Table 5. Peptides and proteins identified in scorpion venoms from the Brazilian Amazon.
| Scorpion | Toxin (synonym) | UniProt ID | MW (Da) | Sequence | Class | Tested channels/Characterization assays | Activity | Ref. |
|---|---|---|---|---|---|---|---|---|
| Tityus. obscurus | Tc1 | P83243 | 2446 | ACGSCRKKCKGSGKCINGRCKCY | α-KTx 13.1 | Shaker B K+-channels | Blocks Shaker B K+-channels | [39] |
| Tityus obscurus | Tc30 | P60210 | 3878 | VFINVKCRGSKECLPACKAAVGKAAGKCMNGKCKCYP | α-KTx 4.4 | Kv1.3 and Shaker B K+ (analog of the mammalian Kv1.1) | Blocks Shaker B( Kv1.1) and Kv1.3 | [40] |
| Tc32 | P60211 | 3521 | TGPQTTCQAAMCEAGCKGLGKSMESCQGDTCKCKA | α-KTx 18.1 | Kv1.3 and Shaker B K+ (analog of the mammalian Kv1.1) | Blocks Shaker B( Kv1.1) and Kv1.3 | ||
| Tityus obscurus | To2 (Tc48a) | - | 7310 | DKDGYLMEGDGCMNGCLTRKASYCVDQCKEVGGKNGY... | NaTx | - | - | [41] |
| To3 (Tc49a) | - | 7141 | KDGYLVGNDGCKYNCLTRPGHYCANECSRVKGAD... | NaTx | - | - | ||
| To1 (Tc49b) | - | 7405 | KKEGYLVGNDGCKYGCITRPHQYCVHECELKKGTDGYCAYWLACYCYNMPDWVKTWSSATNKCK | NaTx | Shaker B K+-channels; Na+ currents of granular cells | Changes Na+ currents of granular cells | ||
| To4 (Tc54) | - | 7259 | KDGYLMEYGGCKMSCLMKKGTFCAEECT... | NaTx | - | - | ||
| Brotheas amazonicus | Venom peptide 1 | P86341 | 978 | IWSGIQGAF | - | - | - | [136] |
| Venom peptide 2 | P86340 | 1008 | IWSGIQSAF | - | - | - | ||
| Venom peptide 3 | P86344 | 1045 | IGDIWSGIQG | - | - | - | ||
| Venom peptide 4 | P86339 | 1087 | IIDFIPQIE | - | - | - | ||
| Venom peptide 5 | P86343 | 1192 | FIGDIWSGIQG | - | - | - | ||
| Venom peptide 6 | P86342 | 1249 | GFIGDIWSGIQG | - | - | - | ||
| Venom peptide 7 | P86338 | 1429 | VAIRIIWSDIQD | - | - | - | ||
| Venom peptide 8 | P86337 | 1449 | ISDDIQSIIQGIF | - | - | - | ||
| Tityus obscurus | Tc1 | P83243 | 2446 | ACGSCRKKCK... | KTx | - | - | [42] |
| Tc27 | P84676 | 4103 | DEGPKSDCKP... | - | - | - | ||
| Tc29 | P84677 | 4150 | FNGAVXIW... | - | - | - | ||
| Tc30 | P60210 | 3871 | VFINVKCRGS... | KTx | - | - | ||
| Tc31 | P84678 | 4304 | CSTCLDKP... | - | - | - | ||
| Tc32 | P60211 | 3521 | TGPQTTCQAA... | - | - | - | ||
| Tc33 | P84679 | 3807 | ILNRCCNDDN... | - | - | - | ||
| Tc35 | P84680 | 3926 | TGPQTXXQAA... | - | - | - | ||
| Tc37 | P84681 | 7265 | TAIRKCNPRT... | - | - | - | ||
| Tc39 | P84682 | 2744 | DDDDLEGFSE... | - | - | - | ||
| Tc40 (~To13)1 | P84683 | 7796 | IKNGYPRDS... | - | - | - | ||
| Tc41 (~To14)1 | P84684 | 7109 | KDDYPVDTAK... | - | - | - | ||
| To6 (Tc43) | P84685 | 7266 | LDGYPLSKNN... | - | - | - | ||
| Tc46 | P84686 | 6032 | KEGYLFGSRG... | - | - | - | ||
