Reviewed, UniProtKB/Swiss-Prot P08913 (ADA2A_HUMAN)

Names and origin

Protein names

Recommended name:
    Alpha-2A adrenergic receptor
Alternative name(s):
    Alpha-2A adrenoreceptor
    Alpha-2A adrenoceptor
      Short name=Alpha-2AAR
    Alpha-2 adrenergic receptor subtype C10

Gene names

Name:	ADRA2A
Synonyms:	ADRA2R, ADRAR

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

Protein attributes

Sequence length	450 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Traceable author statement. Source: ProtInc Rho protein signal transduction Traceable author statement. Source: ProtInc actin cytoskeleton organization Traceable author statement. Source: ProtInc activation of MAPK activity Traceable author statement. Source: ProtInc cell motion Traceable author statement. Source: ProtInc negative regulation of adenylate cyclase activity Traceable author statement. Source: ProtInc positive regulation of cell proliferation Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	alpha2-adrenergic receptor activity Traceable author statement. Source: ProtInc potassium channel regulator activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 450

450

Alpha-2A adrenergic receptor

PRO_0000069080

Regions

Topological domain

1 – 33

33

Extracellular By similarity

Transmembrane

34 – 59

26

1 By similarity

Topological domain

60 – 70

11

Cytoplasmic By similarity

Transmembrane

71 – 96

26

2 By similarity

Topological domain

97 – 106

10

Extracellular By similarity

Transmembrane

107 – 129

23

3 By similarity

Topological domain

130 – 151

22

Cytoplasmic By similarity

Transmembrane

152 – 172

21

4 By similarity

Topological domain

173 – 194

22

Extracellular By similarity

Transmembrane

195 – 217

23

5 By similarity

Topological domain

218 – 374

157

Cytoplasmic By similarity

Transmembrane

375 – 395

21

6 By similarity

Topological domain

396 – 409

14

Extracellular By similarity

Transmembrane

410 – 429

20

7 By similarity

Topological domain

430 – 450

21

Cytoplasmic By similarity

Sites

Site

113

1

Implicated in ligand binding

Site

200

1

Implicated in catechol agonist binding and receptor activation

Site

204

1

Implicated in catechol agonist binding and receptor activation

Amino acid modifications

Modified residue

297

1

Phosphoserine Ref.16

Modified residue

298

1

Phosphoserine Ref.16

Modified residue

299

1

Phosphoserine Ref.16

Lipidation

442

1

S-palmitoyl cysteine By similarity

Glycosylation

10

1

N-linked (GlcNAc...) Potential

Glycosylation

14

1

N-linked (GlcNAc...) Potential

Disulfide bond

106 ↔ 188

By similarity

Natural variations

Natural variant

251

1

N → K Rare polymorphism; frequency in Caucasians 0.004 and in African-Americans 0.05; 40% increase in agonist-promoted Gi coupling. dbSNP rs1800035.

VAR_014957

Natural variant

386

1

C → S: dbSNP rs35658213.

VAR_055908

Experimental info

Mutagenesis

79

1

D → N: No change in binding affinity. eliminates guanine nucleotide-sensitive agonist binding. Ref.15

Mutagenesis

113

1

D → N: No binding to yohimbine. Increase in adenylate cyclase activity. Ref.15

Mutagenesis

130

1

D → N: Lower affinity for agonists. Eliminates guanine nucleotide-sensitive agonist binding. Ref.15

Mutagenesis

200

1

S → A: Lower affinity for agonists. No change in guanine nucleotide-sensitive agonist binding. Ref.15

Mutagenesis

204

1

S → A: Lower affinity for agonists. Reduced guanine nucleotide-sensitive agonist binding. Ref.15

Mutagenesis

412

1

F → N: 350-fold reduced affinity for alpha-2 antagonist yohimbine, 3000-fold increase for beta-antagonist alprenolol. Ref.15 Ref.14

Sequence conflict

104

1

A → T in AAA51664. Ref.1

Sequence conflict

124

1

L → P Ref.13

Sequence conflict

157

1

V → C in AAA51664. Ref.1

Sequence conflict

333 – 365

33

PRRGP…RWRGR → RGAGRGRRGSGRRLQGRGRS ASGLPRRRAGAGG in AAA51664. Ref.1

Sequence conflict

333 – 365

33

PRRGP…RWRGR → RGAGRGRRGSGRRLQGRGRS ASGLPRRRAGAGG in AAA51665. Ref.2

Sequence conflict

368

1

R → L in AAA51664. Ref.1

Secondary structure

1

.

.

.

.

.

.

450

Helix Strand Turn

Details...

Helix

119 – 128

10

Helix

130 – 139

10

Helix

140 – 142

3

Sequences

	Sequence		Length	Mass (Da)
	P08913-1 [UniParc]. Last modified February 1, 1996. Version 3. Checksum: A703CF262F04E8AC	FASTA	450	48,957
	10 20 30 40 50 60 MGSLQPDAGN ASWNGTEAPG GGARATPYSL QVTLTLVCLA GLLMLLTVFG NVLVIIAVFT 70 80 90 100 110 120 SRALKAPQNL FLVSLASADI LVATLVIPFS LANEVMGYWY FGKAWCEIYL ALDVLFCTSS 130 140 150 160 170 180 IVHLCAISLD RYWSITQAIE YNLKRTPRRI KAIIITVWVI SAVISFPPLI SIEKKGGGGG 190 200 210 220 230 240 PQPAEPRCEI NDQKWYVISS CIGSFFAPCL IMILVYVRIY QIAKRRTRVP PSRRGPDAVA 250 260 270 280 290 300 APPGGTERRP NGLGPERSAG PGGAEAEPLP TQLNGAPGEP APAGPRDTDA LDLEESSSSD 310 320 330 340 350 360 HAERPPGPRR PERGPRGKGK ARASQVKPGD SLPRRGPGAT GIGTPAAGPG EERVGAAKAS 370 380 390 400 410 420 RWRGRQNREK RFTFVLAVVI GVFVVCWFPF FFTYTLTAVG CSVPRTLFKF FFWFGYCNSS 430 440 450 LNPVIYTIFN HDFRRAFKKI LCRGDRKRIV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor." Kobilka B.K., Matsui H., Kobilka T.S., Yang-Feng T.L., Francke U., Caron M.G., Lefkowitz R.J., Regan J.W. Science 238:650-656(1987) [PubMed: 2823383] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE. Tissue: Platelet.
[2]	"Cloning, sequence analysis, and permanent expression of a human alpha 2-adrenergic receptor in Chinese hamster ovary cells. Evidence for independent pathways of receptor coupling to adenylate cyclase attenuation and activation." Fraser C.M., Arakawa S., McCombie W.R., Venter J.C. J. Biol. Chem. 264:11754-11761(1989) [PubMed: 2568356] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Cloning, sequencing, and expression of the gene encoding the porcine alpha 2-adrenergic receptor. Allosteric modulation by Na+, H+, and amiloride analogs." Guyer C.A., Horstman D.A., Wilson A.L., Clark J.D., Kragoe E.J. Jr., Limbird L.E. J. Biol. Chem. 265:17307-17317(1990) [PubMed: 2170371] [Abstract] Cited for: SEQUENCE REVISION TO 333-365.
[4]	"An Asn to Lys polymorphism in the third intracellular loop of the human alpha 2A-adrenergic receptor imparts enhanced agonist-promoted Gi coupling." Small K.M., Forbes S.L., Brown K.M., Liggett S.B. J. Biol. Chem. 275:38518-38523(2000) [PubMed: 10948191] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-251.
[5]	"Complex haplotypes derived from noncoding polymorphisms of the intronless alpha-2A-adrenergic gene diversify receptor expression." Small K.M., Brown K.M., Seman C.A., Theiss C.T., Liggett S.B. Proc. Natl. Acad. Sci. U.S.A. 103:5472-5477(2006) [PubMed: 16567612] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-251.
[6]	"Cloning and expression of human alpha-2A adrenergic receptor in SY5Y cells." Mao Z.-M., Tang K., Li B.-M., Jing N.-H. Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]	"A search for genetic variability in the human alpha-2 adrenergic receptor on chromosome 10." Castellano M., Giacche' M., Rossi F., Rivadossi F., Perani C., Beschi M., Agabiti Rosei E. Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	"Human alpha-2A adrenergic receptor gene and the genotype of -1296 nucleotide and motionsickness." Liu L., Yuan L. Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[9]	SeattleSNPs variation discovery resource Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-251.
[10]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[11]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: PNS and Testis.
[13]	"Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR." Chhajlani V., Rangel N., Uhlen S., Wikberg J.E.S. FEBS Lett. 280:241-244(1991) [PubMed: 1849485] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 77-209.
[14]	"A point mutation in the seventh hydrophobic domain of the alpha 2 adrenergic receptor increases its affinity for a family of beta receptor antagonists." Suryanarayana S., Daunt D.A., von Zastrow M., Kobilka B.K. J. Biol. Chem. 266:15488-15492(1991) [PubMed: 1678390] [Abstract] Cited for: MUTAGENESIS OF PHE-412.
[15]	"Site-directed mutagenesis of alpha 2a-adrenergic receptors: Identification of amino acids involved in ligand binding and receptor activation by agonists." Wang C.-D., Buck M.A., Fraser C.M. Mol. Pharmacol. 40:168-179(1991) [PubMed: 1678850] [Abstract] Cited for: MUTAGENESIS OF ASPARTIC ACID AND SERINE RESIDUES.
[16]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-297; SER-298 AND SER-299, MASS SPECTROMETRY. Tissue: Epithelium.
[17]	"NMR structure of the second intracellular loop of the alpha 2A adrenergic receptor: evidence for a novel cytoplasmic helix." Chung D.A., Zuiderweg E.R.P., Fowler C.B., Soyer O.S., Mosberg H.I., Neubig R.R. Biochemistry 41:3596-3604(2002) [PubMed: 11888275] [Abstract] Cited for: STRUCTURE BY NMR OF 118-149, PROBABLE TOPOLOGY.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

