Details for: ADRA2B

Gene ID: 151

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: ADRA2B

Ensembl ID: ENSG00000274286

Description: adrenoceptor alpha 2B

Cell Significance Landscape

Associated with

Significant Cells

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

  • suprabasal keratinocyte CL4033013
    CSI 2.63
    rCSI 4.29%
    PRS 97.38
  • pericyte CL0000669
    CSI 2.6
    rCSI 6.92%
    PRS 97.38
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.72
    rCSI 4.98%
    PRS 99.96

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.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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    • 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 [ADRA2B](/details-gene/151) encodes the alpha-2B adrenergic receptor, a member of the G protein-coupled receptor (GPCR) family. This receptor is a key component of the sympathetic nervous system, mediating cellular responses to the catecholamines epinephrine and norepinephrine. **Overall**, the expression profile of [ADRA2B](/details-gene/151) indicates high significance in cell types crucial for cutaneous and vascular function, including [suprabasal keratinocyte](/details-cell/CL4033013), [pericyte](/details-cell/CL0000669), and [microcirculation associated smooth muscle cell](/details-cell/CL0008035). Its function is central to processes such as vasoconstriction, blood pressure regulation, and platelet aggregation. Genetic variations in [ADRA2B](/details-gene/151) have been associated with altered receptor function and clinical conditions, including cortical myoclonus and epilepsy ([Link](https://doi.org/10.1002/ana.24028)). ## Cellular Roles and Expression Landscape The expression pattern of [ADRA2B](/details-gene/151) suggests a specialized role in the integumentary and cardiovascular systems. **Overall**, the gene shows the highest significance in [suprabasal keratinocyte](/details-cell/CL4033013) (CSI: 2.63), indicating a potential function in epidermal homeostasis or response to stress. Its prominent role in the vasculature is highlighted by high significance in [pericyte](/details-cell/CL0000669) (CSI: 2.60) and [microcirculation associated smooth muscle cell](/details-cell/CL0008035) (CSI: 1.72). This is consistent with the receptor's established involvement in mediating vasoconstriction in response to sympathetic stimulation. The concentrated expression in these specific cell types suggests that [ADRA2B](/details-gene/151) is not a broadly expressed housekeeping gene but rather a critical effector molecule in tissues that regulate blood flow and form barrier functions. ## Pathways and Molecular Function [ADRA2B](/details-gene/151) functions as an '[Alpha2-adrenergic receptor activity](/details-gene/GO:0004938)' that binds epinephrine ([GO:0051379](https://www.ebi.ac.uk/QuickGO/term/GO:0051379)) and initiates intracellular signaling cascades. As a GPCR located on the '[Plasma membrane](/details-gene/GO:0005886)', it primarily couples to inhibitory G proteins, as detailed in the '[G alpha (i) signalling events](/details-gene/R-HSA-418594)' pathway. This interaction typically leads to the inhibition of adenylate cyclase, which in turn modulates downstream effectors. The functional annotations align closely with its observed cellular roles. Its involvement in the '[Regulation of vascular associated smooth muscle contraction](/details-gene/GO:0003056)' and '[Positive regulation of blood pressure](/details-gene/GO:0045777)' pathways directly reflects its high expression in pericytes and smooth muscle cells. Furthermore, [ADRA2B](/details-gene/151) is a key participant in '[Hemostasis](/details-gene/R-HSA-109582)', specifically contributing to '[Platelet activation, signaling and aggregation](/details-gene/R-HSA-76002)'. This highlights its dual role in both vascular tone and thrombosis. The receptor's activity is also linked to the '[Mapk cascade](/details-gene/GO:0000165)', suggesting it influences broader cellular processes like proliferation and differentiation. ## Research Directions While [ADRA2B](/details-gene/151) is well-studied in the context of cardiovascular physiology, its high significance in keratinocytes remains less explored. Furthermore, reports linking mutations in the gene to cortical myoclonus and epilepsy ([Link](https://doi.org/10.1002/ana.24028)) suggest that its function in the central nervous system warrants deeper investigation. Based on the available data, several testable hypotheses can be proposed: 1. Given its high expression in [suprabasal keratinocyte](/details-cell/CL4033013), signaling through [ADRA2B](/details-gene/151) may regulate terminal differentiation of epidermal cells or modulate the skin's response to catecholamine surges during physiological stress. 2. Polymorphisms that affect receptor phosphorylation and desensitization ([Link](https://doi.org/10.1074/jbc.m008118200)) may underlie individual variability in cutaneous blood flow, potentially contributing to the pathophysiology of conditions like Raynaud's phenomenon. 3. In the central nervous system, aberrant [ADRA2B](/details-gene/151) signaling in specific neuronal subtypes may lead to hyperexcitability, contributing to the seizure phenotype observed in patients with certain mutations. A key experiment to test the first hypothesis would be to investigate the role of [ADRA2B](/details-gene/151) in epidermal stratification. Using CRISPR-Cas9 to knock out [ADRA2B](/details-gene/151) in primary human keratinocytes, one could generate 3D organotypic skin cultures. The impact of the knockout could then be assessed by comparing the tissue architecture, the expression of differentiation markers (e.g., KRT1, LOR, FLG) via immunofluorescence and qPCR, and the culture's response to adrenergic agonists. As a cell surface GPCR, [ADRA2B](/details-gene/151) is a highly tractable therapeutic target. Its role in vasoconstriction has already been exploited by alpha-2 adrenergic agonists (e.g., for sedation, glaucoma) and antagonists (e.g., for hypertension). The data suggests that developing more selective modulators could be beneficial. For instance, a selective [ADRA2B](/details-gene/151) antagonist could potentially treat peripheral vasospastic disorders with fewer systemic side effects. Conversely, the neurological link suggests that brain-penetrant modulators targeting this receptor could be explored as novel anti-epileptic or anti-myoclonic agents. The therapeutic strategy would depend on the specific pathology, involving either inhibition for conditions of receptor overactivity or activation where signaling is deficient.

