ID   SRTX_ATREN              Reviewed;         543 AA.
AC   P13208; P13209; P13210;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1994, sequence version 2.
DT   22-FEB-2023, entry version 122.
DE   RecName: Full=Sarafotoxin;
DE   Contains:
DE     RecName: Full=Sarafotoxin-A, Ser-isoform;
DE              Short=SRTX-A;
DE              Short=Sarafotoxin-A;
DE     AltName: Full=S6A;
DE   Contains:
DE     RecName: Full=Sarafotoxin-C;
DE              Short=SRTX-C;
DE     AltName: Full=S6C;
DE   Contains:
DE     RecName: Full=Sarafotoxin-B;
DE              Short=SRTX-B;
DE     AltName: Full=S6B;
DE   Contains:
DE     RecName: Full=Sarafotoxin-E;
DE              Short=SRTX-E;
DE     AltName: Full=S6E;
DE   Contains:
DE     RecName: Full=Sarafotoxin-A, Thr-isoform;
DE   Flags: Precursor;
OS   Atractaspis engaddensis (Israeli burrowing asp) (Israeli mole viper).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Lamprophiidae; Atractaspidinae; Atractaspis.
OX   NCBI_TaxID=1343144;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=8428983; DOI=10.1016/s0021-9258(18)53658-9;
RA   Ducancel F., Matre V., Dupont C., Lajeunesse E., Wollberg Z., Bdolah A.,
RA   Kochva E., Boulain J.-C., Menez A.;
RT   "Cloning and sequence analysis of cDNAs encoding precursors of
RT   sarafotoxins. Evidence for an unusual 'rosary-type' organization.";
RL   J. Biol. Chem. 268:3052-3055(1993).
RN   [2]
RP   PROTEIN SEQUENCE (SARAFOTOXINS A; B AND C), TOXIC DOSE, AND SUBCELLULAR
RP   LOCATION.
RC   TISSUE=Venom;
RX   PubMed=3176048; DOI=10.1016/0041-0101(88)90234-6;
RA   Takasaki C., Tamiya N., Bdolah A., Wollberg Z., Kochva E.;
RT   "Sarafotoxins S6: several isotoxins from Atractaspis engaddensis (burrowing
RT   asp) venom that affect the heart.";
RL   Toxicon 26:543-548(1988).
RN   [3]
RP   PROTEIN SEQUENCE (SARAFOTOXINS A; B AND C), TOXIC DOSE, AND SUBCELLULAR
RP   LOCATION.
RC   TISSUE=Venom;
RX   PubMed=2845579; DOI=10.1126/science.2845579;
RA   Kloog Y., Ambar I., Sokolovsky M., Kochva E., Wollberg Z., Bdolah A.;
RT   "Sarafotoxin, a novel vasoconstrictor peptide: phosphoinositide hydrolysis
RT   in rat heart and brain.";
RL   Science 242:268-270(1988).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 108-130.
RC   TISSUE=Liver;
RX   PubMed=1339278; DOI=10.1016/0006-291x(92)90249-k;
RA   Takasaki C., Itoh Y., Onda H., Fujino M.;
RT   "Cloning and sequence analysis of a snake, Atractaspis engaddensis gene
RT   encoding sarafotoxin S6c.";
RL   Biochem. Biophys. Res. Commun. 189:1527-1533(1992).
RN   [5]
RP   DISULFIDE BONDS, AND SYNTHESIS OF SARAFOTOXIN B.
RX   PubMed=2080919;
RA   Aimoto S., Hojoh H., Takasaki C.;
RT   "Studies on the disulfide bridges of sarafotoxins. Chemical synthesis of
RT   sarafotoxin S6B and its homologue with different disulfide bridges.";
RL   Biochem. Int. 21:1051-1057(1990).
RN   [6]
RP   FUNCTION, TOXIN TARGET, AND MUTAGENESIS OF TRP-170 AND TRP-450.
RX   PubMed=21889567; DOI=10.1016/j.biochi.2011.08.014;
RA   Mourier G., Hajj M., Cordier F., Zorba A., Gao X., Coskun T., Herbet A.,
RA   Marcon E., Beau F., Delepierre M., Ducancel F., Servent D.;
RT   "Pharmacological and structural characterization of long-sarafotoxins, a
RT   new family of endothelin-like peptides: role of the C-terminus extension.";
RL   Biochimie 94:461-470(2012).
RN   [7]
RP   STRUCTURE BY NMR OF SARAFOTOXIN B.
