ID 3SIM1_DENAN Reviewed; 66 AA. AC P81030; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 1. DT 05-OCT-2016, entry version 79. DE RecName: Full=Three-finger muscarinic toxin 1 {ECO:0000303|PubMed:8154745}; DE Short=MT1 {ECO:0000303|PubMed:8154745}; DE Short=MTx1 {ECO:0000303|PubMed:7778123}; OS Dendroaspis angusticeps (Eastern green mamba) (Naja angusticeps). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; OC Toxicofera; Serpentes; Colubroidea; Elapidae; Elapinae; Dendroaspis. OX NCBI_TaxID=8618; RN [1] RP PROTEIN SEQUENCE, AND SUBCELLULAR LOCATION. RC TISSUE=Venom; RX PubMed=8154745; DOI=10.1111/j.1749-6632.1994.tb26623.x; RA Karlsson E., Jolkkonen M., Satyapan N., Adem A., Kumlin E., RA Hellman U., Wernstedt C.; RT "Protein toxins that bind to muscarinic acetylcholine receptors."; RL Ann. N. Y. Acad. Sci. 710:153-161(1994). RN [2] RP PROTEIN SEQUENCE, AND SUBCELLULAR LOCATION. RC TISSUE=Venom; RX PubMed=7570626; DOI=10.1016/0041-0101(94)00102-E; RA Jolkkonen M., Adem A., Hellman U., Wernstedt C., Karlsson E.; RT "A snake toxin against muscarinic acetylcholine receptors: amino acid RT sequence, subtype specificity and effect on guinea-pig ileum."; RL Toxicon 33:399-410(1995). RN [3] RP FUNCTION. RX PubMed=7778123; DOI=10.1016/0041-0101(94)00161-Z; RA Kornisiuk E., Jerusalinsky D., Cervenansky C., Harvey A.L.; RT "Binding of muscarinic toxins MTx1 and MTx2 from the venom of the RT green mamba Dendroaspis angusticeps to cloned human muscarinic RT cholinoceptors."; RL Toxicon 33:11-18(1995). RN [4] RP SYNTHESIS, MUTAGENESIS OF ARG-34, AND FUNCTION. RC TISSUE=Venom; RX PubMed=12488533; DOI=10.1124/mol.63.1.26; RA Mourier G., Dutertre S., Fruchart-Gaillard C., Menez A., Servent D.; RT "Chemical synthesis of MT1 and MT7 muscarinic toxins: critical role of RT Arg-34 in their interaction with M1 muscarinic receptor."; RL Mol. Pharmacol. 63:26-35(2003). RN [5] RP FUNCTION. RX PubMed=21557730; DOI=10.1111/j.1476-5381.2011.01468.x; RA Naereoja K., Kukkonen J.P., Rondinelli S., Toivola D.M., Meriluoto J., RA Naesman J.; RT "Adrenoceptor activity of muscarinic toxins identified from mamba RT venoms."; RL Br. J. Pharmacol. 164:538-550(2011). RN [6] RP SYNTHESIS, AND FUNCTION. RX PubMed=24793485; DOI=10.1016/j.biochi.2014.04.009; RA Blanchet G., Collet G., Mourier G., Gilles N., Fruchart-Gaillard C., RA Marcon E., Servent D.; RT "Polypharmacology profiles and phylogenetic analysis of three-finger RT toxins from mamba venom: case of aminergic toxins."; RL Biochimie 103:109-117(2014). RN [7] RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 1-16 AND 49-57, SYNTHESIS, RP AND DISULFIDE BOND. RX PubMed=22720062; DOI=10.1371/journal.pone.0039166; RA Fruchart-Gaillard C., Mourier G., Blanchet G., Vera L., Gilles N., RA Menez R., Marcon E., Stura E.A., Servent D.; RT "Engineering of three-finger fold toxins creates ligands with original RT pharmacological profiles for muscarinic and adrenergic receptors."; RL PLoS ONE 7:E39166-E39166(2012). CC -!