ID ADA2C_DIDVI Reviewed; 469 AA. AC P35405; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 06-JUN-2002, sequence version 2. DT 04-NOV-2026, entry version 108. DE RecName: Full=Alpha-2C adrenergic receptor {ECO:0000250|UniProtKB:P18825}; DE AltName: Full=Alpha-2C adrenoreceptor; DE Short=Alpha-2C adrenoceptor; DE Short=Alpha-2CAR; GN Name=ADRA2C; OS Didelphis virginiana (North American opossum) (Didelphis marsupialis OS virginiana). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Metatheria; Didelphimorphia; Didelphidae; Didelphis. OX NCBI_TaxID=9267; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Kidney; RX PubMed=7509437; DOI=10.1016/s0026-895x(25)09912-2; RA Blaxall H.S., Cerutis D., Hass N.A., Iversen L.J., Bylund D.B.; RT "Cloning and expression of the alpha 2C-adrenergic receptor from the OK RT cell line."; RL Mol. Pharmacol. 45:176-181(1994). RN [2] RP SEQUENCE REVISION TO 60; 75; 110; 143; 326-332; 365 AND 432. RA Bylund D.B.; RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Alpha-2 adrenergic receptors are G protein-coupled receptors CC for catecholamines that activate the G(i/o) protein pathway, thereby CC promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage- CC gated calcium channels suppression (By similarity). ADRA2A and ADRA2C CC mediates the presynaptic feedback inhibition of neurotransmitter CC release from noradrenergic nerve terminals in sympathetic and central CC nervous systems. ADRA2A inhibits transmitter release at high CC stimulation frequencies, whereas ADRA2C modulates neurotransmission at CC lower levels of nerve activity (By similarity). CC {ECO:0000250|UniProtKB:P18825, ECO:0000250|UniProtKB:Q01337}. CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P18825}. CC -!- SIMILARITY: Belongs to the G protein-coupled receptor 1 family. CC Adrenergic receptor subfamily. ADRA2C 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; U04310; AAA17566.2; -; mRNA. DR AlphaFoldDB; P35405; -. DR SMR; P35405; -. DR BindingDB; P35405; -. DR GlyCosmos; P35405; 2 sites, No reported glycans. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0004938; F:alpha2-adrenergic receptor activity; ISS:UniProtKB. DR GO; GO:0051379; F:epinephrine binding; IEA:TreeGrafter. DR GO; GO:0010700; P:negative regulation of norepinephrine secretion; ISS:UniProtKB. DR GO; GO:0030168; P:platelet activation; IEA:InterPro. DR GO; GO:0006940; P:regulation of smooth muscle contraction; IEA:InterPro. DR GO; GO:0019229; P:regulation of vasoconstriction; IEA:InterPro. DR CDD; cd15323; 7tmA_alpha2C_AR; 1. DR FunFam; 1.20.1070.10:FF:000100; alpha-2B adrenergic receptor; 1. DR FunFam; 1.20.1070.10:FF:000245; Alpha-2C adrenergic receptor; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 2. DR InterPro; IPR002233; ADR_fam. DR InterPro; IPR000735; ADRA2C_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:SF25; ALPHA-2C ADRENERGIC RECEPTOR; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR01103; ADRENERGICR. DR PRINTS; PR00560; ADRENRGCA2CR. 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. PE 2: Evidence at transcript level; KW Cell membrane; Disulfide bond; G protein-coupled receptor; Glycoprotein; KW Membrane; Receptor; Transducer; Transmembrane; Transmembrane helix. FT CHAIN 1..469 FT /note="Alpha-2C adrenergic receptor" FT /id="PRO_0000069104" FT TOPO_DOM 1..33 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 34..59 FT /note="Helical; Name=1" FT /evidence="ECO:0000250|UniProtKB:P18825" FT TOPO_DOM 60..72 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 73..95 FT /note="Helical; Name=2" FT /evidence="ECO:0000250|UniProtKB:P18825" FT TOPO_DOM 96..106 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 107..132 FT /note="Helical; Name=3" FT /evidence="ECO:0000250|UniProtKB:P18825" FT TOPO_DOM 133..152 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 153..172 FT /note="Helical; Name=4" FT /evidence="ECO:0000250|UniProtKB:P18825" FT TOPO_DOM 173..193 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 194..216 FT /note="Helical; Name=5" FT /evidence="ECO:0000250|UniProtKB:P18825" FT TOPO_DOM 217..390 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 391..415 FT /note="Helical; Name=6" FT /evidence="ECO:0000250|UniProtKB:P18825" FT TOPO_DOM 416..423 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 424..447 FT /note="Helical; Name=7" FT /evidence="ECO:0000250|UniProtKB:P18825" FT TOPO_DOM 448..469 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 1..29 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 232..261 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 279..353 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..29 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 279..296 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 301..310 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 331..353 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 116 FT /note="Implicated in ligand binding" FT /evidence="ECO:0000250" FT SITE 199 FT /note="Implicated in catechol agonist binding and receptor FT activation" FT /evidence="ECO:0000250" FT SITE 203 FT /note="Implicated in catechol agonist binding and receptor FT activation" FT /evidence="ECO:0000250" FT CARBOHYD 8 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 20 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 109..187 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" SQ SEQUENCE 469 AA; 53223 MW; 6F97D3718CC15C18 CRC64; MDLQLTTNST DSGDRGGSSN ESLQRQPPSQ YSPAEVAGLA AVVSFLIVFT IVGNVLVVIA VLTSRALKAP QNLFQVSLAS ADILVATLVM PFSLANELMN YWYFGKVWCV IYLALDVLFC TSSIVHLCAI SLDRYWSVTQ AVEYNLKRTP RRIKGIIVTV WLISAVISFP PLISLYRDPE DDLYPQCELN DETWYILSSC IGSFFAPCII MVLVYVRIYR VAKLRTRTLS EKRTVPEGSS QTENGLSRPP VGAGPSTAAA AAASLRLQAG ENGHYHLHHH HHHLHHHHHH HHHQLRKSAE LEDIELEESS TSENRRRRRS REEAAARKGS RGFSFSFSST KGGQSAGAGS RLSRASNRSL EFFSTHRRRK RSSLCRRKVT QAREKRFTFV LAVVMGVFVV CWFPFFFTYS LYGICREACQ VPETLFKFFF WIGYCNSSLN PVIYTIFNQD FRRSFKHILF KKKKKTSLQ //