| To2 (Tc48a) | P60212 | 7318 | NKDGYLMEGDGCKMGCLTRKASYCVDQCKEVGGKDGYCYAWLSCYCYNMPDSVEIWDSKNNKCGK | NaTx | Na+-channel | Changes Na+-channel | ||
| To3 (Tc48b) | P69213 | 7385 | KDGYLVGNDG... | NaTx | - | - | ||
| To3 (Tc49a) | P69213 | 7152 | KDGYLVGNDG... | NaTx | - | - | ||
| To1 (Tc49b) | P60214 | 7405 | KKEGYLVGND... | NaTx | - | - | ||
| Tc50 | P84688 | 7073 | LDGYPLSKIN... | - | - | - | ||
| To4 (Tc54) | P60215 | 7253 | KDGYLMEYGG... | NaTx | - | - | ||
| Tc56 | P84689 | 7299 | EKGKEILGKI... | - | - | - | ||
| Tc58 | P84690 | 5504 | KKFGGFLXXI... | - | - | - | ||
| Tc61 (~To8)1 | P84691 | 7105 | KEGYLLGSRG... | - | - | - | ||
| Tc64 | P84692 | 7628 | GLRQKVQSLV... | - | - | - | ||
| To5 (Tc66) | P84693 | 6935 | SYSGYPVTQK... | - | - | - | ||
| Tc83 | P84694 | 25402 | NDQCLVIEIL... | - | - | - | ||
| Tityus obscurus | To3 (Tc48b) | P69213 | 7385 | KDGYLVGNDGCKYNCLTRPGHYCANECSRVKGKDGYCYAWMACYCYSMPDWVKTWSRSTNRCGR | α-toxin | Na+-currents of cultured rat pituitary GH3 cells | Changes Na+-currents of cultured rat pituitary GH3 cells | [43] |
| Tityus obscurus | To1 (Tc49b) | P60214 | 7405 | MTRFVLFISCFFLIDMIVECKKEGYLVGNDGCKYGCITRPHQYCVHECELKKGTDGYCAYWLACYCYNMPDWVKTWSSATNKCKGK | All proteins shared sequence identity with NaTx. | - (proteomic) | - | [44] |
| To2 (Tc48a) | P60212 | 7318 | MIRFVLFISCFFLIGTVVECNKDGYLMEGDGCKMGCLTRKASYCVDQCKEVGGKDGYCYAWLSCYCYNMPDSVEIWDSKNNKCGKGK | |||||
| To3 (Tc48b/Tc49a) | P69213 | 7385 | MTRFVLFISCFFVIGMVVECKDGYLVGNDGCKYNCLTRPGHYCANECSRVKGKDGYCYAWMACYCYSMPDWVKTWSRSTNRCGRGK | |||||
| To4 (Tc54) | P60215 | 7253 | MTRFVLFISCFFLIGMIVECKDGYLMEYGGCKMSCLMKKGTFCAEECTRMKGKDGYCYAWLACYCYNMPDWVKIWNRATNKCGKRK | |||||
| To5 | P84693 | 6937 | MKAIIFFIGCLMLIDLVAGSRSGYPVTQKGCVYSCFWGSNWWCNAECTALGGSSGYCAWPSCWCYSLPDNRNIWGSYPNNCGKK | |||||
| To6 (Tc43) | P84685 | 7266 | MSIFPIILALLLIGLDEGEALDGYPLSKNNYCKIYCPDEKVCKWSCKHRAGATNGKGDCINKGCYCYDVAPGTEMYPGRLPCNPY | |||||
| To7 (Tc50) | P84688 | 7073 | MSIFPIVLALLLIGLEETEALDGYPLSKINNCKIYCPDDDVCKWTCKHRAGATNGKGDCIWYGCYCYDVAPGTKMYPGSSPCYA | |||||
| To8 | H1ZZH7 | 7050* | MTRFVLFISCFFLIGMVVECKEGYLLGSRGCKMNCLTRPEKFCELECSLVGGENGYCAYWLACYCYNVPESVKLWESDTNECGKRK | |||||
| To9 | H1ZZH8 | 7155* | MNYSTLIAVASLLTAGTESKKDGYPVKEGDCAFPCGYDNEYCDKLCKERKADSGYCYWGNILCYCYGLPDKAAIKGYGRCRPGKK | |||||
| To10 | H1ZZH9 | 6940* | MNYSTLIAVASLLTAGTESKKDGYPVEGSCAFPCGYDNAYCDKLCKERKADSGYCYWVNILCYCYGLPDNAAIKGYGRCKPGKK | |||||
| To11 | H1ZZI0 | 7154* | MTRFVLFISCFFLIGMIVECKDGYLVGNDGCKYNCLTRPGHYCANECSRVKGKDGYCYAWMACYCYNMPNWVKTWSRATNKCGKRK | |||||
| To12 | H1ZZI1 | 7171* | MKGLILFICGFMMIGVILAKEGYPMDHEGCKFSCFIRPSGFCERYCKTHLSASTGYCAWPACYCYGVPANQKVWDYYNNKCGK | |||||
| To13 | H1ZZI2 | 8054* | MKTLFLIITSFILLEVEGIKNGYPRDSKGCTFECGQDAKHGDDYCDKMCKTTLKGEGGDCDFEYAECWCDNIPDTVVTWKNKEPKCKQI | |||||
