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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

  • activation of MAPK activity by adrenergic receptor signaling pathway Source: BHF-UCL
  • activation of protein kinase B activity Source: BHF-UCL
  • adenylate cyclase-activating adrenergic receptor signaling pathway Source: GO_Central
  • cell-cell signaling Source: ProtInc
  • epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway Source: BHF-UCL
  • G-protein coupled receptor signaling pathway Source: ProtInc
  • negative regulation of epinephrine secretion Source: BHF-UCL
  • negative regulation of norepinephrine secretion Source: BHF-UCL
  • platelet activation Source: InterPro
  • positive regulation of neuron differentiation Source: BHF-UCL
  • regulation of smooth muscle contraction Source: InterPro
  • regulation of vasoconstriction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:G66-32609-MONOMER.
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: Unplaced

Organism-specific databases

HGNCiHGNC:282. ADRA2B.

Subcellular locationi

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 – 369CytoplasmicBy similarityAdd BLAST176
Transmembranei370 – 393Helical; Name=6By similarityAdd BLAST24
Topological domaini394 – 402ExtracellularBy similarity9
Transmembranei403 – 423Helical; Name=7By similarityAdd BLAST21
Topological domaini424 – 447CytoplasmicBy similarityAdd BLAST24

GO - Cellular componenti

  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

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.
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.
DB00575. Clonidine.
DB00363. Clozapine.
DB01151. Desipramine.
DB01142. Doxepin.
DB04855. Dronedarone.
DB06262. Droxidopa.
DB01363. Ephedra.
DB00668. Epinephrine.
DB01049. Ergoloid mesylate.
DB00696. Ergotamine.
DB00292. Etomidate.
DB00800. Fenoldopam.
DB00629. Guanabenz.
DB01018. Guanfacine.
DB00589. Lisuride.
DB00408. Loxapine.
DB00934. Maprotiline.
DB01365. Mephentermine.
DB01577. Methamphetamine.
DB01403. Methotrimeprazine.
DB06148. Mianserin.
DB00368. Norepinephrine.
DB00540. Nortriptyline.
DB00334. Olanzapine.
DB00935. Oxymetazoline.
DB01267. Paliperidone.
DB01186. Pergolide.
DB00925. Phenoxybenzamine.
DB00413. Pramipexole.
DB00457. Prazosin.
DB01224. Quetiapine.
DB00734. Risperidone.
DB00268. Ropinirole.
DB05271. Rotigotine.
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 – 447Alpha-2B adrenergic receptorAdd BLAST447

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi85 ↔ 164PROSITE-ProRule annotation
Lipidationi439S-palmitoyl cysteineSequence analysis1

Keywords - PTMi

Disulfide bond, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP18089.
PeptideAtlasiP18089.
PRIDEiP18089.

PTM databases

PhosphoSitePlusiP18089.

Expressioni

Gene expression databases

BgeeiENSG00000222040.
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. 1 interactor.
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.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi294 – 308Asp/Glu-rich (acidic)Add BLAST15

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.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP18089.
KOiK04139.
PhylomeDBiP18089.
TreeFamiTF316350.

Family and domain databases

InterProiIPR002233. ADR_fam.
IPR000207. ADRA2B_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01103. ADRENERGICR.
PR00559. ADRENRGCA2BR.
PR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

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
EEEEEECEPQ AVPVSPASAC SPPLQQPQGS RVLATLRGQV LLGRGVGAIG
360 370 380 390 400
GQWWRRRAQL TREKRFTFVL AVVIGVFVLC WFPFFFSYSL GAICPKHCKV
410 420 430 440
PHGLFQFFFW IGYCNSSLNP VIYTIFNQDF RRAFRRILCR PWTQTAW
Length:447
Mass (Da):49,566
Last modified:April 16, 2014 - v3
Checksum:iB33D4B5B719C1C45
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti359 – 360QL → HV in AAA51666 (PubMed:2164221).Curated2
Sequence conflicti359 – 360QL → HV no nucleotide entry (PubMed:2172775).Curated2

