DRS4_PHYSA
ID DRS4_PHYSA Reviewed; 27 AA.
AC P80280;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 25-MAY-2022, entry version 68.
DE RecName: Full=Dermaseptin-S4 {ECO:0000303|PubMed:11850249, ECO:0000303|PubMed:11937508, ECO:0000303|PubMed:18644413};
DE Short=DRS-S4 {ECO:0000303|PubMed:18644413};
DE AltName: Full=Dermaseptin IV {ECO:0000303|PubMed:8306981};
DE Short=DS IV {ECO:0000303|PubMed:8306981};
DE AltName: Full=Dermaseptin-4 {ECO:0000303|PubMed:16307969};
DE Short=DS4 {ECO:0000303|PubMed:16307969};
OS Phyllomedusa sauvagei (Sauvage's leaf frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Neobatrachia; Hyloidea; Hylidae; Phyllomedusinae;
OC Phyllomedusa.
OX NCBI_TaxID=8395;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Skin secretion;
RX PubMed=8306981; DOI=10.1111/j.1432-1033.1994.tb19924.x;
RA Mor A., Nicolas P.;
RT "Isolation and structure of novel defensive peptides from frog skin.";
RL Eur. J. Biochem. 219:145-154(1994).
RN [2]
RP FUNCTION, AND SUBUNIT.
RX PubMed=9395500; DOI=10.1074/jbc.272.50.31609;
RA Ghosh J.K., Shaool D., Guillaud P., Ciceron L., Mazier D., Kustanovich I.,
RA Shai Y., Mor A.;
RT "Selective cytotoxicity of dermaseptin S3 toward intraerythrocytic
RT Plasmodium falciparum and the underlying molecular basis.";
RL J. Biol. Chem. 272:31609-31616(1997).
RN [3]
RP POTENTIAL THERAPEUTIC USAGE.
RX PubMed=11587797; DOI=10.1016/s0196-9781(01)00504-6;
RA Feder R., Nehushtai R., Mor A.;
RT "Affinity driven molecular transfer from erythrocyte membrane to target
RT cells.";
RL Peptides 22:1683-1690(2001).
RN [4]
RP POTENTIAL THERAPEUTIC USAGE IN TREATMENT OF BACTERIAL INFECTIONS.
RX PubMed=11850249; DOI=10.1128/aac.46.3.689-694.2002;
RA Navon-Venezia S., Feder R., Gaidukov L., Carmeli Y., Mor A.;
RT "Antibacterial properties of dermaseptin S4 derivatives with in vivo
RT activity.";
RL Antimicrob. Agents Chemother. 46:689-694(2002).
RN [5]
RP POTENTIAL THERAPEUTIC USAGE.
RX PubMed=12119035; DOI=10.1021/bi0201466;
RA Hariton-Gazal E., Feder R., Mor A., Graessmann A., Brack-Werner R.,
RA Jans D., Gilon C., Loyter A.;
RT "Targeting of nonkaryophilic cell-permeable peptides into the nuclei of
RT intact cells by covalently attached nuclear localization signals.";
RL Biochemistry 41:9208-9214(2002).
RN [6]
RP POTENTIAL THERAPEUTIC USAGE IN TREATMENT OF MALARIA.
RX PubMed=11937508; DOI=10.1074/jbc.m202089200;
RA Efron L., Dagan A., Gaidukov L., Ginsburg H., Mor A.;
RT "Direct interaction of dermaseptin S4 aminoheptanoyl derivative with
RT intraerythrocytic malaria parasite leading to increased specific
RT antiparasitic activity in culture.";
RL J. Biol. Chem. 277:24067-24072(2002).
RN [7]
RP POTENTIAL THERAPEUTIC USAGE IN PREVENTION OF HERPES SIMPLEX VIRUS TYPE 1
RP INFECTION.
RX PubMed=11782932; DOI=10.1002/jmv.2134;
RA Belaid A., Aouni M., Khelifa R., Trabelsi A., Jemmali M., Hani K.;
RT "In vitro antiviral activity of dermaseptins against herpes simplex virus
RT type 1.";
RL J. Med. Virol. 66:229-234(2002).
RN [8]
RP FUNCTION AS SPERMICIDE.
RX PubMed=16307969; DOI=10.1016/j.contraception.2005.06.055;
RA Zairi A., Belaid A., Gahbiche A., Hani K.;
RT "Spermicidal activity of dermaseptins.";
RL Contraception 72:447-453(2005).
RN [9]
RP POTENTIAL THERAPEUTIC USAGE IN PREVENTION OF HIV-1 INFECTION.
RX PubMed=15780876; DOI=10.1016/j.virol.2005.02.002;
RA Lorin C., Saidi H., Belaid A., Zairi A., Baleux F., Hocini H., Belec L.,
RA Hani K., Tangy F.;
RT "The antimicrobial peptide dermaseptin S4 inhibits HIV-1 infectivity in
RT vitro.";
RL Virology 334:264-275(2005).
RN [10]
RP POTENTIAL THERAPEUTIC USAGE IN TREATMENT OF BACTERIAL INFECTIONS.
