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Protein

Alpha-2B adrenergic receptor

Gene

ADRA2B

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 clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei92Implicated in ligand bindingBy similarity1
Sitei176Implicated in catechol agonist bindingBy similarity1
Sitei180Implicated in catechol agonist bindingBy similarity1

GO - Molecular functioni

  • alpha2-adrenergic receptor activity Source: BHF-UCL
  • epinephrine binding Source: BHF-UCL

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-418594 G alpha (i) signalling events
R-HSA-418597 G alpha (z) signalling events
SignaLinkiP18089

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-2B adrenergic receptor
Alternative name(s):
Alpha-2 adrenergic receptor subtype C2
Alpha-2B adrenoreceptor
Short name:
Alpha-2B adrenoceptor
Short name:
Alpha-2BAR
Gene namesi
Name:ADRA2B
Synonyms:ADRA2L1, ADRA2RL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000274286.1
HGNCiHGNC:282 ADRA2B
MIMi104260 gene
neXtProtiNX_P18089

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 – 12ExtracellularBy similarityAdd BLAST12
Transmembranei13 – 38Helical; Name=1By similarityAdd BLAST26
Topological domaini39 – 48CytoplasmicBy similarity10
Transmembranei49 – 69Helical; Name=2By similarityAdd BLAST21
Topological domaini70 – 86ExtracellularBy similarityAdd BLAST17
Transmembranei87 – 107Helical; Name=3By similarityAdd BLAST21
Topological domaini108 – 128CytoplasmicBy similarityAdd BLAST21
Transmembranei129 – 149Helical; Name=4By similarityAdd BLAST21
Topological domaini150 – 172ExtracellularBy similarityAdd BLAST23
Transmembranei173 – 193Helical; Name=5By similarityAdd BLAST21
Topological domaini194 – 368CytoplasmicBy similarityAdd BLAST175
Transmembranei369 – 389Helical; Name=6By similarityAdd BLAST21
Topological domaini390 – 405ExtracellularBy similarityAdd BLAST16
Transmembranei406 – 426Helical; Name=7By similarityAdd BLAST21
Topological domaini427 – 450CytoplasmicBy similarityAdd BLAST24

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Epilepsy, familial adult myoclonic, 2 (FAME2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of cortical myoclonic tremor with epilepsy, a syndrome characterized by cortical myoclonus and variable occurrence of epileptic seizures. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom; both complex partial as well as generalized tonic clonic seizures are described. Some patients exhibit mild cognitive impairment.
See also OMIM:607876
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073953225 – 229HGGAL → QFGR in FAME2; gain of function; decreases interaction with PPP1R9B upon activation by neurotransmitter. 1 Publication5

Keywords - Diseasei

Epilepsy

Organism-specific databases

DisGeNETi151
MalaCardsiADRA2B
MIMi607876 phenotype
OpenTargetsiENSG00000274286
Orphaneti86814 Benign adult familial myoclonic epilepsy
PharmGKBiPA36