Polymorphismi

A rare polymorphic frameshift in position 448 produces a protein of 542 residues.
The gene is polymorphic at position 300. The sequence shown here is found with a frequency of 0.31 in Caucasians and 0.12 in African-Americans. It exhibits impaired phosphorylation and desensitization by GRKs compared to the sequence including a stretch of glutamic acid at that position.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025099211G → A.1 PublicationCorresponds to variant rs9333568dbSNPEnsembl.1
Natural variantiVAR_073953225 – 229HGGAL → QFGR in FAME2; gain of function; decreases interaction with PPP1R9B upon activation by neurotransmitter. 1 Publication5
Natural variantiVAR_070775300E → EEEE.5 Publications1
Natural variantiVAR_033462373V → I.Corresponds to variant rs29000569dbSNPEnsembl.1
Natural variantiVAR_025100376V → G.1 Publication1
Natural variantiVAR_033463376V → I.Corresponds to variant rs29000569dbSNPEnsembl.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.
AC092603 Genomic DNA. Translation: AAX93218.1.
M38742 Genomic DNA. Translation: AAA62823.1.
PIRiA37223.
RefSeqiNP_000673.2. NM_000682.6.
UniGeneiHs.247686.

Genome annotation databases

GeneIDi151.
KEGGihsa:151.

Keywords - Coding sequence diversityi

Polymorphism

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.
AC092603 Genomic DNA. Translation: AAX93218.1.
M38742 Genomic DNA. Translation: AAA62823.1.
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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106660. 3 interactors.
DIPiDIP-61453N.
IntActiP18089. 1 interactor.
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.
DB00575. Clonidine.
DB00363. Clozapine.
DB01151. Desipramine.
DB01142. Doxepin.
DB04855. Dronedarone.
DB06262. Droxidopa.
DB01363. Ephedra.
DB00668. Epinephrine.
DB01049. Ergoloid mesylate.
DB00696. Ergotamine.
DB00292. Etomidate.
DB00800. Fenoldopam.
DB00629. Guanabenz.
DB01018. Guanfacine.
DB00589. Lisuride.
DB00408. Loxapine.
DB00934. Maprotiline.
DB01365. Mephentermine.
DB01577. Methamphetamine.
DB01403. Methotrimeprazine.
DB06148. Mianserin.
DB00368. Norepinephrine.
DB00540. Nortriptyline.
DB00334. Olanzapine.
DB00935. Oxymetazoline.
DB01267. Paliperidone.
DB01186. Pergolide.
DB00925. Phenoxybenzamine.
DB00413. Pramipexole.
DB00457. Prazosin.
DB01224. Quetiapine.
DB00734. Risperidone.
DB00268. Ropinirole.
DB05271. Rotigotine.
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.

Protocols and materials databases

DNASUi151.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi151.
KEGGihsa:151.

Organism-specific databases

CTDi151.
DisGeNETi151.
GeneCardsiADRA2B.
H-InvDBHIX0161945.
HGNCiHGNC:282. ADRA2B.
HPAiHPA066029.
MalaCardsiADRA2B.
MIMi104260. gene.
607876. phenotype.
neXtProtiNX_P18089.
Orphaneti86814. Benign adult familial myoclonic epilepsy.
PharmGKBiPA36.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP18089.
KOiK04139.
PhylomeDBiP18089.
TreeFamiTF316350.

Enzyme and pathway databases

BioCyciZFISH:G66-32609-MONOMER.
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.
PROiP18089.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000222040.
CleanExiHS_ADRA2B.

Family and domain databases

InterProiIPR002233. ADR_fam.
IPR000207. ADRA2B_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01103. ADRENERGICR.
PR00559. ADRENRGCA2BR.
PR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiADA2B_HUMAN
AccessioniPrimary (citable) accession number: P18089
Secondary accession number(s): Q4TUH9, Q53RF2, Q9BZK0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: April 16, 2014
Last modified: November 2, 2016
This is version 172 of the entry and version 3 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.