3SIM1_DENAN
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 03-AUG-2022, entry version 96.
DE RecName: Full=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; Toxicofera;
OC 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., Hellman U.,
RA 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 green
RT mamba Dendroaspis angusticeps to cloned human muscarinic 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 Arg-
RT 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 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 toxins
RT 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, AND
RP 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) adrenergic
CC receptors. Reversibly binds to M1 (CHRM1) muscarinic acetylcholine
CC receptors, probably by interacting with the orthosteric site
CC (PubMed:7778123, PubMed:12488533, PubMed:24793485). Also reveals a
CC slightly weaker effect at M3 (CHRM3) and M4 (CHRM4) receptors
CC (PubMed:7778123, PubMed:12488533, PubMed:24793485). The order of
CC potency is 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, DRD2,
CC DRD3, DRD4, DRD5), histaminic receptors (HRH1, HRH3, HRH4) and
CC serotoninergic receptors (HTR1A, HTR2A, HTR2B, HTR2C, HTR5A, HTR6,
CC HTR7) (PubMed:21557730, PubMed:24793485). Does not show interaction
CC with muscarinic receptors (CHRM2, CHRM3, CHRM5) (PubMed:7778123,
CC PubMed:12488533, PubMed:24793485). {ECO:0000269|PubMed:12488533,
CC ECO:0000269|PubMed:21557730, ECO:0000269|PubMed:24793485}.
CC -!- MISCELLANEOUS: Is classified as a P-type cytotoxin, since a proline
CC residue stands at position 33 (Pro-31 in standard classification).
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the snake three-finger toxin family. Short-chain
CC subfamily. Aminergic toxin sub-subfamily.
CC {ECO:0000305|PubMed:24793485}.
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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 AlphaFoldDB; P81030; -.
DR SMR; P81030; -.
DR TCDB; 1.C.74.1.6; the snake cytotoxin (sct) family.
DR EvolutionaryTrace; P81030; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR CDD; cd00206; snake_toxin; 1.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR003571; Snake_3FTx.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR InterPro; IPR018354; Snake_toxin_con_site.
DR InterPro; IPR035076; Toxin/TOLIP.
DR Pfam; PF00087; Toxin_TOLIP; 1.
DR SUPFAM; SSF57302; SSF57302; 1.
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
FT /note="Muscarinic toxin 1"
FT /evidence="ECO:0000269|PubMed:7570626,
FT ECO:0000269|PubMed:8154745"
FT /id="PRO_0000093641"
FT DISULFID 3..24
FT /evidence="ECO:0000269|PubMed:22720062,
FT ECO:0000312|PDB:3FEV, ECO:0000312|PDB:3NEQ,
FT ECO:0000312|PDB:4DO8"
FT DISULFID 17..42
FT /evidence="ECO:0000269|PubMed:22720062,
FT ECO:0000312|PDB:3FEV, ECO:0000312|PDB:3NEQ,
FT ECO:0000312|PDB:4DO8"
FT DISULFID 46..58
FT /evidence="ECO:0000269|PubMed:22720062,
FT ECO:0000312|PDB:3FEV, ECO:0000312|PDB:3NEQ,
FT ECO:0000312|PDB:4DO8"
FT DISULFID 59..64
FT /evidence="ECO:0000269|PubMed:22720062,
FT ECO:0000312|PDB:3FEV, ECO:0000312|PDB:3NEQ,
FT ECO:0000312|PDB:4DO8"
FT MUTAGEN 34
FT /note="R->A: Binds with 170-fold reduced affinity to M1
FT muscarinic acetylcholine receptors."
FT /evidence="ECO:0000269|PubMed:12488533"
FT STRAND 2..8
FT /evidence="ECO:0007829|PDB:3FEV"
FT STRAND 11..16
FT /evidence="ECO:0007829|PDB:3FEV"
FT STRAND 23..26
FT /evidence="ECO:0007829|PDB:3FEV"
FT STRAND 35..45
FT /evidence="ECO:0007829|PDB:4DO8"
FT STRAND 54..59
FT /evidence="ECO:0007829|PDB:3NEQ"
FT TURN 62..65
FT /evidence="ECO:0007829|PDB:4DO8"
SQ SEQUENCE 66 AA; 7518 MW; EAAC074F4A00DD3E CRC64;
LTCVTSKSIF GITTENCPDG QNLCFKKWYY IVPRYSDITW GCAATCPKPT NVRETIRCCE
TDKCNE
