Human Gene ADRA2A (ENST00000280155.4) from GENCODE V44
  Description: Homo sapiens adrenoceptor alpha 2A (ADRA2A), mRNA. (from RefSeq NM_000681)
RefSeq Summary (NM_000681): Alpha-2-adrenergic receptors are members of the G protein-coupled receptor superfamily. The alpha-2-adrenergic receptors are a type of adrenergic receptors (for adrenaline or epinephrine), which inhibit adenylate cyclase. These receptors include 3 highly homologous subtypes: alpha2A, alpha2B, and alpha2C. They are involved in regulating the release of neurotransmitter molecules from sympathetic nerves and from adrenergic neurons in the central nervous system. The sympathetic nervous system regulates cardiovascular function by activating adrenergic receptors in the heart, blood vessels and kidney. Studies in mouse revealed that both the alpha2A and alpha2C receptor subtypes were required for presynaptic transmitter release from the sympathetic nervous system in the heart and from central noradrenergic neurons. The alpha-2-adrenergic receptors are also involved in catecholamine signaling by extracellular regulated protein kinase 1 and 2 (ERK1/2) pathways. A clear association between the alpha-2-adrenergic receptor and disease has not been yet established. [provided by RefSeq, Sep 2019]. Sequence Note: The 5'-most in-frame translation initiation codon is selected for this RefSeq based on good conservation across mammalian species. A possible downstream start codon would result in a protein that is 15 aa shorter at the N-terminus. The literature, including PMIDs:2823383, 2568356, 1354394 and 1678390, assumes the use of the downstream start codon based on initial cloning reports, but there is no experimental evidence indicating which start codon is preferentially used in vivo.
Gencode Transcript: ENST00000280155.4
Gencode Gene: ENSG00000150594.7
Transcript (Including UTRs)
   Position: hg38 chr10:111,077,029-111,080,907 Size: 3,879 Total Exon Count: 1 Strand: +
Coding Region
   Position: hg38 chr10:111,077,997-111,079,394 Size: 1,398 Coding Exon Count: 1 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr10:111,077,029-111,080,907)mRNA (may differ from genome)Protein (465 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: ADA2A_HUMAN
DESCRIPTION: RecName: Full=Alpha-2A adrenergic receptor; AltName: Full=Alpha-2 adrenergic receptor subtype C10; AltName: Full=Alpha-2A adrenoreceptor; Short=Alpha-2A adrenoceptor; Short=Alpha-2AAR;
FUNCTION: Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
SIMILARITY: Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2A sub-subfamily.
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/adra2a/";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: ADRA2A
Diseases sorted by gene-association score: adra2a-related altered drug metabolism* (100), horner's syndrome (11), gilles de la tourette syndrome (10), motion sickness (9), attention deficit-hyperactivity disorder (8), dyscalculia (7), orthostatic intolerance (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 42.66 RPKM in Cervix - Ectocervix
Total median expression: 310.54 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -428.10968-0.442 Picture PostScript Text
3' UTR -454.001513-0.300 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000276 - 7TM_GPCR_Rhodpsn
IPR001946 - Adren_rcpt_A2A
IPR002233 - Adrnrgc_rcpt
IPR017452 - GPCR_Rhodpsn_supfam

Pfam Domains:
PF00001 - 7 transmembrane receptor (rhodopsin family)

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1HLL - NMR 1HO9 - NMR 1HOD - NMR 1HOF - NMR


ModBase Predicted Comparative 3D Structure on P08913
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologGenome BrowserNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsemblEnsembl  
Protein SequenceProtein SequenceProtein SequenceProtein Sequence  
AlignmentAlignmentAlignmentAlignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004871 signal transducer activity
GO:0004930 G-protein coupled receptor activity
GO:0004935 adrenergic receptor activity
GO:0004938 alpha2-adrenergic receptor activity
GO:0005515 protein binding
GO:0019901 protein kinase binding
GO:0031692 alpha-1B adrenergic receptor binding
GO:0031696 alpha-2C adrenergic receptor binding
GO:0031996 thioesterase binding
GO:0032795 heterotrimeric G-protein binding
GO:0042803 protein homodimerization activity
GO:0046982 protein heterodimerization activity
GO:0051379 epinephrine binding
GO:0051380 norepinephrine binding

