Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P18089

- ADA2B_HUMAN

UniProt

P18089 - ADA2B_HUMAN

Protein

Alpha-2B adrenergic receptor

Gene

ADRA2B

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 153 (01 Oct 2014)
      Sequence version 3 (16 Apr 2014)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei92 – 921Implicated in ligand bindingBy similarity
    Sitei176 – 1761Implicated in catechol agonist bindingBy similarity
    Sitei180 – 1801Implicated in catechol agonist bindingBy similarity

    GO - Molecular functioni

    1. alpha2-adrenergic receptor activity Source: BHF-UCL
    2. epinephrine binding Source: BHF-UCL
    3. protein binding 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. angiogenesis Source: Ensembl
    4. blood coagulation Source: Reactome
    5. cell-cell signaling Source: ProtInc
    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. MAPK cascade Source: Ensembl
    10. negative regulation of epinephrine secretion Source: BHF-UCL
    11. negative regulation of norepinephrine secretion Source: BHF-UCL
    12. platelet activation Source: Reactome
    13. positive regulation of blood pressure Source: Ensembl
    14. positive regulation of neuron differentiation Source: BHF-UCL
    15. positive regulation of uterine smooth muscle contraction Source: Ensembl
    16. regulation of vascular smooth muscle contraction Source: Ensembl

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Enzyme and pathway databases

    ReactomeiREACT_16927. Adrenoceptors.
    REACT_19180. Adrenaline signalling through Alpha-2 adrenergic receptor.
    REACT_19231. G alpha (i) signalling events.
    REACT_19333. G alpha (z) signalling events.
    SignaLinkiP18089.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Alpha-2B adrenergic receptor
    Alternative name(s):
    Alpha-2 adrenergic receptor subtype C2
    Alpha-2B adrenoreceptor
    Short name:
    Alpha-2B adrenoceptor
    Short name:
    Alpha-2BAR
    Gene namesi
    Name:ADRA2B
    Synonyms:ADRA2L1, ADRA2RL1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:282. ADRA2B.

    Subcellular locationi

    Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
    Note: Interaction with RAB26 mediates transport from the Golgi to the cell membrane.

    GO - Cellular componenti

    1. integral component of plasma membrane Source: ProtInc
    2. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    Orphaneti86814. Benign adult familial myoclonic epilepsy.
    PharmGKBiPA36.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 447447Alpha-2B adrenergic receptorPRO_0000069094Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi85 ↔ 164PROSITE-ProRule annotation
    Lipidationi439 – 4391S-palmitoyl cysteineSequence Analysis

    Keywords - PTMi

    Disulfide bond, Lipoprotein, Palmitate

    Proteomic databases

    PaxDbiP18089.
    PRIDEiP18089.

    Expressioni

    Gene expression databases

    ArrayExpressiP18089.
    BgeeiP18089.
    CleanExiHS_ADRA2B.
    GenevestigatoriP18089.

    Interactioni

    Subunit structurei

    Interacts with RAB26.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    RAB26Q9ULW54EBI-9077302,EBI-958239

    Protein-protein interaction databases

    BioGridi106660. 3 interactions.
    IntActiP18089. 1 interaction.
    STRINGi9606.ENSP00000387281.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2CVAmodel-A97-128[»]
    ProteinModelPortaliP18089.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1212ExtracellularBy similarityAdd
    BLAST
    Topological domaini39 – 4810CytoplasmicBy similarity
    Topological domaini70 – 8617ExtracellularBy similarityAdd
    BLAST
    Topological domaini108 – 12821CytoplasmicBy similarityAdd
    BLAST
    Topological domaini150 – 17223ExtracellularBy similarityAdd
    BLAST
    Topological domaini194 – 369176CytoplasmicBy similarityAdd
    BLAST
    Topological domaini394 – 4029ExtracellularBy similarity
    Topological domaini424 – 44724CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei13 – 3826Helical; Name=1By similarityAdd
    BLAST
    Transmembranei49 – 6921Helical; Name=2By similarityAdd
    BLAST
    Transmembranei87 – 10721Helical; Name=3By similarityAdd
    BLAST
    Transmembranei129 – 14921Helical; Name=4By similarityAdd
    BLAST
    Transmembranei173 – 19321Helical; Name=5By similarityAdd
    BLAST
    Transmembranei370 – 39324Helical; Name=6By similarityAdd
    BLAST
    Transmembranei403 – 42321Helical; Name=7By similarityAdd
    BLAST

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi294 – 30815Asp/Glu-rich (acidic)Add
    BLAST

    Sequence similaritiesi

    Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2B sub-subfamily.PROSITE-ProRule annotation

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG249628.
    HOGENOMiHOG000239242.
    HOVERGENiHBG106962.
    InParanoidiP18089.
    KOiK04139.
    OrthoDBiEOG7J9VPT.
    PhylomeDBiP18089.
    TreeFamiTF316350.

