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Protein

Alpha-2C adrenergic receptor

Gene

ADRA2C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei131Implicated in ligand bindingBy similarity1
Sitei214Implicated in catechol agonist binding and receptor activationBy similarity1
Sitei218Implicated in catechol agonist binding and receptor activationBy similarity1

GO - Molecular functioni

  • alpha-2A adrenergic receptor binding Source: BHF-UCL
  • alpha2-adrenergic receptor activity Source: BHF-UCL
  • epinephrine binding Source: BHF-UCL
  • protein heterodimerization activity Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-390696. Adrenoceptors.
R-HSA-392023. Adrenaline signalling through Alpha-2 adrenergic receptor.
R-HSA-400042. Adrenaline,noradrenaline inhibits insulin secretion.
R-HSA-418594. G alpha (i) signalling events.
R-HSA-418597. G alpha (z) signalling events.
R-HSA-5683826. Surfactant metabolism.
SignaLinkiP18825.

Names & Taxonomyi

Protein namesi
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 namesi
Name:ADRA2C
Synonyms:ADRA2L2, ADRA2RL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000184160.7.
HGNCiHGNC:283. ADRA2C.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 51ExtracellularBy similarityAdd BLAST51
Transmembranei52 – 76Helical; Name=1By similarityAdd BLAST25
Topological domaini77 – 88CytoplasmicBy similarityAdd BLAST12
Transmembranei89 – 114Helical; Name=2By similarityAdd BLAST26
Topological domaini115 – 124ExtracellularBy similarity10
Transmembranei125 – 147Helical; Name=3By similarityAdd BLAST23
Topological domaini148 – 168CytoplasmicBy similarityAdd BLAST21
Transmembranei169 – 191Helical; Name=4By similarityAdd BLAST23
Topological domaini192 – 207ExtracellularBy similarityAdd BLAST16
Transmembranei208 – 231Helical; Name=5By similarityAdd BLAST24
Topological domaini232 – 379CytoplasmicBy similarityAdd BLAST148
Transmembranei380 – 407Helical; Name=6By similarityAdd BLAST28
Topological domaini408 – 420ExtracellularBy similarityAdd BLAST13
Transmembranei421 – 441Helical; Name=7By similarityAdd BLAST21
Topological domaini442 – 462CytoplasmicBy similarityAdd BLAST21

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi152.
OpenTargetsiENSG00000184160.
PharmGKBiPA37.

Chemistry databases

ChEMBLiCHEMBL1916.
DrugBankiDB08838. Agmatine.
DB00543. Amoxapine.
DB00182. Amphetamine.
DB00714. Apomorphine.
DB01238. Aripiprazole.
DB06216. Asenapine.
DB00217. Bethanidine.
DB09128. Brexpiprazole.
DB00484. Brimonidine.
DB01200. Bromocriptine.
DB00248. Cabergoline.
DB01136. Carvedilol.
DB00477. Chlorpromazine.
DB09202. Cirazoline.
DB00575. Clonidine.
DB00363. Clozapine.
DB01151. Desipramine.
DB01142. Doxepin.
DB04855. Dronedarone.
DB06262. Droxidopa.
DB01363. Ephedra.
DB05492. Epicept NP-1.
DB00668. Epinephrine.
DB01049. Ergoloid mesylate.
DB06678. Esmirtazapine.
DB00800. Fenoldopam.
DB04946. Iloperidone.
DB06707. Levonordefrin.
DB00589. Lisuride.
DB00408. Loxapine.
DB08815. Lurasidone.
DB00934. Maprotiline.
DB01365. Mephentermine.
DB01577. Methamphetamine.
DB01403. Methotrimeprazine.
DB06148. Mianserin.
DB00370. Mirtazapine.
DB00368. Norepinephrine.
DB00540. Nortriptyline.
DB00334. Olanzapine.
DB05461. OPC-28326.
DB00935. Oxymetazoline.
DB01267. Paliperidone.
DB01186. Pergolide.
DB00925. Phenoxybenzamine.
DB00413. Pramipexole.
DB01224. Quetiapine.
DB00734. Risperidone.
DB00268. Ropinirole.
DB13025. Tiapride.
DB00697. Tizanidine.
DB00797. Tolazoline.
DB06694. Xylometazoline.
DB01392. Yohimbine.
DB00246. Ziprasidone.
GuidetoPHARMACOLOGYi27.

Polymorphism and mutation databases

BioMutaiADRA2C.
DMDMi20141211.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000691051 – 462Alpha-2C adrenergic receptorAdd BLAST462

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi19N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi33N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi124 ↔ 202PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP18825.
PeptideAtlasiP18825.
PRIDEiP18825.

