NDB4D_VAEMS
ID NDB4D_VAEMS Reviewed; 68 AA.
AC I0DEB3;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 15.
DE RecName: Full=Amphipathic peptide CT1 {ECO:0000303|PubMed:22342498};
DE Short=VmCT1 {ECO:0000303|PubMed:22342498};
DE AltName: Full=Non-disulfide-bridged peptide 4.13 {ECO:0000303|PubMed:24184590};
DE Short=NDBP-4.13 {ECO:0000303|PubMed:24184590};
DE AltName: Full=Non-disulfide-bridged peptide 5.13 {ECO:0000303|PubMed:23624072};
DE Short=NDBP-5.13 {ECO:0000303|PubMed:23624072};
DE Flags: Precursor;
OS Vaejovis mexicanus smithi (Mexican scorpion) (Vaejovis smithi).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Iurida; Chactoidea; Vaejovidae; Vaejovis.
OX NCBI_TaxID=1562928;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 24-36, FUNCTION, CIRCULAR
RP DICHROISM ANALYSIS, AND PROBABLE AMIDATION AT PHE-36.
RC TISSUE=Venom gland;
RX PubMed=22342498; DOI=10.1016/j.peptides.2012.02.002;
RA Ramirez-Carreto S., Quintero-Hernandez V., Jimenez-Vargas J.M., Corzo G.,
RA Possani L.D., Becerril B., Ortiz E.;
RT "Gene cloning and functional characterization of four novel antimicrobial-
RT like peptides from scorpions of the family Vaejovidae.";
RL Peptides 34:290-295(2012).
RN [2]
RP FUNCTION, MUTAGENESIS OF GLY-26; ALA-27; ASN-30; ALA-32 AND SER-34, AND
RP SYNTHESIS OF 24-36.
RX PubMed=27912176; DOI=10.1016/j.ejmech.2016.11.040;
RA Pedron C.N., Torres M.T., Lima J.A.D.S., Silva P.I., Silva F.D.,
RA Oliveira V.X.;
RT "Novel designed VmCT1 analogs with increased antimicrobial activity.";
RL Eur. J. Med. Chem. 126:456-463(2017).
RN [3]
RP FUNCTION, MUTAGENESIS OF PHE-24; GLY-26; ASN-30; VAL-31; ALA-32; SER-34 AND
RP VAL-35, AND SYNTHESIS OF 24-36.
RX PubMed=31212183; DOI=10.1016/j.bioorg.2019.103038;
RA Pedron C.N., Araujo I., da Silva Junior P.I., Dias da Silva F.,
RA Torres M.T., Oliveira Junior V.X.;
RT "Repurposing the scorpion venom peptide VmCT1 into an active peptide
RT against Gram-negative ESKAPE pathogens.";
RL Bioorg. Chem. 90:103038-103038(2019).
RN [4]
RP FUNCTION, MUTAGENESIS OF PHE-24; GLY-26; ASN-30; ALA-32; SER-34 AND VAL-35,
RP AND SYNTHESIS OF 24-36.
RX PubMed=31181304; DOI=10.1016/j.ejps.2019.06.006;
RA Pedron C.N., de Oliveira C.S., da Silva A.F., Andrade G.P.,
RA da Silva Pinhal M.A., Cerchiaro G., da Silva Junior P.I., da Silva F.D.,
RA Torres M.T., Oliveira V.X.;
RT "The effect of lysine substitutions in the biological activities of the
RT scorpion venom peptide VmCT1.";
RL Eur. J. Pharm. Sci. 136:104952-104952(2019).
RN [5]
RP FUNCTION ON TRYPANOSOMA CRUZI, MUTAGENESIS OF GLY-26; ASN-30 AND SER-34,
RP AND SYNTHESIS OF 24-36.
RX PubMed=33004083; DOI=10.1017/s0031182020001882;
RA Pedron C.N., Freire K.A., Torres M.T., Lima D.B., Monteiro M.L.,
RA Menezes R.R.P.P.B., Martins A.M.C., Oliveira V.X.;
RT "Arg-substituted VmCT1 analogs reveals promising candidate for the
RT development of new antichagasic agent.";
RL Parasitology 147:1810-1818(2020).
RN [6]
RP FUNCTION ON PLASMODIUM, MUTAGENESIS OF GLY-26; ASN-30 AND SER-34, AND
RP SYNTHESIS OF 24-36.
RX PubMed=33442881; DOI=10.1002/psc.3296;
RA Pedron C.N., Silva A.F., Torres M.T., Oliveira C.S., Andrade G.P.,
RA Cerchiaro G., Pinhal M.A.S., de la Fuente-Nunez C., Oliveira Junior V.X.;
RT "Net charge tuning modulates the antiplasmodial and anticancer properties
RT of peptides derived from scorpion venom.";
RL J. Pept. Sci. 27:e3296-e3296(2021).
RN [7]
RP NOMENCLATURE.
