ID   3SIM3_DENAN             Reviewed;          65 AA.
AC   P81031; Q9PRH6;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   16-FEB-2004, sequence version 2.
DT   22-FEB-2023, entry version 85.
DE   RecName: Full=Muscarinic toxin 3;
DE            Short=MT3;
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, FUNCTION, AND SUBCELLULAR LOCATION.
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, SUBCELLULAR LOCATION, AND FUNCTION.
RX   PubMed=7925952; DOI=10.1016/0014-5793(94)00933-3;
RA   Jolkkonen M., van Giersbergen P.L., Hellman U., Wernstedt C., Karlsson E.;
RT   "A toxin from the green mamba Dendroaspis angusticeps: amino acid sequence
RT   and selectivity for muscarinic m4 receptors.";
RL   FEBS Lett. 352:91-94(1994).
RN   [3]
RP   FUNCTION.
RX   PubMed=9862767;
RA   Olianas M.C., Ingianni A., Maullu C., Adem A., Karlsson E., Onali P.;
RT   "Selectivity profile of muscarinic toxin 3 in functional assays of cloned
RT   and native receptors.";
RL   J. Pharmacol. Exp. Ther. 288:164-170(1999).
RN   [4]
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   [5]
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).
CC   -!- FUNCTION: Potent antagonist (IC(50)=1-10 nM) of M4 (CHRM4) muscarinic
CC       receptors (PubMed:8154745, PubMed:24793485, PubMed:21557730), and
CC       CHRM1, ADRA1A (PubMed:8154745), ADRA2A and ADRA2C adrenergic receptors.
CC       Also antagonises ADRA1B and ADRA1D adrenergic receptors with a 10-times
CC       lower affinity (PubMed:24793485). {ECO:0000269|PubMed:21557730,
CC       ECO:0000269|PubMed:24793485, ECO:0000269|PubMed:8154745}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24793485,
CC       ECO:0000269|PubMed:7925952}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC   -!- MISCELLANEOUS: Negative results: does not show interaction with
CC       adrenergic receptors (ADRA2B, ADRB1, ADRB2), dopaminergic receptors
CC       (DRD1, DRD2, DRD3, DRD4, DRD5), histaminic receptors (HRH1, HRH3,
CC       HRH4), muscarinic receptors (CHRM1, CHRM2, CHRM3, CHRM5), and
CC       serotoninergic receptors (HTR1A, HTR2A, HTR2B, HTR2C, HTR5A, HTR6,
CC       HTR7). {ECO:0000269|PubMed:21557730, ECO:0000269|PubMed:24793485,
CC       ECO:0000269|PubMed:7925952}.
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   PIR; S48648; S48648.
DR   AlphaFoldDB; P81031; -.
DR   SMR; P81031; -.
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; CD59; 1.
DR   InterPro; IPR003572; Cytotoxin_Cobra.
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   PRINTS; PR00282; CYTOTOXIN.
DR   SUPFAM; SSF57302; Snake toxin-like; 1.
DR   PROSITE; PS00272; SNAKE_TOXIN; 1.
PE   1: Evidence at protein level;
KW   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..65
FT                   /note="Muscarinic toxin 3"
FT                   /evidence="ECO:0000269|PubMed:7925952,
FT                   ECO:0000269|PubMed:8154745"
FT                   /id="PRO_0000093642"
FT   DISULFID        3..24
FT                   /evidence="ECO:0000250|UniProtKB:P60301"
FT   DISULFID        17..42
FT                   /evidence="ECO:0000250|UniProtKB:P60301"
FT   DISULFID        46..57
FT                   /evidence="ECO:0000250|UniProtKB:P60301"
FT   DISULFID        58..63
FT                   /evidence="ECO:0000250|UniProtKB:P60301"
SQ   SEQUENCE   65 AA;  7387 MW;  901B12D2F89AAFFE CRC64;
     LTCVTKNTIF GITTENCPAG QNLCFKRWHY VIPRYTEITR GCAATCPIPE NYDSIHCCKT
     DKCNE
//