TPB_RANTE
ID TPB_RANTE Reviewed; 61 AA.
AC P79874;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 25-MAY-2022, entry version 68.
DE RecName: Full=Temporin-1Tb {ECO:0000303|PubMed:27351824, ECO:0000303|PubMed:28443279};
DE Short=TB {ECO:0000303|PubMed:30718667};
DE AltName: Full=Temporin-B {ECO:0000303|PubMed:16867990, ECO:0000303|PubMed:30718667, ECO:0000303|PubMed:9022710};
DE Flags: Precursor;
OS Rana temporaria (European common frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Neobatrachia; Ranoidea; Ranidae; Rana; Rana.
OX NCBI_TaxID=8407;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 47-59, FUNCTION, AMIDATION
RP AT LEU-59, SYNTHESIS OF 47-59, AND SUBCELLULAR LOCATION.
RC TISSUE=Skin, and Skin secretion;
RX PubMed=9022710; DOI=10.1111/j.1432-1033.1996.0788r.x;
RA Simmaco M., Mignogna G., Canofeni S., Miele R., Mangoni M.L., Barra D.;
RT "Temporins, antimicrobial peptides from the European red frog Rana
RT temporaria.";
RL Eur. J. Biochem. 242:788-792(1996).
RN [2]
RP FUNCTION.
RX PubMed=10691983; DOI=10.1046/j.1432-1327.2000.01143.x;
RA Mangoni M.L., Rinaldi A.C., Di Giulio A., Mignogna G., Bozzi A., Barra D.,
RA Simmaco M.;
RT "Structure-function relationships of temporins, small antimicrobial
RT peptides from amphibian skin.";
RL Eur. J. Biochem. 267:1447-1454(2000).
RN [3]
RP FUNCTION.
RX PubMed=11576327; DOI=10.1034/j.1399-3011.2001.00896.x;
RA Rinaldi A.C., Di Giulio A., Liberi M., Gualtieri G., Oratore A., Bozzi A.,
RA Schinina M.E., Simmaco M.;
RT "Effects of temporins on molecular dynamics and membrane permeabilization
RT in lipid vesicles.";
RL J. Pept. Res. 58:213-220(2001).
RN [4]
RP FUNCTION.
RX PubMed=15513914; DOI=10.1074/jbc.m410795200;
RA Mangoni M.L., Saugar J.M., Dellisanti M., Barra D., Simmaco M., Rivas L.;
RT "Temporins, small antimicrobial peptides with leishmanicidal activity.";
RL J. Biol. Chem. 280:984-990(2005).
RN [5]
RP FUNCTION, AND SUBUNIT.
RX PubMed=16867990; DOI=10.1074/jbc.m606031200;
RA Rosenfeld Y., Barra D., Simmaco M., Shai Y., Mangoni M.L.;
RT "A synergism between temporins toward Gram-negative bacteria overcomes
RT resistance imposed by the lipopolysaccharide protective layer.";
RL J. Biol. Chem. 281:28565-28574(2006).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHARMACEUTICAL.
RX PubMed=24514087; DOI=10.1128/aac.02801-13;
RA Di Grazia A., Luca V., Segev-Zarko L.A., Shai Y., Mangoni M.L.;
RT "Temporins A and B stimulate migration of HaCaT keratinocytes and kill
RT intracellular Staphylococcus aureus.";
RL Antimicrob. Agents Chemother. 58:2520-2527(2014).
RN [7]
RP FUNCTION.
RX PubMed=25668079; DOI=10.3390/molecules20022775;
RA Eggimann G.A., Sweeney K., Bolt H.L., Rozatian N., Cobb S.L., Denny P.W.;
RT "The role of phosphoglycans in the susceptibility of Leishmania mexicana to
RT the temporin family of anti-microbial peptides.";
RL Molecules 20:2775-2785(2015).
RN [8]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=27351824; DOI=10.1080/08927014.2016.1194401;
RA Maisetta G., Grassi L., Di Luca M., Bombardelli S., Medici C.,
RA Brancatisano F.L., Esin S., Batoni G.;
RT "Anti-biofilm properties of the antimicrobial peptide temporin 1Tb and its
RT ability, in combination with EDTA, to eradicate Staphylococcus epidermidis
RT biofilms on silicone catheters.";
RL Biofouling 32:787-800(2016).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF LEU-47; GLY-52; GLY-53 AND LEU-59.
RX PubMed=28443279; DOI=10.3389/fchem.2017.00024;
RA Grassi L., Maisetta G., Maccari G., Esin S., Batoni G.;
RT "Analogs of the frog-skin antimicrobial peptide temporin 1Tb exhibit a
RT wider spectrum of activity and a stronger antibiofilm potential as compared
RT to the parental peptide.";
RL Front. Chem. 5:24-24(2017).
RN [10]
RP FUNCTION AS ANTIVIRAL PEPTIDE.
RX PubMed=29483113; DOI=10.1128/aac.02367-17;
RA Marcocci M.E., Amatore D., Villa S., Casciaro B., Aimola P., Franci G.,
RA Grieco P., Galdiero M., Palamara A.T., Mangoni M.L., Nencioni L.;
RT "The amphibian antimicrobial peptide temporin B inhibits in vitro herpes
RT simplex virus 1 infection.";
RL Antimicrob. Agents Chemother. 62:0-0(2018).
RN [11]
RP STRUCTURE BY NMR OF 47-59 IN COMPLEX WITH TEMPORIN-1TL IN LPS MICELLES.
RX PubMed=21586570; DOI=10.1074/jbc.m110.189662;
RA Bhunia A., Saravanan R., Mohanram H., Mangoni M.L., Bhattacharjya S.;
RT "NMR structures and interactions of temporin-1Tl and temporin-1Tb with
RT lipopolysaccharide micelles: mechanistic insights into outer membrane
RT permeabilization and synergistic activity.";
RL J. Biol. Chem. 286:24394-24406(2011).
RN [12]
RP STRUCTURE BY NMR OF TEMPORIN-B AND ITS ANALOG TB_KKG6A IN SDS MICELLES,
RP SUBUNIT, AND MUTAGENESIS OF LEU-47; GLY-52; GLY-53 AND LEU-59.
RX PubMed=30718667; DOI=10.1038/s41598-018-37630-3;
RA Manzo G., Ferguson P.M., Gustilo V.B., Hind C.K., Clifford M., Bui T.T.,
RA Drake A.F., Atkinson R.A., Sutton J.M., Batoni G., Lorenz C.D.,
RA Phoenix D.A., Mason A.J.;
RT "Minor sequence modifications in temporin B cause drastic changes in
RT antibacterial potency and selectivity by fundamentally altering membrane
RT activity.";
RL Sci. Rep. 9:1385-1385(2019).
CC -!- FUNCTION: Amphipathic alpha-helical antimicrobial peptide with potent
CC activity against Gram-positive bacteria, weak activity against Gram-
CC negative bacteria, and moderate activity against fungi (PubMed:9022710,
CC PubMed:27351824, PubMed:30718667). Mainly acts by causing membrane
CC permeabilization, but is unable to forme pore-like openings (Probable).
CC Is also able to penetrate eukaryotic cells (keratinocytes), and kill
CC intracellular S.aureus (both wild-type and MRSA) without injuring host
CC cells (PubMed:24514087). Shows inhibitory effect on biofilm formation
CC of Gram-positive bacteria, but not of Gram-negative bacteria
CC (PubMed:27351824, PubMed:28443279). Shows antiviral activity against
CC herpes simplex virus 1 (HSV-1) by disrupting the viral envelope
CC (PubMed:29483113). Also displays anti-leishmania activity by damaging
CC parasite membrane (PubMed:15513914, PubMed:25668079). Does not show
CC hemolytic activity (PubMed:9022710, PubMed:15513914, PubMed:28443279).
CC Acts synergistically with temporin-L that improves temporin-1Tb
CC activity by preventing its self-association in lipopolysaccharides
CC (LPS) (PubMed:16867990, PubMed:21586570). In vitro, promotes cell
CC migration and wound healing (PubMed:24514087).
