P80280 (DMS4_PHYSA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Dermaseptin-4 Alternative name(s): DS IV Dermaseptin-S4 Short name=DS4
Organism	Phyllomedusa sauvagei (Sauvage's leaf frog)
Taxonomic identifier	8395 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amphibia › Batrachia › Anura › Neobatrachia › Hyloidea › Hylidae › Phyllomedusinae › Phyllomedusa

Protein attributes

Sequence length	27 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Possesses a potent antimicrobial activity against Gram-negative and Gram-positive bacteria, fungi, protozoa, and the enveloped herpes simplex virus type 1. Probably acts by disturbing membrane functions with its amphipathic structure. Binds to healthy erythrocytes (this binding is receptor independent), and has strong hemolytic activity. Does not bind to P.falciparum infected erythrocytes, but accumulates within the parasite. Kills the parasite, and only at high concentrations has a hemolytic activity on the host cell. Ref.1 Ref.2
Subcellular location	Secreted.
Tissue specificity	Expressed by the skin glands.
Pharmaceutical use	Derivatives of this peptide may be used as therapeutic agents to treat bacterial infections and malaria, and to prevent infection by herpes simplex virus type 1 and HIV-1.
Sequence similarities	Belongs to the frog skin active peptide (FSAP) family. Dermaseptin subfamily.

Ontologies

Keywords
Biological process	Cytolysis Hemolysis
Cellular component	Secreted
Molecular function	Amphibian defense peptide Antibiotic Antimicrobial Fungicide
Technical term	3D-structure Direct protein sequencing Pharmaceutical
Gene Ontology (GO)
Biological_process	cytolysis Inferred from electronic annotation. Source: UniProtKB-KW defense response to bacterium Inferred from electronic annotation. Source: UniProtKB-KW defense response to fungus Inferred from electronic annotation. Source: UniProtKB-KW hemolysis in other organism Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Peptide

1 – 27

27

Dermaseptin-4

PRO_0000043642

Experimental info

Mutagenesis

4

1

M → K: K4-S4-(1-13) selectively disrupts the plasma membrane of the intracellular parasite P.falciparum without harming that of the mammalian host cell; when associated with 14-A--A-27 DEL.

Mutagenesis

14 – 27

14

Missing: K4-S4-(1-13) selectively disrupts the plasma membrane of the intracellular parasite P.falciparum without harming that of the mammalian host cell; when associated with K-4.

Secondary structure

1

.

.

.

.

27

Helix Strand Turn

Details...

Turn

4 – 6

3

Beta strand

7 – 11

5

Sequences

	Sequence		Length	Mass (Da)
	P80280 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: 43C94D2DC19721A8	FASTA	27	2,779
	10 20 ALWMTLLKKV LKAAAKALNA VLVGANA

References

[1]	"Isolation and structure of novel defensive peptides from frog skin." Mor A., Nicolas P. Eur. J. Biochem. 219:145-154(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE, FUNCTION. Tissue: Skin secretion.
[2]	"Selective cytotoxicity of dermaseptin S3 toward intraerythrocytic Plasmodium falciparum and the underlying molecular basis." Ghosh J.K., Shaool D., Guillaud P., Ciceron L., Mazier D., Kustanovich I., Shai Y., Mor A. J. Biol. Chem. 272:31609-31616(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[3]	"Affinity driven molecular transfer from erythrocyte membrane to target cells." Feder R., Nehushtai R., Mor A. Peptides 22:1683-1690(2001) [PubMed] [Europe PMC] [Abstract] Cited for: POTENTIAL THERAPEUTIC USAGE.
[4]	"Antibacterial properties of dermaseptin S4 derivatives with in vivo activity." Navon-Venezia S., Feder R., Gaidukov L., Carmeli Y., Mor A. Antimicrob. Agents Chemother. 46:689-694(2002) [PubMed] [Europe PMC] [Abstract] Cited for: POTENTIAL THERAPEUTIC USAGE IN TREATMENT OF BACTERIAL INFECTIONS.
[5]	"Targeting of nonkaryophilic cell-permeable peptides into the nuclei of intact cells by covalently attached nuclear localization signals." Hariton-Gazal E., Feder R., Mor A., Graessmann A., Brack-Werner R., Jans D., Gilon C., Loyter A. Biochemistry 41:9208-9214(2002) [PubMed] [Europe PMC] [Abstract] Cited for: POTENTIAL THERAPEUTIC USAGE.
[6]	"Direct interaction of dermaseptin S4 aminoheptanoyl derivative with intraerythrocytic malaria parasite leading to increased specific antiparasitic activity in culture." Efron L., Dagan A., Gaidukov L., Ginsburg H., Mor A. J. Biol. Chem. 277:24067-24072(2002) [PubMed] [Europe PMC] [Abstract] Cited for: POTENTIAL THERAPEUTIC USAGE IN TREATMENT OF MALARIA.
[7]	"In vitro antiviral activity of dermaseptins against herpes simplex virus type 1." Belaid A., Aouni M., Khelifa R., Trabelsi A., Jemmali M., Hani K. J. Med. Virol. 66:229-234(2002) [PubMed] [Europe PMC] [Abstract] Cited for: POTENTIAL THERAPEUTIC USAGE IN PREVENTION OF HERPES SIMPLEX VIRUS TYPE 1 INFECTION.
[8]	"The antimicrobial peptide dermaseptin S4 inhibits HIV-1 infectivity in vitro." Lorin C., Saidi H., Belaid A., Zairi A., Baleux F., Hocini H., Belec L., Hani K., Tangy F. Virology 334:264-275(2005) [PubMed] [Europe PMC] [Abstract] Cited for: POTENTIAL THERAPEUTIC USAGE IN PREVENTION OF HIV-1 INFECTION.
[9]	"Physicochemical properties that enhance discriminative antibacterial activity of short dermaseptin derivatives." Rotem S., Radzishevsky I., Mor A. Antimicrob. Agents Chemother. 50:2666-2672(2006) [PubMed] [Europe PMC] [Abstract] Cited for: POTENTIAL THERAPEUTIC USAGE IN TREATMENT OF BACTERIAL INFECTIONS.
[10]	"Consequences of N-acylation on structure and membrane binding properties of dermaseptin derivative K4-S4-(1-13)." Shalev D.E., Rotem S., Fish A., Mor A. J. Biol. Chem. 281:9432-9438(2006) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-14 OF MUTANT MET-4 AND 14-ALA--ALA-27 DEL.

Cross-references

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DCX	NMR	-	A	1-13	[»]
2DD6	NMR	-	A	1-13	[»]

ModBase

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Protocols and materials databases

StructuralBiologyKnowledgebase

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Family and domain databases

ProtoNet

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Other

EvolutionaryTrace

P80280.

Entry information

Entry name

DMS4_PHYSA

Accession

Primary (citable) accession number: P80280

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	April 3, 2013
This is version 54 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program