Chemistry databases

ChEMBLiCHEMBL1942
DrugBankiDB00543 Amoxapine
DB00182 Amphetamine
DB00714 Apomorphine
DB00964 Apraclonidine
DB01238 Aripiprazole
DB06216 Asenapine
DB00217 Bethanidine
DB00484 Brimonidine
DB01200 Bromocriptine
DB00248 Cabergoline
DB01136 Carvedilol
DB00477 Chlorpromazine
DB09202 Cirazoline
DB00575 Clonidine
DB00363 Clozapine
DB01151 Desipramine
DB01142 Doxepin
DB04855 Dronedarone
DB06262 Droxidopa
DB01363 Ephedra
DB05492 Epicept NP-1
DB00668 Epinephrine
DB01049 Ergoloid mesylate
DB00696 Ergotamine
DB06678 Esmirtazapine
DB00292 Etomidate
DB00800 Fenoldopam
DB00629 Guanabenz
DB01018 Guanfacine
DB06707 Levonordefrin
DB00589 Lisuride
DB00408 Loxapine
DB00934 Maprotiline
DB01365 Mephentermine
DB01577 Methamphetamine
DB01403 Methotrimeprazine
DB06148 Mianserin
DB00368 Norepinephrine
DB00540 Nortriptyline
DB00334 Olanzapine
DB05461 OPC-28326
DB00935 Oxymetazoline
DB01267 Paliperidone
DB01186 Pergolide
DB00925 Phenoxybenzamine
DB00413 Pramipexole
DB00457 Prazosin
DB01224 Quetiapine
DB00734 Risperidone
DB00268 Ropinirole
DB05271 Rotigotine
DB13025 Tiapride
DB00697 Tizanidine
DB00797 Tolazoline
DB00726 Trimipramine
DB06694 Xylometazoline
DB01392 Yohimbine
DB00246 Ziprasidone
GuidetoPHARMACOLOGYi26

Polymorphism and mutation databases

BioMutaiADRA2B
DMDMi27151763

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000690941 – 450Alpha-2B adrenergic receptorAdd BLAST450

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi85 ↔ 164PROSITE-ProRule annotation
Lipidationi442S-palmitoyl cysteineSequence analysis1

Keywords - PTMi

Disulfide bond, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP18089
PeptideAtlasiP18089
PRIDEiP18089
ProteomicsDBi53548

PTM databases

PhosphoSitePlusiP18089

Expressioni

Gene expression databases

BgeeiENSG00000274286 Expressed in 84 organ(s), highest expression level in apex of heart
CleanExiHS_ADRA2B

Organism-specific databases

HPAiHPA066029

Interactioni

Subunit structurei

Interacts with RAB26 (PubMed:23105096). Interacts with PPP1R9B (PubMed:24114805).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RAB26Q9ULW54EBI-9077302,EBI-958239

Protein-protein interaction databases

BioGridi106660, 3 interactors
DIPiDIP-61453N
IntActiP18089, 3 interactors
STRINGi9606.ENSP00000387281

Chemistry databases

BindingDBiP18089

Structurei

3D structure databases

ProteinModelPortaliP18089
SMRiP18089
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi294 – 311Asp/Glu-rich (acidic)Add BLAST18

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2B sub-subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00760000118795
HOGENOMiHOG000239242
HOVERGENiHBG106962
InParanoidiP18089
KOiK04139
OMAiWCEVYLA
OrthoDBiEOG091G06VI
PhylomeDBiP18089
TreeFamiTF316350

Family and domain databases

InterProiView protein in InterPro
IPR002233 ADR_fam
IPR000207 ADRA2B_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR01103 ADRENERGICR
PR00559 ADRENRGCA2BR
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.

P18089-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDHQDPYSVQ ATAAIAAAIT FLILFTIFGN ALVILAVLTS RSLRAPQNLF
60 70 80 90 100
LVSLAAADIL VATLIIPFSL ANELLGYWYF RRTWCEVYLA LDVLFCTSSI
110 120 130 140 150
VHLCAISLDR YWAVSRALEY NSKRTPRRIK CIILTVWLIA AVISLPPLIY
160 170 180 190 200
KGDQGPQPRG RPQCKLNQEA WYILASSIGS FFAPCLIMIL VYLRIYLIAK
210 220 230 240 250
RSNRRGPRAK GGPGQGESKQ PRPDHGGALA SAKLPALASV ASAREVNGHS
260 270 280 290 300
KSTGEKEEGE TPEDTGTRAL PPSWAALPNS GQGQKEGVCG ASPEDEAEEE
310 320 330 340 350
EEEEEEEEEC EPQAVPVSPA SACSPPLQQP QGSRVLATLR GQVLLGRGVG
360 370 380 390 400
AIGGQWWRRR AQLTREKRFT FVLAVVIGVF VLCWFPFFFS YSLGAICPKH
410 420 430 440 450
CKVPHGLFQF FFWIGYCNSS LNPVIYTIFN QDFRRAFRRI LCRPWTQTAW
Length:450
Mass (Da):49,954
Last modified:March 15, 2017 - v4
Checksum:i06E43857152A68ED
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti362 – 363QL → HV in AAA51666 (PubMed:2164221).Curated2
Sequence conflicti362 – 363QL → HV no nucleotide entry (PubMed:2172775).Curated2