CC {ECO:0000269|PubMed:15513914, ECO:0000269|PubMed:16867990,
CC ECO:0000269|PubMed:21586570, ECO:0000269|PubMed:24514087,
CC ECO:0000269|PubMed:25668079, ECO:0000269|PubMed:27351824,
CC ECO:0000269|PubMed:28443279, ECO:0000269|PubMed:29483113,
CC ECO:0000269|PubMed:30718667, ECO:0000269|PubMed:9022710,
CC ECO:0000305|PubMed:10691983, ECO:0000305|PubMed:11576327}.
CC -!- SUBUNIT: Homo-oligomerizes in membranes as homodimers, homotrimers, or
CC even homotetramers (Probable). Oligomerizes in presence of LPS
CC (PubMed:16867990, PubMed:21586570). In Gram-positive bacterial mimetic
CC membranes, the aggregation is weakly pronounced, and penetration
CC proceeds more rapidly and is deeper than in Gram-negative bacterial
CC mimetic membranes where aggregation is high (PubMed:30718667). Homo-
CC oligomerization is prevented by temporin-L (PubMed:16867990,
CC PubMed:21586570). {ECO:0000269|PubMed:16867990,
CC ECO:0000269|PubMed:21586570, ECO:0000269|PubMed:30718667,
CC ECO:0000305|PubMed:30718667}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9022710}. Target
CC cell membrane {ECO:0000269|PubMed:30718667}. Target cell, target cell
CC cytoplasm {ECO:0000269|PubMed:24514087}. Note=Contact and insertion
CC into membrane begin at the N-terminus. {ECO:0000250|UniProtKB:P69019}.
CC -!- TISSUE SPECIFICITY: Expressed by the skin glands.
CC {ECO:0000305|PubMed:9022710}.
CC -!- BIOTECHNOLOGY: Has potential application in preventing device infection
CC by S.epidermidis biofilm, since it has the ability, in combination with
CC EDTA, to eradicate S.epidermidis biofilms on silicone catheters.
CC {ECO:0000305|PubMed:27351824}.
CC -!- PHARMACEUTICAL: Is an attractive candidate for the generation of new
CC therapeutics to treat S.aureus-related epithelial (skin) infections. It
CC has (i) a long-lasting existence in nature as active molecule which is
CC able to exert a direct antimicrobial activity, which should guarantee
CC the success of the antimicrobial efficacy of temporin-based anti-
CC infective agents; (ii) a membrane-perturbing activity on bacteria,
CC which should limit the induction of microbial resistance; (iii) the
CC ability to kill both reference S.aureus and MRSA strains, once
CC internalized by human epidermal cells and to treat them; (iv) the
CC ability to stimulate migration of these cells; (v) a chemoattractic
CC property for human monocytes; (vi) an exogenous (nonmammalian) nature,
CC which should allow beneficial effects in clinical medicine, reducing
CC the possible risk of inducing an autoimmune response; and, (vii) a
CC small size, which should allow a low production cost.
CC {ECO:0000305|PubMed:24514087}.
CC -!- SIMILARITY: Belongs to the frog skin active peptide (FSAP) family.
CC Temporin subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=The antimicrobial peptide database;
CC URL="https://wangapd3.com/database/query_output.php?ID=00095";
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DR EMBL; Y09393; CAA70562.1; -; mRNA.
DR PDB; 6GIJ; NMR; -; A=45-59.
DR PDB; 6GIL; NMR; -; A=47-59.
DR PDBsum; 6GIJ; -.
DR PDBsum; 6GIL; -.
DR AlphaFoldDB; P79874; -.
DR BMRB; P79874; -.
DR SMR; P79874; -.
DR TCDB; 1.C.52.1.6; the dermaseptin (dermaseptin) family.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0050832; P:defense response to fungus; IEA:UniProtKB-KW.
