STXA_SYNHO
ID STXA_SYNHO Reviewed; 703 AA.
AC Q98989;
DT 01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Stonustoxin subunit alpha {ECO:0000303|PubMed:8810331};
DE Short=SNTX subunit alpha {ECO:0000303|PubMed:8810331};
DE AltName: Full=DELTA-synanceitoxin-Sh1a {ECO:0000305};
DE Short=DELTA-SYTX-Sh1a {ECO:0000305};
DE AltName: Full=Trachynilysin subunit alpha {ECO:0000303|PubMed:12177053};
DE Short=TLY subunit alpha {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], AND PROTEIN SEQUENCE OF 27-48; 348-356; 510-518
RP AND 681-693.
RC TISSUE=Venom, and 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 FUNCTION, SUBUNIT, TOXIC DOSE, AND SUBCELLULAR LOCATION.
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 [3]
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 [4]
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 [5]
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 [6]
RP FUNCTION.
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 [7]
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 [8]
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 [9]
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 [10]
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 [11]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 1-703 IN COMPLEX WITH SUBUNIT B,
RP FUNCTION AS PORE-FORMING TOXIN, AND MODEL OF PREPORE FORMATION.
RC TISSUE=Venom;
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
CC has 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); non-
CC covalently linked. {ECO:0000269|PubMed:1790672,
CC ECO:0000305|PubMed:26627714}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1790672}.
CC Note=Secreted into the venom gland lumen (PubMed:8810331). The
CC secretion is proved by the fact that the complete sequence shown in
CC this entry is found in the venom gland's lumen, although no signal
CC peptide has been found (PubMed:8810331). This protein may follow a
CC novel secretion pathway (PubMed:8810331). It has been reported that
CC venom-secreting cells of stonefishes do not possess Golgi apparatus and
CC 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; U36237; AAC60022.1; -; mRNA.
DR PDB; 4WVM; X-ray; 3.10 A; A=1-703.
DR PDBsum; 4WVM; -.
DR AlphaFoldDB; Q98989; -.
DR SMR; Q98989; -.
DR TCDB; 1.C.125.1.1; the pore-forming stonustoxin (stonustoxin) family.
DR PRIDE; Q98989; -.
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; Hemostasis impairing toxin; Ion channel impairing toxin;
KW Myotoxin; Neurotoxin; Platelet aggregation activating toxin;
KW Potassium channel impairing toxin; Secreted; Toxin.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q91453"
FT CHAIN 2..703
FT /note="Stonustoxin subunit alpha"
FT /evidence="ECO:0000305|PubMed:8810331"
FT /id="PRO_0000221555"
FT DOMAIN 508..703
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REGION 2..265
FT /note="Structural MACPF/CDC pore-forming domain"
FT /evidence="ECO:0000305|PubMed:26627714"
FT REGION 266..385
FT /note="Structural FAT domain"
FT /evidence="ECO:0000305|PubMed:26627714"
FT REGION 386..517
FT /note="Thioredoxin (THX) domain"
FT /evidence="ECO:0000305|PubMed:26627714"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 45..56
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 61..67
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 72..79
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 87..91
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 103..115
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 149..155
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 167..175
FT /evidence="ECO:0007829|PDB:4WVM"
FT TURN 176..180
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 193..200
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 203..209
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 219..228
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 242..248
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 269..290
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 293..297
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 299..330
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 338..349
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 354..375
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 376..378
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 389..397
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 402..409
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 417..426
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 445..447
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 449..468
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 475..481
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 487..496
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 499..504
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 513..515
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 519..523
FT /evidence="ECO:0007829|PDB:4WVM"
FT TURN 533..535
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 540..542
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 548..551
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 553..555
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 563..565
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 567..575
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 580..601
FT /evidence="ECO:0007829|PDB:4WVM"
FT HELIX 608..610
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 614..624
FT /evidence="ECO:0007829|PDB:4WVM"
FT TURN 625..627
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 628..633
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 636..640
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 648..655
FT /evidence="ECO:0007829|PDB:4WVM"
FT TURN 656..659
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 660..667
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 670..678
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 685..690
FT /evidence="ECO:0007829|PDB:4WVM"
FT STRAND 698..702
FT /evidence="ECO:0007829|PDB:4WVM"
SQ SEQUENCE 703 AA; 79524 MW; 933A6800D4C2577F CRC64;
MSSDLVMPAL GRPFTLGMLY DARREKLIPG FSLFGDETLQ KYQSSNAQRS SEFKIVASDS
TESKSSAMDI EASLGVSFLG GLVEVGGSAK YLNNTKKYQN QSRVTLKYKA TTVYKQFTAP
PGTVTVQETA ITEKGLATHV VTSILYGANA FFVSDSDKVE DTNLQDIQGK MEAAIKKIPT
ISIEGSASVQ LTDEEKSLAS NLSCKFHGDF LLESLPTTFE DAVKTYQTLP TLIGEDGANS
VPMKVWLAPL KSYNSKAQQL IQEINVSKVR RIHTTLEELH KLKRRANEAM DVKLVQRIPL
IHDKISNFQQ IFQDYMLTVQ KKIAEKLPLV RAGTESEQSL QKIIDDRAQS PFSNEKVSKW
LDAVEREIAV LKSCAGMVEG TQAKFVSNQT ELDREVLVGK VKHAVCFIFT SVERNDPYLK
VLSDYWESPP SNNAKDVAPS TEDKWCFSTE VVLKMQQRAQ TFCDHVNDFE KSRNVGFFIT
ALENGKFQGA SIYYYKEGSL ATQDFTFPRM PFVQGYKKRS DLLWYACDLT FDRNTINNWI
SLSDNDTFAA SEHGKRQNYP KHPERFVSFN QVLCNEGLMG KHYWEVEWNG YIDVGIAYIS
IPRKEIDFAS AFGYNTYSWV LSYNPKIGYI ERHKKREYNV RAPNPGFKRL GLFLDWRYGS
ISFYAVSSDE VHHLHTFKTK FTEPVYPAFS IGPAGNHGTL RLL
