DEFM0_ARTOT
ID DEFM0_ARTOT Reviewed; 81 AA.
AC I1T3C7;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2012, sequence version 1.
DT 25-MAY-2022, entry version 20.
DE RecName: Full=Fungal defensin micasin {ECO:0000303|PubMed:22586077};
DE AltName: Full=Fungal defensin-like peptide {ECO:0000303|PubMed:22586077};
DE Short=DLP {ECO:0000303|PubMed:22586077};
DE Short=fDLP {ECO:0000303|PubMed:22586077};
DE Flags: Precursor;
OS Arthroderma otae (Microsporum canis).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Onygenales; Arthrodermataceae; Microsporum.
OX NCBI_TaxID=63405;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 44-81, FUNCTION, STRUCTURE BY NMR
RP OF 44-81, AND DISULFIDE BONDS.
RX PubMed=22586077; DOI=10.1073/pnas.1201263109;
RA Zhu S., Gao B., Harvey P.J., Craik D.J.;
RT "Dermatophytic defensin with antiinfective potential.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:8495-8500(2012).
RN [2]
RP FUNCTION, MUTAGENESIS OF PHE-49; GLU-51; HIS-57; ARG-63; LYS-64; PHE-65;
RP LEU-72; ARG-73 AND LYS-80, AND 3D-STRUCTURE MODELING OF WILD-TYPE PEPTIDE
RP AND MUTANTS.
RX PubMed=27084888; DOI=10.1096/fj.201500157;
RA Wu J., Gao B., Zhu S.;
RT "Single-point mutation-mediated local amphipathic adjustment dramatically
RT enhances antibacterial activity of a fungal defensin.";
RL FASEB J. 30:2602-2614(2016).
CC -!- FUNCTION: Antibacterial peptide with potent activity against both Gram-
CC positive and Gram-negative bacteria (PubMed:22586077). May kill
CC bacteria via an intracellular action mode to affect protein folding
CC (PubMed:22586077). Does not show effects on tested filamentous fungi or
CC on the yeast S.cerevisiae (PubMed:22586077). Does not act by destroying
CC the membrane integrity, which is consistent with its nonamphiphilic
CC architecture (PubMed:22586077). Acts more rapidly than vancomycin,
CC suggesting it does not act by inhibiting cell-wall biosynthesis
CC (PubMed:22586077). Does not cause hemolysis and has no cytotoxic effect
CC on HEK cells (PubMed:22586077, PubMed:27084888). In vivo, is as
CC efficient as vancomycin to protect mouse peritonitis models from
CC S.aureus and P.aeruginosa infections (PubMed:22586077).
CC {ECO:0000269|PubMed:22586077, ECO:0000269|PubMed:27084888}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:22586077}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to a
CC beta-sheet by disulfide bonds (CSalpha/beta).
CC {ECO:0000305|PubMed:22586077}.
CC -!- MISCELLANEOUS: The Cys-47-Pro-48 bond adopts an unusual cis
CC conformation. {ECO:0000305|PubMed:22586077}.
CC -!- SIMILARITY: Belongs to the invertebrate defensin family. {ECO:0000305}.
CC -!- CAUTION: Micasin should not be confused with micasin-1, the second
CC defensin-like peptide from A.canis, which shows low sequence similarity
CC compared to micasin. {ECO:0000305|PubMed:22586077}.
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DR EMBL; JN014007; AEM44801.1; -; mRNA.
DR PDB; 2LR5; NMR; -; A=44-81.
DR PDBsum; 2LR5; -.
DR AlphaFoldDB; I1T3C7; -.
DR SMR; I1T3C7; -.
DR TCDB; 1.C.47.1.10; the insect/fungal defensin (insect/fungal defensin) family.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR Gene3D; 3.30.30.10; -; 1.
DR InterPro; IPR001542; Defensin_invertebrate/fungal.
DR InterPro; IPR036574; Scorpion_toxin-like_sf.
DR Pfam; PF01097; Defensin_2; 1.
DR SUPFAM; SSF57095; SSF57095; 1.
DR PROSITE; PS51378; INVERT_DEFENSINS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial;
KW Cleavage on pair of basic residues; Defensin; Disulfide bond; Secreted;
KW Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..43
FT /evidence="ECO:0000305|PubMed:22586077"
FT /id="PRO_0000449426"
FT CHAIN 44..81
FT /note="Fungal defensin micasin"
FT /evidence="ECO:0000305|PubMed:22586077"
FT /id="PRO_5003653316"
FT DISULFID 47..68
FT /evidence="ECO:0000269|PubMed:22586077,
FT ECO:0007744|PDB:2LR5"
FT DISULFID 54..76
FT /evidence="ECO:0000269|PubMed:22586077,
FT ECO:0007744|PDB:2LR5"
FT DISULFID 58..78
FT /evidence="ECO:0000269|PubMed:22586077,
FT ECO:0007744|PDB:2LR5"
FT MUTAGEN 49
FT /note="F->A: Complete loss of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:27084888"
FT MUTAGEN 51
FT /note="E->A,K,R,Q: Important increase of antibacterial
FT activity. This mutant may act by selectively inhibiting
FT peptidoglycan biosynthesis through complex formation with
FT the cell wall precursor lipid II (1:1 molar ratio) thus
FT inhibiting cell wall synthesis. No change in hemolysis
FT induction and cytotoxicity."
FT /evidence="ECO:0000250|UniProtKB:Q53I06,
FT ECO:0000269|PubMed:27084888"
FT MUTAGEN 51
FT /note="E->D: 3-fold decrease in antibacterial activity."
FT /evidence="ECO:0000269|PubMed:27084888"
FT MUTAGEN 51
FT /note="E->L: Small increase of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:27084888"
FT MUTAGEN 57
FT /note="H->A: Complete loss of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:27084888"
FT MUTAGEN 63
FT /note="R->A: Important decrease in antibacterial activity."
FT /evidence="ECO:0000269|PubMed:27084888"
FT MUTAGEN 64
FT /note="K->A: Important decrease in antibacterial activity."
FT /evidence="ECO:0000269|PubMed:27084888"
FT MUTAGEN 65
FT /note="F->A: Complete loss of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:27084888"
FT MUTAGEN 72
FT /note="L->A: Complete loss of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:27084888"
FT MUTAGEN 73
FT /note="R->A: Complete loss of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:27084888"
FT MUTAGEN 80
FT /note="K->A: 3-fold decrease in antibacterial activity."
FT /evidence="ECO:0000269|PubMed:27084888"
SQ SEQUENCE 81 AA; 8330 MW; 5B355163DC2E69DA CRC64;
MQFTKLATIL LVSLMGSAAI AAPATNNAAV DAAADATPAV EKRGFGCPFN ENECHAHCLS
IGRKFGFCAG PLRATCTCGK Q