RX   PubMed=2037041; DOI=10.1016/0014-5793(91)80488-o;
RA   Mills R.G., Atkins A.R., Harvey T., Junius F.K., Smith R., King G.F.;
RT   "Conformation of sarafotoxin-6b in aqueous solution determined by NMR
RT   spectroscopy and distance geometry.";
RL   FEBS Lett. 282:247-252(1991).
RN   [8]
RP   STRUCTURE BY NMR OF SARAFOTOXIN B.
RX   PubMed=20504727; DOI=10.1016/0197-0186(91)90141-y;
RA   Aumelas A., Chiche L., Mahe E., Le-Nguyen D., Sizun P., Berthault P.,
RA   Perly B.;
RT   "1H NMR study of the solution structure of sarafotoxin-S6b.";
RL   Neurochem. Int. 18:471-475(1991).
RN   [9]
RP   STRUCTURE BY NMR OF SARAFOTOXIN B.
RX   PubMed=7849060; DOI=10.1021/bi00006a024;
RA   Atkins A.R., Martin R.C., Smith R.;
RT   "1H NMR studies of sarafotoxin SRTb, a nonselective endothelin receptor
RT   agonist, and IRL 1620, an ETB receptor-specific agonist.";
RL   Biochemistry 34:2026-2033(1995).
CC   -!- FUNCTION: Vasoconstrictor activity. These toxins cause cardiac arrest
CC       probably as a result of coronary vasospasm.
CC       {ECO:0000269|PubMed:21889567}.
CC   -!- FUNCTION: [Sarafotoxin-B]: Vasoconstrictor activity. Causes cardiac
CC       arrest probably as a result of coronary vasospasm (By similarity).
CC       Displays high agonistic activities towards endothelin-2 receptor
CC       (EDNRB) (displays affinity in the picomolar range) and endothelin-1
CC       receptor (EDNRA) (lower affinities) (PubMed:21889567). {ECO:0000250,
CC       ECO:0000269|PubMed:21889567}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2845579,
CC       ECO:0000269|PubMed:3176048}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:2845579, ECO:0000305|PubMed:3176048}.
CC   -!- TOXIC DOSE: [Sarafotoxin-A, Ser-isoform]: LD(50) is 0.015 mg/kg by
CC       intravenous injection into mice. {ECO:0000269|PubMed:2845579,
CC       ECO:0000269|PubMed:3176048}.
CC   -!- TOXIC DOSE: [Sarafotoxin-A, Thr-isoform]: LD(50) is 0.015 mg/kg by
CC       intravenous injection into mice. {ECO:0000269|PubMed:2845579,
CC       ECO:0000269|PubMed:3176048}.
CC   -!- TOXIC DOSE: [Sarafotoxin-B]: LD(50) is 0.015 mg/kg by intravenous
CC       injection into mice. {ECO:0000269|PubMed:2845579,
CC       ECO:0000269|PubMed:3176048}.
CC   -!- TOXIC DOSE: [Sarafotoxin-C]: LD(50) is 0.3 mg/kg by intravenous
CC       injection into mice. {ECO:0000269|PubMed:3176048}.
CC   -!- SIMILARITY: Belongs to the endothelin/sarafotoxin family.
CC       {ECO:0000305}.
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DR   EMBL; L07528; AAA48515.1; -; mRNA.
DR   EMBL; D13322; BAA02579.2; -; Genomic_DNA.
DR   PIR; A46601; A46601.
DR   PDB; 1SRB; NMR; -; A=430-450.
DR   PDB; 6LRY; X-ray; 3.00 A; B=430-450.
DR   PDBsum; 1SRB; -.
DR   PDBsum; 6LRY; -.
DR   AlphaFoldDB; P13208; -.
DR   SMR; P13208; -.
DR   EvolutionaryTrace; P13208; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0019229; P:regulation of vasoconstriction; IEA:InterPro.
DR   GO; GO:0042310; P:vasoconstriction; IEA:UniProtKB-KW.
DR   InterPro; IPR020475; Endothelin.
DR   InterPro; IPR019764; Endothelin_toxin_CS.
DR   InterPro; IPR001928; Endothln-like_toxin.
DR   PANTHER; PTHR13874; ENDOTHELIN; 1.
DR   PANTHER; PTHR13874:SF9; ENDOTHELIN-2; 1.
DR   Pfam; PF00322; Endothelin; 12.
DR   SMART; SM00272; END; 12.
DR   PROSITE; PS00270; ENDOTHELIN; 12.
