Alpha-2B adrenergic receptor - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P18089 (ADA2B_HUMAN)

Last modified November 3, 2009. Version 104. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Alpha-2B adrenergic receptor
Alternative name(s):
    Alpha-2B adrenoreceptor
    Alpha-2B adrenoceptor
    Alpha-2 adrenergic receptor subtype C2

Gene names

Name:	ADRA2B
Synonyms:	ADRA2L1, ADRA2RL1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	450 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

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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.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Polymorphism	A rare polymorphic framshift in position 451 produces a protein of 542 residues.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

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Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Ref.1 Inferred from Experiment. Source: Reactome cell-cell signaling Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	alpha2-adrenergic receptor activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 450

450

Alpha-2B adrenergic receptor

PRO_0000069094

Regions

Topological domain

1 – 12

Extracellular By similarity

Transmembrane

13 – 38

1 By similarity

Topological domain

39 – 49

Cytoplasmic By similarity

Transmembrane

50 – 75

2 By similarity

Topological domain

76 – 85

Extracellular By similarity

Transmembrane

86 – 108

3 By similarity

Topological domain

109 – 130

Cytoplasmic By similarity

Transmembrane

131 – 153

4 By similarity

Topological domain

154 – 169

Extracellular By similarity

Transmembrane

170 – 193

5 By similarity

Topological domain

194 – 372

179

Cytoplasmic By similarity

Transmembrane

373 – 396

6 By similarity

Topological domain

397 – 405

Extracellular By similarity

Transmembrane

406 – 429

7 By similarity

Topological domain

430 – 450

Cytoplasmic By similarity

Compositional bias

294 – 311

Asp/Glu-rich (acidic)

Sites

Site

Implicated in ligand binding By similarity

Site

176

Implicated in catechol agonist binding By similarity

Site

180

Implicated in catechol agonist binding By similarity

Amino acid modifications

Lipidation

442

S-palmitoyl cysteine Potential

Disulfide bond

85 ↔ 164

By similarity

Natural variations

Natural variant

211

G → A: dbSNP rs9333568. Ref.6

VAR_025099

Natural variant

301 – 303

Missing Common polymorphism; frequency in Caucasians 0.31 and in African-Americans 0.12; impaired phosphorylation and desensitization by GRKs.

VAR_014958

Natural variant

376

V → I: dbSNP rs29000569.

VAR_033462

Natural variant

379

V → G

VAR_025100

Natural variant

379

V → I: dbSNP rs29000569.

VAR_033463

Experimental info

Sequence conflict

362 – 363

QL → HV Ref.1

Sequence conflict

362 – 363

QL → HV Ref.2

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Sequences

Sequence

Length

Mass (Da)

Tools

P18089-1 [UniParc].

Last modified December 13, 2002. Version 2.
Checksum: 06E43857152A68ED
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FASTA

450

49,954

        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 
EEEEEEEEEC EPQAVPVSPA SACSPPLQQP QGSRVLATLR GQVLLGRGVG AIGGQWWRRR 

       370        380        390        400        410        420 
AQLTREKRFT FVLAVVIGVF VLCWFPFFFS YSLGAICPKH CKVPHGLFQF FFWIGYCNSS 

       430        440        450 
LNPVIYTIFN QDFRRAFRRI LCRPWTQTAW

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References

	« Hide 'large scale' referencesShow '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: 2164221] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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: 2172775] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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: 11056163] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT 301-GLU--GLU-303 DEL.
[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: 15037199] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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].
[6]	SeattleSNPs variation discovery resource Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-211 AND GLY-379, 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. Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT 301-GLU--GLU-303 DEL.
[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: 2173582] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-389.
+	Additional computationally mapped references.

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Web resources

SeattleSNPs

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Cross-references

Sequence databases

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.

IPI

IPI00297315.

PIR

A37223.

RefSeq

NP_000673.2.

UniGene

Hs.247686

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CVA	model	-	A	97-128	[»]

ModBase

Search...

Protein family/group databases

GPCRDB

Search...

Proteomic databases

PRIDE

P18089.

Genome annotation databases

Ensembl

ENST00000409345; ENSP00000387281; ENSG00000222040; Homo sapiens. [Genome view]

GeneID

151.

KEGG

hsa:151.

Organism-specific databases

CTD

151.

GeneCards

GC02M096200.

H-InvDB

HIX0030044.

HGNC

HGNC:282. ADRA2B.

MIM

104260. gene.

PharmGKB

PA36.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P18089.

Enzyme and pathway databases

Reactome

REACT_14797. Signaling by GPCR.
REACT_604. Hemostasis.

Gene expression databases

Bgee

P18089.

CleanEx

HS_ADRA2B.

Genevestigator

P18089.

Family and domain databases

InterPro

IPR000276. 7TM_GPCR_Rhodpsn.
IPR015695. Adren_rcpt_A2A/B/C.
IPR000207. Adren_rcpt_A2B.
IPR002233. Adrnrgc_rcpt.
IPR017452. GPCR_Rhodpsn_supfam.
[Graphical view]

PANTHER

PTHR19266:SF56. Alpha-2A_Recept. 1 hit.

Pfam

PF00001. 7tm_1. 1 hit.
[Graphical view]

PRINTS

PR01103. ADRENERGICR.
PR00559. ADRENRGCA2BR.
PR00237. GPCRRHODOPSN.

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00217. Bethanidine.
DB00484. Brimonidine.
DB04840. Debrisoquin.
DB00696. Ergotamine.
DB00800. Fenoldopam.
DB00226. Guanadrel Sulfate.
DB01170. Guanethidine.
DB04948. Lofexidine.
DB00368. Norepinephrine.
DB01392. Yohimbine.

NextBio

599.

SOURCE

Search...

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Entry information

Entry name

ADA2B_HUMAN

Accession

Primary (citable) accession number: P18089
Secondary accession number(s): Q4TUH9, Q53RF2, Q9BZK0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	December 13, 2002
Last modified:	November 3, 2009
This is version 104 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.

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