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P18089 (ADA2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:ADRA2B
Synonyms:ADRA2L1, ADRA2RL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length447 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 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. Ref.9

Subunit structure

Interacts with RAB26. Ref.9

Subcellular location

Cell membrane; Multi-pass membrane protein. Note: Interaction with RAB26 mediates transport from the Golgi to the cell membrane. Ref.9

Polymorphism

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.

Sequence similarities

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

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Lipoprotein
Palmitate
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Traceable author statement Ref.1. Source: ProtInc

MAPK cascade

Inferred from electronic annotation. Source: Ensembl

activation of MAPK activity by adrenergic receptor signaling pathway

Inferred from direct assay PubMed 17215105. Source: BHF-UCL

activation of protein kinase B activity

Inferred from direct assay PubMed 17215105. Source: BHF-UCL

angiogenesis

Inferred from electronic annotation. Source: Ensembl

blood coagulation

Traceable author statement. Source: Reactome

cell-cell signaling

Traceable author statement Ref.1. Source: ProtInc

epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway

Inferred from direct assay PubMed 17215105. Source: BHF-UCL

female pregnancy

Inferred from electronic annotation. Source: Ensembl

negative regulation of epinephrine secretion

Non-traceable author statement PubMed 16531006. Source: BHF-UCL

negative regulation of norepinephrine secretion

Non-traceable author statement PubMed 16531006. Source: BHF-UCL

platelet activation

Traceable author statement. Source: Reactome

positive regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron differentiation

Inferred from direct assay PubMed 17215105. Source: BHF-UCL

positive regulation of uterine smooth muscle contraction

Inferred from electronic annotation. Source: Ensembl

regulation of vascular smooth muscle contraction

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentintegral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionalpha2-adrenergic receptor activity

Inferred from direct assay PubMed 17215105. Source: BHF-UCL

epinephrine binding

Inferred from direct assay PubMed 17215105. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 16531006. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 447447Alpha-2B adrenergic receptor
PRO_0000069094

Regions

Topological domain1 – 1212Extracellular By similarity
Transmembrane13 – 3826Helical; Name=1; By similarity
Topological domain39 – 4810Cytoplasmic By similarity
Transmembrane49 – 6921Helical; Name=2; By similarity
Topological domain70 – 8617Extracellular By similarity
Transmembrane87 – 10721Helical; Name=3; By similarity
Topological domain108 – 12821Cytoplasmic By similarity
Transmembrane129 – 14921Helical; Name=4; By similarity
Topological domain150 – 17223Extracellular By similarity
Transmembrane173 – 19321Helical; Name=5; By similarity
Topological domain194 – 369176Cytoplasmic By similarity
Transmembrane370 – 39324Helical; Name=6; By similarity
Topological domain394 – 4029Extracellular By similarity
Transmembrane403 – 42321Helical; Name=7; By similarity
Topological domain424 – 44724Cytoplasmic By similarity
Compositional bias294 – 30815Asp/Glu-rich (acidic)

Sites

Site921Implicated in ligand binding By similarity
Site1761Implicated in catechol agonist binding By similarity
Site1801Implicated in catechol agonist binding By similarity

Amino acid modifications

Lipidation4391S-palmitoyl cysteine Potential
Disulfide bond85 ↔ 164 By similarity

Natural variations

Natural variant2111G → A. Ref.6
Corresponds to variant rs9333568 [ dbSNP | Ensembl ].
VAR_025099
Natural variant3001E → EEEE. Ref.1 Ref.2 Ref.4 Ref.5 Ref.8
VAR_070775
Natural variant3731V → I.
Corresponds to variant rs29000569 [ dbSNP | Ensembl ].
VAR_033462
Natural variant3761V → G. Ref.6
VAR_025100
Natural variant3761V → I.
Corresponds to variant rs29000569 [ dbSNP | Ensembl ].
VAR_033463

Experimental info

Sequence conflict359 – 3602QL → HV in AAA51666. Ref.1
Sequence conflict359 – 3602QL → HV no nucleotide entry Ref.2

Sequences

Sequence LengthMass (Da)Tools
P18089 [UniParc].

Last modified April 16, 2014. Version 3.
Checksum: B33D4B5B719C1C45

FASTA44749,566
        10         20         30         40         50         60 
MDHQDPYSVQ ATAAIAAAIT FLILFTIFGN ALVILAVLTS RSLRAPQNLF LVSLAAADIL 

        70         80         90        100        110        120 
VATLIIPFSL ANELLGYWYF RRTWCEVYLA LDVLFCTSSI VHLCAISLDR YWAVSRALEY 

       130        140        150        160        170        180 
NSKRTPRRIK CIILTVWLIA AVISLPPLIY KGDQGPQPRG RPQCKLNQEA WYILASSIGS 

       190        200        210        220        230        240 
FFAPCLIMIL VYLRIYLIAK RSNRRGPRAK GGPGQGESKQ PRPDHGGALA SAKLPALASV 

       250        260        270        280        290        300 
ASAREVNGHS KSTGEKEEGE TPEDTGTRAL PPSWAALPNS GQGQKEGVCG ASPEDEAEEE 

       310        320        330        340        350        360 
EEEEEECEPQ AVPVSPASAC SPPLQQPQGS RVLATLRGQV LLGRGVGAIG GQWWRRRAQL 

