DEF_COPTR
ID DEF_COPTR Reviewed; 80 AA.
AC A9XFZ7;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 1.
DT 25-MAY-2022, entry version 48.
DE RecName: Full=Defensin coprisin {ECO:0000303|PubMed:20721297};
DE Flags: Precursor;
OS Copris tripartitus (Dung beetle).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Coleoptera; Polyphaga; Scarabaeiformia;
OC Scarabaeidae; Scarabaeinae; Coprini; Copris.
OX NCBI_TaxID=438892;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SYNTHESIS OF 38-80, AND INDUCTION BY
RP BACTERIA.
RC TISSUE=Larva;
RX PubMed=20721297; DOI=10.1155/2009/136284;
RA Hwang J.S., Lee J., Kim Y.J., Bang H.S., Yun E.Y., Kim S.R., Suh H.J.,
RA Kang B.R., Nam S.H., Jeon J.P., Kim I., Lee D.G.;
RT "Isolation and characterization of a defensin-like peptide (coprisin) from
RT the dung beetle, Copris tripartitus.";
RL Int. J. Pept. 2009:0-0(2009).
RN [2]
RP FUNCTION, AND SYNTHESIS OF 38-80.
RX PubMed=22542795; DOI=10.1016/j.freeradbiomed.2012.03.012;
RA Lee J., Hwang J.S., Hwang I.S., Cho J., Lee E., Kim Y., Lee D.G.;
RT "Coprisin-induced antifungal effects in Candida albicans correlate with
RT apoptotic mechanisms.";
RL Free Radic. Biol. Med. 52:2302-2311(2012).
RN [3]
RP PHARMACEUTICAL (COPA3).
RX PubMed=26432335; DOI=10.1007/s13277-015-4162-z;
RA Lee J.H., Kim I.W., Shin Y.P., Park H.J., Lee Y.S., Lee I.H., Kim M.A.,
RA Yun E.Y., Nam S.H., Ahn M.Y., Kang D., Hwang J.S.;
RT "Enantiomeric CopA3 dimer peptide suppresses cell viability and tumor
RT xenograft growth of human gastric cancer cells.";
RL Tumor Biol. 37:3237-3245(2016).
RN [4]
RP PHARMACEUTICAL (DCOPW3).
RX PubMed=30393205; DOI=10.1016/j.bbamem.2018.10.014;
RA Lee J., Kim S., Sim J.Y., Lee D., Kim H.H., Hwang J.S., Lee D.G.,
RA Park Z.Y., Kim J.I.;
RT "A potent antibacterial activity of new short d-enantiomeric lipopeptide
RT against multi drug resistant bacteria.";
RL Biochim. Biophys. Acta 1861:34-42(2019).
RN [5] {ECO:0007744|PDB:2LN4}
RP STRUCTURE BY NMR OF 38-80, FUNCTION, DISULFIDE BONDS, SYNTHESIS OF 38-80,
RP AND PHARMACEUTICAL (COPA3).
RX PubMed=23137439; DOI=10.1016/j.bbamem.2012.10.028;
RA Lee E., Kim J.K., Shin S., Jeong K.W., Shin A., Lee J., Lee D.G.,
RA Hwang J.S., Kim Y.;
RT "Insight into the antimicrobial activities of coprisin isolated from the
RT dung beetle, Copris tripartitus, revealed by structure-activity
RT relationships.";
RL Biochim. Biophys. Acta 1828:271-283(2013).
CC -!- FUNCTION: Potent broad-spectrum antibacterial peptide against both
CC Gram-positive (B.subtilis, S.epidermidis, and S.aureus) and Gram-
CC negative bacteria (E.coli, S.typhimurium, and P.aeruginosa)
CC (PubMed:20721297, PubMed:23137439). Is also active against all
CC antibiotic-resistant bacterial strains tested (PubMed:23137439).
