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Protein

Alpha-2A adrenergic receptor

Gene

ADRA2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei113Implicated in ligand binding1
Sitei200Implicated in catechol agonist binding and receptor activation1
Sitei204Implicated in catechol agonist binding and receptor activation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-390696 Adrenoceptors
R-HSA-392023 Adrenaline signalling through Alpha-2 adrenergic receptor
R-HSA-400042 Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-418594 G alpha (i) signalling events
R-HSA-418597 G alpha (z) signalling events
R-HSA-5683826 Surfactant metabolism
SignaLinkiP08913
SIGNORiP08913

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-2A adrenergic receptor
Alternative name(s):
Alpha-2 adrenergic receptor subtype C10
Alpha-2A adrenoreceptor
Short name:
Alpha-2A adrenoceptor
Short name:
Alpha-2AAR
Gene namesi
Name:ADRA2A
Synonyms:ADRA2R, ADRAR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000150594.6
HGNCiHGNC:281 ADRA2A
MIMi104210 gene
neXtProtiNX_P08913

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 33ExtracellularBy similarityAdd BLAST33
Transmembranei34 – 59Helical; Name=1By similarityAdd BLAST26
Topological domaini60 – 70CytoplasmicBy similarityAdd BLAST11
Transmembranei71 – 96Helical; Name=2By similarityAdd BLAST26
Topological domaini97 – 106ExtracellularBy similarity10
Transmembranei107 – 129Helical; Name=3By similarityAdd BLAST23
Topological domaini130 – 151CytoplasmicBy similarityAdd BLAST22
Transmembranei152 – 172Helical; Name=4By similarityAdd BLAST21
Topological domaini173 – 194ExtracellularBy similarityAdd BLAST22
Transmembranei195 – 217Helical; Name=5By similarityAdd BLAST23
Topological domaini218 – 374CytoplasmicBy similarityAdd BLAST157
Transmembranei375 – 395Helical; Name=6By similarityAdd BLAST21
Topological domaini396 – 409ExtracellularBy similarityAdd BLAST14
Transmembranei410 – 429Helical; Name=7By similarityAdd BLAST20
Topological domaini430 – 450CytoplasmicBy similarityAdd BLAST21

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi79D → N: No change in binding affinity. eliminates guanine nucleotide-sensitive agonist binding. 1 Publication1
Mutagenesisi113D → N: No binding to yohimbine. Increase in adenylate cyclase activity. 1 Publication1
Mutagenesisi130D → N: Lower affinity for agonists. Eliminates guanine nucleotide-sensitive agonist binding. 1 Publication1
Mutagenesisi200S → A: Lower affinity for agonists. No change in guanine nucleotide-sensitive agonist binding. 1 Publication1
Mutagenesisi204S → A: Lower affinity for agonists. Reduced guanine nucleotide-sensitive agonist binding. 1 Publication1
Mutagenesisi412F → N: 350-fold reduced affinity for alpha-2 antagonist yohimbine, 3000-fold increase for beta-antagonist alprenolol. 1 Publication1

