FRE21_SPHLA
ID FRE21_SPHLA Reviewed; 71 AA.
AC L0L3V3;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2013, sequence version 1.
DT 25-MAY-2022, entry version 23.
DE RecName: Full=Frenatin 2.3S {ECO:0000303|PubMed:24704757, ECO:0000303|PubMed:27049440};
DE Short=F2.3S {ECO:0000303|PubMed:30044391};
DE Contains:
DE RecName: Full=Frenatin 2.1S {ECO:0000303|PubMed:24704757};
DE Short=F2.1S {ECO:0000305};
DE Flags: Precursor;
OS Sphaenorhynchus lacteus (Orinoco lime treefrog) (Hyla lactea).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Neobatrachia; Hyloidea; Hylidae; Hylinae; Dendropsophini;
OC Sphaenorhynchus.
OX NCBI_TaxID=279984;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION AS ANTIVIRAL PEPTIDE, AND SYNTHESIS OF
RP 55-71.
RC TISSUE=Skin;
RX PubMed=27049440; DOI=10.1038/ja.2016.16;
RA Munoz-Camargo C., Mendez M.C., Salazar V., Moscoso J., Narvaez D.,
RA Torres M.M., Florez F.K., Groot H., Mitrani E.;
RT "Frog skin cultures secrete anti-yellow fever compounds.";
RL J. Antibiot. 69:783-790(2016).
RN [2]
RP PROTEIN SEQUENCE OF 55-70, FUNCTION, MASS SPECTROMETRY, SUBCELLULAR
RP LOCATION, AND AMIDATION AT GLY-70.
RC TISSUE=Skin secretion;
RX PubMed=24704757; DOI=10.1016/j.peptides.2014.03.020;
RA Conlon J.M., Mechkarska M., Radosavljevic G., Attoub S., King J.D.,
RA Lukic M.L., McClean S.;
RT "A family of antimicrobial and immunomodulatory peptides related to the
RT frenatins from skin secretions of the Orinoco lime frog Sphaenorhynchus
RT lacteus (Hylidae).";
RL Peptides 56:132-140(2014).
RN [3]
RP FUNCTION, AND BIOASSAY.
RX PubMed=25861850; DOI=10.1016/j.peptides.2015.03.028;
RA Pantic J.M., Radosavljevic G.D., Jovanovic I.P., Arsenijevic N.N.,
RA Conlon J.M., Lukic M.L.;
RT "In vivo administration of the frog skin peptide frenatin 2.1S induces
RT immunostimulatory phenotypes of mouse mononuclear cells.";
RL Peptides 71:269-275(2015).
RN [4]
RP FUNCTION, SYNTHESIS OF 55-70, AND PHARMACEUTICAL.
RX PubMed=28526557; DOI=10.1016/j.peptides.2017.05.006;
RA Pantic J.M., Jovanovic I.P., Radosavljevic G.D., Gajovic N.M.,
RA Arsenijevic N.N., Conlon J.M., Lukic M.L.;
RT "The frog skin host-defense peptide frenatin 2.1S enhances recruitment,
RT activation and tumoricidal capacity of NK cells.";
RL Peptides 93:44-50(2017).
RN [5]
RP FUNCTION.
RC TISSUE=Skin;
RX PubMed=30044391; DOI=10.3390/ijms19082170;
RA Munoz-Camargo C., Salazar V.A., Barrero-Guevara L., Camargo S.,
RA Mosquera A., Groot H., Boix E.;
RT "Unveiling the multifaceted mechanisms of antibacterial activity of buforin
RT II and frenatin 2.3S peptides from skin micro-organs of the Orinoco lime
RT treefrog (Sphaenorhynchus lacteus).";
RL Int. J. Mol. Sci. 19:0-0(2018).
RN [6]
RP FUNCTION AS INSULINOTROPIC PEPTIDE.
RX PubMed=30244134; DOI=10.1016/j.biochi.2018.09.008;
RA Musale V., Guilhaudis L., Abdel-Wahab Y.H.A., Flatt P.R., Conlon J.M.;
RT "Insulinotropic activity of the host-defense peptide frenatin 2D:
RT conformational, structure-function and mechanistic studies.";
RL Biochimie 156:12-21(2019).
CC -!- FUNCTION: [Frenatin 2.1S]: Antimicrobial peptide with potent activity
CC against Gram-negative bacteria (PubMed:24704757). Shows
CC immunostimulatory actions both in vitro and in vivo (PubMed:24704757,
CC PubMed:25861850, PubMed:28526557). In vitro, is cytotoxic to non-small
CC cell lung adenocarcinoma A549 cells (PubMed:24704757). Also, stimulates
CC production of pro-inflammatory cytokines by mouse peritoneal
CC macrophages and down-regulates production of the anti-inflammatory
CC cytokine IL-10 by lipopolysaccharide (LPS)-stimulated cells
CC (PubMed:24704757). In vivo, intraperitoneal injection in mice enhances
CC the activation state and homing capacity of Th1 type lymphocytes and
CC promotes the recruitment, activation and tumoricidal capacities of
CC peritoneal NK cells (PubMed:25861850, PubMed:28526557). Has a very weak
CC activity in stimulation of insulin release and a weak hemolytic
CC activity (PubMed:27049440, PubMed:30244134).
