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P18825 (ADA2C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length462 AA.
Sequence statusComplete.
Protein existenceEvidence 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 componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Traceable author statement Ref.2. Source: ProtInc

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

blood coagulation

Traceable author statement. Source: Reactome

cell-cell signaling

Traceable author statement Ref.2. 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 PubMed 17215105. Source: BHF-UCL

female pregnancy

Inferred from electronic annotation. Source: Ensembl

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

negative regulation of uterine smooth muscle contraction

Inferred from electronic annotation. Source: Ensembl

platelet activation

Traceable author statement. Source: Reactome

positive regulation of neuron differentiation

Inferred from direct assay PubMed 17215105. Source: BHF-UCL

positive regulation of vasoconstriction

Inferred from electronic annotation. Source: Ensembl

regulation of insulin secretion

Traceable author statement. Source: Reactome

regulation of sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentaxon terminus

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 16605244. Source: BHF-UCL

endosome

Traceable author statement PubMed 10196213. Source: ProtInc

integral component of plasma membrane

Inferred from direct assay PubMed 16605244. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionalpha-2A adrenergic receptor binding

Inferred from physical interaction PubMed 16605244. Source: BHF-UCL

alpha2-adrenergic receptor activity

Inferred from direct assay PubMed 17215105. Source: BHF-UCL

epinephrine binding

Inferred from direct assay PubMed 17215105. Source: BHF-UCL

protein heterodimerization activity

Inferred from physical interaction PubMed 16605244. Source: BHF-UCL

protein homodimerization activity

Inferred from direct assay PubMed 16605244. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 462462Alpha-2C adrenergic receptor
PRO_0000069105

Regions

Topological domain1 – 5151Extracellular By similarity
Transmembrane52 – 7625Helical; Name=1; By similarity
Topological domain77 – 8812Cytoplasmic By similarity
Transmembrane89 – 11426Helical; Name=2; By similarity
Topological domain115 – 12410Extracellular By similarity
Transmembrane125 – 14723Helical; Name=3; By similarity
Topological domain148 – 16821Cytoplasmic By similarity
Transmembrane169 – 19123Helical; Name=4; By similarity
Topological domain192 – 20716Extracellular By similarity
Transmembrane208 – 23124Helical; Name=5; By similarity
Topological domain232 – 379148Cytoplasmic By similarity
Transmembrane380 – 40728Helical; Name=6; By similarity
Topological domain408 – 42013Extracellular By similarity
Transmembrane421 – 44121Helical; Name=7; By similarity
Topological domain442 – 46221Cytoplasmic By similarity
Compositional bias294 – 30815Arg-rich (basic)

Sites

Site1311Implicated in ligand binding By similarity
Site2141Implicated in catechol agonist binding and receptor activation By similarity
Site2181Implicated in catechol agonist binding and receptor activation By similarity

Amino acid modifications

Glycosylation191N-linked (GlcNAc...) Potential
Glycosylation331N-linked (GlcNAc...) Potential
Disulfide bond124 ↔ 202 By similarity

Natural variations

Natural variant322 – 3254Missing.
VAR_012747

Experimental info

Sequence conflict2391L → R Ref.1
Sequence conflict2391L → R Ref.2
Sequence conflict3291E → Q Ref.1
Sequence conflict3291E → Q Ref.2
Sequence conflict4011S → I Ref.1
Sequence conflict4011S → I Ref.2
Sequence conflict4461R → P Ref.1
Sequence conflict4461R → P Ref.2

Sequences

Sequence LengthMass (Da)Tools
P18825 [UniParc].

Last modified February 11, 2002. Version 2.
Checksum: E1EF9CA21E7F6EDA

FASTA46249,522
        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 

« Hide

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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.
PIRA31237.
RefSeqNP_000674.2. NM_000683.3.
UniGeneHs.123022.

3D structure databases

ProteinModelPortalP18825.
SMRP18825. Positions 52-454.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106661. 3 interactions.
STRING9606.ENSP00000386069.

Chemistry

BindingDBP18825.
ChEMBLCHEMBL1916.
DrugBankDB00217. Bethanidine.
DB00484. Brimonidine.
DB04840. Debrisoquin.
DB00800. Fenoldopam.
DB00226. Guanadrel Sulfate.
DB01170. Guanethidine.
DB04948. Lofexidine.
DB00368. Norepinephrine.
DB01392. Yohimbine.
GuidetoPHARMACOLOGY27.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP18825.

Polymorphism databases

DMDM20141211.

Proteomic databases

PaxDbP18825.
PRIDEP18825.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330055; ENSP00000386069; ENSG00000184160.
GeneID152.
KEGGhsa:152.
UCSCuc003ghm.3. human.

Organism-specific databases

CTD152.
GeneCardsGC04P003804.
H-InvDBHIX0031484.
HGNCHGNC:283. ADRA2C.
HPAHPA057688.
MIM104250. gene.
neXtProtNX_P18825.
PharmGKBPA37.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG249628.
HOGENOMHOG000239242.
HOVERGENHBG106962.
InParanoidP18825.
KOK04140.
OMACKLNDET.
PhylomeDBP18825.
TreeFamTF316350.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_604. Hemostasis.
SignaLinkP18825.

Gene expression databases

ArrayExpressP18825.
BgeeP18825.
CleanExHS_ADRA2C.
GenevestigatorP18825.

Family and domain databases

Gene3D1.20.1070.10. 2 hits.
InterProIPR002233. ADR_fam.
IPR000735. ADRA2C_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24248. PTHR24248. 1 hit.
PTHR24248:SF25. PTHR24248:SF25. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR01103. ADRENERGICR.
PR00560. ADRENRGCA2CR.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiAlpha-2C_adrenergic_receptor.
GenomeRNAi152.
NextBio603.
PROP18825.
SOURCESearch...

Entry information

Entry nameADA2C_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries