DRS2_PHYBI
ID DRS2_PHYBI Reviewed; 81 AA.
AC P31107; P80283;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 2.
DT 25-MAY-2022, entry version 79.
DE RecName: Full=Dermaseptin-B2 {ECO:0000303|PubMed:18644413, ECO:0000303|PubMed:19113844};
DE Short=DRS-B2 {ECO:0000303|PubMed:18644413, ECO:0000303|PubMed:19113844};
DE AltName: Full=Adenoregulin {ECO:0000303|PubMed:1438301, ECO:0000303|PubMed:8466537};
DE AltName: Full=Dermaseptin BII {ECO:0000303|PubMed:8306981};
DE Flags: Precursor;
GN Name=ADR;
OS Phyllomedusa bicolor (Two-colored leaf frog) (Rana bicolor).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Neobatrachia; Hyloidea; Hylidae; Phyllomedusinae;
OC Phyllomedusa.
OX NCBI_TaxID=8393;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skin;
RX PubMed=8466537; DOI=10.1006/bbrc.1993.1314;
RA Amiche M., Ducancel F., Lajeunesse E., Boulain J.-C., Menez A., Nicolas P.;
RT "Molecular cloning of a cDNA encoding the precursor of adenoregulin from
RT frog skin. Relationships with the vertebrate defensive peptides,
RT dermaseptins.";
RL Biochem. Biophys. Res. Commun. 191:983-990(1993).
RN [2]
RP PROTEIN SEQUENCE OF 46-78, FUNCTION, SUBCELLULAR LOCATION, MASS
RP SPECTROMETRY, AND SYNTHESIS OF 46-78.
RC TISSUE=Skin secretion;
RX PubMed=1438301; DOI=10.1073/pnas.89.22.10960;
RA Daly J.W., Caceres J., Moni R.W., Gusovsky F., Moos M. Jr., Seamon K.B.,
RA Milton K., Myers C.W.;
RT "Frog secretions and hunting magic in the upper Amazon: identification of a
RT peptide that interacts with an adenosine receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:10960-10963(1992).
RN [3]
RP FUNCTION.
RX PubMed=7842473; DOI=10.1007/bf02090781;
RA Shin Y., Moni R.W., Lueders J.E., Daly J.W.;
RT "Effects of the amphiphilic peptides mastoparan and adenoregulin on
RT receptor binding, G proteins, phosphoinositide breakdown, cyclic AMP
RT generation, and calcium influx.";
RL Cell. Mol. Neurobiol. 14:133-157(1994).
RN [4]
RP IDENTIFICATION, AND FUNCTION.
RC TISSUE=Skin;
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 [5]
RP FUNCTION.
RX PubMed=8565049; DOI=10.1007/bf02071881;
RA Moni R.W., Romero F.S., Daly J.W.;
RT "The amphiphilic peptide adenoregulin enhances agonist binding to A1-
RT adenosine receptors and 35SGTP gamma S to brain membranes.";
RL Cell. Mol. Neurobiol. 15:465-493(1995).
RN [6]
RP FUNCTION, AND SYNTHESIS OF 46-78.
RX PubMed=12709067; DOI=10.1046/j.1432-1033.2003.03584.x;
RA Vanhoye D., Bruston F., Nicolas P., Amiche M.;
RT "Antimicrobial peptides from hylid and ranin frogs originated from a 150-
RT million-year-old ancestral precursor with a conserved signal peptide but a
RT hypermutable antimicrobial domain.";
RL Eur. J. Biochem. 270:2068-2081(2003).
RN [7]
RP AMIDATION AT VAL-78.
RX PubMed=15766883; DOI=10.1016/j.pep.2004.12.007;
RA Cao W., Zhou Y., Ma Y., Luo Q., Wei D.;
RT "Expression and purification of antimicrobial peptide adenoregulin with C-
RT amidated terminus in Escherichia coli.";
RL Protein Expr. Purif. 40:404-410(2005).
RN [8]
RP FUNCTION.
RX PubMed=16401077; DOI=10.1021/bi051711i;
RA Lequin O., Ladram A., Chabbert L., Bruston F., Convert O., Vanhoye D.,
RA Chassaing G., Nicolas P., Amiche M.;
RT "Dermaseptin S9, an alpha-helical antimicrobial peptide with a hydrophobic
RT core and cationic termini.";
RL Biochemistry 45:468-480(2006).
RN [9]
RP FUNCTION.
RX PubMed=18637027; DOI=10.1111/j.1742-4658.2008.06554.x;
RA Auvynet C., El Amri C., Lacombe C., Bruston F., Bourdais J., Nicolas P.,
RA Rosenstein Y.;
RT "Structural requirements for antimicrobial versus chemoattractant
RT activities for dermaseptin S9.";
RL FEBS J. 275:4134-4151(2008).
RN [10]
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 [11]
RP STRUCTURE BY NMR OF 46-78 AND 46-68 IN SDS MICELLES, FUNCTION, MECHANISM OF
RP ACTION, SUBCELLULAR LOCATION, MUTAGENESIS OF 69-ALA--GLN-81, AND SYNTHESIS
RP OF 46-78 AND 46-68.
RX PubMed=19113844; DOI=10.1021/bi802025a;
RA Galanth C., Abbassi F., Lequin O., Ayala-Sanmartin J., Ladram A.,
RA Nicolas P., Amiche M.;
RT "Mechanism of antibacterial action of dermaseptin B2: interplay between
RT helix-hinge-helix structure and membrane curvature strain.";
RL Biochemistry 48:313-327(2009).
