ID   TXPR2_ALOMR             Reviewed;          64 AA.
AC   B3EWH0;
DT   03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2012, sequence version 1.
DT   25-MAY-2022, entry version 24.
DE   RecName: Full=Purotoxin-2 {ECO:0000303|PubMed:22842000, ECO:0000303|PubMed:27412961};
DE            Short=PT2 {ECO:0000303|PubMed:22842000, ECO:0000303|PubMed:27412961};
OS   Alopecosa marikovskyi (Wolf spider) (Lycosa kazakhstanicus).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Araneomorphae; Entelegynae; Lycosoidea; Lycosidae; Alopecosa.
OX   NCBI_TaxID=2066572;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND
RP   AMIDATION AT LEU-64.
RC   TISSUE=Venom;
RX   PubMed=22842000; DOI=10.1016/j.bbamem.2012.07.016;
RA   Kabanova N.V., Vassilevski A.A., Rogachevskaja O.A., Bystrova M.F.,
RA   Korolkova Y.V., Pluzhnikov K.A., Romanov R.A., Grishin E.V.,
RA   Kolesnikov S.S.;
RT   "Modulation of P2X3 receptors by spider toxins.";
RL   Biochim. Biophys. Acta 1818:2868-2875(2012).
RN   [2]
RP   STRUCTURE BY NMR, DISULFIDE BOND, AND DOMAIN.
RX   PubMed=27412961; DOI=10.1042/bcj20160573;
RA   Oparin P.B., Nadezhdin K.D., Berkut A.A., Arseniev A.S., Grishin E.V.,
RA   Vassilevski A.A.;
RT   "Structure of purotoxin-2 from wolf spider: modular design and membrane-
RT   assisted mode of action in arachnid toxins.";
RL   Biochem. J. 473:3113-3126(2016).
CC   -!- FUNCTION: Enhances the high-affinity desensitization of human P2RX3
CC       purinoceptors (PubMed:22842000). At 50 nM, the toxin decreases the
CC       IC(50) for ambient ATP from 2.67 nM to 0.77 nM in human P2RX3
CC       (PubMed:22842000). {ECO:0000269|PubMed:22842000}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22842000}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:22842000}.
CC   -!- DOMAIN: The toxin is composed of 2 domains: a highly rigid N-terminal
CC       inhibitor cystine knot (knottin) domain and a rather flexible C-
CC       terminal linear cationic cytotoxin domain that forms amphiphilic alpha-
CC       helices. {ECO:0000269|PubMed:27412961}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000269|PubMed:27412961}.
CC   -!- PTM: Amidation at Leu-64 is not mandatory for activity on P2RX3.
CC       {ECO:0000269|PubMed:22842000}.
CC   -!- MASS SPECTROMETRY: Mass=7255.5; Mass_error=0.5; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:22842000};
CC   -!- MISCELLANEOUS: The toxin does not affect mouse P2RX2 or P2RX2/P2RX3
CC       purinoceptors (PubMed:22842000). The toxin (and its derivatives
CC       composed of N-terminal or C-terminal domains) are inactive against a
CC       number of bacterial strains (PubMed:27412961).
CC       {ECO:0000269|PubMed:22842000, ECO:0000269|PubMed:27412961}.
CC   -!- SIMILARITY: Belongs to the neurotoxin 19 (CSTX) family. 05 (U4-Lctx)
CC       subfamily. {ECO:0000305}.
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DR   PDB; 2MZF; NMR; -; A=1-64.
DR   PDB; 2MZG; NMR; -; A=1-64.
DR   PDBsum; 2MZF; -.
DR   PDBsum; 2MZG; -.
DR   AlphaFoldDB; B3EWH0; -.
DR   BMRB; B3EWH0; -.
DR   SMR; B3EWH0; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0019855; F:calcium channel inhibitor activity; IDA:UniProtKB.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR019553; Spider_toxin_CSTX_knottin.
DR   InterPro; IPR011142; Spider_toxin_CSTX_Knottin_CS.
DR   Pfam; PF10530; Toxin_35; 1.
DR   PROSITE; PS60029; SPIDER_CSTX; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Calcium channel impairing toxin;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Knottin; Neurotoxin; Secreted; Toxin.
FT   PEPTIDE         1..64
FT                   /note="Purotoxin-2"
FT                   /evidence="ECO:0000269|PubMed:22842000"
FT                   /id="PRO_0000419528"
FT   REGION          1..44
FT                   /note="Knottin domain"
FT                   /evidence="ECO:0000305"
FT   REGION          45..64
FT                   /note="Linear cationic cytotoxin domain"
FT                   /evidence="ECO:0000305"
FT   MOD_RES         64
FT                   /note="Leucine amide"
FT                   /evidence="ECO:0000269|PubMed:22842000"
FT   DISULFID        4..19
FT                   /evidence="ECO:0000269|PubMed:27412961,
FT                   ECO:0000312|PDB:2MZF, ECO:0000312|PDB:2MZG"
FT   DISULFID        11..28
FT                   /evidence="ECO:0000269|PubMed:27412961,
FT                   ECO:0000312|PDB:2MZF, ECO:0000312|PDB:2MZG"
FT   DISULFID        18..44
FT                   /evidence="ECO:0000269|PubMed:27412961,
FT                   ECO:0000312|PDB:2MZF, ECO:0000312|PDB:2MZG"
FT   DISULFID        30..42
FT                   /evidence="ECO:0000269|PubMed:27412961,
FT                   ECO:0000312|PDB:2MZF, ECO:0000312|PDB:2MZG"
FT   STRAND          7..9
FT                   /evidence="ECO:0007829|PDB:2MZG"
FT   STRAND          22..24
FT                   /evidence="ECO:0007829|PDB:2MZG"
FT   STRAND          27..31
FT                   /evidence="ECO:0007829|PDB:2MZF"
FT   TURN            36..38
FT                   /evidence="ECO:0007829|PDB:2MZF"
FT   STRAND          41..45
FT                   /evidence="ECO:0007829|PDB:2MZF"
FT   HELIX           48..63
FT                   /evidence="ECO:0007829|PDB:2MZG"
SQ   SEQUENCE   64 AA;  7264 MW;  BB96626328CFCC59 CRC64;
     AKACTPLLHD CSHDRHSCCR GDMFKYVCDC FYPEGEDKTE VCSCQQPKSH KIAEKIIDKA
     KTTL