    Family and domain databases

    Gene3Di1.20.1070.10. 2 hits.
    InterProiIPR002233. ADR_fam.
    IPR000207. ADRA2B_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view]
    PANTHERiPTHR24248:SF26. PTHR24248:SF26. 1 hit.
    PfamiPF00001. 7tm_1. 1 hit.
    [Graphical view]
    PRINTSiPR01103. ADRENERGICR.
    PR00559. ADRENRGCA2BR.
    PR00237. GPCRRHODOPSN.
    PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P18089-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDHQDPYSVQ ATAAIAAAIT FLILFTIFGN ALVILAVLTS RSLRAPQNLF    50
    LVSLAAADIL VATLIIPFSL ANELLGYWYF RRTWCEVYLA LDVLFCTSSI 100
    VHLCAISLDR YWAVSRALEY NSKRTPRRIK CIILTVWLIA AVISLPPLIY 150
    KGDQGPQPRG RPQCKLNQEA WYILASSIGS FFAPCLIMIL VYLRIYLIAK 200
    RSNRRGPRAK GGPGQGESKQ PRPDHGGALA SAKLPALASV ASAREVNGHS 250
    KSTGEKEEGE TPEDTGTRAL PPSWAALPNS GQGQKEGVCG ASPEDEAEEE 300
    EEEEEECEPQ AVPVSPASAC SPPLQQPQGS RVLATLRGQV LLGRGVGAIG 350
    GQWWRRRAQL TREKRFTFVL AVVIGVFVLC WFPFFFSYSL GAICPKHCKV 400
    PHGLFQFFFW IGYCNSSLNP VIYTIFNQDF RRAFRRILCR PWTQTAW 447
    Length:447
    Mass (Da):49,566
    Last modified:April 16, 2014 - v3
    Checksum:iB33D4B5B719C1C45
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti359 – 3602QL → HV in AAA51666. (PubMed:2164221)Curated
    Sequence conflicti359 – 3602QL → HV no nucleotide entry (PubMed:2172775)Curated

    Polymorphismi

    A rare polymorphic frameshift in position 448 produces a protein of 542 residues.
    The gene is polymorphic at position 300. The sequence shown here is found with a frequency of 0.31 in Caucasians and 0.12 in African-Americans. It exhibits impaired phosphorylation and desensitization by GRKs compared to the sequence including a stretch of glutamic acid at that position.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti211 – 2111G → A.1 Publication
    Corresponds to variant rs9333568 [ dbSNP | Ensembl ].
    VAR_025099
    Natural varianti300 – 3001E → EEEE.5 Publications
    VAR_070775
    Natural varianti373 – 3731V → I.
    Corresponds to variant rs29000569 [ dbSNP | Ensembl ].
    VAR_033462
    Natural varianti376 – 3761V → G.1 Publication
    VAR_025100
    Natural varianti376 – 3761V → I.
    Corresponds to variant rs29000569 [ dbSNP | Ensembl ].
    VAR_033463

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M34041 Genomic DNA. Translation: AAA51666.1.
    AF316895 Genomic DNA. Translation: AAK01635.1.
    AF005900 Genomic DNA. Translation: AAB62558.1.
    AY548167 Genomic DNA. Translation: AAS55646.1.
    DQ057076 Genomic DNA. Translation: AAY43127.1.
    AC092603 Genomic DNA. Translation: AAX93218.1.
    M38742 Genomic DNA. Translation: AAA62823.1.
    PIRiA37223.
    RefSeqiNP_000673.2. NM_000682.6.
    UniGeneiHs.247686.

    Genome annotation databases

    GeneIDi151.
    KEGGihsa:151.
    UCSCiuc021vlh.1. human.

    Polymorphism databases

    DMDMi27151763.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M34041 Genomic DNA. Translation: AAA51666.1 .
    AF316895 Genomic DNA. Translation: AAK01635.1 .
    AF005900 Genomic DNA. Translation: AAB62558.1 .
    AY548167 Genomic DNA. Translation: AAS55646.1 .
    DQ057076 Genomic DNA. Translation: AAY43127.1 .
    AC092603 Genomic DNA. Translation: AAX93218.1 .
    M38742 Genomic DNA. Translation: AAA62823.1 .
    PIRi A37223.
    RefSeqi NP_000673.2. NM_000682.6.
    UniGenei Hs.247686.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2CVA model - A 97-128 [» ]
    ProteinModelPortali P18089.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106660. 3 interactions.
    IntActi P18089. 1 interaction.
    STRINGi 9606.ENSP00000387281.

    Chemistry

    BindingDBi P18089.
    ChEMBLi CHEMBL2095203.
    DrugBanki DB00217. Bethanidine.
    DB00484. Brimonidine.
    DB04840. Debrisoquin.
    DB00696. Ergotamine.
    DB00800. Fenoldopam.
    DB00226. Guanadrel Sulfate.
    DB01170. Guanethidine.
    DB04948. Lofexidine.
    DB00368. Norepinephrine.
    DB01392. Yohimbine.
    GuidetoPHARMACOLOGYi 26.

