ID   3SIMA_DENPO             Reviewed;          66 AA.
AC   P80494;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   25-MAY-2022, entry version 88.
DE   RecName: Full=Muscarinic toxin alpha {ECO:0000303|PubMed:8536706};
DE            Short=MT-alpha {ECO:0000303|PubMed:8536706};
OS   Dendroaspis polylepis polylepis (Black mamba).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Elapidae; Elapinae; Dendroaspis.
OX   NCBI_TaxID=8620;
RN   [1]
RP   PROTEIN SEQUENCE, SUBCELLULAR LOCATION, AND FUNCTION.
RC   TISSUE=Venom;
RX   PubMed=8536706; DOI=10.1111/j.1432-1033.1995.579_b.x;
RA   Jolkkonen M., van Giersbergen P.L.M., Hellman U., Wernstedt C., Oras A.,
RA   Satyapan N., Adem A., Karlsson E.;
RT   "Muscarinic toxins from the black mamba Dendroaspis polylepis.";
RL   Eur. J. Biochem. 234:579-585(1995).
RN   [2]
RP   MECHANISM OF BINDING, AND FUNCTION.
RX   PubMed=10978757; DOI=10.1016/s0041-0101(00)00141-0;
RA   Jolkkonen M., Oras A., Toomela T., Karlsson E., Jarv J., Akerman K.E.;
RT   "Kinetic evidence for different mechanisms of interaction of black mamba
RT   toxins MT alpha and MT beta with muscarinic receptors.";
RL   Toxicon 39:377-382(2001).
RN   [3]
RP   FUNCTION.
RX   PubMed=20466015; DOI=10.1016/j.toxicon.2010.05.001;
RA   Koivula K., Rondinelli S., Nasman J.;
RT   "The three-finger toxin MTalpha is a selective alpha(2B)-adrenoceptor
RT   antagonist.";
RL   Toxicon 56:440-447(2010).
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   MUTAGENESIS OF LEU-31.
RX   PubMed=28578406; DOI=10.1038/s41598-017-02953-0;
RA   Blanchet G., Alili D., Protte A., Upert G., Gilles N., Tepshi L.,
RA   Stura E.A., Mourier G., Servent D.;
RT   "Ancestral protein resurrection and engineering opportunities of the mamba
RT   aminergic toxins.";
RL   Sci. Rep. 7:2701-2701(2017).
CC   -!- FUNCTION: Selectively binds with high-affinity to the a2B-adrenoceptor
CC       subtype (ADRA2B) (PubMed:20466015). The toxin reversibly binds to
CC       ADRA2B, and its mode of inhibition is non-competitive
CC       (PubMed:20466015). The toxin has also been described to bind with high
CC       affinity to all muscarinic receptor subtypes (Ki=23 nM (on CHRM1),
CC       Ki=44 nM (on CHRM2), Ki=3 nM (on CHRM3), Ki=5 nM (on CHRM4), and Ki=8
CC       nM (on CHRM5)) but no other data support these affinity values
CC       (PubMed:8536706). {ECO:0000269|PubMed:10978757,
CC       ECO:0000269|PubMed:20466015, ECO:0000269|PubMed:21557730,
CC       ECO:0000269|PubMed:8536706}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8536706}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC   -!- MISCELLANEOUS: Does not affect most adrenoceptors (ADRA1A, ADRA1B,
CC       ADRA2A AND ADRA2C) and muscarinic receptors (PubMed:20466015,
CC       PubMed:21557730). Does not affect beta-1 (ADRB1) and beta-2 (ADRB2)
CC       adrenoceptors (PubMed:21557730). {ECO:0000269|PubMed:20466015,
CC       ECO:0000269|PubMed:21557730}.
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   PIR; S67984; S67984.
DR   AlphaFoldDB; P80494; -.
DR   SMR; P80494; -.
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   Direct protein sequencing; Disulfide bond;
KW   G-protein coupled receptor impairing toxin; Neurotoxin;
KW   Postsynaptic neurotoxin; Secreted; Toxin.
FT   CHAIN           1..66
FT                   /note="Muscarinic toxin alpha"
FT                   /evidence="ECO:0000269|PubMed:8536706"
FT                   /id="PRO_0000093648"
FT   DISULFID        3..24
FT                   /evidence="ECO:0000250|UniProtKB:P60301"
FT   DISULFID        17..42
FT                   /evidence="ECO:0000250|UniProtKB:P60301"
FT   DISULFID        46..58
FT                   /evidence="ECO:0000250|UniProtKB:P60301"
FT   DISULFID        59..64
FT                   /evidence="ECO:0000250|UniProtKB:P60301"
FT   MUTAGEN         31
FT                   /note="L->I: In AncTx6; 10-fold decrease in inhibition
FT                   potency on adrenergic receptor ADRA2B."
FT                   /evidence="ECO:0000269|PubMed:28578406"
SQ   SEQUENCE   66 AA;  7554 MW;  EAA70BDFB3F0AD3E CRC64;
     LTCVTSKSIF GITTENCPDG QNLCFKKWYY LNHRYSDITW GCAATCPKPT NVRETIHCCE
     TDKCNE