P18825 (ADA2C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alpha-2C adrenergic receptor

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

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.
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. Adrenergic receptor subfamily. ADRA2C sub-subfamily.
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 Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of MAPK activity by adrenergic receptor signaling pathway Inferred from direct assay. Source: BHF-UCL activation of protein kinase B activity Inferred from direct assay. Source: BHF-UCL blood coagulation Traceable author statement. Source: Reactome cell-cell signaling Traceable author statement. Source: ProtInc energy reserve metabolic process Traceable author statement. Source: Reactome epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway Inferred from direct assay. Source: BHF-UCL negative regulation of epinephrine secretion Non-traceable author statement. Source: BHF-UCL negative regulation of norepinephrine secretion Non-traceable author statement. Source: BHF-UCL positive regulation of neuron differentiation Inferred from direct assay. Source: BHF-UCL regulation of insulin secretion Traceable author statement. Source: Reactome
Cellular component	endosome Traceable author statement. Source: ProtInc integral to plasma membrane Inferred from direct assay. Source: BHF-UCL
Molecular function	alpha-2A adrenergic receptor binding Inferred from physical interaction. Source: BHF-UCL alpha2-adrenergic receptor activity Inferred from direct assay. Source: BHF-UCL epinephrine binding Inferred from direct assay. Source: BHF-UCL protein heterodimerization activity Inferred from physical interaction. Source: BHF-UCL protein homodimerization activity Inferred from direct assay. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 462	462	Alpha-2C adrenergic receptor		PRO_0000069105
Regions
	Topological domain	1 – 51	51	Extracellular By similarity
	Transmembrane	52 – 76	25	Helical; Name=1; By similarity
	Topological domain	77 – 88	12	Cytoplasmic By similarity
	Transmembrane	89 – 114	26	Helical; Name=2; By similarity
	Topological domain	115 – 124	10	Extracellular By similarity
	Transmembrane	125 – 147	23	Helical; Name=3; By similarity
	Topological domain	148 – 168	21	Cytoplasmic By similarity
	Transmembrane	169 – 191	23	Helical; Name=4; By similarity
	Topological domain	192 – 207	16	Extracellular By similarity
	Transmembrane	208 – 231	24	Helical; Name=5; By similarity
	Topological domain	232 – 379	148	Cytoplasmic By similarity
	Transmembrane	380 – 407	28	Helical; Name=6; By similarity
	Topological domain	408 – 420	13	Extracellular By similarity
	Transmembrane	421 – 441	21	Helical; Name=7; By similarity
	Topological domain	442 – 462	21	Cytoplasmic By similarity
	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.		VAR_012747
Experimental info
	Sequence conflict	239	1	L → R Ref.1
	Sequence conflict	239	1	L → R Ref.2
	Sequence conflict	329	1	E → Q Ref.1
	Sequence conflict	329	1	E → Q Ref.2
	Sequence conflict	401	1	S → I Ref.1
	Sequence conflict	401	1	S → I Ref.2
	Sequence conflict	446	1	R → P Ref.1
	Sequence conflict	446	1	R → P Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P18825 [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
EMBL GenBank DDBJ	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.
IPI	IPI00002437.
PIR	A31237.
RefSeq	NP_000674.2. NM_000683.3.
UniGene	Hs.123022.
3D structure databases
ProteinModelPortal	P18825.
SMR	P18825. Positions 55-454.
ModBase	Search...
Protein-protein interaction databases
STRING	P18825.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P18825.
Polymorphism databases
DMDM	20141211.
Proteomic databases
PRIDE	P18825.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000330055; ENSP00000386069; ENSG00000184160.
GeneID	152.
KEGG	hsa:152.
UCSC	uc003ghm.1. human.
Organism-specific databases
CTD	152.
GeneCards	GC04P003804.
H-InvDB	HIX0031484.
HGNC	HGNC:283. ADRA2C.
MIM	104250. gene.
neXtProt	NX_P18825.
PharmGKB	PA37.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG445348.
HOVERGEN	HBG106962.
InParanoid	P18825.
OMA	CRRKVAQ.
PhylomeDB	P18825.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction. REACT_111217. Metabolism. REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	P18825.
Bgee	P18825.
CleanEx	HS_ADRA2C.
Genevestigator	P18825.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR000735. Adren_rcpt_A2C. IPR002233. Adrnrgc_rcpt. IPR017452. GPCR_Rhodpsn_supfam. [Graphical view]
KO	K04140.
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]
ProtoNet	Search...
Other
DrugBank	DB00217. Bethanidine. DB00484. Brimonidine. DB04840. Debrisoquin. DB00800. Fenoldopam. DB00226. Guanadrel Sulfate. DB01170. Guanethidine. DB04948. Lofexidine. DB00368. Norepinephrine. DB01392. Yohimbine.
NextBio	603.
SOURCE	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:	December 14, 2011
This is version 110 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.