CC Induces apoptosis in C.albicans, but does not disrupt the fungal plasma
CC membrane at all (PubMed:22542795). Acts by permeabilizing the bacterial
CC cell membrane, but not human membranes (PubMed:23137439). Also shows
CC potent anti-inflammatory activities, since it reduces both LPS-induced
CC nitric oxide release and pro-inflammatory cytokine production
CC (PubMed:23137439). Anti-inflammatory activities are initiated by
CC suppressing the binding of LPS to toll-like receptor 4 (TLR4), and
CC subsequently inhibiting the phosphorylation of p38 mitogen-activated
CC protein kinase (MAPK) and nuclear translocation of NF-kB (TNFRSF11A)
CC (PubMed:23137439). Does not show hemolytic activity against human
CC erythrocytes (PubMed:23137439). {ECO:0000269|PubMed:20721297,
CC ECO:0000269|PubMed:22542795, ECO:0000269|PubMed:23137439}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23137439}. Target
CC cell membrane {ECO:0000269|PubMed:23137439}.
CC -!- INDUCTION: Up-regulated from 4 hours after E.coli bacteria injection
CC and higher expression level is reached at 16 hours.
CC {ECO:0000269|PubMed:20721297}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to
CC antiparallel beta-sheets by disulfide bonds (CS-alpha/beta)
CC (PubMed:23137439). The alpha-helix is amphipathic (PubMed:23137439).
CC {ECO:0000269|PubMed:23137439}.
CC -!- PHARMACEUTICAL: Coprisin-derivatives (such as CopA3, and dCopW3) may be
CC used as potent antibiotic therapeutic agent, or in treatment against
CC tumors. {ECO:0000269|PubMed:23137439, ECO:0000269|PubMed:26432335,
CC ECO:0000269|PubMed:30393205}.
CC -!- MISCELLANEOUS: The nonamer peptide CopA3 exhibits potent antibacterial
CC activities (MIC=4-8 ug/mL) against both E.coli and S.aureus. This
CC peptide (LLCIALRKK-NH2) is shorter than the mature peptide, amidated
CC and with a Leu at position 60 instead of a His residue.
CC {ECO:0000269|PubMed:20721297}.
CC -!- SIMILARITY: Belongs to the invertebrate defensin family. Type 1
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: Several experiments have been done with an amidated coprisin,
CC although the amide donor for C-terminal amidation (usually a Gly
CC residue) is missing in the precursor sequence.
CC {ECO:0000305|PubMed:20721297, ECO:0000305|PubMed:22542795}.
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DR EMBL; EF208958; ABP97087.1; -; mRNA.
DR PDB; 2LN4; NMR; -; A=38-80.
DR PDBsum; 2LN4; -.
DR AlphaFoldDB; A9XFZ7; -.
DR SMR; A9XFZ7; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0050832; P:defense response to fungus; IEA:UniProtKB-KW.
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 Gene3D; 3.30.30.10; -; 1.
DR InterPro; IPR017982; Defensin_insect.
DR InterPro; IPR001542; Defensin_invertebrate/fungal.
DR InterPro; IPR003614; Scorpion_toxin-like.
DR InterPro; IPR036574; Scorpion_toxin-like_sf.
DR Pfam; PF01097; Defensin_2; 1.
DR PRINTS; PR00271; DEFENSIN.
DR SMART; SM00505; Knot1; 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; Fungicide;
KW Immunity; Innate immunity; Membrane; Pharmaceutical; Secreted; Signal;
KW Target cell membrane; Target membrane.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..37
FT /evidence="ECO:0000305|PubMed:20721297"
FT /id="PRO_0000452544"
FT CHAIN 38..80
FT /note="Defensin coprisin"
FT /evidence="ECO:0000305|PubMed:20721297"
FT /id="PRO_5002746492"
FT DISULFID 40..71
FT /evidence="ECO:0000269|PubMed:23137439,
FT ECO:0007744|PDB:2LN4"
FT DISULFID 57..76
FT /evidence="ECO:0000269|PubMed:23137439,
FT ECO:0007744|PDB:2LN4"
FT DISULFID 61..78
FT /evidence="ECO:0000269|PubMed:23137439,
FT ECO:0007744|PDB:2LN4"
FT HELIX 56..65
FT /evidence="ECO:0007829|PDB:2LN4"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:2LN4"
FT STRAND 75..79
FT /evidence="ECO:0007829|PDB:2LN4"
SQ SEQUENCE 80 AA; 8560 MW; 13FEDEF422C7D899 CRC64;
MAKLIAFALV ASLCLSMVLC NPLPEEVQEE GLVRQKRVTC DVLSFEAKGI AVNHSACALH
CIALRKKGGS CQNGVCVCRN
