P18089 (ADA2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	ADRA2B
Synonyms:	ADRA2L1, ADRA2RL1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	450 AA.
Sequence status	Complete.
Protein existence	Evidence 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 451 produces a protein of 542 residues.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2B sub-subfamily.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Lipoprotein Palmitate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara 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: Compara 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: Compara regulation of vascular smooth muscle contraction Inferred from electronic annotation. Source: Compara
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	alpha2-adrenergic receptor activity Inferred from direct assay PubMed 17215105. Source: BHF-UCL epinephrine binding Inferred from direct assay PubMed 17215105. Source: BHF-UCL
Complete GO annotation...

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	12	Extracellular By similarity
	Transmembrane	13 – 38	26	Helical; Name=1; By similarity
	Topological domain	39 – 49	11	Cytoplasmic By similarity
	Transmembrane	50 – 75	26	Helical; Name=2; By similarity
	Topological domain	76 – 85	10	Extracellular By similarity
	Transmembrane	86 – 108	23	Helical; Name=3; By similarity
	Topological domain	109 – 130	22	Cytoplasmic By similarity
	Transmembrane	131 – 153	23	Helical; Name=4; By similarity
	Topological domain	154 – 169	16	Extracellular By similarity
	Transmembrane	170 – 193	24	Helical; Name=5; By similarity
	Topological domain	194 – 372	179	Cytoplasmic By similarity
	Transmembrane	373 – 396	24	Helical; Name=6; By similarity
	Topological domain	397 – 405	9	Extracellular By similarity
	Transmembrane	406 – 429	24	Helical; Name=7; By similarity
	Topological domain	430 – 450	21	Cytoplasmic By similarity
	Compositional bias	294 – 311	18	Asp/Glu-rich (acidic)
Sites
	Site	92	1	Implicated in ligand binding By similarity
	Site	176	1	Implicated in catechol agonist binding By similarity
	Site	180	1	Implicated in catechol agonist binding By similarity
Amino acid modifications
	Lipidation	442	1	S-palmitoyl cysteine Potential
	Disulfide bond	85 ↔ 164		By similarity
Natural variations
	Natural variant	211	1	G → A. Ref.6 Corresponds to variant rs9333568 [ dbSNP | Ensembl ].		VAR_025099
	Natural variant	301 – 303	3	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	1	V → I. Corresponds to variant rs29000569 [ dbSNP | Ensembl ].		VAR_033462
	Natural variant	379	1	V → G. Ref.6		VAR_025100
	Natural variant	379	1	V → I. Corresponds to variant rs29000569 [ dbSNP | Ensembl ].		VAR_033463
Experimental info
	Sequence conflict	362 – 363	2	QL → HV Ref.1
	Sequence conflict	362 – 363	2	QL → HV Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P18089 [UniParc]. Last modified December 13, 2002. Version 2. Checksum: 06E43857152A68ED	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

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. , 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], 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-389.
[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

SeattleSNPs

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.

IPI

IPI00297315.

PIR

A37223.

RefSeq

NP_000673.2. NM_000682.5.

UniGene

Hs.247686.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

P18089.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000387281.

Protein family/group databases

GPCRDB

Search...

Polymorphism databases

DMDM

27151763.

Proteomic databases

PaxDb

P18089.

PRIDE

P18089.

Protocols and materials databases

DNASU

151.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000409345; ENSP00000387281; ENSG00000222040.

GeneID

151.

KEGG

hsa:151.

UCSC

uc021vlh.1. human.

Organism-specific databases

CTD

151.

GeneCards

GC02M096778.

H-InvDB

HIX0161945.

HGNC

HGNC:282. ADRA2B.

MIM

104260. gene.

neXtProt

NX_P18089.

PharmGKB

PA36.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG249628.

HOGENOM

HOG000239242.

HOVERGEN

HBG106962.

InParanoid

P18089.

KO

K04139.

OrthoDB

EOG4R502W.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P18089.

Bgee

P18089.

CleanEx

HS_ADRA2B.

Genevestigator

P18089.

Family and domain databases

InterPro

IPR000207. Adren_rcpt_A2B.
IPR002233. Adrnrgc_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]

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

BindingDB

P18089.

ChEMBL

CHEMBL1942.

DrugBank

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

GenomeRNAi

151.

NextBio

599.

SOURCE

Search...

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:	May 1, 2013
This is version 138 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.