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P18825

- ADA2C_HUMAN

UniProt

P18825 - ADA2C_HUMAN

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Protein

Alpha-2C adrenergic receptor

Gene

ADRA2C

Organism
Homo sapiens (Human)
Status
Reviewed - 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)LengthDescriptionGraphical viewFeature identifierActions
Sitei131 – 1311Implicated in ligand bindingBy similarity
Sitei214 – 2141Implicated in catechol agonist binding and receptor activationBy similarity
Sitei218 – 2181Implicated in catechol agonist binding and receptor activationBy similarity

GO - Molecular functioni

  1. alpha-2A adrenergic receptor binding Source: BHF-UCL
  2. alpha2-adrenergic receptor activity Source: BHF-UCL
  3. epinephrine binding Source: BHF-UCL
  4. protein heterodimerization activity Source: BHF-UCL
  5. protein homodimerization activity Source: BHF-UCL

GO - Biological processi

  1. activation of MAPK activity by adrenergic receptor signaling pathway Source: BHF-UCL
  2. activation of protein kinase B activity Source: BHF-UCL
  3. blood coagulation Source: Reactome
  4. cell-cell signaling Source: ProtInc
  5. energy reserve metabolic process Source: Reactome
  6. epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway Source: BHF-UCL
  7. female pregnancy Source: Ensembl
  8. G-protein coupled receptor signaling pathway Source: ProtInc
  9. negative regulation of epinephrine secretion Source: BHF-UCL
  10. negative regulation of norepinephrine secretion Source: BHF-UCL
  11. negative regulation of uterine smooth muscle contraction Source: Ensembl
  12. platelet activation Source: Reactome
  13. positive regulation of neuron differentiation Source: BHF-UCL
  14. positive regulation of vasoconstriction Source: Ensembl
  15. regulation of insulin secretion Source: Reactome
  16. regulation of sensory perception of pain Source: Ensembl
  17. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_16927. Adrenoceptors.
REACT_18339. Adrenaline,noradrenaline inhibits insulin secretion.
REACT_19180. Adrenaline signalling through Alpha-2 adrenergic receptor.
REACT_19231. G alpha (i) signalling events.
REACT_19333. G alpha (z) signalling events.
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
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:283. ADRA2C.

Subcellular locationi

GO - Cellular componenti

  1. axon terminus Source: Ensembl
  2. cytoplasm Source: BHF-UCL
  3. endosome Source: ProtInc
  4. integral component of plasma membrane Source: BHF-UCL
  5. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA37.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 462462Alpha-2C adrenergic receptorPRO_0000069105Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi19 – 191N-linked (GlcNAc...)Sequence Analysis
Glycosylationi33 – 331N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi124 ↔ 202PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP18825.
PRIDEiP18825.

PTM databases

PhosphoSiteiP18825.

Expressioni

Gene expression databases

BgeeiP18825.
CleanExiHS_ADRA2C.
ExpressionAtlasiP18825. baseline and differential.
GenevestigatoriP18825.

Organism-specific databases

HPAiHPA057688.

Interactioni

Protein-protein interaction databases

BioGridi106661. 3 interactions.
STRINGi9606.ENSP00000386069.

Structurei

3D structure databases

ProteinModelPortaliP18825.
SMRiP18825. Positions 52-454.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5151ExtracellularBy similarityAdd
BLAST
Topological domaini77 – 8812CytoplasmicBy similarityAdd
BLAST
Topological domaini115 – 12410ExtracellularBy similarity
Topological domaini148 – 16821CytoplasmicBy similarityAdd
BLAST
Topological domaini192 – 20716ExtracellularBy similarityAdd
BLAST
Topological domaini232 – 379148CytoplasmicBy similarityAdd
BLAST
Topological domaini408 – 42013ExtracellularBy similarityAdd
BLAST
Topological domaini442 – 46221CytoplasmicBy similarityAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei52 – 7625Helical; Name=1By similarityAdd
BLAST
Transmembranei89 – 11426Helical; Name=2By similarityAdd
BLAST
Transmembranei125 – 14723Helical; Name=3By similarityAdd
BLAST
Transmembranei169 – 19123Helical; Name=4By similarityAdd
BLAST
Transmembranei208 – 23124Helical; Name=5By similarityAdd
BLAST
Transmembranei380 – 40728Helical; Name=6By similarityAdd
BLAST
Transmembranei421 – 44121Helical; Name=7By similarityAdd
BLAST

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi294 – 30815Arg-rich (basic)Add
BLAST

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

eggNOGiNOG249628.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP18825.
KOiK04140.
OMAiICREACE.
PhylomeDBiP18825.
TreeFamiTF316350.

Family and domain databases

Gene3Di1.20.1070.10. 2 hits.
InterProiIPR002233. ADR_fam.
IPR000735. ADRA2C_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24248:SF25. PTHR24248:SF25. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01103. ADRENERGICR.
PR00560. ADRENRGCA2CR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

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 AAA35513.1 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.

