TPA_RANTE
ID TPA_RANTE Reviewed; 13 AA.
AC P56917;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 29-SEP-2021, entry version 48.
DE RecName: Full=Temporin-1Ta {ECO:0000303|PubMed:24039798};
DE Short=TA {ECO:0000303|PubMed:24039798};
DE AltName: Full=Temporin-A {ECO:0000303|PubMed:16867990, ECO:0000303|PubMed:9022710};
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 PROTEIN SEQUENCE, AMIDATION AT LEU-13, SYNTHESIS, AND SUBCELLULAR LOCATION.
RC TISSUE=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 BIOTECHNOLOGY.
RX PubMed=15198205; DOI=10.1023/b:trag.0000026076.72779.60;
RA Osusky M., Osuska L., Hancock R.E., Kay W.W., Misra S.;
RT "Transgenic potatoes expressing a novel cationic peptide are resistant to
RT late blight and pink rot.";
RL Transgenic Res. 13:181-190(2004).
RN [5]
RP FUNCTION AS ANTIVIRAL PEPTIDE.
RX PubMed=15193922; DOI=10.1016/j.virol.2004.02.029;
RA Chinchar V.G., Bryan L., Silphadaung U., Noga E., Wade D.,
RA Rollins-Smith L.;
RT "Inactivation of viruses infecting ectothermic animals by amphibian and
RT piscine antimicrobial peptides.";
RL Virology 323:268-275(2004).
RN [6]
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 [7]
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 [8]
RP FUNCTION, AND BIOASSAY.
RX PubMed=18255189; DOI=10.1016/j.peptides.2007.12.011;
RA Simonetti O., Cirioni O., Goteri G., Ghiselli R., Kamysz W., Kamysz E.,
RA Silvestri C., Orlando F., Barucca C., Scalise A., Saba V., Scalise G.,
RA Giacometti A., Offidani A.;
RT "Temporin A is effective in MRSA-infected wounds through bactericidal
RT activity and acceleration of wound repair in a murine model.";
RL Peptides 29:520-528(2008).
RN [9]
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 [10]
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 [11]
RP FUNCTION AS INSULINOTROPIC PEPTIDE, AND BIOASSAY.
RX PubMed=29349894; DOI=10.1002/psc.3065;
RA Musale V., Casciaro B., Mangoni M.L., Abdel-Wahab Y.H.A., Flatt P.R.,
RA Conlon J.M.;
RT "Assessment of the potential of temporin peptides from the frog Rana
RT temporaria (Ranidae) as anti-diabetic agents.";
RL J. Pept. Sci. 24:1-12(2018).
RN [12]
RP STRUCTURE BY NMR IN SDS AND DPC MICELLES, FUNCTION, AND MUTAGENESIS OF
RP PRO-3.
RX PubMed=18370376; DOI=10.1021/jm701604t;
RA Carotenuto A., Malfi S., Saviello M.R., Campiglia P., Gomez-Monterrey I.,
RA Mangoni M.L., Gaddi L.M., Novellino E., Grieco P.;
RT "A different molecular mechanism underlying antimicrobial and hemolytic
RT actions of temporins A and L.";
RL J. Med. Chem. 51:2354-2362(2008).
RN [13]
RP STRUCTURE BY NMR IN LPS MICELLES, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=24039798; DOI=10.1371/journal.pone.0072718;
RA Saravanan R., Joshi M., Mohanram H., Bhunia A., Mangoni M.L.,
RA Bhattacharjya S.;
RT "NMR structure of temporin-1 Ta in lipopolysaccharide micelles: mechanistic
RT insight into inactivation by outer membrane.";
RL PLoS ONE 8:e72718-e72718(2013).
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:15513914, PubMed:16867990, PubMed:18255189, PubMed:18370376).
CC Mainly acts by causing membrane permeabilization (Probable). Is also
CC able to kill S.aureus (both wild-type and MRSA) that are internalized
CC in human keratinocytes without injuring host cells (PubMed:24514087).
CC Rapidly inactivates both channel catfish herpesvirus (ED(50)=15 uM) and
CC frog virus 3 (ED(50)=58 uM) over a wide temperature range
CC (PubMed:15193922). Also displays anti-leishmania activity by damaging
CC parasite membrane (PubMed:15513914, PubMed:25668079). Acts
CC synergistically with temporin-L which improves temporin-1Ta activity by
CC preventing its self-association in lipopolysaccharides (LPS)
CC (PubMed:16867990). Does not show hemolytic activity (PubMed:15513914).
