SRTX_ATREN
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 25-MAY-2022, entry version 120.
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; PTHR13874; 12.
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
