STXB_SYNHO
ID STXB_SYNHO Reviewed; 700 AA.
AC Q91453; Q98986;
DT 01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Stonustoxin subunit beta {ECO:0000303|PubMed:8810331};
DE Short=SNTX subunit beta {ECO:0000303|PubMed:8810331};
DE AltName: Full=DELTA-synanceitoxin-Sh1b {ECO:0000305};
DE Short=DELTA-SYTX-Sh1b {ECO:0000305};
DE AltName: Full=Trachynilysin subunit beta {ECO:0000303|PubMed:12177053};
DE Short=TLY subunit beta {ECO:0000303|PubMed:12177053};
OS Synanceia horrida (Estuarine stonefish) (Scorpaena horrida).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC Eupercaria; Perciformes; Scorpaenoidei; Synanceiidae; Synanceiinae;
OC Synanceia.
OX NCBI_TaxID=13279;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=8810331; DOI=10.1074/jbc.271.41.25575;
RA Ghadessy F.J., Chen D., Kini R.M., Chung M.C.M., Jeyaseelan K., Khoo H.E.,
RA Yuen R.;
RT "Stonustoxin is a novel lethal factor from stonefish (Synanceja horrida)
RT venom. cDNA cloning and characterization.";
RL J. Biol. Chem. 271:25575-25581(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-507.
RX PubMed=7725338; DOI=10.1016/0041-0101(94)90329-8;
RA Ghadessy F.J., Jeyaseelan K., Chung M.C.M., Khoo H.E., Yuen R.;
RT "A genomic region encoding stonefish (Synanceja horrida) stonustoxin beta-
RT subunit contains an intron.";
RL Toxicon 32:1684-1688(1994).
RN [3]
RP PROTEIN SEQUENCE OF 2-40; 77-91; 105-110; 318-325; 484-492; 494-512 AND
RP 622-631, SUBCELLULAR LOCATION, SUBUNIT, FUNCTION, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=1790672; DOI=10.1016/0305-0491(91)90143-2;
RA Poh C.H., Yuen R., Khoo H.E., Chung M., Gwee M., Gopalakrishnakone P.;
RT "Purification and partial characterization of stonustoxin (lethal factor)
RT from Synanceja horrida venom.";
RL Comp. Biochem. Physiol. 99B:793-798(1991).
RN [4]
RP PROTEIN SEQUENCE OF 2-38, SUBCELLULAR LOCATION, FUNCTION, AND SUBUNIT.
RC TISSUE=Venom;
RX PubMed=8921306; DOI=10.1111/j.1460-9568.1996.tb00736.x;
RA Colasante C., Meunier F.A., Kreger A.S., Molgo J.;
RT "Selective depletion of clear synaptic vesicles and enhanced quantal
RT transmitter release at frog motor nerve endings produced by trachynilysin,
RT a protein toxin isolated from stonefish (Synanceia trachynis) venom.";
RL Eur. J. Neurosci. 8:2149-2156(1996).
RN [5]
RP FUNCTION.
RX PubMed=8310447; DOI=10.1016/0041-0101(93)90212-2;
RA Low K.S., Gwee M.C., Yuen R., Gopalakrishnakone P., Khoo H.E.;
RT "Stonustoxin: a highly potent endothelium-dependent vasorelaxant in the
RT rat.";
RL Toxicon 31:1471-1478(1993).
RN [6]
RP FUNCTION IN NEUROMUSCULAR INHIBITION.
RX PubMed=8079369; DOI=10.1016/0041-0101(94)90205-4;
RA Low K.S., Gwee M.C., Yuen R., Gopalakrishnakone P., Khoo H.E.;
RT "Stonustoxin: effects on neuromuscular function in vitro and in vivo.";
RL Toxicon 32:573-581(1994).
RN [7]
RP FUNCTION ON PLATELET AGGREGATION.