CC In vitro, stimulates insulin release from pancreatic beta-cells in a
CC dose-dependent manner without increasing intracellular calcium,
CC protects beta-cells against cytokine-induced apoptosis and augments
CC beta-cells proliferation (PubMed:29349894). In vivo, intraperitoneal
CC injection together with a glucose load into mice does not have effect
CC on plasma glucose levels (PubMed:29349894). In vivo, when tested on
CC mice with methicillin-resistant S.aureus (MRSA)-infected wounds, this
CC peptide inhibits bacterial growth and shows wound healing effect
CC (PubMed:18255189). In vitro, promotes cell migration and wound healing
CC (PubMed:24514087). {ECO:0000269|PubMed:15193922,
CC ECO:0000269|PubMed:15513914, ECO:0000269|PubMed:16867990,
CC ECO:0000269|PubMed:18255189, ECO:0000269|PubMed:18370376,
CC ECO:0000269|PubMed:24514087, ECO:0000269|PubMed:25668079,
CC ECO:0000269|PubMed:29349894, ECO:0000269|PubMed:9022710,
CC ECO:0000305|PubMed:10691983, ECO:0000305|PubMed:11576327}.
CC -!- SUBUNIT: Forms helical oligomeric structures in LPS lipids, the major
CC constituent of Gram-negative bacteria outer membrane (Probable). Adopts
CC monomeric helical conformations when bound to bacterial (anionic) and
CC eukaryotic (zwitterionic) model membranes (PubMed:18370376). In Gram-
CC positive bacterial mimetic membranes, the aggregation is weakly
CC pronounced, and penetration proceeds more rapidly and is deeper than in
CC Gram-negative bacterial mimetic membranes where aggregation is high (By
CC similarity). Self-association is prevented by temporin-L
CC (PubMed:16867990). {ECO:0000250|UniProtKB:P79874,
CC ECO:0000269|PubMed:16867990, ECO:0000269|PubMed:18370376,
CC ECO:0000305|PubMed:24039798}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9022710}. Target
CC cell membrane {ECO:0000269|PubMed:24039798}. Target cell, target cell
CC cytoplasm {ECO:0000269|PubMed:24514087}.
CC -!- TISSUE SPECIFICITY: Expressed by the skin glands.
CC {ECO:0000305|PubMed:9022710}.
CC -!- DOMAIN: Adopts helical conformation in LPS micelles fro residues L4-
CC I12. {ECO:0000269|PubMed:24039798}.
CC -!- BIOTECHNOLOGY: Could be used to protect potato plants from fungi
CC Phytophthora infestans, Phytophthora erythroseptica and bacterium
CC Erwinia carotovora, since the analog N-terminally modified MsrA3
CC (F1MASRHMF), when expressed in potato plants, conveys strong resistance
CC to late blight and pink rot phytopathogens in addition to the bacterial
CC pathogen Erwinia carotovora. Transgenic tubers remained disease-free
CC during storage for more than 2 years. {ECO:0000269|PubMed:15198205}.
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=00094";
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DR PDB; 2MAA; NMR; -; A=1-13.
DR PDBsum; 2MAA; -.
DR BMRB; P56917; -.
DR SMR; P56917; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid 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.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Amphibian defense peptide; Antibiotic;
KW Antimicrobial; Antiviral protein; Direct protein sequencing; Immunity;
KW Innate immunity; Lipid-binding; Membrane; Pharmaceutical; Secreted;
KW Target cell cytoplasm; Target cell membrane; Target membrane.
FT PEPTIDE 1..13
FT /note="Temporin-1Ta"
FT /evidence="ECO:0000269|PubMed:9022710"
FT /id="PRO_0000043579"
FT MOD_RES 13
FT /note="Leucine amide"
FT /evidence="ECO:0000269|PubMed:9022710"
FT MUTAGEN 3
FT /note="P->Q: Weak increase in activity against Gram-
FT positive and Gram-negative bacteria and fungi, and
FT important increase in hemolytic activity."
FT /evidence="ECO:0000269|PubMed:18370376"
FT TURN 3..7
FT /evidence="ECO:0007829|PDB:2MAA"
FT HELIX 8..11
FT /evidence="ECO:0007829|PDB:2MAA"
SQ SEQUENCE 13 AA; 1398 MW; 2653612B9DECD408 CRC64;
FLPLIGRVLS GIL
