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   03-MAY-2023, entry version 69.
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:0031640; P:killing of cells of 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
//