RX PubMed=8533137; DOI=10.1016/0041-0101(95)00046-o;
RA Khoo H.E., Hon W.M., Lee S.H., Yuen R.;
RT "Effects of stonustoxin (lethal factor from Synanceja horrida venom) on
RT platelet aggregation.";
RL Toxicon 33:1033-1041(1995).
RN [8]
RP FUNCTION IN CYTOLYSIS.
RC TISSUE=Venom;
RX PubMed=9271089; DOI=10.1042/bj3250685;
RA Chen D., Kini R.M., Yuen R., Khoo H.E.;
RT "Haemolytic activity of stonustoxin from stonefish (Synanceja horrida)
RT venom: pore formation and the role of cationic amino acid residues.";
RL Biochem. J. 325:685-691(1997).
RN [9]
RP FUNCTION.
RX PubMed=11931843; DOI=10.1016/s0006-2952(02)00857-2;
RA Sung J.M., Low K.S., Khoo H.E.;
RT "Characterization of the mechanism underlying stonustoxin-mediated relaxant
RT response in the rat aorta in vitro.";
RL Biochem. Pharmacol. 63:1113-1118(2002).
RN [10]
RP FUNCTION.
RX PubMed=12177053; DOI=10.1074/jbc.m203433200;
RA Ouanounou G., Malo M., Stinnakre J., Kreger A.S., Molgo J.;
RT "Trachynilysin, a neurosecretory protein isolated from stonefish (Synanceia
RT trachynis) venom, forms nonselective pores in the membrane of NG108-15
RT cells.";
RL J. Biol. Chem. 277:39119-39127(2002).
RN [11]
RP CRYSTALLIZATION.
RX PubMed=10600575; DOI=10.1006/jsbi.1999.4193;
RA Yew W.S., Kolatkar P.R., Kuhn P., Khoo H.E.;
RT "Crystallization and preliminary crystallographic study of stonustoxin, a
RT protein lethal factor isolated from the stonefish (Synanceja horrida)
RT venom.";
RL J. Struct. Biol. 128:216-218(1999).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 1-700 IN COMPLEX WITH SUBUNIT A,
RP FUNCTION AS PORE-FORMING TOXIN, AND MODEL OF PREPORE FORMATION.
RX PubMed=26627714; DOI=10.1073/pnas.1507622112;
RA Ellisdon A.M., Reboul C.F., Panjikar S., Huynh K., Oellig C.A.,
RA Winter K.L., Dunstone M.A., Hodgson W.C., Seymour J., Dearden P.K.,
RA Tweten R.K., Whisstock J.C., McGowan S.;
RT "Stonefish toxin defines an ancient branch of the perforin-like
RT superfamily.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:15360-15365(2015).
CC -!- FUNCTION: This lethal (towards mammals) heterodimer induces hemolytic
CC activities due to its ability to form pores in the cell membrane
CC (PubMed:1790672, PubMed:9271089, PubMed:12177053, PubMed:26627714). The
CC pore may be composed of 10 SNTX-alpha/beta heterodimers
CC (PubMed:26627714). The toxin elicits potent hypotension which is
CC endothelium-dependent and appears to be mediated by the nitric oxide
CC pathway and activation of potassium channels (PubMed:8310447,
CC PubMed:11931843). In addition, it displays edema-inducing activities,
CC increases vascular permeability. It also shows myotoxic activities and
CC interferes irreversibly with neuromuscular function (PubMed:8079369).
CC It also induces irreversible platelet aggregation in rabbit or rat but
CC not in human or mouse whole blood (PubMed:8533137). In addition, it has
CC been observed to increase spontaneous quantal acetylcholine release
CC from isolated frog cutaneous pectoris motor endings (PubMed:8921306).
CC {ECO:0000269|PubMed:11931843, ECO:0000269|PubMed:1790672,
CC ECO:0000269|PubMed:26627714, ECO:0000269|PubMed:8079369,
CC ECO:0000269|PubMed:8921306, ECO:0000269|PubMed:9271089}.
