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Protein

Alpha-2C adrenergic receptor

Gene

ADRA2C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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
MIMi104250 gene
neXtProtiNX_P18825

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
ProteomicsDBi53608

PTM databases

iPTMnetiP18825
PhosphoSitePlusiP18825

Expressioni

Gene expression databases

BgeeiENSG00000184160 Expressed in 213 organ(s), highest expression level in decidua
CleanExiHS_ADRA2C
ExpressionAtlasiP18825 baseline and differential
GenevisibleiP18825 HS

Organism-specific databases

HPAiHPA057688

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106661, 4 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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RGL0D6RGL0_HUMAN
Alpha-2C adrenergic receptor
ADRA2C
374Annotation score:

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

Cross-referencesi

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

3D structure databases

ProteinModelPortaliP18825
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106661, 4 interactors
IntActiP18825, 11 interactors
STRINGi9606.ENSP00000386069

Chemistry databases

BindingDBiP18825
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

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP18825
PhosphoSitePlusiP18825

Polymorphism and mutation databases

BioMutaiADRA2C
DMDMi20141211

Proteomic databases

PaxDbiP18825
PeptideAtlasiP18825
PRIDEiP18825
ProteomicsDBi53608

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000330055; ENSP00000386069; ENSG00000184160
GeneIDi152
KEGGihsa:152

Organism-specific databases

CTDi152
DisGeNETi152
EuPathDBiHostDB:ENSG00000184160.7
GeneCardsiADRA2C
H-InvDBiHIX0031484
HGNCiHGNC:283 ADRA2C
HPAiHPA057688
MIMi104250 gene
neXtProtiNX_P18825
OpenTargetsiENSG00000184160
PharmGKBiPA37
GenAtlasiSearch...

Phylogenomic databases

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

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

Miscellaneous databases

GeneWikiiAlpha-2C_adrenergic_receptor
GenomeRNAii152
PROiPR:P18825
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000184160 Expressed in 213 organ(s), highest expression level in decidua
CleanExiHS_ADRA2C
ExpressionAtlasiP18825 baseline and differential
GenevisibleiP18825 HS

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
ProtoNetiSearch...

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 10, 2018
This is version 167 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. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  4. SIMILARITY comments
    Index of protein domains and families
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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