| To14 | H1ZZI3 | 7953* | MNCLMLIFVVFLLAFGVECKKDDYPVDTAKRNCMLDCNVWDDEGYCDKFCKGRKADSGYCYKLKAACYCYGLPDDSPTKTSGRCNPNVR | |||||
| To15 | H1ZZI4 | 7195* | MKGIILLISCLMLIEVVVGGKEGYPLDSSGCKAGCFFGTNSWCNTECKRKSAAKGYCAWPSCYCYEFTDDSKIWNAKTNKCYK | |||||
| Tityus obscurus | Recombinant toxin Tc32 | P60211 | - | GSTGPQTTCQAAMCEAGCKGLGKSMESCQGDTCKCKA | α-KTx | Electrophysiological assays on periglomerular cells of olfactory bulb; three-dimensional (3D) solution structure determined by 1H NMR spectroscopy. | Blocks Kv1.1 and Kv1.3 | [45] |
| Tityus obscurus | ToPI1 | - | 3807 | DDCKDVCKARKGKCEFGICKC... | Serine peptidase inhibitor | Trypsin and chymotrypsin inhibitory assays; viability of the tumor cells HeLa (from human cervical cancer) and B16F10 (from murine melanoma) and non-tumor murine fibroblasts (NIH-3T3); EAG1, EAG2, hKv1.4, hKv1.1, hERG1, hERG2, hERG3 (5 uM) | Potent trypsin inhibitory activity; did not reduce the viability of tumor cells; no visible behavioral and/or physiological changes in mice; stable at the range of pH 3.0 to 9.0 even at 95 °C; | [148] |
| Brotheas amazonicus | - | - | - | - | Serine proteases | Proteolytic activity using SDS-PAGE | Proteolytic activity inhibited by PMSF | [149] |
| Tityus obscurus | ToAp1 | A0A1D3IXR7 | - | FIGMIPGLIGGLISAFK-NH2 | AMP, NDBP subfamily 4 | Antifungal activity against planktonic cells of Candida spp. and Cryptococcus neoformans and Candida albicans biofilms | Active against biofilm formation. Lower than 50% of hemolysis in all the tested concentrations. Active against C. neoformans and all Candida spp. (except for C. glabrata). | [150] |
| ToAp2 | A0A1D3IXJ5 | - | MQFKKQLLVIFFAYFLVVNESEAFFGTLFKLGSKLIPGVMKLFSKKKERSLMKRELKNLYDPYQRSVEMERLLKELPLY | AMP, NDBP subfamily 3 | Active against biofilm formation and all strains tested (MIC 3.12 to 200 μM). Hemolysis maintained at about 50%. | |||
| ToAP2S1 | - | - | FFGTLFKLLSKLIPGLMKLFSKLLER-NH2 | AMP, NDBP subfamily 3 | Hemolysis percent higher than 50% in concentrations up to 25 μM. No antifungal activity. | |||
| ToAp3 | - | - | FIGMIPGLIGGLISAIK-NH2 | AMP, NDBP subfamily 4 | Active against C. neoformans and all Candida spp. (except for C. glabrata). | |||
| ToAp4 | - | - | FFSLIPSLIGGLVSAIK-NH2 | AMP, NDBP subfamily 4 | No antifungal activity. | |||
| NDBP-4.23 | S6D3A7 | - | FLGMIPGLIGGLISAFK-NH2 | AMP, NDBP subfamily 4 | Active against biofilm formation. Lower than 50% of hemolysis in all the tested concentrations. | |||
| ToAcP | A0A1D3IY23 | - | EEDDLLGFSEEDLKAIKEHRAKNA-NH2 | AMP, NDBP subfamily not designated | No antifungal activity. | |||