RX PubMed=23624072; DOI=10.1016/j.peptides.2013.03.026;
RA Zeng X.C., Zhou L., Shi W., Luo X., Zhang L., Nie Y., Wang J., Wu S.,
RA Cao B., Cao H.;
RT "Three new antimicrobial peptides from the scorpion Pandinus imperator.";
RL Peptides 45:28-34(2013).
RN [8]
RP NOMENCLATURE.
RX PubMed=24184590; DOI=10.1016/j.peptides.2013.10.021;
RA Almaaytah A., Albalas Q.;
RT "Scorpion venom peptides with no disulfide bridges: a review.";
RL Peptides 51:35-45(2014).
CC -!- FUNCTION: Cationic amphipathic peptide with antibacterial activities
CC against both Gram-positive and Gram-negative bacteria (PubMed:22342498,
CC PubMed:27912176, PubMed:31212183). Also shows antifungal activities
CC (PubMed:27912176). Is mildly hemolytic against human erythrocytes
CC (PubMed:22342498, PubMed:27912176, PubMed:31212183). In addition, when
CC tested in vitro on the parasite Trypanosoma cruzi (responsible of the
CC Chagas disease), is able to reduce the number of the three forms
CC (epimastigote, trypomastigote and amastigote) (PubMed:33004083). Also
CC shows antiplasmodial and cytotoxic activity (tested on Plasmodium
CC gallinaceum, and MCF-7 breast cancer cell line) (PubMed:33442881).
CC {ECO:0000269|PubMed:22342498, ECO:0000269|PubMed:27912176,
CC ECO:0000269|PubMed:31212183, ECO:0000269|PubMed:33004083,
CC ECO:0000269|PubMed:33442881}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Target cell membrane
CC {ECO:0000250}. Note=Forms a helical membrane channel in the prey.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- SIMILARITY: Belongs to the non-disulfide-bridged peptide (NDBP)
CC superfamily. Short antimicrobial peptide (group 4) family.
CC {ECO:0000305}.
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DR EMBL; JQ086325; AFH87944.1; -; mRNA.
DR AlphaFoldDB; I0DEB3; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Amidation; Antibiotic; Antimicrobial; Cleavage on pair of basic residues;
KW Cytolysis; Hemolysis; Membrane; Secreted; Signal; Target cell membrane;
KW Target membrane.
FT SIGNAL 1..23
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22342498"
FT PEPTIDE 24..36
FT /note="Amphipathic peptide CT1"
FT /evidence="ECO:0000305|PubMed:22342498"
FT /id="PRO_0000418781"
FT PROPEP 40..68
FT /evidence="ECO:0000250"
FT /id="PRO_0000418782"
FT SITE 29
FT /note="Important for activity"
FT /evidence="ECO:0000250"
FT MOD_RES 36
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000305|PubMed:22342498"
FT MUTAGEN 24
FT /note="F->G: Decrease in antibacterial activity against the
FT antibiotic-resistant bacterium S.aureus, and no change in
FT absence of antibacterial activity against both antibiotic-
FT resistant bacteria E.cloacae and P.aeruginosa, as well as
FT in decrease in hemolytic activity."
FT /evidence="ECO:0000269|PubMed:31212183"
FT MUTAGEN 24
FT /note="F->K: Decrease in antibacterial activity, increase
FT in antifungal activity and decrease in hemolytic activity.
FT Important decrease or loss in antibacterial, antifungal and
FT hemolytic activities; when associated with K-35."
FT /evidence="ECO:0000269|PubMed:31181304"
FT MUTAGEN 26
FT /note="G->K: No change or increase in antibacterial and
FT antifungal activities, and increase in hemolytic activity.
FT Increase in antibacterial, antifungal and hemolytic
FT activities; when associated with K-30. No change or
FT increase in antibacterial, antifungal and hemolytic
FT activities; when associated with K-34. Increase or no
FT change in antibacterial activity, and increase in
FT antifungal and hemolytic activities; when associated with
FT K-30 and K-34."
FT /evidence="ECO:0000269|PubMed:27912176,
FT ECO:0000269|PubMed:31181304"
FT MUTAGEN 26
FT /note="G->R: Decrease in antibacterial activity against the
FT antibiotic-resistant bacterium S.aureus, and important
FT increase in absence of antibacterial activity against both
FT antibiotic-resistant bacteria E.cloacae and P.aeruginosa,
FT as well as in increase in hemolytic activity. Increase in
FT trypanocidal activity. No change in antiplasmodial
FT activity. Small decrease in cytotoxic activity."
FT /evidence="ECO:0000269|PubMed:31212183,
FT ECO:0000269|PubMed:33004083, ECO:0000269|PubMed:33442881"
FT MUTAGEN 27
FT /note="A->E: Decrease in antibacterial and antifungal
FT activities, and decrease in hemolytic activity."
FT /evidence="ECO:0000269|PubMed:27912176"
FT MUTAGEN 30
FT /note="N->E: Increase, decrease or no change in
FT antibacterial and antifungal activities, depending on the
FT strains tested, and increase in hemolytic activity.
FT Decrease in antibacterial and antifungal activities, and
FT increase in hemolytic activity; when associated with W-32."