Polymorphismi

A rare polymorphic frameshift in position 451 produces a protein of 545 residues.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025099211G → A1 PublicationCorresponds to variant dbSNP:rs9333568Ensembl.1
Natural variantiVAR_073953225 – 229HGGAL → QFGR in FAME2; gain of function; decreases interaction with PPP1R9B upon activation by neurotransmitter. 1 Publication5
Natural variantiVAR_070775301 – 303Missing Polymorphism; found with a frequency of 0.31 in Caucasians and 0.12 in African-Americans; exhibits impaired phosphorylation and desensitization by G protein-coupled receptor kinases; does not affect ligand-binding. 2 Publications3
Natural variantiVAR_033462376V → I. Corresponds to variant dbSNP:rs29000569Ensembl.1
Natural variantiVAR_025100379V → G1 PublicationCorresponds to variant dbSNP:rs527655811Ensembl.1
Natural variantiVAR_033463379V → I. Corresponds to variant dbSNP:rs29000569Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34041 Genomic DNA Translation: AAA51666.1
AF316895 Genomic DNA Translation: AAK01635.1
AF005900 Genomic DNA Translation: AAB62558.1
AY548167 Genomic DNA Translation: AAS55646.1
DQ057076 Genomic DNA Translation: AAY43127.1
EU332847 Genomic DNA Translation: ABY87536.1
AC092603 Genomic DNA Translation: AAX93218.1
KF573706 Genomic DNA No translation available.
CH471207 Genomic DNA Translation: EAW71390.1
BC133021 mRNA Translation: AAI33022.1
BC136537 mRNA Translation: AAI36538.1
M38742 Genomic DNA Translation: AAA62823.1
CCDSiCCDS56129.1
PIRiA37223
RefSeqiNP_000673.2, NM_000682.6
UniGeneiHs.247686

Genome annotation databases

EnsembliENST00000620793; ENSP00000480573; ENSG00000274286
GeneIDi151
KEGGihsa:151
UCSCiuc032nvj.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34041 Genomic DNA Translation: AAA51666.1
AF316895 Genomic DNA Translation: AAK01635.1
AF005900 Genomic DNA Translation: AAB62558.1
AY548167 Genomic DNA Translation: AAS55646.1
DQ057076 Genomic DNA Translation: AAY43127.1
EU332847 Genomic DNA Translation: ABY87536.1
AC092603 Genomic DNA Translation: AAX93218.1
KF573706 Genomic DNA No translation available.
CH471207 Genomic DNA Translation: EAW71390.1
BC133021 mRNA Translation: AAI33022.1
BC136537 mRNA Translation: AAI36538.1
M38742 Genomic DNA Translation: AAA62823.1
CCDSiCCDS56129.1
PIRiA37223
RefSeqiNP_000673.2, NM_000682.6
UniGeneiHs.247686

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CVAmodel-A97-128[»]
ProteinModelPortaliP18089
SMRiP18089
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106660, 3 interactors
DIPiDIP-61453N
IntActiP18089, 3 interactors
STRINGi9606.ENSP00000387281