- FUNCTION: Shows a non-competitive interaction with adrenergic and CC muscarinic receptors. Binds to alpha-2b (ADRA2B) (IC(50)=2.3 nM), CC alpha-1a (ADRA1A), alpha-1b (ADRA1B), and alpha-2c (ADRA2C) CC adrenergic receptors. Reversibly binds to M1 (CHRM1) muscarinic CC acetylcholine receptors, probably by interacting with the CC orthosteric site (PubMed:7778123, PubMed:12488533, CC PubMed:24793485). Also reveals a slightly weaker effect at M3 CC (CHRM3) (PubMed:7778123) and M4 (CHRM4) receptors CC (PubMed:12488533, PubMed:24793485). The order of potency is CC ADRA2B>>CHRM1>ADRA1A>ADRA1B>ADRA2C/CHRM4 (PubMed:24793485). CC {ECO:0000269|PubMed:12488533, ECO:0000269|PubMed:21557730, CC ECO:0000269|PubMed:24793485, ECO:0000269|PubMed:7778123}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7570626, CC ECO:0000269|PubMed:8154745}. CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}. CC -!- MISCELLANEOUS: Does not show interaction with adrenergic receptors CC (ADRA1D, ADRA2A, ADRB1, ADRB2), dopaminergic receptors (DRD1, CC DRD2, DRD3, DRD4, DRD5), histaminic receptors (HRH1, HRH3, HRH4) CC and serotoninergic receptors (HTR1A, HTR2A, HTR2B, HTR2C, HTR5A, CC HTR6, HTR7) (PubMed:21557730, PubMed:24793485). Does not show CC interaction with muscarinic receptors (CHRM2, CHRM3, CHRM5) CC (PubMed:7778123, PubMed:12488533, PubMed:24793485). CC {ECO:0000269|PubMed:12488533, ECO:0000269|PubMed:21557730, CC ECO:0000269|PubMed:24793485}. CC -!- SIMILARITY: Belongs to the snake three-finger toxin family. Short- CC chain subfamily. Aminergic toxin sub-subfamily. CC {ECO:0000305|PubMed:24793485}. 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 PDB; 3FEV; X-ray; 1.30 A; A/B/C=1-16. DR PDB; 3NEQ; X-ray; 1.25 A; A/B=49-57. DR PDB; 4DO8; X-ray; 1.80 A; A/B=1-66. DR PDBsum; 3FEV; -. DR PDBsum; 3NEQ; -. DR PDBsum; 4DO8; -. DR ProteinModelPortal; P81030; -. DR TCDB; 1.C.74.1.6; the snake cytotoxin (sct) family. DR HOVERGEN; HBG006553; -. DR EvolutionaryTrace; P81030; -. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0035792; C:other organism postsynaptic membrane; IEA:UniProtKB-KW. DR GO; GO:0009405; P:pathogenesis; IEA:InterPro. DR CDD; cd00206; snake_toxin; 1. DR InterPro; IPR003571; Snake_3FTx. DR InterPro; IPR018354; Snake_toxin_con_site. DR PROSITE; PS00272; SNAKE_TOXIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; Disulfide bond; KW G-protein coupled acetylcholine receptor impairing toxin; KW G-protein coupled receptor impairing toxin; Neurotoxin; KW Postsynaptic neurotoxin; Secreted; Toxin. FT CHAIN 1 66 Three-finger muscarinic toxin 1. FT {ECO:0000269|PubMed:7570626, FT ECO:0000269|PubMed:8154745}. FT /FTId=PRO_0000093641. FT DISULFID 3 24 {ECO:0000269|PubMed:22720062}. FT DISULFID 17 42 {ECO:0000269|PubMed:22720062}. FT DISULFID 46 58 {ECO:0000269|PubMed:22720062}. FT DISULFID 59 64 {ECO:0000269|PubMed:22720062}. FT MUTAGEN 34 34 R->A: Binds with 170-fold reduced FT affinity to M1 muscarinic acetylcholine FT receptors. {ECO:0000269|PubMed:12488533}. FT STRAND 2 8 {ECO:0000244|PDB:3FEV}. FT STRAND 11 16 {ECO:0000244|PDB:3FEV}. FT STRAND 23 32 {ECO:0000244|PDB:4DO8}. FT STRAND 35 45 {ECO:0000244|PDB:4DO8}. FT STRAND 54 57 {ECO:0000244|PDB:3NEQ}. FT TURN 62 65 {ECO:0000244|PDB:4DO8}. SQ SEQUENCE 66 AA; 7518 MW; EAAC074F4A00DD3E CRC64; LTCVTSKSIF GITTENCPDG QNLCFKKWYY IVPRYSDITW GCAATCPKPT NVRETIRCCE TDKCNE //