Genular Protein ID: 1059118239

Symbol: ADA2B_HUMAN

Name: Alpha-2B adrenergic receptor

UniProtKB Accession Codes:

P18089 A2RUS0 Q4TUH9 Q53RF2 Q9BZK0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 81 DrugCentral 1 EMBL 12 EMDB 1 Ensembl 1 GO 23 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GuidetoPHARMACOLOGY 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 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 1 RNAct 1 Reactome 4 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 2164221

Title: Expansion of the alpha 2-adrenergic receptor family: cloning and characterization of a human alpha 2-adrenergic receptor subtype, the gene for which is located on chromosome 2.

PubMed ID: 2164221

DOI: 10.1073/pnas.87.13.5094

PubMed ID: 2172775

Title: Cloning, expression, and pharmacological characterization of a human alpha 2B-adrenergic receptor.

PubMed ID: 2172775

PubMed ID: 11056163

Title: Polymorphic deletion of three intracellular acidic residues of the alpha 2B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated phosphorylation and desensitization.

PubMed ID: 11056163

DOI: 10.1074/jbc.m008118200

PubMed ID: 15037199

Title: Cloning, characterisation and identification of several polymorphisms in the promoter region of the human alpha2B-adrenergic receptor gene.

PubMed ID: 15037199

DOI: 10.1016/j.bcp.2003.09.029

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 2173582

Title: In vitro amplification by polymerase chain reaction of a partial gene encoding the third subtype of alpha-2 adrenergic receptor in humans.

PubMed ID: 2173582

DOI: 10.1016/0006-291x(90)90748-c

PubMed ID: 23105096

Title: Rab26 modulates the cell surface transport of alpha2-adrenergic receptors from the Golgi.

PubMed ID: 23105096

DOI: 10.1074/jbc.m112.410936

PubMed ID: 24114805

Title: The alpha2B-adrenergic receptor is mutant in cortical myoclonus and epilepsy.

PubMed ID: 24114805

DOI: 10.1002/ana.24028

PubMed ID: 27901063

Title: Regulation of alpha2B-Adrenergic Receptor Cell Surface Transport by GGA1 and GGA2.

PubMed ID: 27901063

DOI: 10.1038/srep37921

PubMed ID: 26811329

Title: GGA3 Interacts with a G Protein-Coupled Receptor and Modulates Its Cell Surface Export.

PubMed ID: 26811329

DOI: 10.1128/mcb.00009-16

Sequence Information:

  • Length: 450
  • Mass: 49954
  • Checksum: 06E43857152A68ED
  • Sequence:
    • MDHQDPYSVQ ATAAIAAAIT FLILFTIFGN ALVILAVLTS RSLRAPQNLF LVSLAAADIL 
VATLIIPFSL ANELLGYWYF RRTWCEVYLA LDVLFCTSSI VHLCAISLDR YWAVSRALEY 
NSKRTPRRIK CIILTVWLIA AVISLPPLIY KGDQGPQPRG RPQCKLNQEA WYILASSIGS 
FFAPCLIMIL VYLRIYLIAK RSNRRGPRAK GGPGQGESKQ PRPDHGGALA SAKLPALASV 
ASAREVNGHS KSTGEKEEGE TPEDTGTRAL PPSWAALPNS GQGQKEGVCG ASPEDEAEEE 
EEEEEEEEEC EPQAVPVSPA SACSPPLQQP QGSRVLATLR GQVLLGRGVG AIGGQWWRRR 
AQLTREKRFT FVLAVVIGVF VLCWFPFFFS YSLGAICPKH CKVPHGLFQF FFWIGYCNSS 
LNPVIYTIFN QDFRRAFRRI LCRPWTQTAW