    Protein family/group databases

    GPCRDBi Search...

    Polymorphism databases

    DMDMi 27151763.

    Proteomic databases

    PaxDbi P18089.
    PRIDEi P18089.

    Protocols and materials databases

    DNASUi 151.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 151.
    KEGGi hsa:151.
    UCSCi uc021vlh.1. human.

    Organism-specific databases

    CTDi 151.
    GeneCardsi GC02M096778.
    H-InvDB HIX0161945.
    HGNCi HGNC:282. ADRA2B.
    MIMi 104260. gene.
    neXtProti NX_P18089.
    Orphaneti 86814. Benign adult familial myoclonic epilepsy.
    PharmGKBi PA36.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG249628.
    HOGENOMi HOG000239242.
    HOVERGENi HBG106962.
    InParanoidi P18089.
    KOi K04139.
    OrthoDBi EOG7J9VPT.
    PhylomeDBi P18089.
    TreeFami TF316350.

    Enzyme and pathway databases

    Reactomei REACT_16927. Adrenoceptors.
    REACT_19180. Adrenaline signalling through Alpha-2 adrenergic receptor.
    REACT_19231. G alpha (i) signalling events.
    REACT_19333. G alpha (z) signalling events.
    SignaLinki P18089.

    Miscellaneous databases

    GeneWikii Alpha-2B_adrenergic_receptor.
    GenomeRNAii 151.
    NextBioi 599.
    PROi P18089.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P18089.
    Bgeei P18089.
    CleanExi HS_ADRA2B.
    Genevestigatori P18089.

    Family and domain databases

    Gene3Di 1.20.1070.10. 2 hits.
    InterProi IPR002233. ADR_fam.
    IPR000207. ADRA2B_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view ]
    PANTHERi PTHR24248:SF26. PTHR24248:SF26. 1 hit.
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR01103. ADRENERGICR.
    PR00559. ADRENRGCA2BR.
    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. "Expansion of the alpha 2-adrenergic receptor family: cloning and characterization of a human alpha 2-adrenergic receptor subtype, the gene for which is located on chromosome 2."
      Lomasney J.W., Lorenz W., Allen L.F., King K., Regan J.W., Yang-Feng T.L., Caron M.G., Lefkowitz R.J.
      Proc. Natl. Acad. Sci. U.S.A. 87:5094-5098(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-GLU-GLU-300 INS.
    2. "Cloning, expression, and pharmacological characterization of a human alpha 2B-adrenergic receptor."
      Weinshank R.L., Zgombick J.M., Macchi M., Adham N., Lichtblau H., Branchek T.A., Hartig P.R.
      Mol. Pharmacol. 38:681-688(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-GLU-GLU-300 INS.
    3. "Polymorphic deletion of three intracellular acidic residues of the alpha 2B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated phosphorylation and desensitization."
      Small K.M., Brown K.M., Forbes S.L., Liggett S.B.
      J. Biol. Chem. 276:4917-4922(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "Cloning, characterisation and identification of several polymorphisms in the promoter region of the human alpha2B-adrenergic receptor gene."
      Cayla C., Heinonen P., Viikari L., Schaak S., Snapir A., Bouloumie A., Karvonen M.K., Pesonen U., Scheinin M., Paris H.
      Biochem. Pharmacol. 67:469-478(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-GLU-GLU-300 INS.
    5. "Isolation of complete coding sequence for adrenergic receptor alpha 2B (ADRA2B)."
      Kopatz S.A., Aronstam R.S., Sharma S.V.
      Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-GLU-GLU-300 INS.
    6. SeattleSNPs variation discovery resource
      Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-211; GLU-GLU-GLU-300 INS AND GLY-376, FRAMESHIFT POLYMORPHISM.
    7. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "In vitro amplification by polymerase chain reaction of a partial gene encoding the third subtype of alpha-2 adrenergic receptor in humans."
      Chang A.C., Ho T.F., Chang N.-C.A.
      Biochem. Biophys. Res. Commun. 172:817-823(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-386, VARIANT GLU-GLU-GLU-300 INS.
    9. "Rab26 modulates the cell surface transport of alpha2-adrenergic receptors from the Golgi."
      Li C., Fan Y., Lan T.H., Lambert N.A., Wu G.
      J. Biol. Chem. 287:42784-42794(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH RAB26, SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiADA2B_HUMAN
    AccessioniPrimary (citable) accession number: P18089
    Secondary accession number(s): Q4TUH9, Q53RF2, Q9BZK0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1990
    Last sequence update: April 16, 2014
    Last modified: October 1, 2014
    This is version 153 of the entry and version 3 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. Human chromosome 2
      Human chromosome 2: 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. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3