| Tityus obscurus | To4 (Tc54) | P60215 | - | KDGYLMEYGGCKMSCLMKKGTFCAEECTRMKGKDGYCYAWLACYCYNMPDWVKIWNRATNKC | β-toxin | hNav (1.1- 1.7) | Changes hNav 1.1, hNav 1.2 and hNav 1.4 | [46] |
| Tityus obscurus | Transcripts with proteomic evidence | - | - | - | Angiotensin converting enzyme like Cysteine-rich protein, allergen V5/Tpx-1-related Endothelin-converting enzyme-like Hyaluronidase Metalloproteinase Serine and cysteine proteinases Phospholipase A2 KTx Proteinase inhibitors NaTx | - | - | [47] |
| Tityus metuendus | 1 (24.41 min) | - | 3927 | TPFRYCNPRNCAKECQGRCKETTYCDEVCKCSGW | KTx | - | - | [98] |
| 2 (24.66 min) | - | 1735 | KVLAPAEEAPAEAPAAAE | bradykinin-potentiating peptide | - | - | ||
| 3 (28.33 min) | - | 4004 | TAIGNCNPFTCDKECKTKGNKRGYCENYNCECSKW | - | Shaker-type ion-channels | - | ||
| 4 (30.07 min) | - | 7796/7767 | KKNDYPVDTAKRNCMLDCNVWDDEGYCDNFCKGRKAESGYCYKLDAACYCYGLPDDSPTKTSGRCNPNV | NaTx | - | - | ||
| 5 | - | 7318/7385 | NKDGYLMEGDGCKMGCLTRKASYCVDQCKEVGGKDGYCYAWLSCYCYNMPDSVEIWDSKNNKCGK | NaTx | - | - | ||
| 37.26 min | - | 6961 | KEGYLLGSRGCKMNCLTxPGNYCELECSLVGGxNG... | - | - | - | ||
| 42.10 min | - | 7153 | SRRGYPVTQKGxVYSSFWGSN... | - | - | - | ||
| - | - | - | - | Angiotensin converting enzyme like Endothelin-converting enzyme-like Hyaluronidase Metalloproteinase | - | - | ||
| Tityus obscurus | - | - | - | 320 non-disulfide bond-containing peptides (NDBPs) | Fragments of hypotensins, KTx and the allergen 5 protein | - | - | [135] |
| Tityus obscurus | To1 (Tc49b) | P60214 | - | KKEGYLVGNDGCKYGCITRPHQYCVHECELKKGTDGYCAYWLACYCYNMPDWVKTWSSATNKCK | β-toxin | hNaV (1.1-1.7), BgNaV1, VdNaV1 | Changes NaV 1.3, NaV 1.6, BgNaV1, VdNaV1 | [48] |
| Tityus obscurus | Synthetic peptide ToAP2 (P6) | - | - | FFGTLFKLGSKLIPGVMKLFSKKKER | AMP, NDBP subfamily 3 | Antiretroviral and cytotoxic activities | Active against simian immunodeficiency virus (SIV) replication in the HUT-78 cell line and in primary human leukocytes | [151] |
(~To)1: N-terminal with which it shares identity (this work); *theoretical molecular mass reported (other molecular masses were determined experimentally); …: sequence not complete (N-terminal fragment); AMP: antimicrobial peptide; BgNav: Nav from the German cockroach Blattella germanica; EAG: ether-à-go-go channel; 1H NMR: proton nuclear magnetic resonance; hERG: the human Ether-à-go-go-related gene; hNav: Nav from humans; KTx: potassium channel toxin; Kv: voltage-gated potassium channel; MIC: minimum inhibitory concentration; NaTx: sodium channel toxin; Nav: voltage-gated sodium channel; NDBP: non-disulfide-bridged peptide; Ref.: reference; VdNav: Nav from the mite Varroa destructor.