Organism-specific databases

DisGeNETi150
PharmGKBiPA35

Chemistry databases

ChEMBLiCHEMBL1867
DrugBankiDB01472 4-Methoxyamphetamine
DB00321 Amitriptyline
DB00543 Amoxapine
DB00182 Amphetamine
DB00714 Apomorphine
DB00964 Apraclonidine
DB01238 Aripiprazole
DB06216 Asenapine
DB00865 Benzphetamine
DB00217 Bethanidine
DB00484 Brimonidine
DB01200 Bromocriptine
DB00248 Cabergoline
DB01136 Carvedilol
DB00477 Chlorpromazine
DB09202 Cirazoline
DB00575 Clonidine
DB00363 Clozapine
DB01151 Desipramine
DB00633 Dexmedetomidine
DB00320 Dihydroergotamine
DB00449 Dipivefrin
DB01142 Doxepin
DB04855 Dronedarone
DB06262 Droxidopa
DB01363 Ephedra
DB05492 Epicept NP-1
DB00751 Epinastine
DB00668 Epinephrine
DB01049 Ergoloid mesylate
DB00696 Ergotamine
DB06678 Esmirtazapine
DB00800 Fenoldopam
DB06623 Flupirtine
DB00629 Guanabenz
DB01018 Guanfacine
DB06707 Levonordefrin
DB00589 Lisuride
DB04948 Lofexidine
DB00408 Loxapine
DB08815 Lurasidone
DB00934 Maprotiline
DB01365 Mephentermine
DB01577 Methamphetamine
DB01403 Methotrimeprazine
DB00968 Methyldopa
DB06148 Mianserin
DB00370 Mirtazapine
DB06711 Naphazoline
DB01149 Nefazodone
DB00368 Norepinephrine
DB00540 Nortriptyline
DB00334 Olanzapine
DB00935 Oxymetazoline
DB01267 Paliperidone
DB01186 Pergolide
DB00925 Phenoxybenzamine
DB00692 Phentolamine
DB00397 Phenylpropanolamine
DB00413 Pramipexole
DB00457 Prazosin
DB01608 Propericiazine
DB00852 Pseudoephedrine
DB01224 Quetiapine
DB00734 Risperidone
DB00268 Ropinirole
DB13025 Tiapride
DB00697 Tizanidine
DB00797 Tolazoline
DB00656 Trazodone
DB00726 Trimipramine
DB06694 Xylometazoline
DB01392 Yohimbine
DB00246 Ziprasidone
DB01624 Zuclopenthixol
GuidetoPHARMACOLOGYi25

Polymorphism and mutation databases

BioMutaiADRA2A
DMDMi1351829

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000690801 – 450Alpha-2A adrenergic receptorAdd BLAST450

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi10N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi14N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi106 ↔ 188PROSITE-ProRule annotation
Modified residuei331PhosphoserineBy similarity1
Modified residuei353Omega-N-methylarginineBy similarity1
Lipidationi442S-palmitoyl cysteineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Methylation, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiP08913
PeptideAtlasiP08913
PRIDEiP08913
ProteomicsDBi52176

PTM databases

iPTMnetiP08913
PhosphoSitePlusiP08913

Expressioni

Gene expression databases

BgeeiENSG00000150594 Expressed in 177 organ(s), highest expression level in adipose tissue of abdominal region
CleanExiHS_ADRA2A
GenevisibleiP08913 HS

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106659, 8 interactors
CORUMiP08913
DIPiDIP-61452N
IntActiP08913, 6 interactors
STRINGi9606.ENSP00000280155

Chemistry databases

BindingDBiP08913

Structurei

Secondary structure

1450
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP08913
SMRiP08913
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08913

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2A sub-subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
HOGENOMiHOG000239242
HOVERGENiHBG106962
InParanoidiP08913
KOiK04138
OrthoDBiEOG091G06VI
PhylomeDBiP08913
TreeFamiTF316350

Family and domain databases

InterProiView protein in InterPro
IPR002233 ADR_fam
IPR001946 ADRA2A_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR01103 ADRENERGICR
PR00558 ADRENRGCA2AR
PR00237 GPCRRHODOPSN
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequencei

Sequence statusi: Complete.