Chemistry databases

BindingDBiP18089
ChEMBLiCHEMBL1942
DrugBankiDB00543 Amoxapine
DB00182 Amphetamine
DB00714 Apomorphine
DB00964 Apraclonidine
DB01238 Aripiprazole
DB06216 Asenapine
DB00217 Bethanidine
DB00484 Brimonidine
DB01200 Bromocriptine
DB00248 Cabergoline
DB01136 Carvedilol
DB00477 Chlorpromazine
DB09202 Cirazoline
DB00575 Clonidine
DB00363 Clozapine
DB01151 Desipramine
DB01142 Doxepin
DB04855 Dronedarone
DB06262 Droxidopa
DB01363 Ephedra
DB05492 Epicept NP-1
DB00668 Epinephrine
DB01049 Ergoloid mesylate
DB00696 Ergotamine
DB06678 Esmirtazapine
DB00292 Etomidate
DB00800 Fenoldopam
DB00629 Guanabenz
DB01018 Guanfacine
DB06707 Levonordefrin
DB00589 Lisuride
DB00408 Loxapine
DB00934 Maprotiline
DB01365 Mephentermine
DB01577 Methamphetamine
DB01403 Methotrimeprazine
DB06148 Mianserin
DB00368 Norepinephrine
DB00540 Nortriptyline
DB00334 Olanzapine
DB05461 OPC-28326
DB00935 Oxymetazoline
DB01267 Paliperidone
DB01186 Pergolide
DB00925 Phenoxybenzamine
DB00413 Pramipexole
DB00457 Prazosin
DB01224 Quetiapine
DB00734 Risperidone
DB00268 Ropinirole
DB05271 Rotigotine
DB13025 Tiapride
DB00697 Tizanidine
DB00797 Tolazoline
DB00726 Trimipramine
DB06694 Xylometazoline
DB01392 Yohimbine
DB00246 Ziprasidone
GuidetoPHARMACOLOGYi26

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSitePlusiP18089

Polymorphism and mutation databases

BioMutaiADRA2B
DMDMi27151763

Proteomic databases

PaxDbiP18089
PeptideAtlasiP18089
PRIDEiP18089
ProteomicsDBi53548

Protocols and materials databases

DNASUi151
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000620793; ENSP00000480573; ENSG00000274286
GeneIDi151
KEGGihsa:151
UCSCiuc032nvj.2 human

Organism-specific databases

CTDi151
DisGeNETi151
EuPathDBiHostDB:ENSG00000274286.1
GeneCardsiADRA2B
H-InvDBiHIX0161945
HGNCiHGNC:282 ADRA2B
HPAiHPA066029
MalaCardsiADRA2B
MIMi104260 gene
607876 phenotype
neXtProtiNX_P18089
OpenTargetsiENSG00000274286
Orphaneti86814 Benign adult familial myoclonic epilepsy
PharmGKBiPA36
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00760000118795
HOGENOMiHOG000239242
HOVERGENiHBG106962
InParanoidiP18089
KOiK04139
OMAiWCEVYLA
OrthoDBiEOG091G06VI
PhylomeDBiP18089
TreeFamiTF316350

Enzyme and pathway databases

ReactomeiR-HSA-390696 Adrenoceptors
R-HSA-392023 Adrenaline signalling through Alpha-2 adrenergic receptor
R-HSA-418594 G alpha (i) signalling events
R-HSA-418597 G alpha (z) signalling events
SignaLinkiP18089

Miscellaneous databases

GeneWikiiAlpha-2B_adrenergic_receptor
GenomeRNAii151
PROiPR:P18089
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000274286 Expressed in 84 organ(s), highest expression level in apex of heart
CleanExiHS_ADRA2B

Family and domain databases

InterProiView protein in InterPro
IPR002233 ADR_fam
IPR000207 ADRA2B_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR01103 ADRENERGICR
PR00559 ADRENRGCA2BR
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 nameiADA2B_HUMAN
AccessioniPrimary (citable) accession number: P18089
Secondary accession number(s): A2RUS0
, Q4TUH9, Q53RF2, Q9BZK0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: March 15, 2017
Last modified: September 12, 2018
This is version 187 of the entry and version 4 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, Reference proteome
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Main funding by: National Institutes of Health

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