CC -!- SUBUNIT: Heterodimer of alpha and beta subunits (PubMed:1790672,
CC PubMed:8921306); non-covalently linked. {ECO:0000269|PubMed:1790672,
CC ECO:0000269|PubMed:8921306, ECO:0000305|PubMed:26627714}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1790672,
CC ECO:0000269|PubMed:8921306}. Note=Secreted into the venom gland lumen
CC (PubMed:8810331). The secretion is proved by the fact that the complete
CC sequence shown in this entry is found in the venom gland's lumen,
CC although no signal peptide has been found (PubMed:8810331). This
CC protein may follow a novel secretion pathway (PubMed:8810331). It has
CC been reported that venom-secreting cells of stonefishes do not possess
CC Golgi apparatus and rough endoplasmic reticulum (PubMed:8810331).
CC {ECO:0000269|PubMed:8810331}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:8810331}.
CC -!- DOMAIN: The first domain (residues 2-265) is structurally homologous to
CC the membrane attack complex-ferforin/cholesterol-dependent cytolysin
CC (MACPF/CDC) pore-forming domain. It makes numerous contacts with the
CC FAT domain and comprise essentially the core pore-forming machinery.
CC {ECO:0000305|PubMed:26627714}.
CC -!- DOMAIN: The second domain is structurally homologous to the focal
CC adhesion-targeting (FAT) domain (266-385). It makes numerous in cis
CC contacts with the MACPF/CDC domain (first domain) and the thioredoxin
CC (THX) domain (third domain) as well as extensive in trans interactions
CC at the SNTX-alpha/beta interface. {ECO:0000305|PubMed:26627714}.
CC -!- DOMAIN: The third domain corresponds to the thioredoxin (THX) domain.
CC It makes numerous contacts with the second domain (FAT domain). Since
CC it lacks the canonical catalytic residues, it may only play a purely
CC structural role. {ECO:0000305|PubMed:26627714}.
CC -!- DOMAIN: The fourth domain corresponds to the B30.2/SPRY domain. This
CC domain would be responsible for initial interaction with the cell
CC surface through either lipid- or protein-mediated interactions.
CC {ECO:0000305|PubMed:26627714}.
CC -!- PTM: Intrachain disulfide bonds may be present in the heterodimer
CC (PubMed:8810331). {ECO:0000305|PubMed:8810331}.
CC -!- PTM: Not glycosylated. {ECO:0000305|PubMed:8810331}.
CC -!- TOXIC DOSE: LD(50) of stonustoxin is 0.017 mg/kg by intravenous
CC injection. {ECO:0000269|PubMed:1790672}.
CC -!- SIMILARITY: Belongs to the SNTX/VTX toxin family. {ECO:0000305}.
CC -!- CAUTION: The toxin name trachynilysin was given according to the
CC species S.trachynis. This species has finally been reclassified as a
CC synonym of S.horrida. {ECO:0000305}.
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DR EMBL; U32516; AAC60021.1; -; mRNA.
DR PIR; I51333; A61527.
DR PDB; 4WVM; X-ray; 3.10 A; B=1-700.
DR PDBsum; 4WVM; -.
DR AlphaFoldDB; Q91453; -.
DR SMR; Q91453; -.
DR TCDB; 1.C.125.1.1; the pore-forming stonustoxin (stonustoxin) family.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
DR Gene3D; 2.60.120.920; -; 1.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR003879; Butyrophylin_SPRY.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR006574; PRY.
DR InterPro; IPR003877; SPRY_dom.
DR InterPro; IPR040581; Thioredoxin_11.
DR Pfam; PF13765; PRY; 1.
DR Pfam; PF00622; SPRY; 1.
DR Pfam; PF18078; Thioredoxin_11; 1.
DR PRINTS; PR01407; BUTYPHLNCDUF.
DR SMART; SM00589; PRY; 1.
