ID ADA2B_HUMAN Reviewed; 450 AA. AC P18089; A2RUS0; Q4TUH9; Q53RF2; Q9BZK0; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 15-MAR-2017, sequence version 4. DT 02-SEP-2026, entry version 230. DE RecName: Full=Alpha-2B adrenergic receptor {ECO:0000303|PubMed:2172775}; DE AltName: Full=Alpha-2 adrenergic receptor subtype C2 {ECO:0000303|PubMed:2164221}; DE AltName: Full=Alpha-2B adrenoreceptor; DE Short=Alpha-2B adrenoceptor; DE Short=Alpha-2BAR; GN Name=ADRA2B {ECO:0000312|HGNC:HGNC:282}; Synonyms=ADRA2L1, ADRA2RL1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION. RX PubMed=2164221; DOI=10.1073/pnas.87.13.5094; RA Lomasney J.W., Lorenz W., Allen L.F., King K., Regan J.W., Yang-Feng T.L., RA Caron M.G., Lefkowitz R.J.; RT "Expansion of the alpha 2-adrenergic receptor family: cloning and RT characterization of a human alpha 2-adrenergic receptor subtype, the gene RT for which is located on chromosome 2."; RL Proc. Natl. Acad. Sci. U.S.A. 87:5094-5098(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION. RX PubMed=2172775; DOI=10.1016/s0026-895x(25)09495-7; RA Weinshank R.L., Zgombick J.M., Macchi M., Adham N., Lichtblau H., RA Branchek T.A., Hartig P.R.; RT "Cloning, expression, and pharmacological characterization of a human alpha RT 2B-adrenergic receptor."; RL Mol. Pharmacol. 38:681-688(1990). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT 301-GLU--GLU-303 DEL, AND RP FUNCTION. RX PubMed=11056163; DOI=10.1074/jbc.m008118200; RA Small K.M., Brown K.M., Forbes S.L., Liggett S.B.; RT "Polymorphic deletion of three intracellular acidic residues of the alpha RT 2B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated RT phosphorylation and desensitization."; RL J. Biol. Chem. 276:4917-4922(2001). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=15037199; DOI=10.1016/j.bcp.2003.09.029; RA Cayla C., Heinonen P., Viikari L., Schaak S., Snapir A., Bouloumie A., RA Karvonen M.K., Pesonen U., Scheinin M., Paris H.; RT "Cloning, characterisation and identification of several polymorphisms in RT the promoter region of the human alpha2B-adrenergic receptor gene."; RL Biochem. Pharmacol. 67:469-478(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Kopatz S.A., Aronstam R.S., Sharma S.V.; RT "Isolation of complete coding sequence for adrenergic receptor alpha 2B RT (ADRA2B)."; RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-211 AND GLY-379, AND RP FRAMESHIFT POLYMORPHISM. RG SeattleSNPs variation discovery resource; RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT 301-GLU--GLU-303 RP DEL. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-389. RX PubMed=2173582; DOI=10.1016/0006-291x(90)90748-c; RA Chang A.C., Ho T.F., Chang N.-C.A.; RT "In vitro amplification by polymerase chain reaction of a partial gene RT encoding the third subtype of alpha-2 adrenergic receptor in humans."; RL Biochem. Biophys. Res. Commun. 