3SIM2_DENAN
ID 3SIM2_DENAN Reviewed; 86 AA.
AC P18328; Q9PRY3;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 25-MAY-2022, entry version 111.
DE RecName: Full=Muscarinic toxin 2;
DE Short=MT2;
DE Short=MTx2 {ECO:0000303|PubMed:7778123};
DE Flags: Precursor;
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 NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=1862524; DOI=10.1016/0041-0101(91)90026-n;
RA Ducancel F., Rowan E.G., Cassar E., Harvey A.L., Menez A., Boulain J.-C.;
RT "Amino acid sequence of a muscarinic toxin deduced from the cDNA nucleotide
RT sequence.";
RL Toxicon 29:516-520(1991).
RN [2]
RP PROTEIN SEQUENCE OF 22-86, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=1862525; DOI=10.1016/0041-0101(91)90027-o;
RA Karlsson E., Risinger C., Jolkkonen M., Wernstedt C., Adem A.;
RT "Amino acid sequence of a snake venom toxin that binds to the muscarinic
RT acetylcholine receptor.";
RL Toxicon 29:521-526(1991).
RN [3]
RP PROTEIN SEQUENCE OF 22-86.
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 [4]
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 [5]
RP MECHANISM OF BINDING.
RX PubMed=7925953; DOI=10.1016/0014-5793(94)00926-0;
RA Toomela T., Jolkkonen M., Rinken A., Jarv J., Karlsson E.;
RT "Two-step binding of green mamba toxin to muscarinic acetylcholine
RT receptor.";
RL FEBS Lett. 352:95-97(1994).
RN [6]
RP STRUCTURE BY NMR, DISULFIDE BONDS, AND MODELING.
RX PubMed=7827075; DOI=10.1021/bi00004a019;
RA Segalas I., Roumestand C., Zinn-Justin S., Gilquin B., Menez R., Menez A.,
RA Toma F.;
RT "Solution structure of a green mamba toxin that activates muscarinic
RT acetylcholine receptors, as studied by nuclear magnetic resonance and
RT molecular modeling.";
RL Biochemistry 34:1248-1260(1995).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-65, AND DISULFIDE BONDS.
RA Menez R., Le Du M.H., Gaucher J.F., Menez A.;
RT "X-ray structure of muscarinic toxin 2.";
RL Submitted (JUL-2000) to the PDB data bank.
CC -!- FUNCTION: Binds irreversibly to M1 (CHRM1) muscarinic acetylcholine
CC receptors, and reveals a slightly weaker effect on M3 (CHRM3)
CC receptors. The mechanism of toxin-receptor interaction comprises at
CC least two steps. The first step is fast with no competition between the
CC toxin and the antagonist. The second step is slow with formation of a
CC more stable toxin-receptor complex and inhibition of the antagonist
CC binding. {ECO:0000269|PubMed:7778123}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1862525}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC -!- MISCELLANEOUS: Has no effect on M2 (CHRM2) and M4 (CHRM4) receptors.
CC {ECO:0000305|PubMed:7778123}.
CC -!- MISCELLANEOUS: Is classified as a P-type cytotoxin, since a proline
CC residue stands at position 54 (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. {ECO:0000305}.
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DR EMBL; X52292; CAA36541.1; -; mRNA.
DR PIR; A37910; A37910.
DR PDB; 1FF4; X-ray; 1.50 A; A=22-86.
DR PDBsum; 1FF4; -.
DR AlphaFoldDB; P18328; -.
DR SMR; P18328; -.
DR EvolutionaryTrace; P18328; -.
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; Signal; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:1862525,
FT ECO:0000269|PubMed:8154745"
FT CHAIN 22..86
FT /note="Muscarinic toxin 2"
FT /evidence="ECO:0000269|PubMed:1862525,
FT ECO:0000269|PubMed:8154745"
FT /id="PRO_0000035480"
FT DISULFID 24..45
FT /evidence="ECO:0000269|PubMed:7827075, ECO:0000269|Ref.7,
FT ECO:0000312|PDB:1FF4"
FT DISULFID 38..63
FT /evidence="ECO:0000269|PubMed:7827075, ECO:0000269|Ref.7,
FT ECO:0000312|PDB:1FF4"
FT DISULFID 67..78
FT /evidence="ECO:0000269|PubMed:7827075, ECO:0000269|Ref.7,
FT ECO:0000312|PDB:1FF4"
FT DISULFID 79..84
FT /evidence="ECO:0000269|PubMed:7827075, ECO:0000269|Ref.7,
FT ECO:0000312|PDB:1FF4"
FT STRAND 23..27
FT /evidence="ECO:0007829|PDB:1FF4"
FT STRAND 31..37
FT /evidence="ECO:0007829|PDB:1FF4"
FT STRAND 44..55
FT /evidence="ECO:0007829|PDB:1FF4"
FT STRAND 57..66
FT /evidence="ECO:0007829|PDB:1FF4"
FT STRAND 76..79
FT /evidence="ECO:0007829|PDB:1FF4"
FT TURN 82..85
FT /evidence="ECO:0007829|PDB:1FF4"
SQ SEQUENCE 86 AA; 9375 MW; 6F062C970074D653 CRC64;
MKTLLLTLVV VTIVCLDLGY TLTCVTTKSI GGVTTEDCPA GQNVCFKRWH YVTPKNYDII
KGCAATCPKV DNNDPIRCCG TDKCND