CC {ECO:0000269|PubMed:24704757, ECO:0000269|PubMed:25861850,
CC ECO:0000269|PubMed:27049440, ECO:0000269|PubMed:28526557,
CC ECO:0000269|PubMed:30244134}.
CC -!- FUNCTION: [Frenatin 2.3S]: Antimicrobial peptide with potent activity
CC against some Gram-positive and Gram-negative bacteria
CC (PubMed:30044391). Has a multifunctional mode of action
CC (PubMed:30044391). It displays depolarization and bacterial cell
CC leakage, and can also internalize into bacterial cells and alter
CC specific gene expression involved in bacterial resistance mechanisms
CC (PubMed:30044391). Does not agglutinate bacteria and lipid vesicles,
CC even a high concentrations (PubMed:30044391). Also displays moderate
CC cellular protection against yellow fever virus (YFV)-infected Vero
CC cells without causing significant cytotoxicity (PubMed:27049440). Shows
CC a weak hemolytic activity, and is not cytotoxic to monocytes
CC (PubMed:30044391). Frenatin 2.3S (version without Gly-71) shows no or
CC very weak antibacterial activity, shows no or very weak cytotoxicity to
CC lung adenocarcinoma A549 cells and shows very weak hemolysis
CC (PubMed:24704757). It only stimulates production of pro-inflammatory
CC cytokines IL-23 (but not IL-1beta and TNF-alpha) by mouse peritoneal
CC macrophages and has no effect on the production of the anti-
CC inflammatory cytokine IL-10 (PubMed:24704757). Frenatin 2.3S (version
CC without Gly-71) very weakly stimulates insulin release
CC (PubMed:30244134). {ECO:0000269|PubMed:24704757,
CC ECO:0000269|PubMed:27049440, ECO:0000269|PubMed:30044391,
CC ECO:0000269|PubMed:30244134}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24704757}.
CC -!- TISSUE SPECIFICITY: Expressed by the skin glands.
CC {ECO:0000305|PubMed:24704757}.
CC -!- PTM: Frenatin 2.3S is not amidated. {ECO:0000269|PubMed:24704757}.
CC -!- MASS SPECTROMETRY: Mass=1518.0; Method=MALDI; Note=Frenatin 2.1S,
CC amidated.; Evidence={ECO:0000269|PubMed:24704757};
CC -!- MASS SPECTROMETRY: Mass=1518.9; Method=MALDI; Note=Frenatin 2.3S,
CC without Gly-71, non-amidated.; Evidence={ECO:0000269|PubMed:24704757};
CC -!- PHARMACEUTICAL: [Frenatin 2.1S]: May be regarded as a candidate for
CC antitumor immunotherapy, since an injection of this peptide led to a
CC marked increase in the number and tumoricidal capacity of activated
CC peritoneal natural killer (NK) cells in the peritoneal cavity.
CC {ECO:0000269|PubMed:28526557}.
CC -!- SIMILARITY: Belongs to the frog skin active peptide (FSAP) family.
CC Frenatin subfamily. {ECO:0000305}.
CC -!- CAUTION: A paper describes Frenatin 2.3S as a non-amidated peptide of
CC 17 amino acids (PubMed:27049440). In contrast, another report describes
CC it as a non-amidated peptide of 16 amino acids (PubMed:24704757). Since
CC the absence of a C-terminal Gly is generally explained by the activity
CC of Gly as an amide donor, it is possible that Frenatin 2.3S described
CC by PubMed:24704757 comes from another gene, and should be presented in
CC another entry. {ECO:0000305|PubMed:24704757,
CC ECO:0000305|PubMed:27049440}.
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DR EMBL; JX489597; AGB51284.1; -; Genomic_RNA.
DR AlphaFoldDB; L0L3V3; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0050688; P:regulation of defense response to virus; IEA:UniProtKB-KW.
DR InterPro; IPR004275; Frog_antimicrobial_propeptide.
DR Pfam; PF03032; FSAP_sig_propep; 1.
PE 1: Evidence at protein level;
KW Amidation; Amphibian defense peptide; Antibiotic; Antimicrobial;
KW Antiviral protein; Cleavage on pair of basic residues;
KW Direct protein sequencing; DNA-binding; Immunity; Innate immunity;
KW Pharmaceutical; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..54
FT /evidence="ECO:0000305|PubMed:24704757"
FT /id="PRO_0000450233"
FT PEPTIDE 55..71
FT /note="Frenatin 2.3S"
FT /evidence="ECO:0000305|PubMed:27049440"
FT /id="PRO_0000450234"
FT PEPTIDE 55..70
FT /note="Frenatin 2.1S"
FT /evidence="ECO:0000269|PubMed:24704757"
FT /id="PRO_5003945333"
FT REGION 21..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 27..42
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 70
FT /note="Glycine amide; in Frenatin 2.1S"
FT /evidence="ECO:0000269|PubMed:24704757"
SQ SEQUENCE 71 AA; 7908 MW; 20DC7AF3D70AEFB0 CRC64;
MAFLKKSLFL VLFLGLVSLS MGEREKREEE EEEEEENKEE EANEEGKGES EEKRGLVGTL
LGHIGKAILG G