172:817-823(1990). RN [11] RP FUNCTION, INTERACTION WITH RAB26, AND SUBCELLULAR LOCATION. RX PubMed=23105096; DOI=10.1074/jbc.m112.410936; RA Li C., Fan Y., Lan T.H., Lambert N.A., Wu G.; RT "Rab26 modulates the cell surface transport of alpha2-adrenergic receptors RT from the Golgi."; RL J. Biol. Chem. 287:42784-42794(2012). RN [12] RP SUBCELLULAR LOCATION, AND INTERACTION WITH GGA1 AND GGA2. RX PubMed=27901063; DOI=10.1038/srep37921; RA Zhang M., Huang W., Gao J., Terry A.V., Wu G.; RT "Regulation of alpha2B-Adrenergic Receptor Cell Surface Transport by GGA1 RT and GGA2."; RL Sci. Rep. 6:37921-37921(2016). RN [13] RP SUBCELLULAR LOCATION, INTERACTION WITH GGA3, AND FUNCTION. RX PubMed=26811329; DOI=10.1128/mcb.00009-16; RA Zhang M., Davis J.E., Li C., Gao J., Huang W., Lambert N.A., RA Terry A.V. Jr., Wu G.; RT "GGA3 Interacts with a G Protein-Coupled Receptor and Modulates Its Cell RT Surface Export."; RL Mol. Cell. Biol. 36:1152-1163(2016). RN [14] RP SUBCELLULAR LOCATION, AND INTERACTION WITH RAB43. RX PubMed=29069590; DOI=10.1016/j.celrep.2017.10.011; RA Li C., Wei Z., Fan Y., Huang W., Su Y., Li H., Dong Z., Fukuda M., RA Khater M., Wu G.; RT "The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting RT of GPCRs."; RL Cell Rep. 21:1089-1101(2017). RN [15] {ECO:0007744|PDB:6K41, ECO:0007744|PDB:6K42} RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 9-450 IN COMPLEX WITH RP G PROTEINS, AND DISULFIDE BONDS. RX PubMed=32152538; DOI=10.1038/s41589-020-0492-2; RA Yuan D., Liu Z., Kaindl J., Maeda S., Zhao J., Sun X., Xu J., Gmeiner P., RA Wang H.W., Kobilka B.K.; RT "Activation of the alpha2B adrenoceptor by the sedative sympatholytic RT dexmedetomidine."; RL Nat. Chem. Biol. 16:507-512(2020). RN [16] RP INVOLVEMENT IN FAME2, VARIANT FAME2 225-HIS--LEU-229 DELINS RP GLN-PHE-GLY-ARG, CHARACTERIZATION OF VARIANT FAME2 225-HIS--LEU-229 DELINS RP GLN-PHE-GLY-ARG, INTERACTION WITH PPP1R9B, AND SUBCELLULAR LOCATION. RX PubMed=24114805; DOI=10.1002/ana.24028; RA De Fusco M., Vago R., Striano P., Di Bonaventura C., Zara F., Mei D., RA Kim M.S., Muallem S., Chen Y., Wang Q., Guerrini R., Casari G.; RT "The alpha2B-adrenergic receptor is mutant in cortical myoclonus and RT epilepsy."; RL Ann. Neurol. 75:77-87(2014). CC -!- FUNCTION: Alpha-2 adrenergic receptors are G protein-coupled receptors CC for catecholamines that activate G(i/o) protein pathway, thereby CC promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage- CC gated calcium channels suppression (PubMed:11056163, PubMed:2164221, CC PubMed:2172775, PubMed:23105096, PubMed:26811329). Control a variety of CC physiological processes, such as regulation of blood pressure, CC lipolysis and insulin release (PubMed:2164221). The rank order of CC potency for agonists of ADRA2B is clonidine > norepinephrine > CC epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > CC serotonin > p-synephrine / p-octopamine. For antagonists, the rank CC order is yohimbine > chlorpromazine > phentolamine > mianserine > CC spiperone > prazosin > alprenolol > propanolol > pindolol CC (PubMed:2164221, PubMed:2172775). {ECO:0000269|PubMed:11056163, CC ECO:0000269|PubMed:2164221, ECO:0000269|PubMed:2172775, CC ECO:0000269|PubMed:23105096, ECO:0000269|PubMed:26811329}. CC -!