FT /evidence="ECO:0000269|PubMed:27912176"
FT MUTAGEN 30
FT /note="N->K: Increase in antibacterial and antifungal
FT activities on almost all strains tested, and increase in
FT hemolytic activity. Increase in antibacterial, antifungal
FT and hemolytic activities; when associated with K-26.
FT Increase, decrease or no change in antibacterial activity,
FT and increase in antifungal and hemolytic activities; when
FT associated with K-34. Increase or no change in
FT antibacterial activity, and increase in antifungal and
FT hemolytic activities; when associated with K-26 and K-34."
FT /evidence="ECO:0000269|PubMed:27912176,
FT ECO:0000269|PubMed:31181304"
FT MUTAGEN 30
FT /note="N->R: Decrease in antibacterial activity against the
FT antibiotic-resistant bacterium S.aureus, and important
FT increase in antibacterial activity against both antibiotic-
FT resistant bacteria E.cloacae and P.aeruginosa, as well as
FT in increase in hemolytic activity. Increase in trypanocidal
FT activity. No change in antiplasmodial activity. Small
FT decrease in cytotoxic activity."
FT /evidence="ECO:0000269|PubMed:31212183,
FT ECO:0000269|PubMed:33004083, ECO:0000269|PubMed:33442881"
FT MUTAGEN 31
FT /note="V->P: Loss in antibacterial activity against the
FT antibiotic-resistant bacterium S.aureus, and no change in
FT absence of antibacterial activity against both antibiotic-
FT resistant bacteria E.cloacae and P.aeruginosa, as well as
FT loss in hemolytic activity."
FT /evidence="ECO:0000269|PubMed:31212183"
FT MUTAGEN 32
FT /note="A->F,L: No change in antibacterial activity against
FT the antibiotic-resistant bacterieum S.aureus, E.cloacae and
FT P.aeruginosa, as well as in increase in hemolytic
FT activity."
FT /evidence="ECO:0000269|PubMed:31212183"
FT MUTAGEN 32
FT /note="A->K: Important decrease or loss in antibacterial,
FT antifungal and hemolytic activities."
FT /evidence="ECO:0000269|PubMed:31181304"
FT MUTAGEN 32
FT /note="A->W: No change or increase in antibacterial
FT activities, no change or decrease in antifungal activities,
FT and increase in hemolytic activity. Decrease in
FT antibacterial and antifungal activities, and increase in
FT hemolytic activity; when associated with E-30."
FT /evidence="ECO:0000269|PubMed:27912176"
FT MUTAGEN 34
FT /note="S->K: Increase in antibacterial and antifungal
FT activities on almost all strains tested, and increase in
FT hemolytic activity. No change or increase in antibacterial,
FT antifungal and hemolytic activities; when associated with
FT K-26. Increase, decrease or no change in antibacterial
FT activity, and increase in antifungal and hemolytic
FT activities; when associated with K-30. Increase or no
FT change in antibacterial activity, and increase in
FT antifungal and hemolytic activities; when associated with
FT K-26 and K-34."
FT /evidence="ECO:0000269|PubMed:27912176,
FT ECO:0000269|PubMed:31181304"
FT MUTAGEN 34
FT /note="S->R: Decrease in antibacterial activity against the
FT antibiotic-resistant bacterium S.aureus, and important
FT increase in antibacterial activity against both antibiotic-
FT resistant bacteria E.cloacae and P.aeruginosa, as well as
FT in increase in hemolytic activity. Increase in trypanocidal
FT activity of trypomastigote forms, and decrease in
FT trypanocidal activity of epimastigote forms. Loss of
FT antiplasmodial activity. Small decrease in cytotoxic
FT activity."
FT /evidence="ECO:0000269|PubMed:31212183,
FT ECO:0000269|PubMed:33004083, ECO:0000269|PubMed:33442881"
FT MUTAGEN 35
FT /note="V->K: Important decrease or loss in antibacterial,
FT antifungal and hemolytic activities; when associated with
FT K-24."
FT /evidence="ECO:0000269|PubMed:31181304"
FT MUTAGEN 35
FT /note="V->L: No change in antibacterial activity against
FT the antibiotic-resistant bacterium S.aureus, E.cloacae and
FT P.aeruginosa, as well as in increase in hemolytic
FT activity."
FT /evidence="ECO:0000269|PubMed:31212183"
FT MUTAGEN 35
FT /note="V->Y: Decrease in antibacterial activity against the
FT antibiotic-resistant bacterium S.aureus, and no change in
FT absence of antibacterial activity against both antibiotic-
FT resistant bacteria E.cloacae and P.aeruginosa, as well as
FT no change in hemolytic activity."
FT /evidence="ECO:0000269|PubMed:31212183"
SQ SEQUENCE 68 AA; 7770 MW; C143F4BD92D21178 CRC64;
MKTQFVILIV AVVLLQLISH SEAFLGALWN VAKSVFGKRG LRNFDDLDDT FEPEMSEADL
KYLQDLLR
