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Protein

Alpha-2B adrenergic receptor

Gene

ADRA2B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

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.

PTM databases

PhosphoSitePlusiP18089.

Expressioni

Gene expression databases

BgeeiENSG00000274286.
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

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

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: November 22, 2017
This is version 182 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

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families