PE   1: Evidence at protein level;
KW   3D-structure; Cardiotoxin; Direct protein sequencing; Disulfide bond;
KW   G-protein coupled receptor impairing toxin; Repeat; Secreted; Signal;
KW   Toxin; Vasoactive; Vasoconstrictor.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   PROPEP          24..69
FT                   /id="PRO_0000008123"
FT   PEPTIDE         70..90
FT                   /note="Sarafotoxin-A, Ser-isoform"
FT                   /id="PRO_0000008124"
FT   PROPEP          92..109
FT                   /id="PRO_0000008125"
FT   PEPTIDE         110..130
FT                   /note="Sarafotoxin-C"
FT                   /id="PRO_0000008126"
FT   PROPEP          132..149
FT                   /id="PRO_0000008127"
FT   PEPTIDE         150..170
FT                   /note="Sarafotoxin-B"
FT                   /id="PRO_0000008128"
FT   PROPEP          172..189
FT                   /id="PRO_0000008129"
FT   PEPTIDE         190..210
FT                   /note="Sarafotoxin-C"
FT                   /id="PRO_0000008130"
FT   PROPEP          212..229
FT                   /id="PRO_0000008131"
FT   PEPTIDE         230..250
FT                   /note="Sarafotoxin-C"
FT                   /id="PRO_0000008132"
FT   PROPEP          252..269
FT                   /id="PRO_0000008133"
FT   PEPTIDE         270..290
FT                   /note="Sarafotoxin-E"
FT                   /id="PRO_0000008134"
FT   PROPEP          292..309
FT                   /id="PRO_0000008135"
FT   PEPTIDE         310..330
FT                   /note="Sarafotoxin-A, Ser-isoform"
FT                   /id="PRO_0000008136"
FT   PROPEP          332..349
FT                   /id="PRO_0000008137"
FT   PEPTIDE         350..370
FT                   /note="Sarafotoxin-C"
FT                   /id="PRO_0000008138"
FT   PROPEP          372..389
FT                   /id="PRO_0000008139"
FT   PEPTIDE         390..410
FT                   /note="Sarafotoxin-C"
FT                   /id="PRO_0000008140"
FT   PROPEP          412..429
FT                   /id="PRO_0000008141"
FT   PEPTIDE         430..450
FT                   /note="Sarafotoxin-B"
FT                   /id="PRO_0000008142"
FT   PROPEP          452..469
FT                   /id="PRO_0000008143"
FT   PEPTIDE         470..490
FT                   /note="Sarafotoxin-A, Ser-isoform"
FT                   /id="PRO_0000008144"
FT   PROPEP          492..509
FT                   /id="PRO_0000008145"
FT   PEPTIDE         510..530
FT                   /note="Sarafotoxin-A, Thr-isoform"
FT                   /id="PRO_0000008146"
FT   PROPEP          532..543
FT                   /id="PRO_0000008147"
FT   REPEAT          51..90
FT                   /note="1"
FT   REPEAT          91..130
FT                   /note="2"
FT   REPEAT          131..170
FT                   /note="3"
FT   REPEAT          171..210
FT                   /note="4"
FT   REPEAT          211..250
FT                   /note="5"
FT   REPEAT          251..290
FT                   /note="6"
FT   REPEAT          291..330
FT                   /note="7"
FT   REPEAT          331..370
FT                   /note="8"
FT   REPEAT          371..410
FT                   /note="9"
FT   REPEAT          411..450
FT                   /note="10"
FT   REPEAT          451..490
FT                   /note="11"
FT   REPEAT          491..530
FT                   /note="12"
FT   REGION          45..65
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          51..530
FT                   /note="12 X 40 AA tandem repeats"
FT   SITE            90
FT                   /note="Endothelin-receptor binding site"
FT                   /evidence="ECO:0000250"
FT   SITE            130
FT                   /note="Endothelin-receptor binding site"
FT                   /evidence="ECO:0000250"
FT   SITE            170
FT                   /note="Endothelin-receptor binding site"
FT                   /evidence="ECO:0000250"
FT   SITE            210
FT                   /note="Endothelin-receptor binding site"
FT                   /evidence="ECO:0000250"
FT   SITE            250
FT                   /note="Endothelin-receptor binding site"
FT                   /evidence="ECO:0000250"
FT   SITE            290
