CAMP_CRODU
ID CAMP_CRODU Reviewed; 194 AA.
AC U5KJM4;
DT 04-MAR-2015, integrated into UniProtKB/Swiss-Prot.
DT 22-JAN-2014, sequence version 1.
DT 25-MAY-2022, entry version 22.
DE RecName: Full=Crotalicidin {ECO:0000303|PubMed:25100358, ECO:0000303|PubMed:26465972};
DE Short=Ctn {ECO:0000303|PubMed:26465972};
DE AltName: Full=Cathelicidin-related antimicrobial peptide {ECO:0000303|PubMed:25100358, ECO:0000303|PubMed:26465972};
DE Short=CRAMP {ECO:0000303|PubMed:25100358, ECO:0000303|PubMed:26465972};
DE AltName: Full=Vipericidin {ECO:0000303|PubMed:25100358, ECO:0000303|PubMed:26465972};
DE Flags: Precursor;
OS Crotalus durissus terrificus (South American rattlesnake).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Crotalus.
OX NCBI_TaxID=8732;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 161-194, AND FUNCTION.
RC TISSUE=Venom gland;
RX PubMed=25100358; DOI=10.1007/s00726-014-1801-4;
RA Falcao C.B., de La Torre B.G., Perez-Peinado C., Barron A.E., Andreu D.,
RA Radis-Baptista G.;
RT "Vipericidins: a novel family of cathelicidin-related peptides from the
RT venom gland of South American pit vipers.";
RL Amino Acids 46:2561-2571(2014).
RN [2]
RP FUNCTION, SYNTHESIS OF 161-194, AND MUTAGENESIS OF 161-LYS--VAL-174 AND
RP 175-LYS--PHE-194.
RX PubMed=27876749; DOI=10.1038/ja.2016.135;
RA Cavalcante C.S., Falcao C.B., Fontenelle R.O., Andreu D.,
RA Radis-Baptista G.;
RT "Anti-fungal activity of Ctn[15-34], the C-terminal peptide fragment of
RT crotalicidin, a rattlesnake venom gland cathelicidin.";
RL J. Antibiot. 70:231-237(2017).
RN [3]
RP FUNCTION, SYNTHESIS OF 161-194, PHARMACEUTICAL, AND MUTAGENESIS OF
RP 161-LYS--VAL-174 AND 175-LYS--PHE-194.
RX PubMed=29208061; DOI=10.1017/s0031182017001846;
RA Bandeira I.C.J., Bandeira-Lima D., Mello C.P., Pereira T.P.,
RA De Menezes R.R.P.P.B., Sampaio T.L., Falcao C.B., Radis-Baptista G.,
RA Martins A.M.C.;
RT "Antichagasic effect of crotalicidin, a cathelicidin-like vipericidin,
RT found in Crotalus durissus terrificus rattlesnake's venom gland.";
RL Parasitology 145:1059-1064(2018).
RN [4]
RP STRUCTURE BY NMR OF 161-194, SYNTHESIS OF 161-194, FUNCTION, AND
RP MUTAGENESIS OF 161-LYS--VAL-174 AND 175-LYS--PHE-194.
RX PubMed=26465972; DOI=10.1021/acs.jmedchem.5b01142;
RA Falcao C.B., Perez-Peinado C., de la Torre B.G., Mayol X.,
RA Zamora-Carreras H., Jimenez M.A., Radis-Baptista G., Andreu D.;
RT "Structural dissection of crotalicidin, a rattlesnake venom cathelicidin,
RT retrieves a fragment with antimicrobial and antitumor activity.";
RL J. Med. Chem. 58:8553-8563(2015).
CC -!- FUNCTION: Potent antimicrobial peptide against Gram-negative
CC (P.aeruginosa, K.pneumoniae, E.coli, A.baumannii) (PubMed:25100358,
CC PubMed:26465972). Shows moderate activities against Gram-positive
CC bacteria (E.faecalis, S.aureus, S.pyogenes) (PubMed:25100358,
CC PubMed:26465972). Also shows antifungal activity against standard and
CC clinical isolates of yeasts (MIC=10-40 uM) and dermatophytes (MIC=1-5
CC uM) (PubMed:27876749). Adopts an amphipathic alpha helical
CC conformation, that may allow to partition into the target membrane
CC (PubMed:26465972). Shows high toxicity towards human fibroblasts
CC (micromolar ranges) (PubMed:26465972). Shows low hemolytic activities
CC on human erythrocytes (PubMed:25100358, PubMed:26465972). Also shows
CC toxicity (micromolar ranges) when tested on many leukemia cell lines
CC (PubMed:26465972). In addition, when tested in vitro on the parasite
CC Trypanosoma cruzi (responsible of the Chagas disease), is able to
CC reduce the number of the three forms (epimastigote, trypomastigote and
CC amastigote) by inducing cell death through necrosis (PubMed:29208061).
CC {ECO:0000269|PubMed:25100358, ECO:0000269|PubMed:26465972,
CC ECO:0000269|PubMed:29208061}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:25100358}. Target
CC cell membrane {ECO:0000305|PubMed:26465972}. Note=Forms a helical
CC membrane channel in the prey (By similarity).
CC {ECO:0000250|UniProtKB:B6D434, ECO:0000305|PubMed:26465972}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:25100358}.
CC -!- PHARMACEUTICAL: Promising drug candidate or lead for the development of
CC new drugs to treat Chagas disease (also called American
CC Trypanosomiasis). Shows a high selectivity index (SI) of 203.2 to the
CC trypomastigote forms. {ECO:0000305|PubMed:29208061}.
CC -!- MISCELLANEOUS: The putative mature sequence has been predicted by AMPA,
CC a predictive algorithm for identification of peptide stretches with
CC antimicrobial properties. {ECO:0000305|PubMed:25100358}.
CC -!- SIMILARITY: Belongs to the cathelicidin family. {ECO:0000305}.
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DR EMBL; JX948107; AGS36138.1; -; mRNA.
DR PDB; 2MWT; NMR; -; A=161-194.
DR PDBsum; 2MWT; -.
DR AlphaFoldDB; U5KJM4; -.
DR BMRB; U5KJM4; -.
DR SMR; U5KJM4; -.
DR PRIDE; U5KJM4; -.
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:0050832; P:defense response to fungus; IEA:UniProtKB-KW.
DR GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
DR InterPro; IPR001894; Cathelicidin-like.
DR InterPro; IPR046350; Cystatin_sf.
DR PANTHER; PTHR10206; PTHR10206; 1.
DR SUPFAM; SSF54403; SSF54403; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial;
KW Cleavage on pair of basic residues; Disulfide bond; Fungicide; Membrane;
KW Pharmaceutical; Secreted; Signal; Target cell membrane; Target membrane.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..164
FT /evidence="ECO:0000305|PubMed:25100358"
FT /id="PRO_0000432135"
FT PEPTIDE 161..194
FT /note="Crotalicidin"
FT /evidence="ECO:0000305|PubMed:25100358"
FT /id="PRO_0000432136"
FT REGION 125..156
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 125..149
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 79..90
FT /evidence="ECO:0000250"
FT DISULFID 101..118
FT /evidence="ECO:0000250"
FT MUTAGEN 161..174
FT /note="Missing: Ctn[15-34]; Unstructured segment that shows
FT only slight decrease in antibacterial activity, and in
FT toxicity on leukemia cell lines. Shows loss of hemolytic
FT activity, loss of cytotoxicity on fibroblasts, and decrease
FT in anti-trypanosomal activity. Against fungi, shows a loss
FT of activity against dermatophytes, but an increase of
FT activity against pathogenic fungi, including several
FT Candida species."
FT /evidence="ECO:0000269|PubMed:26465972,
FT ECO:0000269|PubMed:27876749, ECO:0000269|PubMed:29208061"
FT MUTAGEN 175..194
FT /note="Missing: Ctn[1-14]; Alpha-helical segment that shows
FT loss of antibacterial activity, loss of hemolytic activity,
FT loss of cytotoxicity on fibroblasts, and on leukemia cell
FT lines, and decrease in anti-trypanosomal activity. Against
FT fungi, shows a loss of activity against dermatophytes, but
FT an increase of activity against pathogenic fungi, including
FT several Candida species."
FT /evidence="ECO:0000269|PubMed:26465972,
FT ECO:0000269|PubMed:27876749, ECO:0000269|PubMed:29208061"
FT HELIX 163..181
FT /evidence="ECO:0007829|PDB:2MWT"
FT STRAND 184..187
FT /evidence="ECO:0007829|PDB:2MWT"
SQ SEQUENCE 194 AA; 22006 MW; E2BBE720F1C3960C CRC64;
MQGFFWKTWL VLAVCGTPAS LAHRPLSYGE ALELAVSVYN GKAGEASLYR LLEAVPQPEW
DPSSEGSQQL NFTLKETACQ VEEERSLEEC GFQEDGVVLE CTGYYFFGET PPVVVLSCVP
VGGVEEEEEE EEEEQKAEAE NDEEVEKEKG DEEKDQPKRV KRFKKFFKKV KKSVKKRLKK
IFKKPMVIGV TIPF