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 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 3D-structure; Amidation; Amphibian defense peptide; Antibiotic;
KW Antimicrobial; Antiviral protein; Cleavage on pair of basic residues;
KW Direct protein sequencing; Fungicide; Immunity; Innate immunity;
KW Lipid-binding; Membrane; Pharmaceutical; Secreted; Signal;
KW Target cell cytoplasm; Target cell membrane; Target membrane.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..44
FT /evidence="ECO:0000305|PubMed:9022710"
FT /id="PRO_0000003471"
FT PEPTIDE 47..59
FT /note="Temporin-1Tb"
FT /evidence="ECO:0000269|PubMed:9022710"
FT /id="PRO_0000003472"
FT MOD_RES 59
FT /note="Leucine amide"
FT /evidence="ECO:0000269|PubMed:9022710"
FT MUTAGEN 47
FT /note="L->F: In amidated TB_L1FK; increase in antimicrobial
FT activity against Gram-positive and Gram-negative bacteria
FT and against fungi. No change in inhibition of biofilm
FT formation of both Gram-positive and Gram-negative bacteria.
FT Increase in bacteria spectrum of activity. No important
FT change in penetration in membranes and peptide aggregation
FT at their surface. Increase of hemolytic activity."
FT /evidence="ECO:0000269|PubMed:28443279,
FT ECO:0000269|PubMed:30718667"
FT MUTAGEN 52
FT /note="G->A: In amidated TB_KKG6A; increase or loss
FT (contreversial depending on reference) of activity against
FT Gram-positive bacteria, no change in activity against Gram-
FT negative bacteria (except an increase of activity against
FT A.baumanii and E.coli), and decrease in activity against
FT fungi. Important increase in inhibition of biofilm
FT formation of Gram-negative bacteria. Decrease in bacteria
FT spectrum of activity. Important decrease of penetration
FT into membranes, and decrease in peptide aggregation at
FT membrane surface. Increase of hemolytic activity."
FT /evidence="ECO:0000269|PubMed:28443279,
FT ECO:0000269|PubMed:30718667"
FT MUTAGEN 53
FT /note="Missing: In amidated TB_L1FK; increase in
FT antimicrobial activity against Gram-positive and Gram-
FT negative bacteria and against fungi. No change in
FT inhibition of biofilm formation of both Gram-positive and
FT Gram-negative bacteria. Increase in bacteria spectrum of
FT activity. No important change in penetration in membranes
FT and peptide aggregation at their surface. Increase of
FT hemolytic activity."
FT /evidence="ECO:0000269|PubMed:28443279,
FT ECO:0000269|PubMed:30718667"
FT MUTAGEN 59
FT /note="L->LK: In amidated TB_L1FK; increase in
FT antimicrobial activity against Gram-positive and Gram-
FT negative bacteria and against fungi. No change in
FT inhibition of biofilm formation of both Gram-positive and
FT Gram-negative bacteria. Increase in bacteria spectrum of
FT activity. No important change in penetration in membranes
FT and peptide aggregation at their surface. Increase of
FT hemolytic activity."
FT /evidence="ECO:0000269|PubMed:28443279,
FT ECO:0000269|PubMed:30718667"
FT MUTAGEN 59
FT /note="L->LKK: In amidated TB_KKG6A; increase or loss
FT (contreversial depending on reference) of activity against
FT Gram-positive bacteria, no change in activity against Gram-
FT negative bacteria (except an increase of activity against
FT A.baumanii and E.coli), and decrease in activity against
FT fungi. Important increase in inhibition of biofilm
FT formation of Gram-negative bacteria. Decrease in bacteria
FT spectrum of activity. Important decrease of penetration
FT into membranes, and decrease in peptide aggregation at
FT membrane surface. Increase of hemolytic activity."
FT /evidence="ECO:0000269|PubMed:28443279,
FT ECO:0000269|PubMed:30718667"
FT HELIX 48..55
FT /evidence="ECO:0007829|PDB:6GIJ"
SQ SEQUENCE 61 AA; 7101 MW; B73F75689C300357 CRC64;
MFTLKKSLLL LFFLGTINLS LCEEERNAEE ERRDEPDERD VQVEKRLLPI VGNLLKSLLG
K