       370        380        390        400        410        420 
TREKRFTFVL AVVIGVFVLC WFPFFFSYSL GAICPKHCKV PHGLFQFFFW IGYCNSSLNP 

       430        440 
VIYTIFNQDF RRAFRRILCR PWTQTAW 

« Hide

References

« Hide 'large scale' references
[1]"Expansion of the alpha 2-adrenergic receptor family: cloning and characterization of a human alpha 2-adrenergic receptor subtype, the gene for which is located on chromosome 2."
Lomasney J.W., Lorenz W., Allen L.F., King K., Regan J.W., Yang-Feng T.L., Caron M.G., Lefkowitz R.J.
Proc. Natl. Acad. Sci. U.S.A. 87:5094-5098(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-GLU-GLU-300 INS.
[2]"Cloning, expression, and pharmacological characterization of a human alpha 2B-adrenergic receptor."
Weinshank R.L., Zgombick J.M., Macchi M., Adham N., Lichtblau H., Branchek T.A., Hartig P.R.
Mol. Pharmacol. 38:681-688(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-GLU-GLU-300 INS.
[3]"Polymorphic deletion of three intracellular acidic residues of the alpha 2B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated phosphorylation and desensitization."
Small K.M., Brown K.M., Forbes S.L., Liggett S.B.
J. Biol. Chem. 276:4917-4922(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Cloning, characterisation and identification of several polymorphisms in the promoter region of the human alpha2B-adrenergic receptor gene."
Cayla C., Heinonen P., Viikari L., Schaak S., Snapir A., Bouloumie A., Karvonen M.K., Pesonen U., Scheinin M., Paris H.
Biochem. Pharmacol. 67:469-478(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-GLU-GLU-300 INS.
[5]"Isolation of complete coding sequence for adrenergic receptor alpha 2B (ADRA2B)."
Kopatz S.A., Aronstam R.S., Sharma S.V.
Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-GLU-GLU-300 INS.
[6]SeattleSNPs variation discovery resource
Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-211; GLU-GLU-GLU-300 INS AND GLY-376, FRAMESHIFT POLYMORPHISM.
[7]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"In vitro amplification by polymerase chain reaction of a partial gene encoding the third subtype of alpha-2 adrenergic receptor in humans."
Chang A.C., Ho T.F., Chang N.-C.A.
Biochem. Biophys. Res. Commun. 172:817-823(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-386, VARIANT GLU-GLU-GLU-300 INS.
[9]"Rab26 modulates the cell surface transport of alpha2-adrenergic receptors from the Golgi."
Li C., Fan Y., Lan T.H., Lambert N.A., Wu G.
J. Biol. Chem. 287:42784-42794(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RAB26, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS56129.1.
PIRA37223.
RefSeqNP_000673.2. NM_000682.6.
UniGeneHs.247686.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CVAmodel-A97-128[»]
ProteinModelPortalP18089.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106660. 3 interactions.
STRING9606.ENSP00000387281.

Chemistry

BindingDBP18089.
ChEMBLCHEMBL2095203.
DrugBankDB00217. Bethanidine.
DB00484. Brimonidine.
DB04840. Debrisoquin.
DB00696. Ergotamine.
DB00800. Fenoldopam.
DB00226. Guanadrel Sulfate.
DB01170. Guanethidine.
DB04948. Lofexidine.
DB00368. Norepinephrine.
DB01392. Yohimbine.
GuidetoPHARMACOLOGY26.

Protein family/group databases

GPCRDBSearch...

Polymorphism databases

DMDM27151763.

Proteomic databases

PaxDbP18089.
PRIDEP18089.

Protocols and materials databases

DNASU151.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000409345; ENSP00000387281; ENSG00000222040.
GeneID151.
KEGGhsa:151.
UCSCuc021vlh.1. human.

Organism-specific databases

CTD151.
GeneCardsGC02M096778.
H-InvDBHIX0161945.
HGNCHGNC:282. ADRA2B.
MIM104260. gene.
neXtProtNX_P18089.
Orphanet86814. Benign adult familial myoclonic epilepsy.
PharmGKBPA36.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG249628.
HOGENOMHOG000239242.
HOVERGENHBG106962.
InParanoidP18089.
KOK04139.
OrthoDBEOG7J9VPT.
PhylomeDBP18089.
TreeFamTF316350.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.
SignaLinkP18089.

Gene expression databases

ArrayExpressP18089.
BgeeP18089.
CleanExHS_ADRA2B.
GenevestigatorP18089.

Family and domain databases

Gene3D1.20.1070.10. 2 hits.
InterProIPR002233. ADR_fam.
IPR000207. ADRA2B_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24248:SF26. PTHR24248:SF26. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR01103. ADRENERGICR.
PR00559. ADRENRGCA2BR.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiAlpha-2B_adrenergic_receptor.
GenomeRNAi151.
NextBio599.
PROP18089.
SOURCESearch...

Entry information

Entry nameADA2B_HUMAN
AccessionPrimary (citable) accession number: P18089
Secondary accession number(s): Q4TUH9, Q53RF2, Q9BZK0
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: April 16, 2014
Last modified: July 9, 2014
This is version 151 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries