Reviewed, UniProtKB/Swiss-Prot P18825 (ADA2C_HUMAN)

Names and origin

Protein names

Recommended name:
    Alpha-2C adrenergic receptor
Alternative name(s):
    Alpha-2C adrenoreceptor
    Alpha-2C adrenoceptor
    Alpha-2 adrenergic receptor subtype C4

Gene names

Name:	ADRA2C
Synonyms:	ADRA2L2, ADRA2RL2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	462 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Polymorphism	The Del322-325 variant has a significant loss of function. It is approximately 10 times more frequent in African-Americans compared with Caucasians (allele frequencies 0.381 versus 0.040).
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.
Sequence caution	The sequence AAA35513.1 differs from that shown. Reason: Frameshift at positions 270, 296 and 300. The sequence AAC78723.1 differs from that shown. Reason: Frameshift at positions 270, 296 and 300.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Ref.2 Traceable author statement. Source: ProtInc activation of MAPK activity Traceable author statement. Source: ProtInc cell-cell signaling Ref.2 Traceable author statement. Source: ProtInc
Cellular component	endosome Traceable author statement. Source: ProtInc integral to plasma membrane Ref.2 Traceable author statement. Source: ProtInc
Molecular function	alpha2-adrenergic receptor activity Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 462	462	Alpha-2C adrenergic receptor
Regions
	Topological domain	1 – 51	51	Extracellular Potential
	Transmembrane	52 – 76	25	1 Potential
	Topological domain	77 – 88	12	Cytoplasmic Potential
	Transmembrane	89 – 114	26	2 Potential
	Topological domain	115 – 124	10	Extracellular Potential
	Transmembrane	125 – 147	23	3 Potential
	Topological domain	148 – 168	21	Cytoplasmic Potential
	Transmembrane	169 – 191	23	4 Potential
	Topological domain	192 – 207	16	Extracellular Potential
	Transmembrane	208 – 231	24	5 Potential
	Topological domain	232 – 379	148	Cytoplasmic Potential
	Transmembrane	380 – 407	28	6 Potential
	Topological domain	408 – 420	13	Extracellular Potential
	Transmembrane	421 – 441	21	7 Potential
	Topological domain	442 – 462	21	Cytoplasmic Potential
	Compositional bias	294 – 308	15	Arg-rich (basic)
Sites
	Site	131	1	Implicated in ligand binding By similarity
	Site	214	1	Implicated in catechol agonist binding and receptor activation By similarity
	Site	218	1	Implicated in catechol agonist binding and receptor activation By similarity
Amino acid modifications
	Glycosylation	19	1	N-linked (GlcNAc...) Potential
	Glycosylation	33	1	N-linked (GlcNAc...) Potential
	Disulfide bond	124 ↔ 202		By similarity
Natural variations
	Natural variant	322 – 325	4	Missing
Experimental info
	Sequence conflict	239	1	L → R Ref.1 Ref.2
	Sequence conflict	329	1	E → Q Ref.1 Ref.2
	Sequence conflict	401	1	S → I Ref.1 Ref.2
	Sequence conflict	446	1	R → P Ref.1 Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P18825-1 [UniParc]. Last modified February 11, 2002. Version 2. Checksum: E1EF9CA21E7F6EDA	FASTA	462	49,522
	10 20 30 40 50 60 MASPALAAAL AVAAAAGPNA SGAGERGSGG VANASGASWG PPRGQYSAGA VAGLAAVVGF 70 80 90 100 110 120 LIVFTVVGNV LVVIAVLTSR ALRAPQNLFL VSLASADILV ATLVMPFSLA NELMAYWYFG 130 140 150 160 170 180 QVWCGVYLAL DVLFCTSSIV HLCAISLDRY WSVTQAVEYN LKRTPRRVKA TIVAVWLISA 190 200 210 220 230 240 VISFPPLVSL YRQPDGAAYP QCGLNDETWY ILSSCIGSFF APCLIMGLVY ARIYRVAKLR 250 260 270 280 290 300 TRTLSEKRAP VGPDGASPTT ENGLGAAAGA GENGHCAPPP ADVEPDESSA AAERRRRRGA 310 320 330 340 350 360 LRRGGRRRAG AEGGAGGADG QGAGPGAAES GALTASRSPG PGGRLSRASS RSVEFFLSRR 370 380 390 400 410 420 RRARSSVCRR KVAQAREKRF TFVLAVVMGV FVLCWFPFFF SYSLYGICRE ACQVPGPLFK 430 440 450 460 FFFWIGYCNS SLNPVIYTVF NQDFRRSFKH ILFRRRRRGF RQ

