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P18825

- ADA2C_HUMAN

UniProt

P18825 - ADA2C_HUMAN

Protein

Alpha-2C adrenergic receptor

Gene

ADRA2C

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 133 (01 Oct 2014)
      Sequence version 2 (11 Feb 2002)
      Previous versions | rss
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    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 binding Source: BHF-UCL
    5. protein heterodimerization activity Source: BHF-UCL
    6. 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

    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

    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

    ArrayExpressiP18825.
    BgeeiP18825.
    CleanExiHS_ADRA2C.
    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

    MASPALAAAL AVAAAAGPNA SGAGERGSGG VANASGASWG PPRGQYSAGA    50
    VAGLAAVVGF LIVFTVVGNV LVVIAVLTSR ALRAPQNLFL VSLASADILV 100
    ATLVMPFSLA NELMAYWYFG QVWCGVYLAL DVLFCTSSIV HLCAISLDRY 150
    WSVTQAVEYN LKRTPRRVKA TIVAVWLISA VISFPPLVSL YRQPDGAAYP 200
    QCGLNDETWY ILSSCIGSFF APCLIMGLVY ARIYRVAKLR TRTLSEKRAP 250
    VGPDGASPTT ENGLGAAAGA GENGHCAPPP ADVEPDESSA AAERRRRRGA 300
    LRRGGRRRAG AEGGAGGADG QGAGPGAAES GALTASRSPG PGGRLSRASS 350
    RSVEFFLSRR RRARSSVCRR KVAQAREKRF TFVLAVVMGV FVLCWFPFFF 400
    SYSLYGICRE ACQVPGPLFK FFFWIGYCNS SLNPVIYTVF NQDFRRSFKH 450
    ILFRRRRRGF RQ 462
    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 DB00217. Bethanidine.
    DB00484. Brimonidine.
    DB04840. Debrisoquin.
    DB00800. Fenoldopam.
    DB00226. Guanadrel Sulfate.
    DB01170. Guanethidine.
    DB04948. Lofexidine.
    DB00368. Norepinephrine.
    DB01392. Yohimbine.
    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

    ArrayExpressi P18825.
    Bgeei P18825.
    CleanExi HS_ADRA2C.
    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 1, 2014
    This is version 133 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