Biological Process:
GO:0001819 positive regulation of cytokine production
GO:0006940 regulation of smooth muscle contraction
GO:0007165 signal transduction
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007189 adenylate cyclase-activating G-protein coupled receptor signaling pathway
GO:0007193 adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway
GO:0007265 Ras protein signal transduction
GO:0007266 Rho protein signal transduction
GO:0008284 positive regulation of cell proliferation
GO:0010700 negative regulation of norepinephrine secretion
GO:0019229 regulation of vasoconstriction
GO:0030036 actin cytoskeleton organization
GO:0030168 platelet activation
GO:0030335 positive regulation of cell migration
GO:0032147 activation of protein kinase activity
GO:0032148 activation of protein kinase B activity
GO:0032811 negative regulation of epinephrine secretion
GO:0032870 cellular response to hormone stimulus
GO:0035625 epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway
GO:0042593 glucose homeostasis
GO:0043268 positive regulation of potassium ion transport
GO:0043406 positive regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0045741 positive regulation of epidermal growth factor-activated receptor activity
GO:0045955 negative regulation of calcium ion-dependent exocytosis
GO:0046676 negative regulation of insulin secretion
GO:0050796 regulation of insulin secretion
GO:0050892 intestinal absorption
GO:0050995 negative regulation of lipid catabolic process
GO:0051044 positive regulation of membrane protein ectodomain proteolysis
GO:0051926 negative regulation of calcium ion transport
GO:0061179 negative regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0071875 adrenergic receptor signaling pathway
GO:0071880 adenylate cyclase-activating adrenergic receptor signaling pathway
GO:0071881 adenylate cyclase-inhibiting adrenergic receptor signaling pathway
GO:0071882 phospholipase C-activating adrenergic receptor signaling pathway
GO:0090303 positive regulation of wound healing
GO:1901020 negative regulation of calcium ion transmembrane transporter activity

Cellular Component:
GO:0005737 cytoplasm
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016323 basolateral plasma membrane
GO:0043235 receptor complex