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti239 – 2391L → R(PubMed:2842764)Curated
Sequence conflicti239 – 2391L → R(PubMed:9371698)Curated
Sequence conflicti329 – 3291E → Q(PubMed:2842764)Curated
Sequence conflicti329 – 3291E → Q(PubMed:9371698)Curated
Sequence conflicti401 – 4011S → I(PubMed:2842764)Curated
Sequence conflicti401 – 4011S → I(PubMed:9371698)Curated
Sequence conflicti446 – 4461R → P(PubMed:2842764)Curated
Sequence conflicti446 – 4461R → P(PubMed:9371698)Curated

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).

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti322 – 3254Missing.3 Publications
VAR_012747

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UCSCiuc003ghm.3. human.

Polymorphism databases

DMDMi20141211.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
CCDSi CCDS47004.1.
PIRi A31237.
RefSeqi NP_000674.2. NM_000683.3.
UniGenei Hs.123022.

3D structure databases

ProteinModelPortali P18825.
SMRi P18825. Positions 52-454.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 106661. 3 interactions.
STRINGi 9606.ENSP00000386069.

Chemistry

BindingDBi P18825.
ChEMBLi CHEMBL1916.
DrugBanki DB00543. Amoxapine.
DB00182. Amphetamine.
DB00714. Apomorphine.
DB01238. Aripiprazole.
DB06216. Asenapine.
DB00217. Bethanidine.
DB00484. Brimonidine.
DB01200. Bromocriptine.
DB00248. Cabergoline.
DB01136. Carvedilol.
DB00477. Chlorpromazine.
DB00575. Clonidine.
DB00363. Clozapine.
DB01151. Desipramine.
DB01142. Doxepin.
DB04855. Dronedarone.
DB06262. Droxidopa.
DB01363. Ephedra.
DB00668. Epinephrine.
DB01049. Ergoloid mesylate.
DB00800. Fenoldopam.
DB04946. Iloperidone.
DB00589. Lisuride.
DB00408. Loxapine.
DB08815. Lurasidone.
DB00934. Maprotiline.
DB01365. Mephentermine.
DB01577. Methamphetamine.
DB01403. Methotrimeprazine.
DB06148. Mianserin.
DB00370. Mirtazapine.
DB00368. Norepinephrine.
DB00540. Nortriptyline.
DB00334. Olanzapine.
DB00935. Oxymetazoline.
DB01267. Paliperidone.
DB01186. Pergolide.
DB00925. Phenoxybenzamine.
DB00413. Pramipexole.
DB01224. Quetiapine.
DB00734. Risperidone.
DB00268. Ropinirole.
DB00697. Tizanidine.
DB00797. Tolazoline.
DB06694. Xylometazoline.
DB01392. Yohimbine.
DB00246. Ziprasidone.
GuidetoPHARMACOLOGYi 27.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei P18825.

Polymorphism databases

DMDMi 20141211.

Proteomic databases

PaxDbi P18825.
PRIDEi P18825.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000330055 ; ENSP00000386069 ; ENSG00000184160 .
GeneIDi 152.
KEGGi hsa:152.
UCSCi uc003ghm.3. human.

Organism-specific databases

CTDi 152.
GeneCardsi GC04P003804.
H-InvDB HIX0031484.
HGNCi HGNC:283. ADRA2C.
HPAi HPA057688.
MIMi 104250. gene.
neXtProti NX_P18825.
PharmGKBi PA37.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG249628.
HOGENOMi HOG000239242.
HOVERGENi HBG106962.
InParanoidi P18825.
KOi K04140.
OMAi ICREACE.
PhylomeDBi P18825.
TreeFami TF316350.

Enzyme and pathway databases

Reactomei REACT_16927. Adrenoceptors.
REACT_18339. Adrenaline,noradrenaline inhibits insulin secretion.
REACT_19180. Adrenaline signalling through Alpha-2 adrenergic receptor.
REACT_19231. G alpha (i) signalling events.
REACT_19333. G alpha (z) signalling events.
SignaLinki P18825.

Miscellaneous databases

GeneWikii Alpha-2C_adrenergic_receptor.
GenomeRNAii 152.
NextBioi 603.
PROi P18825.
SOURCEi Search...

Gene expression databases

Bgeei P18825.
CleanExi HS_ADRA2C.
ExpressionAtlasi P18825. baseline and differential.
Genevestigatori P18825.

Family and domain databases

Gene3Di 1.20.1070.10. 2 hits.
InterProi IPR002233. ADR_fam.
IPR000735. ADRA2C_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view ]
PANTHERi PTHR24248:SF25. PTHR24248:SF25. 1 hit.
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR01103. ADRENERGICR.
PR00560. ADRENRGCA2CR.
PR00237. GPCRRHODOPSN.
PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiADA2C_HUMAN
AccessioniPrimary (citable) accession number: P18825
Secondary accession number(s): P35369, Q9HB49
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: February 11, 2002
Last modified: October 29, 2014
This is version 134 of the entry and version 2 of the sequence. [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

External Data

Dasty 3