DR SMART; SM00449; SPRY; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS50188; B302_SPRY; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytolysis; Direct protein sequencing; Disulfide bond;
KW Hemolysis; Ion channel impairing toxin; Myotoxin; Neurotoxin;
KW Potassium channel impairing toxin; Secreted; Toxin.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1790672"
FT CHAIN 2..700
FT /note="Stonustoxin subunit beta"
FT /evidence="ECO:0000305|PubMed:8810331"
FT /id="PRO_0000221556"
FT DOMAIN 506..700
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REGION 2..264
FT /note="Structural MACPF/CDC pore-forming domain"
FT /evidence="ECO:0000250|UniProtKB:Q98989"
FT REGION 265..384
FT /note="Structural FAT domain"
FT /evidence="ECO:0000250|UniProtKB:Q98989"
FT REGION 385..514
FT /note="Thioredoxin (THX) domain"
FT /evidence="ECO:0000250|UniProtKB:Q98989"
FT CONFLICT 35
FT /note="W -> V (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 506
FT /note="Y -> P (in Ref. 2)"
FT /evidence="ECO:0000305"
FT STRAND 6..9
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 47..58
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 62..68
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 73..80
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 90..94
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 104..116
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 140..157
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 165..178
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 195..200
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 203..211
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 220..229
FT /evidence="ECO:0007829|PDB:4WVM"
FT TURN 230..232
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 240..248
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 265..289
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 292..296
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 298..327
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 337..348
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 353..378
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 388..395
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 401..408
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 416..426
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 439..441
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 443..445
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 448..466
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 469..478
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 486..493
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 496..501
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 510..512
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 516..520
FT /evidence="ECO:0007829|PDB:4WVM"
FT TURN 530..532
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 538..540
FT /evidence="ECO:0007829|PDB:4WVM"
FT TURN 541..544
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 545..547
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 562..564
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 566..570
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 575..583
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 588..592
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 603..605
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 609..617
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 625..628
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 631..634
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 638..641
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 643..650
FT /evidence="ECO:0007829|PDB:4WVM"
FT TURN 651..654
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 655..662
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 665..673
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 680..685
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 696..699
FT /evidence="ECO:0007829|PDB:4WVM"
SQ SEQUENCE 700 AA; 79425 MW; 53445821AA3A46C1 CRC64;
MPSDILVVAA LGRPFTLGML YDARNDKLIP GFTLWEDEVI EESTLESSQP SSAFEIIASD
STDDKSSLMD IEASLKASFL GGLVEVGGSA KYLNNQKKFK NQSRVTLQYK ATTSFKQLMT
NLGTKHVEYS ELFENIQATH VVIGILYGAN AFFVFDSNKV DSTNVQEIQG QMEAVIKKIP
SVEISGKASV QLTGEETDIT NSFSCEFHGD FFLTTNPTTF EDAVKTYQQL PQMMGKDNAV
PMTVWLVPMV NFYSEAPQLM ADSSTPILRK VRNTLEAIVQ VQMRCNDALD DPTVNLFTEV
QKKLSDFQKI CDDHMSKLQA TIAKKLFAIR SGDEDESALL NLFEENLQSP FNIESLNMWM
EFEEREINVL RSCMDILTKA KPKVIFNQGV LFKGLYDSKV KHALCYVFTN VTKNDVFLNV
LNEFLDSPQS RPKKLRPSPK DYWYSYDDIP ETMREKAYLF RNLAKEMNNR CVHFFVTAIH
NPKQEGAGIH YYRESIQIID EFTKPYMPGV ESIKDRRELQ WYDCELTLDP ETAHQVLTLS
EGNKKAVSGN TKSPTDHLEK FSHFQQVMCT KGLSGRHYWE LEWSGYVGAG VTYKGIGRKT
STSDSSLGKN EKSWLFEYST KSGYQQIHNS KKTRVTVSST GFKLLGVYLD WPAGTLSFYM
VNKAWVTHLH TFHTKFNEAV YPAFLIGDAQ QKVNGQIKLL