CC -!- FUNCTION: Cationic amphipathic alpha-helical antimicrobial peptide with
CC potent activity against Gram-negative and Gram-positive bacteria, fungi
CC and protozoa (PubMed:8306981, PubMed:12709067, PubMed:16401077,
CC PubMed:18637027, PubMed:19113844). Acts in a synergistic effect in
CC combination with Plasticin-B1 at doses that are not active alone
CC (PubMed:12709067). Acts by disturbing membrane functions
CC (PubMed:19113844). On model mebranes, induces a strong perturbation of
CC anionic lipid bilayers, resides at the hydrocarbon core-water
CC interface, parallel to the plane of the membrane, and interacts
CC preferentially with the polar head groups and glycerol backbone region
CC of the anionic phospholipids, as well as the region of the lipid acyl
CC chain near the bilayer surface (PubMed:19113844). It induces a positive
CC curvature of the bilayer and clustering of anionic lipids, consistent
CC with a carpet mechanism, that may lead to the formation of mixed
CC peptide-phospholipid toroidal, transient pores and membrane
CC permeation/disruption once a threshold peptide accumulation is reached
CC (PubMed:19113844). Also enhances binding of agonists to adenosine A1
CC receptors (ADORA1), adenosine A2a receptors (ADORA2A), alpha-2
CC adrenergic receptors (ADRA2A) and 5-hydroxytryptamine 1A receptors
CC (HTR1A) (PubMed:1438301, PubMed:8565049). In addition, it enhances
CC guanyl nucleotide exchange which may result in the conversion of
CC receptors to a high affinity state complexed with guanyl nucleotide
CC free G-protein (PubMed:7842473). It affects human behavior eliciting
CC profound malaise, followed by listlessness and then euphoria. It does
CC not show cytotoxic activity on CHO cells (PubMed:19113844). It does not
CC act as a chemoattractant (PubMed:18637027). It does not show hemolytic
CC activity (PubMed:8306981, PubMed:19113844).
CC {ECO:0000269|PubMed:12709067, ECO:0000269|PubMed:1438301,
CC ECO:0000269|PubMed:16401077, ECO:0000269|PubMed:18637027,
CC ECO:0000269|PubMed:19113844, ECO:0000269|PubMed:7842473,
CC ECO:0000269|PubMed:8306981, ECO:0000269|PubMed:8565049}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1438301}. Target
CC cell membrane {ECO:0000269|PubMed:19113844}. Note=Firstly parallelly
CC oriented to the membrane surface, the peptide may mix to phospholipids,
CC forming toroidal and transient pores in the membrane.
CC {ECO:0000269|PubMed:19113844}.
CC -!- TISSUE SPECIFICITY: Expressed by the skin glands.
CC {ECO:0000305|PubMed:1438301}.
CC -!- DOMAIN: Has a helix-hinge-helix sructural motif.
CC {ECO:0000269|PubMed:19113844}.
CC -!- PTM: Amidation permits an increased antimicrobial activity against some
CC microorganisms such as T.album and S.cerevisiae.
CC {ECO:0000269|PubMed:15766883}.
CC -!- PTM: May contain a D-amino acid residue, since the natural peptide is
CC not identical in chromatographic properties to the synthetic peptide.
CC {ECO:0000305|PubMed:1438301}.
CC -!- MASS SPECTROMETRY: Mass=3186; Method=Plasma desorption;
CC Evidence={ECO:0000269|PubMed:1438301};
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=0001";
CC -!- WEB RESOURCE: Name=The data repository of antimicrobial peptides
CC (DRAMP);
CC URL="http://dramp.cpu-bioinfor.org/browse/All_Information.php?id=DRAMP01646&dataset=General";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X70278; CAA49763.1; -; mRNA.
DR PIR; JN0462; JN0462.
DR AlphaFoldDB; P31107; -.
DR SMR; P31107; -.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0050832; P:defense response to fungus; IDA:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
DR InterPro; IPR022731; Dermaseptin.
DR InterPro; IPR004275; Frog_antimicrobial_propeptide.
DR Pfam; PF12121; DD_K; 1.
DR Pfam; PF03032; FSAP_sig_propep; 1.
PE 1: Evidence at protein level;
KW Amidation; Amphibian defense peptide; Antibiotic; Antimicrobial;
KW Cleavage on pair of basic residues; Direct protein sequencing; Fungicide;
KW Immunity; Innate immunity; Membrane; Secreted; Signal;
KW Target cell membrane; Target membrane.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..43
FT /evidence="ECO:0000305|PubMed:1438301"
FT /id="PRO_0000007092"
FT PEPTIDE 46..78
FT /note="Dermaseptin-B2"
FT /evidence="ECO:0000269|PubMed:1438301"
FT /id="PRO_0000007093"
FT PROPEP 80..81
FT /evidence="ECO:0000305|PubMed:1438301"
FT /id="PRO_0000007094"
FT REGION 24..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 54..55
FT /note="Hinge region that separates the two alpha-helices
FT that constitute the peptide"
FT /evidence="ECO:0000269|PubMed:19113844"
FT MOD_RES 78
FT /note="Valine amide"
FT /evidence="ECO:0000305|PubMed:15766883"
FT MUTAGEN 69..81
FT /note="Missing: Loss of antibacterial activity. Loss of the
FT hinge region, the shortened peptide is constituted by only
FT one alpha-helix. Retains cationic charges of the full-
FT length peptide."
FT /evidence="ECO:0000269|PubMed:19113844"
SQ SEQUENCE 81 AA; 8844 MW; C26ADB4E9418272D CRC64;
MAFLKKSLFL VLFLGLVSLS ICEEEKRENE DEEEQEDDEQ SEMKRGLWSK IKEVGKEAAK
AAAKAAGKAA LGAVSEAVGE Q