RX PubMed=16870756; DOI=10.1128/aac.00030-06;
RA Rotem S., Radzishevsky I., Mor A.;
RT "Physicochemical properties that enhance discriminative antibacterial
RT activity of short dermaseptin derivatives.";
RL Antimicrob. Agents Chemother. 50:2666-2672(2006).
RN [11]
RP NOMENCLATURE.
RX PubMed=18644413; DOI=10.1016/j.peptides.2008.06.017;
RA Amiche M., Ladram A., Nicolas P.;
RT "A consistent nomenclature of antimicrobial peptides isolated from frogs of
RT the subfamily Phyllomedusinae.";
RL Peptides 29:2074-2082(2008).
RN [12]
RP STRUCTURE BY NMR OF 1-14 OF MUTANT MET-4 AND 14-ALA--ALA-27 DEL, AND
RP MUTAGENESIS OF MET-4 AND 14-ALA--ALA-27.
RX PubMed=16407175; DOI=10.1074/jbc.m513051200;
RA Shalev D.E., Rotem S., Fish A., Mor A.;
RT "Consequences of N-acylation on structure and membrane binding properties
RT of dermaseptin derivative K4-S4-(1-13).";
RL J. Biol. Chem. 281:9432-9438(2006).
CC -!- FUNCTION: Potent antimicrobial peptide with activity against bacteria
CC and protozoa (By similarity). Also has activity against fungi
CC (PubMed:8306981). Also shows activity against enveloped herpes simplex
CC virus type 1 (PubMed:11782932). Probably acts by disturbing membrane
CC functions with its amphipathic structure (Probable). Binds to healthy
CC erythrocytes (this binding is receptor independent), and has strong
CC hemolytic activity (PubMed:9395500). Does not bind to P.falciparum
CC infected erythrocytes, but accumulates within the parasite
CC (PubMed:9395500). Kills the parasite, and only at high concentrations
CC has a hemolytic activity on the host cell (PubMed:9395500). In vitro,
CC shows high spermicidal activities (PubMed:16307969).
CC {ECO:0000250|UniProtKB:P24302, ECO:0000269|PubMed:11782932,
CC ECO:0000269|PubMed:16307969, ECO:0000269|PubMed:8306981,
CC ECO:0000269|PubMed:9395500, ECO:0000305}.
CC -!- SUBUNIT: Monomer and oligomer. Forms aggregates in aqueous
CC environments. {ECO:0000269|PubMed:9395500}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8306981}.
CC -!- TISSUE SPECIFICITY: Expressed by the skin glands.
CC {ECO:0000305|PubMed:8306981}.
CC -!- PHARMACEUTICAL: Derivatives of this peptide may be used as therapeutic
CC agents to treat bacterial infections and malaria, and to prevent
CC infection by herpes simplex virus type 1 and HIV-1.
CC {ECO:0000305|PubMed:11782932, ECO:0000305|PubMed:11937508,
CC ECO:0000305|PubMed:15780876, ECO:0000305|PubMed:9395500}.
CC -!- PHARMACEUTICAL: May be used as a potent vaginal contraceptive, since it
CC shows spermicidal activities. {ECO:0000305|PubMed:16307969}.
CC -!- SIMILARITY: Belongs to the frog skin active peptide (FSAP) family.
CC Dermaseptin subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=The antimicrobial peptide database;
CC URL="https://wangapd3.com/database/query_output.php?ID=0160";
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DR PDB; 2DCX; NMR; -; A=1-13.
DR PDB; 2DD6; NMR; -; A=1-13.
DR PDBsum; 2DCX; -.
DR PDBsum; 2DD6; -.
DR AlphaFoldDB; P80280; -.
DR SMR; P80280; -.
DR EvolutionaryTrace; P80280; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW 3D-structure; Amphibian defense peptide; Antibiotic; Antimicrobial;
KW Cytolysis; Direct protein sequencing; Fungicide; Hemolysis; Pharmaceutical;
KW Secreted.
FT PEPTIDE 1..27
FT /note="Dermaseptin-S4"
FT /evidence="ECO:0000269|PubMed:8306981"
FT /id="PRO_0000043642"
FT MUTAGEN 4
FT /note="M->K: K4-S4-(1-13) selectively disrupts the plasma
FT membrane of the intracellular parasite P.falciparum without
FT harming that of the mammalian host cell; when associated
FT with 14-A--A-27 DEL."
FT MUTAGEN 14..27
FT /note="Missing: K4-S4-(1-13) selectively disrupts the
FT plasma membrane of the intracellular parasite P.falciparum
FT without harming that of the mammalian host cell; when
FT associated with K-4."
FT TURN 4..6
FT /evidence="ECO:0007829|PDB:2DCX"
FT STRAND 7..11
FT /evidence="ECO:0007829|PDB:2DCX"
SQ SEQUENCE 27 AA; 2779 MW; 43C94D2DC19721A8 CRC64;
ALWMTLLKKV LKAAAKALNA VLVGANA