-  Descriptions from all associated GenBank mRNAs
  AF284095 - Homo sapiens alpha-2A adrenergic receptor mRNA, complete cds.
JD456620 - Sequence 437644 from Patent EP1572962.
JD141451 - Sequence 122475 from Patent EP1572962.
JD440324 - Sequence 421348 from Patent EP1572962.
JD422638 - Sequence 403662 from Patent EP1572962.
JD191909 - Sequence 172933 from Patent EP1572962.
JD128359 - Sequence 109383 from Patent EP1572962.
JD129435 - Sequence 110459 from Patent EP1572962.
JD191324 - Sequence 172348 from Patent EP1572962.
JD389775 - Sequence 370799 from Patent EP1572962.
BC050414 - Homo sapiens adrenergic, alpha-2A-, receptor, mRNA (cDNA clone MGC:54083 IMAGE:6198830), complete cds.
JD189464 - Sequence 170488 from Patent EP1572962.
JD082435 - Sequence 63459 from Patent EP1572962.
BC035047 - Homo sapiens adrenergic, alpha-2A-, receptor, mRNA (cDNA clone MGC:41760 IMAGE:5266354), complete cds.
JD278125 - Sequence 259149 from Patent EP1572962.
JD216678 - Sequence 197702 from Patent EP1572962.
JD477922 - Sequence 458946 from Patent EP1572962.
JD408859 - Sequence 389883 from Patent EP1572962.
AB464457 - Synthetic construct DNA, clone: pF1KB9868, Homo sapiens ADRA2A gene for adrenergic, alpha-2A-, receptor, without stop codon, in Flexi system.
DQ575707 - Homo sapiens piRNA piR-43819, complete sequence.
JD483518 - Sequence 464542 from Patent EP1572962.
JD231385 - Sequence 212409 from Patent EP1572962.
JD429439 - Sequence 410463 from Patent EP1572962.
JD269925 - Sequence 250949 from Patent EP1572962.
JD367346 - Sequence 348370 from Patent EP1572962.
JD078471 - Sequence 59495 from Patent EP1572962.
JD365982 - Sequence 347006 from Patent EP1572962.
JD055657 - Sequence 36681 from Patent EP1572962.
JD317484 - Sequence 298508 from Patent EP1572962.
JD361268 - Sequence 342292 from Patent EP1572962.
JD195564 - Sequence 176588 from Patent EP1572962.
JD427161 - Sequence 408185 from Patent EP1572962.
JD443840 - Sequence 424864 from Patent EP1572962.
JD195665 - Sequence 176689 from Patent EP1572962.
JD154418 - Sequence 135442 from Patent EP1572962.
JD166802 - Sequence 147826 from Patent EP1572962.
JD259255 - Sequence 240279 from Patent EP1572962.
JD494279 - Sequence 475303 from Patent EP1572962.
JD282105 - Sequence 263129 from Patent EP1572962.
JD270812 - Sequence 251836 from Patent EP1572962.
JD255123 - Sequence 236147 from Patent EP1572962.
JD490619 - Sequence 471643 from Patent EP1572962.
JD269253 - Sequence 250277 from Patent EP1572962.
JD081860 - Sequence 62884 from Patent EP1572962.
JD520818 - Sequence 501842 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04080 - Neuroactive ligand-receptor interaction

Reactome (by CSHL, EBI, and GO)

Protein P08913 (Reactome details) participates in the following event(s):

R-HSA-390663 Alpha-2 adrenoceptors bind catecholamines
R-HSA-751024 The Ligand:GPCR:Gz complex dissociates
R-HSA-400071 Alpha-2A,alpha-2C Adrenergic Receptors bind adrenaline or noradrenaline
R-HSA-749446 Liganded Gz-activating GPCRs bind inactive heterotrimeric G-protein Gz
R-HSA-749454 The Ligand:GPCR:Gi complex dissociates
R-HSA-749453 Liganded Gz-activating GPCR acts as a GEF for Gz
R-HSA-749456 Liganded Gi-activating GPCRs bind inactive heterotrimeric G-protein Gi
R-HSA-380073 Liganded Gi-activating GPCR acts as a GEF for Gi
R-HSA-390696 Adrenoceptors
R-HSA-392023 Adrenaline signalling through Alpha-2 adrenergic receptor
R-HSA-418597 G alpha (z) signalling events
R-HSA-400042 Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-418594 G alpha (i) signalling events
R-HSA-375280 Amine ligand-binding receptors
R-HSA-76009 Platelet Aggregation (Plug Formation)
R-HSA-388396 GPCR downstream signalling
R-HSA-422356 Regulation of insulin secretion
R-HSA-373076 Class A/1 (Rhodopsin-like receptors)
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-372790 Signaling by GPCR
R-HSA-163685 Energy Metabolism
R-HSA-500792 GPCR ligand binding
R-HSA-109582 Hemostasis
R-HSA-162582 Signal Transduction
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: ADA2A_HUMAN, ADRA2R, ADRAR, B0LPF6, ENST00000280155.1, ENST00000280155.2, ENST00000280155.3, NM_000681, P08913, Q2I8G2, Q2XN99, Q86TH8, Q9BZK1, uc001kzo.1, uc001kzo.2, uc001kzo.3, uc001kzo.4, uc001kzo.5
UCSC ID: ENST00000280155.4
RefSeq Accession: NM_000681
Protein: P08913 (aka ADA2A_HUMAN or A2AA_HUMAN)
CCDS: CCDS7569.2

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.