- SUBUNIT: Interacts with RAB26; RAB26 mediates cell surface transport CC from the Golgi (PubMed:23105096). Interacts with PPP1R9B CC (PubMed:24114805). Interacts with GGA1, GGA2 and GGA3; GGA1, GGA2 and CC GGA3 mediates transport from the Golgi to the cell membrane CC (PubMed:26811329, PubMed:27901063). Interacts with RAB43 (GTP-bound); CC RAB43 mediates ADRA2B ER-to-Golgi cell transport (PubMed:29069590). CC {ECO:0000269|PubMed:23105096, ECO:0000269|PubMed:24114805, CC ECO:0000269|PubMed:26811329, ECO:0000269|PubMed:27901063, CC ECO:0000269|PubMed:29069590}. CC -!- INTERACTION: CC P18089; Q9ULW5: RAB26; NbExp=4; IntAct=EBI-9077302, EBI-958239; CC P18089; O60894: RAMP1; NbExp=2; IntAct=EBI-9077302, EBI-962893; CC P18089; O60895: RAMP2; NbExp=2; IntAct=EBI-9077302, EBI-9009040; CC P18089; O60896: RAMP3; NbExp=3; IntAct=EBI-9077302, EBI-720447; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23105096, CC ECO:0000269|PubMed:26811329, ECO:0000269|PubMed:27901063, CC ECO:0000269|PubMed:29069590}; Multi-pass membrane protein CC {ECO:0000269|PubMed:23105096, ECO:0000269|PubMed:32152538}. CC Note=Interaction with RAB26, GGA1, GGA2 and GGA3 mediates transport CC from the Golgi to the cell membrane. {ECO:0000269|PubMed:23105096, CC ECO:0000269|PubMed:26811329, ECO:0000269|PubMed:27901063}. CC -!- POLYMORPHISM: A rare polymorphic frameshift in position 451 produces a CC protein of 545 residues. {ECO:0000269|Ref.6}. CC -!- DISEASE: Epilepsy, familial adult myoclonic, 2 (FAME2) [MIM:607876]: A CC form of familial myoclonic epilepsy, a neurologic disorder CC characterized by cortical hand tremors, myoclonic jerks and occasional CC generalized or focal seizures with a non-progressive or very slowly CC progressive disease course. Usually, myoclonic tremor is the presenting CC symptom, characterized by tremulous finger movements and myoclonic CC jerks of the limbs increased by action and posture. In a minority of CC patients, seizures are the presenting symptom. Some patients exhibit CC mild cognitive impairment. FAME2 inheritance is autosomal dominant. CC {ECO:0000269|PubMed:24114805}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the G protein-coupled receptor 1 family. CC Adrenergic receptor subfamily. ADRA2B sub-subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M34041; AAA51666.1; -; Genomic_DNA. DR EMBL; AF316895; AAK01635.1; -; Genomic_DNA. DR EMBL; AF005900; AAB62558.1; -; Genomic_DNA. DR EMBL; AY548167; AAS55646.1; -; Genomic_DNA. DR EMBL; DQ057076; AAY43127.1; -; Genomic_DNA. DR EMBL; EU332847; ABY87536.1; -; Genomic_DNA. DR EMBL; AC092603; AAX93218.1; -; Genomic_DNA. DR EMBL; KF573706; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471207; EAW71390.1; -; Genomic_DNA. DR EMBL; BC133021; AAI33022.1; -; mRNA. DR EMBL; BC136537; AAI36538.1; -; mRNA. DR EMBL; M38742; AAA62823.1; -; Genomic_DNA. DR CCDS; CCDS56129.1; -. DR PIR; A37223; A37223. DR RefSeq; NP_000673.2; NM_000682.7. DR PDB; 6K41; EM; 2.90 A; R=9-450. DR