P08913-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGSLQPDAGN ASWNGTEAPG GGARATPYSL QVTLTLVCLA GLLMLLTVFG
60 70 80 90 100
NVLVIIAVFT SRALKAPQNL FLVSLASADI LVATLVIPFS LANEVMGYWY
110 120 130 140 150
FGKAWCEIYL ALDVLFCTSS IVHLCAISLD RYWSITQAIE YNLKRTPRRI
160 170 180 190 200
KAIIITVWVI SAVISFPPLI SIEKKGGGGG PQPAEPRCEI NDQKWYVISS
210 220 230 240 250
CIGSFFAPCL IMILVYVRIY QIAKRRTRVP PSRRGPDAVA APPGGTERRP
260 270 280 290 300
NGLGPERSAG PGGAEAEPLP TQLNGAPGEP APAGPRDTDA LDLEESSSSD
310 320 330 340 350
HAERPPGPRR PERGPRGKGK ARASQVKPGD SLPRRGPGAT GIGTPAAGPG
360 370 380 390 400
EERVGAAKAS RWRGRQNREK RFTFVLAVVI GVFVVCWFPF FFTYTLTAVG
410 420 430 440 450
CSVPRTLFKF FFWFGYCNSS LNPVIYTIFN HDFRRAFKKI LCRGDRKRIV
Length:450
Mass (Da):48,957
Last modified:February 1, 1996 - v3
Checksum:iA703CF262F04E8AC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti104A → T in AAA51664 (PubMed:2823383).Curated1
Sequence conflicti124L → P (PubMed:1849485).Curated1
Sequence conflicti157V → C in AAA51664 (PubMed:2823383).Curated1
Sequence conflicti333 – 365PRRGP…RWRGR → RGAGRGRRGSGRRLQGRGRS ASGLPRRRAGAGG in AAA51664 (PubMed:2823383).CuratedAdd BLAST33
Sequence conflicti333 – 365PRRGP…RWRGR → RGAGRGRRGSGRRLQGRGRS ASGLPRRRAGAGG in AAA51665 (PubMed:2568356).CuratedAdd BLAST33
Sequence conflicti368R → L in AAA51664 (PubMed:2823383).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014957251N → K Rare polymorphism; frequency in Caucasians 0.004 and in African-Americans 0.05; 40% increase in agonist-promoted Gi coupling. 3 PublicationsCorresponds to variant dbSNP:rs1800035Ensembl.1
Natural variantiVAR_055908401C → S. Corresponds to variant dbSNP:rs35658213Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M18415 Genomic DNA Translation: AAA51664.1
M23533 Genomic DNA Translation: AAA51665.1
AF281308 Genomic DNA Translation: AAF91441.1
AF316894 Genomic DNA Translation: AAK01634.1
DQ149926 Genomic DNA Translation: AAZ73101.1
AF284095 mRNA Translation: AAK26743.1
AF262016 Genomic DNA Translation: AAG00447.2
AY032736 Genomic DNA Translation: AAK51162.1
DQ285607 Genomic DNA Translation: ABB72683.1
EU332846 Genomic DNA Translation: ABY87535.1
AL158163 Genomic DNA No translation available.
BC035047 mRNA Translation: AAH35047.1
BC050414 mRNA Translation: AAH50414.4
PIRiA34169
RefSeqiNP_000672.3, NM_000681.3
UniGeneiHs.249159

Genome annotation databases

EnsembliENST00000280155; ENSP00000280155; ENSG00000150594
GeneIDi150
KEGGihsa:150
UCSCiuc001kzo.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M18415 Genomic DNA Translation: AAA51664.1
M23533 Genomic DNA Translation: AAA51665.1
AF281308 Genomic DNA Translation: AAF91441.1
AF316894 Genomic DNA Translation: AAK01634.1
DQ149926 Genomic DNA Translation: AAZ73101.1
AF284095 mRNA Translation: AAK26743.1
AF262016 Genomic DNA Translation: AAG00447.2
AY032736 Genomic DNA Translation: AAK51162.1
DQ285607 Genomic DNA Translation: ABB72683.1
EU332846 Genomic DNA Translation: ABY87535.1
AL158163 Genomic DNA No translation available.
BC035047 mRNA Translation: AAH35047.1
BC050414 mRNA Translation: AAH50414.4
PIRiA34169
RefSeqiNP_000672.3, NM_000681.3
UniGeneiHs.249159

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HLLNMR-A118-149[»]
1HO9NMR-A118-149[»]
1HODNMR-A118-149[»]
1HOFNMR-A118-149[»]
ProteinModelPortaliP08913
SMRiP08913
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106659, 8 interactors
CORUMiP08913
DIPiDIP-61452N
IntActiP08913, 6 interactors
STRINGi9606.ENSP00000280155