PTM databases

iPTMnetiP18825.
PhosphoSitePlusiP18825.

Expressioni

Gene expression databases

BgeeiENSG00000184160.
CleanExiHS_ADRA2C.
ExpressionAtlasiP18825. baseline and differential.
GenevisibleiP18825. HS.

Organism-specific databases

HPAiHPA057688.

Interactioni

GO - Molecular functioni

  • alpha-2A adrenergic receptor binding Source: BHF-UCL
  • protein heterodimerization activity Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi106661. 3 interactors.
IntActiP18825. 11 interactors.
STRINGi9606.ENSP00000386069.

Chemistry databases

BindingDBiP18825.

Structurei

3D structure databases

ProteinModelPortaliP18825.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi294 – 308Arg-rich (basic)Add BLAST15

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2C sub-subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118795.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP18825.
KOiK04140.
OMAiELMNYWY.
OrthoDBiEOG091G06VI.
PhylomeDBiP18825.
TreeFamiTF316350.

Family and domain databases

InterProiView protein in InterPro
IPR002233. ADR_fam.
IPR000735. ADRA2C_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
PANTHERiPTHR24248:SF25. PTHR24248:SF25. 1 hit.
PfamiView protein in Pfam
PF00001. 7tm_1. 1 hit.
PRINTSiPR01103. ADRENERGICR.
PR00560. ADRENRGCA2CR.
PR00237. GPCRRHODOPSN.
SMARTiView protein in SMART
SM01381. 7TM_GPCR_Srsx. 1 hit.
PROSITEiView protein in PROSITE
PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.

Sequencei

Sequence statusi: Complete.

P18825-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASPALAAAL AVAAAAGPNA SGAGERGSGG VANASGASWG PPRGQYSAGA
60 70 80 90 100
VAGLAAVVGF LIVFTVVGNV LVVIAVLTSR ALRAPQNLFL VSLASADILV
110 120 130 140 150
ATLVMPFSLA NELMAYWYFG QVWCGVYLAL DVLFCTSSIV HLCAISLDRY
160 170 180 190 200
WSVTQAVEYN LKRTPRRVKA TIVAVWLISA VISFPPLVSL YRQPDGAAYP
210 220 230 240 250
QCGLNDETWY ILSSCIGSFF APCLIMGLVY ARIYRVAKLR TRTLSEKRAP
260 270 280 290 300
VGPDGASPTT ENGLGAAAGA GENGHCAPPP ADVEPDESSA AAERRRRRGA
310 320 330 340 350
LRRGGRRRAG AEGGAGGADG QGAGPGAAES GALTASRSPG PGGRLSRASS
360 370 380 390 400
RSVEFFLSRR RRARSSVCRR KVAQAREKRF TFVLAVVMGV FVLCWFPFFF
410 420 430 440 450
SYSLYGICRE ACQVPGPLFK FFFWIGYCNS SLNPVIYTVF NQDFRRSFKH
460
ILFRRRRRGF RQ
Length:462
Mass (Da):49,522
Last modified:February 11, 2002 - v2
Checksum:iE1EF9CA21E7F6EDA
GO

Sequence cautioni

The sequence AAA35513 differs from that shown. Reason: Frameshift at positions 270, 296 and 300.Curated
The sequence AAC78723 differs from that shown. Reason: Frameshift at positions 270, 296 and 300.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti239L → R (PubMed:2842764).Curated1
Sequence conflicti239L → R (PubMed:9371698).Curated1
Sequence conflicti329E → Q (PubMed:2842764).Curated1
Sequence conflicti329E → Q (PubMed:9371698).Curated1
Sequence conflicti401S → I (PubMed:2842764).Curated1
Sequence conflicti401S → I (PubMed:9371698).Curated1
Sequence conflicti446R → P (PubMed:2842764).Curated1
Sequence conflicti446R → P (PubMed:9371698).Curated1

Polymorphismi

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).1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_012747322 – 325Missing 3 Publications4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS47004.1.
PIRiA31237.
RefSeqiNP_000674.2. NM_000683.3.
UniGeneiHs.123022.

Genome annotation databases

EnsembliENST00000330055; ENSP00000386069; ENSG00000184160.
GeneIDi152.
KEGGihsa:152.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiADA2C_HUMAN
AccessioniPrimary (citable) accession number: P18825
Secondary accession number(s): P35369, Q9HB49
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: February 11, 2002
Last modified: October 25, 2017
This is version 160 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families