PDB; 6K42; EM; 4.10 A; R=9-450. DR AlphaFoldDB; P18089; -. DR EMDB; EMD-9911; -. DR EMDB; EMD-9912; -. DR SMR; P18089; -. DR BioGRID; 106660; 7. DR CORUM; P18089; -. DR DIP; DIP-61453N; -. DR FunCoup; P18089; 1181. DR IntAct; P18089; 8. DR NDEx; IQUERY-CP-ADRA2B; 6 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000480573; -. DR BindingDB; P18089; -. DR ChEMBL; CHEMBL1942; -. DR DrugBank; DB08550; 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline. DR DrugBank; DB00543; Amoxapine. DR DrugBank; DB00182; Amphetamine. DR DrugBank; DB00714; Apomorphine. DR DrugBank; DB00964; Apraclonidine. DR DrugBank; DB09229; Aranidipine. DR DrugBank; DB01238; Aripiprazole. DR DrugBank; DB14185; Aripiprazole lauroxil. DR DrugBank; DB06216; Asenapine. DR DrugBank; DB00217; Bethanidine. DR DrugBank; DB00484; Brimonidine. DR DrugBank; DB01200; Bromocriptine. DR DrugBank; DB00248; Cabergoline. DR DrugBank; DB01136; Carvedilol. DR DrugBank; DB04846; Celiprolol. DR DrugBank; DB00477; Chlorpromazine. DR DrugBank; DB09202; Cirazoline. DR DrugBank; DB00575; Clonidine. DR DrugBank; DB00363; Clozapine. DR DrugBank; DB01151; Desipramine. DR DrugBank; DB01576; Dextroamphetamine. DR DrugBank; DB11273; Dihydroergocornine. DR DrugBank; DB13345; Dihydroergocristine. DR DrugBank; DB00320; Dihydroergotamine. DR DrugBank; DB11278; DL-Methylephedrine. DR DrugBank; DB09167; Dosulepin. DR DrugBank; DB04855; Dronedarone. DR DrugBank; DB06262; Droxidopa. DR DrugBank; DB01363; Ephedra sinica root. DR DrugBank; DB05492; Epicept NP-1. DR DrugBank; DB00668; Epinephrine. DR DrugBank; DB01049; Ergoloid mesylate. DR DrugBank; DB01175; Escitalopram. DR DrugBank; DB06678; Esmirtazapine. DR DrugBank; DB00292; Etomidate. DR DrugBank; DB09194; Etoperidone. DR DrugBank; DB00800; Fenoldopam. DR DrugBank; DB00629; Guanabenz. DR DrugBank; DB01018; Guanfacine. DR DrugBank; DB00502; Haloperidol. DR DrugBank; DB04946; Iloperidone. DR DrugBank; DB11577; Indigotindisulfonic acid. DR DrugBank; DB08950; Indoramin. DR DrugBank; DB06707; Levonordefrin. DR DrugBank; DB00589; Lisuride. DR DrugBank; DB09195; Lorpiprazole. DR DrugBank; DB00408; Loxapine. DR DrugBank; DB00934; Maprotiline. DR DrugBank; DB20960; Mazapertine. DR DrugBank; DB11428; Medetomidine. DR DrugBank; DB01365; Mephentermine. DR DrugBank; DB01577; Metamfetamine. DR DrugBank; DB01403; Methotrimeprazine. DR DrugBank; DB21271; Mezilamine. DR DrugBank; DB06148; Mianserin. DR DrugBank; DB24348; Milsaperidone. DR DrugBank; DB09205; Moxisylyte. DR DrugBank; DB09242; Moxonidine. DR DrugBank; DB00368; Norepinephrine. DR DrugBank; DB00540; Nortriptyline. DR DrugBank; DB06229; Ocaperidone. DR DrugBank; DB05461; OPC-28326. DR DrugBank; DB00935; Oxymetazoline. DR DrugBank; DB01267; Paliperidone. DR DrugBank; DB00715; Paroxetine. DR DrugBank; DB01186; Pergolide. DR DrugBank; DB00925; Phenoxybenzamine. DR DrugBank; DB00692; Phentolamine. DR DrugBank; DB00397; Phenylpropanolamine. DR DrugBank; DB06153; Pizotifen. DR DrugBank; DB00457; Prazosin. DR DrugBank; DB00433; Prochlorperazine. DR