Chemistry databases

BindingDBiP08913
ChEMBLiCHEMBL1867
DrugBankiDB01472 4-Methoxyamphetamine
DB00321 Amitriptyline
DB00543 Amoxapine
DB00182 Amphetamine
DB00714 Apomorphine
DB00964 Apraclonidine
DB01238 Aripiprazole
DB06216 Asenapine
DB00865 Benzphetamine
DB00217 Bethanidine
DB00484 Brimonidine
DB01200 Bromocriptine
DB00248 Cabergoline
DB01136 Carvedilol
DB00477 Chlorpromazine
DB09202 Cirazoline
DB00575 Clonidine
DB00363 Clozapine
DB01151 Desipramine
DB00633 Dexmedetomidine
DB00320 Dihydroergotamine
DB00449 Dipivefrin
DB01142 Doxepin
DB04855 Dronedarone
DB06262 Droxidopa
DB01363 Ephedra
DB05492 Epicept NP-1
DB00751 Epinastine
DB00668 Epinephrine
DB01049 Ergoloid mesylate
DB00696 Ergotamine
DB06678 Esmirtazapine
DB00800 Fenoldopam
DB06623 Flupirtine
DB00629 Guanabenz
DB01018 Guanfacine
DB06707 Levonordefrin
DB00589 Lisuride
DB04948 Lofexidine
DB00408 Loxapine
DB08815 Lurasidone
DB00934 Maprotiline
DB01365 Mephentermine
DB01577 Methamphetamine
DB01403 Methotrimeprazine
DB00968 Methyldopa
DB06148 Mianserin
DB00370 Mirtazapine
DB06711 Naphazoline
DB01149 Nefazodone
DB00368 Norepinephrine
DB00540 Nortriptyline
DB00334 Olanzapine
DB00935 Oxymetazoline
DB01267 Paliperidone
DB01186 Pergolide
DB00925 Phenoxybenzamine
DB00692 Phentolamine
DB00397 Phenylpropanolamine
DB00413 Pramipexole
DB00457 Prazosin
DB01608 Propericiazine
DB00852 Pseudoephedrine
DB01224 Quetiapine
DB00734 Risperidone
DB00268 Ropinirole
DB13025 Tiapride
DB00697 Tizanidine
DB00797 Tolazoline
DB00656 Trazodone
DB00726 Trimipramine
DB06694 Xylometazoline
DB01392 Yohimbine
DB00246 Ziprasidone
DB01624 Zuclopenthixol
GuidetoPHARMACOLOGYi25

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP08913
PhosphoSitePlusiP08913

Polymorphism and mutation databases

BioMutaiADRA2A
DMDMi1351829

Proteomic databases

PaxDbiP08913
PeptideAtlasiP08913
PRIDEiP08913
ProteomicsDBi52176

Protocols and materials databases

DNASUi150
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000280155; ENSP00000280155; ENSG00000150594
GeneIDi150
KEGGihsa:150
UCSCiuc001kzo.4 human

Organism-specific databases

CTDi150
DisGeNETi150
EuPathDBiHostDB:ENSG00000150594.6
GeneCardsiADRA2A
H-InvDBiHIX0190540
HGNCiHGNC:281 ADRA2A
MIMi104210 gene
neXtProtiNX_P08913
PharmGKBiPA35
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
HOGENOMiHOG000239242
HOVERGENiHBG106962
InParanoidiP08913
KOiK04138
OrthoDBiEOG091G06VI
PhylomeDBiP08913
TreeFamiTF316350

Enzyme and pathway databases

ReactomeiR-HSA-390696 Adrenoceptors
R-HSA-392023 Adrenaline signalling through Alpha-2 adrenergic receptor
R-HSA-400042 Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-418594 G alpha (i) signalling events
R-HSA-418597 G alpha (z) signalling events
R-HSA-5683826 Surfactant metabolism
SignaLinkiP08913
SIGNORiP08913

Miscellaneous databases

EvolutionaryTraceiP08913
GeneWikiiAlpha-2A_adrenergic_receptor
GenomeRNAii150
PROiPR:P08913
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000150594 Expressed in 177 organ(s), highest expression level in adipose tissue of abdominal region
CleanExiHS_ADRA2A
GenevisibleiP08913 HS

Family and domain databases

InterProiView protein in InterPro
IPR002233 ADR_fam
IPR001946 ADRA2A_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR01103 ADRENERGICR
PR00558 ADRENRGCA2AR
PR00237 GPCRRHODOPSN
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiADA2A_HUMAN
AccessioniPrimary (citable) accession number: P08913
Secondary accession number(s): B0LPF6
, Q2I8G2, Q2XN99, Q86TH8, Q9BZK1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: February 1, 1996
Last modified: September 12, 2018
This is version 203 of the entry and version 3 of the sequence. See 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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