:10551867 we identified a novel protein from the human brain interacting with the C terminus of somatostatin receptor subtype 2
GO:0005515 protein binding	IPI PMID:16917505 Direct binding of p85 to sst2 somatostatin receptor reveals ...	MODIFY	Summary: Phospho-Y71 in the first intracellular loop of sst2 binds the C-terminal SH2 of p85 (PIK3R1). Reason: The paper supports a specific interaction with the PI3K regulatory subunit; replace generic protein binding with phosphatidylinositol 3-kinase regulatory subunit binding. Proposed replacements: phosphatidylinositol 3-kinase regulatory subunit binding Supporting Evidence: PMID:16917505 Somatostatin, acting through sst2, inhibits PI3K activity by disrupting a pre-existing complex comprising the sst2 receptor and the p85 PI3K regulatory subunit.
GO:0005515 protein binding	IPI PMID:18653781 Cell growth inhibition and functioning of human somatostatin...	MODIFY	Summary: SSTR2 heterodimerizes with SSTR5 (co-IP and pbFRET). Reason: Generic protein binding is uninformative; the receptor-receptor heterodimer is better captured as protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:18653781 we determined that SSTR2 and SSTR5 heterodimerize
GO:0005515 protein binding	IPI PMID:22651821 Coexpression of human somatostatin receptor-2 (SSTR2) and SS...	MODIFY	Summary: SSTR2 heterodimerizes with SSTR3 in HEK-293 cells. Reason: Generic protein binding is uninformative; replace with protein heterodimerization activity. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:22651821 in basal conditions, SSTR2 and SSTR3 colocalize at the plasma membrane and exhibit heterodimerization
GO:0005737 cytoplasm	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: UniProt SubCell "Cytoplasm" reflects agonist-induced internalization. Reason: The receptor is a multi-pass membrane protein; internalized receptor resides in endocytic membranes, not the cytoplasm proper. The basal and functional location is the plasma membrane. Supporting Evidence: file:human/SSTR2/SSTR2-uniprot.txt Located mainly at the cell surface under basal conditions. Agonist stimulation results in internalization to the cytoplasm. PMID:18653781 followed by receptor internalization and intracellular receptor pooling
GO:0005829 cytosol	IDA GO_REF:0000052	MARK AS OVER ANNOTATED	Summary: HPA immunofluorescence call of cytosol. Reason: A seven-transmembrane receptor cannot reside in the cytosol as a soluble protein; diffuse intracellular staining most plausibly reflects internalized vesicular receptor or antibody background. The curated HPA call is retained as non-informative rather than removed. Supporting Evidence: file:human/SSTR2/SSTR2-uniprot.txt Cell membrane; Multi-pass membrane protein.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: Plasma membrane localization inherited across the opioid/somatostatin receptor clade. Reason: Consistent with direct observation of human SSTR2 at the plasma membrane. Supporting Evidence: PMID:22651821 in basal conditions, SSTR2 and SSTR3 colocalize at the plasma membrane
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: Automated plasma membrane annotation. Reason: Consistent with topology and experimental localization. Supporting Evidence: file:human/SSTR2/SSTR2-uniprot.txt Cell membrane; Multi-pass membrane protein.
GO:0005886 plasma membrane	TAS PMID:7914078 Human somatostatin receptor, SSTR2, is coupled to adenylyl c...	ACCEPT	Summary: Functional receptor expressed at the CHO cell surface. Reason: Ligand-induced signaling requires a cell-surface receptor; plasma membrane is the site of activity. Supporting Evidence: PMID:7914078
GO:0005886 plasma membrane	TAS Reactome:R-HSA-374758	ACCEPT	Summary: Reactome places ligand binding at the plasma membrane. Reason: Consistent with the extracellular ligand-binding receptor. Supporting Evidence: Reactome:R-HSA-374758 The 5 receptors known to date all couple with pertussis toxin-sensitive G proteins to inhibit adenylate cyclase after ligand binding.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-380073	ACCEPT	Summary: Reactome Gi GEF event at the plasma membrane. Reason: Consistent with plasma membrane GPCR activity. Supporting Evidence: Reactome:R-HSA-380073
GO:0005886 plasma membrane	TAS Reactome:R-HSA-749454	ACCEPT	Summary: Reactome Gi dissociation event at the plasma membrane. Reason: Consistent with plasma membrane GPCR activity. Supporting Evidence: Reactome:R-HSA-749454
GO:0005886 plasma membrane	TAS Reactome:R-HSA-749456	ACCEPT	Summary: Reactome liganded GPCR-Gi binding event at the plasma membrane. Reason: Consistent with plasma membrane GPCR activity. Supporting Evidence: Reactome:R-HSA-749456
GO:0007186 G protein-coupled receptor signaling pathway	IEA GO_REF:0000002	MODIFY	Summary: Generic GPCR signaling pathway. Reason: True but general; the evidence supports adenylate cyclase-inhibiting GPCR signaling and the somatostatin signaling pathway (already carried). Proposed replacements: adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway somatostatin signaling pathway Supporting Evidence: PMID:7914078 somatostatin-14 inhibits the adenylyl cyclase in a dose dependent and pertussis toxin-sensitive manner
GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	IEA GO_REF:0000117	MODIFY	Summary: ARBA prediction of cyclic-nucleotide-coupled GPCR signaling. Reason: The sign-specific child, adenylate cyclase-inhibiting GPCR signaling, is what the evidence shows. Proposed replacements: adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway Supporting Evidence: PMID:7914078 somatostatin-14 inhibits the adenylyl cyclase in a dose dependent and pertussis toxin-sensitive manner
GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	TAS PMID:7914078 Human somatostatin receptor, SSTR2, is coupled to adenylyl c...	MODIFY	Summary: SSTR2 inhibits adenylyl cyclase via Gi alpha 1. Reason: Correct essence; the more specific adenylate cyclase-inhibiting pathway term fits the evidence. Proposed replacements: adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway Supporting Evidence: PMID:7914078 human SSTR2 is functionally coupled to Gi alpha 1 protein
GO:0007218 neuropeptide signaling pathway	IBA GO_REF:0000033	MODIFY	Summary: Neuropeptide signaling pathway, inherited. Reason: Somatostatin is a neuropeptide, so the term is true, but the specific somatostatin signaling pathway (GO:0038170, a descendant) is already carried and better describes SSTR2. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000659780 SUPPORTS TRANSFER Ancestral neuropeptide-receptor node; transfer is sound but the somatostatin-specific child term is more informative for SSTR2. Proposed replacements: somatostatin signaling pathway Supporting Evidence: Reactome:R-HSA-374758 affects neurotransmission and cell proliferation via interaction with somatostatin receptors 1-5
GO:0008285 negative regulation of cell population proliferation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA prediction of antiproliferative role. Reason: Supported experimentally (cytostatic signaling, Rb induction) but downstream of core receptor activity. Supporting Evidence: PMID:9892014 cytostatic signaling via these subtypes results in induction of the retinoblastoma protein Rb and G1 cell cycle arrest
GO:0008285 negative regulation of cell population proliferation	TAS PMID:9892014 C-terminal region of human somatostatin receptor 5 is requir...	KEEP AS NON CORE	Summary: hSSTR2 initiates cytostatic signaling leading to Rb induction and G1 arrest in CHO-K1 cells. Reason: Well-documented physiological/pharmacological outcome, downstream of Gi signaling. Supporting Evidence: PMID:9892014 The relative efficacy of these receptors to initiate cytostatic signaling was hSSTR5 > hSSTR2
GO:0016020 membrane	IEA GO_REF:0000120	MODIFY	Summary: Generic membrane. Reason: Correct but general; the specific location is plasma membrane, already carried. Proposed replacements: plasma membrane Supporting Evidence: PMID:22651821 in basal conditions, SSTR2 and SSTR3 colocalize at the plasma membrane
GO:0030165 PDZ domain binding	IPI PMID:10551867 Somatostatin receptor interacting protein defines a novel fa...	KEEP AS NON CORE	Summary: SSTR2 C-terminal tail binds SHANK1 (SSTRIP) PDZ domain. Reason: Supported by yeast two-hybrid, overlay and co-IP; a scaffolding interaction peripheral to receptor activity. Supporting Evidence: PMID:10551867 The interaction of somatostatin receptor subtype 2 with its interacting protein was verified by overlay assays and coimmunoprecipitation experiments
GO:0038170 somatostatin signaling pathway	IEA GO_REF:0000108	ACCEPT	Summary: Logical inference from somatostatin receptor activity. Reason: Core pathway. Supporting Evidence: Reactome:R-HSA-374758
GO:0042923 neuropeptide binding	IBA GO_REF:0000033	MODIFY	Summary: Neuropeptide binding, inherited. Reason: True but general; somatostatin binding (GO:0120023) is the specific ligand-binding activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000659780 SUPPORTS TRANSFER Ancestral neuropeptide-receptor node; somatostatin binding is the specific ligand for this subfamily. Proposed replacements: somatostatin binding Supporting Evidence: file:human/SSTR2/SSTR2-uniprot.txt Receptor for somatostatin-14 and -28.
GO:0043005 neuron projection	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Neuron projection localization inherited from rat SSTR orthologs. Reason: Plausible for the neuronal receptor pool (somatodendritic); peripheral to the core plasma-membrane role. Not independently verified for human. Supporting Evidence: file:human/SSTR2/SSTR2-uniprot.txt Stimulates neuronal migration and axon outgrowth and may participate in neuron development and maturation during brain development.
GO:0071385 cellular response to glucocorticoid stimulus	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Cellular response to glucocorticoid, from rat Sstr2 expression data. Reason: Reflects hormonal regulation of receptor expression rather than participation of SSTR2 in the response; no human evidence. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION SOURCE EVIDENCE WEAK Sources checked: RGD:3763 UNRESOLVED Rat Sstr2 hormone-response annotation likely reflects regulated receptor expression; source paper not inspected. PANTHER:PTN002796148 UNRESOLVED SSTR2 subfamily node; transfer of an expression-response process is not a receptor function.
GO:0071392 cellular response to estradiol stimulus	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Cellular response to estradiol, from rat Sstr2 expression data. Reason: Reflects transcriptional regulation of the receptor rather than receptor function; no human evidence. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION SOURCE EVIDENCE WEAK Sources checked: RGD:3763 UNRESOLVED Rat Sstr2 hormone-response annotation likely reflects regulated receptor expression; source paper not inspected. PANTHER:PTN002796148 UNRESOLVED SSTR2 subfamily node; transfer of an expression-response process is not a receptor function.

Gene Description

Existing Annotations Review

Core Functions

Cell-surface Gi/o-coupled receptor for somatostatin-14/-28 that inhibits adenylyl cyclase and calcium entry, suppressing hormone secretion and cell proliferation.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

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