DrugBank; DB01069; Promethazine. DR DrugBank; DB01224; Quetiapine. DR DrugBank; DB11124; Racepinephrine. DR DrugBank; DB00734; Risperidone. DR DrugBank; DB00268; Ropinirole. DR DrugBank; DB05271; Rotigotine. DR DrugBank; DB09304; Setiptiline. DR DrugBank; DB06764; Tetryzoline. DR DrugBank; DB13025; Tiapride. DR DrugBank; DB00697; Tizanidine. DR DrugBank; DB00797; Tolazoline. DR DrugBank; DB00193; Tramadol. DR DrugBank; DB13064; Tramazoline. DR DrugBank; DB00726; Trimipramine. DR DrugBank; DB11477; Xylazine. DR DrugBank; DB06694; Xylometazoline. DR DrugBank; DB01392; Yohimbine. DR DrugBank; DB00246; Ziprasidone. DR DrugCentral; P18089; -. DR GuidetoPHARMACOLOGY; 26; -. DR PhosphoSitePlus; P18089; -. DR BioMuta; ADRA2B; -. DR DMDM; 27151763; -. DR MassIVE; P18089; -. DR PaxDb; 9606-ENSP00000480573; -. DR PeptideAtlas; P18089; -. DR ProteomicsDB; 53548; -. DR Antibodypedia; 72874; 137 antibodies from 29 providers. DR DNASU; 151; -. DR Ensembl; ENST00000620793.2; ENSP00000480573.1; ENSG00000274286.2. DR GeneID; 151; -. DR KEGG; hsa:151; -. DR MANE-Select; ENST00000620793.2; ENSP00000480573.1; NM_000682.7; NP_000673.2. DR UCSC; uc032nvj.2; human. DR AGR; HGNC:282; -. DR ClinPGx; PA36; -. DR CTD; 151; -. DR DisGeNET; 151; -. DR GeneCards; ADRA2B; -. DR HGNC; HGNC:282; ADRA2B. DR HPA; ENSG00000274286; Low tissue specificity. DR MalaCards; ADRA2B; -. DR MIM; 104260; gene. DR MIM; 607876; phenotype. DR OpenTargets; ENSG00000274286; -. DR Orphanet; 86814; Familial adult myoclonic epilepsy. DR VEuPathDB; HostDB:ENSG00000274286; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT00940000161915; -. DR InParanoid; P18089; -. DR OMA; ANPWKRK; -. DR OrthoDB; 5975661at2759; -. DR PAN-GO; P18089; 3 GO annotations based on evolutionary models. DR PhylomeDB; P18089; -. DR PathwayCommons; P18089; -. DR Reactome; R-HSA-390696; Adrenoceptors. DR Reactome; R-HSA-392023; Adrenaline signalling through Alpha-2 adrenergic receptor. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR Reactome; R-HSA-418597; G alpha (z) signalling events. DR SignaLink; P18089; -. DR SIGNOR; P18089; -. DR Agora; ENSG00000274286; -. DR BioGRID-ORCS; 151; 11 hits in 1156 CRISPR screens. DR ChiTaRS; ADRA2B; human. DR GeneWiki; Alpha-2B_adrenergic_receptor; -. DR GenomeRNAi; 151; -. DR Pharos; P18089; Tclin. DR PRO; PR:P18089; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P18089; protein. DR Bgee; ENSG00000274286; Expressed in apex of heart and 97 other cell types or tissues. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0004938; F:alpha2-adrenergic receptor activity; IDA:BHF-UCL. DR GO; GO:0051379; F:epinephrine binding; IDA:BHF-UCL. DR GO; GO:0071881; P:adenylate cyclase-inhibiting adrenergic receptor signaling pathway; IMP:UniProt. DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IMP:UniProt. DR GO; GO:0071875; P:adrenergic receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0032811; P:negative regulation of epinephrine secretion; NAS:BHF-UCL. DR GO; GO:0010700; P:negative regulation of norepinephrine secretion; TAS:BHF-UCL. DR GO; GO:0030168; P:platelet activation; IEA:InterPro. DR GO; GO:0045777; P:positive regulation of blood pressure; IEA:Ensembl. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:BHF-UCL. DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:BHF-UCL. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:BHF-UCL. DR GO; GO:0070474; P:positive regulation of uterine smooth muscle contraction; IEA:Ensembl. DR GO; GO:0003056; P:regulation of vascular associated smooth muscle contraction; IEA:Ensembl. DR CDD; cd15321; 7tmA_alpha2B_AR; 1. DR FunFam; 1.20.1070.10:FF:000185; Alpha-2B adrenergic receptor; 1. DR FunFam; 1.20.1070.10:FF:000100; alpha-2B adrenergic receptor; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 2. DR InterPro; IPR002233; ADR_fam. DR InterPro; IPR000207; ADRA2B_rcpt. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR24248; ADRENERGIC RECEPTOR-RELATED G-PROTEIN COUPLED RECEPTOR; 1. DR PANTHER; PTHR24248:SF130; ALPHA-2B ADRENERGIC RECEPTOR; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR01103; ADRENERGICR. DR PRINTS; PR00559; ADRENRGCA2BR. DR PRINTS; PR00237; GPCRRHODOPSN. DR SMART; SM01381; 7TM_GPCR_Srsx; 1. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR PDBsum; 6K41; -. DR PDBsum; 6K42; -. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Disulfide bond; Epilepsy; KW G protein-coupled receptor; Lipoprotein; Membrane; Palmitate; KW Proteomics identification; Receptor; Reference proteome; Transducer; KW Transmembrane; Transmembrane helix. FT CHAIN 1..450 FT /note="Alpha-2B adrenergic receptor" FT /id="PRO_0000069094" FT TOPO_DOM 1..12 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 13..35 FT /note="Helical; Name=1" FT /evidence="ECO:0000269|PubMed:32152538, FT ECO:0007744|PDB:6K41" FT TOPO_DOM 36..48 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 49..74 FT /note="Helical; Name=2" FT /evidence="ECO:0000269|PubMed:32152538, FT ECO:0007744|PDB:6K41" FT TOPO_DOM 75..85 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 86..108 FT /note="Helical; Name=3" FT /evidence="ECO:0000269|PubMed:32152538, FT ECO:0007744|PDB:6K41" FT TOPO_DOM 109..129 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 130..148 FT /note="Helical; Name=4" FT /evidence="ECO:0000269|PubMed:32152538, FT ECO:0007744|PDB:6K41" FT TOPO_DOM 149..170 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 171..193 FT /note="Helical; Name=5" FT /evidence="ECO:0000269|PubMed:32152538, FT ECO:0007744|PDB:6K41" FT TOPO_DOM 194..372 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 373..393 FT /note="Helical; Name=6" FT /evidence="ECO:0000269|PubMed:32152538, FT ECO:0007744|PDB:6K41" FT TOPO_DOM 394..407 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 408..428 FT /note="Helical; Name=7" FT /evidence="ECO:0000269|PubMed:32152538, FT ECO:0007744|PDB:6K41" FT TOPO_DOM 429..450 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 204..229 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 241..329 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 246..256 