References

[1]	"Cloning and expression of a human kidney cDNA for an alpha 2-adrenergic receptor subtype." Regan J.W., Kobilka T.S., Yang-Feng T.L., Caron M.G., Lefkowitz R.J., Kobilka B.K. Proc. Natl. Acad. Sci. U.S.A. 85:6301-6305(1988) [PubMed: 2842764] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[2]	"Molecular cloning, sequencing and functional study of the promoter region of the human alpha2C4-adrenergic receptor gene." Schaak S., Devedjian J.C., Cayla C., Sender Y., Paris H. Biochem. J. 328:431-438(1997) [PubMed: 9371698] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Brain.
[3]	"Molecular cloning and expression of a novel human alpha2C-adrenerginc receptor, alpha2CII, gene." Yano K., Takeda M., Sugimoto E., Sagai H. Submitted (OCT-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"A four amino acid deletion polymorphism in the third intracellular loop of the human alpha 2C-adrenergic receptor confers impaired coupling to multiple effectors." Small K.M., Forbes S.L., Rahman F.F., Bridges K.M., Liggett S.B. J. Biol. Chem. 275:23059-23064(2000) [PubMed: 10801795] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT 322-GLY--PRO-325 DEL.
[5]	"Polymorphisms of cardiac presynaptic alpha2C adrenergic receptors: Diverse intragenic variability with haplotype-specific functional effects." Small K.M., Mialet-Perez J., Seman C.A., Theiss C.T., Brown K.M., Liggett S.B. Proc. Natl. Acad. Sci. U.S.A. 101:13020-13025(2004) [PubMed: 15319474] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT 322-GLY--PRO-325 DEL.
[6]	"Isolation of complete coding sequence for adrenergic receptor alpha 2C (ADRA2C)." Kopatz S.A., Aronstam R.S., Sharma S.V. Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT 322-GLY--PRO-325 DEL.
[7]	"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 95-223.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	J03853 mRNA. Translation: AAA35513.1. Frameshift. U72648 Genomic DNA. Translation: AAC78723.1. Frameshift. D13538 Genomic DNA. Translation: BAA02737.1. AF280399 Genomic DNA. Translation: AAG28076.1. AF280400 Genomic DNA. Translation: AAG28077.1. AY605898 Genomic DNA. Translation: AAT02221.1. AY455666 Genomic DNA. Translation: AAR18071.1. X59684 Genomic DNA. No translation available.
PIR	A31237.
RefSeq	NP_000674.2.
UniGene	Hs.123022
3D structure databases
HSSP	HSSP built from PDB template 1HLL based on UniProtKB P08913.
ModBase	Search...
Protein family/group databases
GPCRDB	Search...
Genome annotation databases
Ensembl	ENSG00000184160. Homo sapiens. [Contig view]
GeneID	152.
KEGG	hsa:152.
Organism-specific databases
H-InvDB	HIX0031484.
HGNC	HGNC:283. ADRA2C.
MIM	104250. gene.
PharmGKB	PA37.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	P18825.
Gene expression databases
CleanEx	HS_ADRA2C.
Family and domain databases
InterPro	IPR015695. Adren_rcpt_A2A/B/C. IPR000735. Adren_rcpt_A2C. IPR002233. Adrnrgc_rcpt. IPR000276. GPCR_Rhodpsn. 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. PR00560. ADRENRGCA2CR. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProDom	P18825. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
DrugBank	DB00217. Bethanidine. DB00484. Brimonidine. DB04840. Debrisoquin. DB00800. Fenoldopam. DB00226. Guanadrel Sulfate. DB01170. Guanethidine. DB04948. Lofexidine. DB00368. Norepinephrine. DB01392. Yohimbine.
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

ADA2C_HUMAN

Accession

Primary (citable) accession number: P18825
Secondary accession number(s): P35369, Q9HB49

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	February 11, 2002
Last modified:	July 22, 2008
This is version 81 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)