ID   3SL2_DENPO              Reviewed;          60 AA.
AC   P01414; Q9PS74;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1988, sequence version 1.
DT   25-MAY-2022, entry version 103.
DE   RecName: Full=Toxin FS-2;
DE            Short=FS2;
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, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=880951; DOI=10.1111/j.1432-1033.1977.tb11574.x;
RA   Strydom D.J.;
RT   "Snake venom toxins. The amino-acid sequence of a short-neurotoxin
RT   homologue from Dendroaspis polylepis polylepis (black mamba) venom.";
RL   Eur. J. Biochem. 76:99-106(1977).
RN   [2]
RP   FUNCTION, AND TOXIC DOSE.
RX   PubMed=8826098;
RA   Yasuda O., Morimoto S., Jiang B., Kuroda H., Kimura T., Sakakibara S.,
RA   Fukuo K., Chen S., Tamatani M., Ogihara T.;
RT   "FS2. a mamba venom toxin, is a specific blocker of the L-type calcium
RT   channels.";
RL   Artery 21:287-302(1994).
RN   [3]
RP   SYNTHESIS OF 41-48.
RX   PubMed=9636051; DOI=10.1021/bi9802723;
RA   Kini R.M., Caldwell R.A., Wu Q.Y., Baumgarten C.M., Feher J.J., Evans H.J.;
RT   "Flanking proline residues identify the L-type Ca2+ channel binding site of
RT   calciseptine and FS2.";
RL   Biochemistry 37:9058-9063(1998).
RN   [4]
RP   STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX   PubMed=7727450; DOI=10.1021/bi00017a022;
RA   Albrand J.-P., Blackledge M.J., Pascaud F., Hollecker M., Marion D.;
RT   "NMR and restrained molecular dynamics study of the three-dimensional
RT   solution structure of toxin FS2, a specific blocker of the L-type calcium
RT   channel, isolated from black mamba venom.";
RL   Biochemistry 34:5923-5937(1995).
CC   -!- FUNCTION: Specific blocker of the voltage-dependent L-type calcium
CC       channel (Cav1/CACNA1) (PubMed:8826098). Inhibits cardiac contractions
CC       (By similarity). {ECO:0000250|UniProtKB:P22947,
CC       ECO:0000269|PubMed:8826098}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:880951}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC   -!- TOXIC DOSE: LD(50) is 8 mg/kg by subcutaneous injection.
CC       {ECO:0000269|PubMed:8826098}.
CC   -!- SIMILARITY: Belongs to the snake three-finger toxin family. Short-chain
CC       subfamily. L-type calcium blocker sub-subfamily. {ECO:0000305}.
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DR   PIR; A01684; T6EP3D.
DR   PDB; 1TFS; NMR; -; A=1-60.
DR   PDBsum; 1TFS; -.
DR   AlphaFoldDB; P01414; -.
DR   SMR; P01414; -.
DR   EvolutionaryTrace; P01414; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   Gene3D; 2.10.60.10; -; 1.
DR   InterPro; IPR045860; Snake_toxin-like_sf.
DR   InterPro; IPR018354; Snake_toxin_con_site.
DR   SUPFAM; SSF57302; SSF57302; 1.
DR   PROSITE; PS00272; SNAKE_TOXIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Calcium channel impairing toxin; Cardiotoxin;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Secreted; Toxin; Voltage-gated calcium channel impairing toxin.
FT   CHAIN           1..60
FT                   /note="Toxin FS-2"
FT                   /evidence="ECO:0000269|PubMed:880951"
FT                   /id="PRO_0000093666"
FT   REGION          41..48
FT                   /note="Important for binding to L-type calcium channels"
FT                   /evidence="ECO:0000269|PubMed:9636051"
FT   DISULFID        3..22
FT                   /evidence="ECO:0000269|PubMed:7727450,
FT                   ECO:0000312|PDB:1TFS"
FT   DISULFID        17..39
FT                   /evidence="ECO:0000269|PubMed:7727450,
FT                   ECO:0000312|PDB:1TFS"
FT   DISULFID        41..52
FT                   /evidence="ECO:0000269|PubMed:7727450,
FT                   ECO:0000312|PDB:1TFS"
FT   DISULFID        53..58
FT                   /evidence="ECO:0000269|PubMed:7727450,
FT                   ECO:0000312|PDB:1TFS"
FT   STRAND          2..4
FT                   /evidence="ECO:0007829|PDB:1TFS"
FT   STRAND          7..11
FT                   /evidence="ECO:0007829|PDB:1TFS"
FT   STRAND          14..16
FT                   /evidence="ECO:0007829|PDB:1TFS"
FT   STRAND          20..27
FT                   /evidence="ECO:0007829|PDB:1TFS"
FT   STRAND          30..41
FT                   /evidence="ECO:0007829|PDB:1TFS"
FT   STRAND          48..55
FT                   /evidence="ECO:0007829|PDB:1TFS"
SQ   SEQUENCE   60 AA;  7026 MW;  5124AA4367E5437F CRC64;
     RICYSHKASL PRATKTCVEN TCYKMFIRTH RQYISERGCG CPTAMWPYQT ECCKGDRCNK