FT                   /note="Endothelin-receptor binding site"
FT                   /evidence="ECO:0000250"
FT   SITE            330
FT                   /note="Endothelin-receptor binding site"
FT                   /evidence="ECO:0000250"
FT   SITE            370
FT                   /note="Endothelin-receptor binding site"
FT                   /evidence="ECO:0000250"
FT   SITE            410
FT                   /note="Endothelin-receptor binding site"
FT                   /evidence="ECO:0000250"
FT   SITE            450
FT                   /note="Endothelin-receptor binding site"
FT                   /evidence="ECO:0000250"
FT   SITE            490
FT                   /note="Endothelin-receptor binding site"
FT                   /evidence="ECO:0000250"
FT   SITE            530
FT                   /note="Endothelin-receptor binding site"
FT                   /evidence="ECO:0000250"
FT   DISULFID        70..84
FT                   /evidence="ECO:0000250"
FT   DISULFID        72..80
FT                   /evidence="ECO:0000250"
FT   DISULFID        110..124
FT                   /evidence="ECO:0000250"
FT   DISULFID        112..120
FT                   /evidence="ECO:0000250"
FT   DISULFID        150..164
FT                   /evidence="ECO:0000269|PubMed:2080919"
FT   DISULFID        152..160
FT                   /evidence="ECO:0000269|PubMed:2080919"
FT   DISULFID        190..204
FT                   /evidence="ECO:0000250"
FT   DISULFID        192..200
FT                   /evidence="ECO:0000250"
FT   DISULFID        230..244
FT                   /evidence="ECO:0000250"
FT   DISULFID        232..240
FT                   /evidence="ECO:0000250"
FT   DISULFID        270..284
FT                   /evidence="ECO:0000250"
FT   DISULFID        272..280
FT                   /evidence="ECO:0000250"
FT   DISULFID        310..324
FT                   /evidence="ECO:0000250"
FT   DISULFID        312..320
FT                   /evidence="ECO:0000250"
FT   DISULFID        350..364
FT                   /evidence="ECO:0000250"
FT   DISULFID        352..360
FT                   /evidence="ECO:0000250"
FT   DISULFID        390..404
FT                   /evidence="ECO:0000250"
FT   DISULFID        392..400
FT                   /evidence="ECO:0000250"
FT   DISULFID        430..444
FT                   /evidence="ECO:0000269|PubMed:2080919"
FT   DISULFID        432..440
FT                   /evidence="ECO:0000269|PubMed:2080919"
FT   DISULFID        470..484
FT                   /evidence="ECO:0000250"
FT   DISULFID        472..480
FT                   /evidence="ECO:0000250"
FT   DISULFID        510..524
FT                   /evidence="ECO:0000250"
FT   DISULFID        512..520
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         170
FT                   /note="W->WVNRN,WDEP: Drastic decrease in affinity for ET-B
FT                   receptors (3 and 5-orders or magnitude for VNRN and DEP,
FT                   respectively)."
FT                   /evidence="ECO:0000269|PubMed:21889567"
FT   MUTAGEN         450
FT                   /note="W->WVNRN,DEP: Drastic decrease in affinity for ET-B
FT                   receptors (3 and 5-orders or magnitude for VNRN and DEP,
FT                   respectively)."
FT                   /evidence="ECO:0000269|PubMed:21889567"
FT   STRAND          433..435
FT                   /evidence="ECO:0007829|PDB:1SRB"
FT   HELIX           438..446
FT                   /evidence="ECO:0007829|PDB:6LRY"
SQ   SEQUENCE   543 AA;  62326 MW;  DF84A9631392FE4A CRC64;
     MALLPRLAAG GLLLLLALAA LEGKPAPSAL SQLLEKRSED QAAAGRIIDG GDTKQAARDP
     SPQRNVEPLC SCKDMSDKEC LNFCHQDVIW RDTKQAARDP SPQRNVEPLC TCNDMTDEEC
     LNFCHQDVIW RDTKQAARDP SPQRNVEPLC SCKDMTDKEC LYFCHQDVIW RDTKQAARDP
     SPQRNVEPLC TCNDMTDEEC LNFCHQDVIW RDTKQAARDP SPQRNVEPLC TCNDMTDEEC
     LNFCHQDVIW RDTKQAARDP SPQRNVEPLC TCKDMTDKEC LYFCHQGIIW RDTKQAARDP
     SPQRNVEPLC SCKDMSDKEC LNFCHQDVIW RDTKQAARDP SPQRNVEPLC TCNDMTDEEC
     LNFCHQDVIW RDTKQAARDP SPQRNVEPLC TCNDMTDEEC LNFCHQDVIW RDTKQAARDP
     SPQRNVEPLC SCKDMTDKEC LYFCHQDVIW RDTKQAARDP SPQRNVEPLC SCKDMSDKEC
     LNFCHQDVIW RDTKQAARDP SPQRNVEPLC SCKDMTDKEC LNFCHQDVIW KNADTSANPE
     FLG
//