M18415 Genomic DNA. Translation: AAA51664.1.
M23533 Genomic DNA. Translation: AAA51665.1.
AF281308 Genomic DNA. Translation: AAF91441.1.
AF316894 Genomic DNA. Translation: AAK01634.1.
DQ149926 Genomic DNA. Translation: AAZ73101.1.
AF284095 mRNA. Translation: AAK26743.1.
AF262016 Genomic DNA. Translation: AAG00447.2.
AY032736 Genomic DNA. Translation: AAK51162.1.
DQ285607 Genomic DNA. Translation: ABB72683.1.
EU332846 Genomic DNA. Translation: ABY87535.1.
AL158163 Genomic DNA. Translation: CAH72817.1.
BC035047 mRNA. Translation: AAH35047.1.
BC050414 mRNA. Translation: AAH50414.4.

IPI

IPI00797870.

PIR

A34169.

RefSeq

NP_000672.3.

UniGene

Hs.249159

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HLL	NMR	-	A	118-149	[»]
1HO9	NMR	-	A	118-149	[»]
1HOD	NMR	-	A	118-149	[»]
1HOF	NMR	-	A	118-149	[»]

ModBase

Search...

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P08913.

Proteomic databases

PRIDE

P08913.

Genome annotation databases

Ensembl

ENSG00000150594. Homo sapiens. [Contig view]

GeneID

150.

KEGG

hsa:150.

UCSC

uc001kzo.1. human.

Organism-specific databases

GeneCards

GC10P112826.

H-InvDB

HIX0025918.

HGNC

HGNC:281. ADRA2A.

MIM

104210. gene.

PharmGKB

PA35.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P08913.

HOVERGEN

P08913.

OMA

P08913. QLNGAPG.

Enzyme and pathway databases

Reactome

REACT_14797. Signaling by GPCR.

Gene expression databases

ArrayExpress

P08913.

Bgee

P08913.

CleanEx

HS_ADRA2A.

GermOnline

ENSG00000150594. Homo sapiens.

Family and domain databases

InterPro

IPR000276. 7TM_GPCR_Rhodpsn.
IPR001946. Adren_rcpt_A2A.
IPR015695. Adren_rcpt_A2A/B/C.
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.
PR00558. ADRENRGCA2AR.
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

DB00321. Amitriptyline.
DB00182. Amphetamine.
DB00964. Apraclonidine.
DB00865. Benzphetamine.
DB00217. Bethanidine.
DB00484. Brimonidine.
DB00575. Clonidine.
DB04840. Debrisoquin.
DB00633. Dexmedetomidine.
DB00449. Dipivefrin.
DB00751. Epinastine.
DB00696. Ergotamine.
DB00800. Fenoldopam.
DB00629. Guanabenz.
DB00226. Guanadrel Sulfate.
DB01170. Guanethidine.
DB01018. Guanfacine.
DB04948. Lofexidine.
DB00968. Methyldopa.
DB06148. Mianserin.
DB00370. Mirtazapine.
DB00368. Norepinephrine.
DB00935. Oxymetazoline.
DB00692. Phentolamine.
DB00397. Phenylpropanolamine.
DB00852. Pseudoephedrine.
DB00697. Tizanidine.
DB00656. Trazodone.
DB01392. Yohimbine.

NextBio

595.

SOURCE

Search...

Entry information

Entry name

ADA2A_HUMAN

Accession

Primary (citable) accession number: P08913
Secondary accession number(s): B0LPF6 , Q2I8G2, Q2XN99, Q86TH8, Q9BZK1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	February 1, 1996
Last modified:	July 7, 2009
This is version 114 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)