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 293..311 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 312..326 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 92 FT /note="Implicated in ligand binding" FT /evidence="ECO:0000250" FT SITE 176 FT /note="Implicated in catechol agonist binding" FT /evidence="ECO:0000250" FT SITE 180 FT /note="Implicated in catechol agonist binding" FT /evidence="ECO:0000250" FT LIPID 442 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000255" FT DISULFID 85..164 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521, FT ECO:0000269|PubMed:32152538, ECO:0007744|PDB:6K41, FT ECO:0007744|PDB:6K42" FT VARIANT 211 FT /note="G -> A (in dbSNP:rs9333568)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_025099" FT VARIANT 225..229 FT /note="HGGAL -> QFGR (in FAME2; gain of function; decreases FT interaction with PPP1R9B upon activation by FT neurotransmitter)" FT /evidence="ECO:0000269|PubMed:24114805" FT /id="VAR_073953" FT VARIANT 301..303 FT /note="Missing (found with a frequency of 0.31 in FT Caucasians and 0.12 in African-Americans; exhibits impaired FT phosphorylation and desensitization by G protein-coupled FT receptor kinases; does not affect ligand-binding)" FT /evidence="ECO:0000269|PubMed:11056163, FT ECO:0000269|PubMed:15815621" FT /id="VAR_070775" FT VARIANT 376 FT /note="V -> I (in dbSNP:rs1431850417)" FT /id="VAR_033462" FT VARIANT 379 FT /note="V -> G (in dbSNP:rs527655811)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_025100" FT VARIANT 379 FT /note="V -> I (in dbSNP:rs29000569)" FT /id="VAR_033463" FT CONFLICT 362..363 FT /note="QL -> HV (in Ref. 1; AAA51666 and 2; no nucleotide FT entry)" FT /evidence="ECO:0000305" FT HELIX 12..38 FT /evidence="ECO:0007829|PDB:6K41" FT TURN 46..48 FT /evidence="ECO:0007829|PDB:6K41" FT HELIX 49..60 FT /evidence="ECO:0007829|PDB:6K41" FT HELIX 61..65 FT /evidence="ECO:0007829|PDB:6K41" FT HELIX 66..73 FT /evidence="ECO:0007829|PDB:6K41" FT HELIX 86..115 FT /evidence="ECO:0007829|PDB:6K41" FT HELIX 117..121 FT /evidence="ECO:0007829|PDB:6K41" FT HELIX 126..144 FT /evidence="ECO:0007829|PDB:6K41" FT TURN 146..148 FT /evidence="ECO:0007829|PDB:6K41" FT HELIX 171..177 FT /evidence="ECO:0007829|PDB:6K41" FT HELIX 178..182 FT /evidence="ECO:0007829|PDB:6K41" FT HELIX 183..202 FT /evidence="ECO:0007829|PDB:6K41" FT HELIX 363..392 FT /evidence="ECO:0007829|PDB:6K41" FT HELIX 407..427 FT /evidence="ECO:0007829|PDB:6K41" FT HELIX 431..441 FT /evidence="ECO:0007829|PDB:6K41" SQ SEQUENCE 450 AA; 49954 MW; 06E43857152A68ED CRC64; MDHQDPYSVQ ATAAIAAAIT FLILFTIFGN ALVILAVLTS RSLRAPQNLF LVSLAAADIL VATLIIPFSL ANELLGYWYF RRTWCEVYLA LDVLFCTSSI VHLCAISLDR YWAVSRALEY NSKRTPRRIK CIILTVWLIA AVISLPPLIY KGDQGPQPRG RPQCKLNQEA WYILASSIGS FFAPCLIMIL VYLRIYLIAK RSNRRGPRAK GGPGQGESKQ PRPDHGGALA SAKLPALASV ASAREVNGHS KSTGEKEEGE TPEDTGTRAL PPSWAALPNS GQGQKEGVCG ASPEDEAEEE EEEEEEEEEC EPQAVPVSPA SACSPPLQQP QGSRVLATLR GQVLLGRGVG AIGGQWWRRR AQLTREKRFT FVLAVVIGVF VLCWFPFFFS YSLGAICPKH CKVPHGLFQF FFWIGYCNSS LNPVIYTIFN QDFRRAFRRI LCRPWTQTAW //