DEF4_MESMA
ID DEF4_MESMA Reviewed; 62 AA.
AC P0DQT9;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 1.
DT 03-AUG-2022, entry version 2.
DE RecName: Full=Defensin BmKDfsin4 {ECO:0000303|PubMed:24129506};
DE AltName: Full=4 kDa defensin {ECO:0000250|UniProtKB:P41965};
DE Flags: Precursor;
OS Mesobuthus martensii (Manchurian scorpion) (Buthus martensii).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Mesobuthus.
OX NCBI_TaxID=34649;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC TISSUE=Muscle;
RX PubMed=24129506; DOI=10.1038/ncomms3602;
RA Cao Z., Yu Y., Wu Y., Hao P., Di Z., He Y., Chen Z., Yang W., Shen Z.,
RA He X., Sheng J., Xu X., Pan B., Feng J., Yang X., Hong W., Zhao W., Li Z.,
RA Huang K., Li T., Kong Y., Liu H., Jiang D., Zhang B., Hu J., Hu Y.,
RA Wang B., Dai J., Yuan B., Feng Y., Huang W., Xing X., Zhao G., Li X.,
RA Li Y., Li W.;
RT "The genome of Mesobuthus martensii reveals a unique adaptation model of
RT arthropods.";
RL Nat. Commun. 4:2602-2602(2013).
RN [2]
RP FUNCTION, 3D-STRUCTURE MODELING, RECOMBINANT EXPRESSION, AND MUTAGENESIS OF
RP LYS-37; ARG-43; ARG-44; ARG-45 AND ARG-61.
RX PubMed=26817841; DOI=10.1074/jbc.m115.680611;
RA Meng L., Xie Z., Zhang Q., Li Y., Yang F., Chen Z., Li W., Cao Z., Wu Y.;
RT "Scorpion potassium channel-blocking defensin highlights a functional link
RT with neurotoxin.";
RL J. Biol. Chem. 291:7097-7106(2016).
RN [3]
RP FUNCTION, AND RECOMBINANT EXPRESSION.
RX PubMed=27128943; DOI=10.3390/toxins8050124;
RA Zeng Z., Zhang Q., Hong W., Xie Y., Liu Y., Li W., Wu Y., Cao Z.;
RT "A scorpion defensin BmKDfsin4 inhibits hepatitis B virus replication in
RT vitro.";
RL Toxins 8:0-0(2016).
CC -!- FUNCTION: Dual-function peptide with antimicrobial and potassium
CC channel-blocking activities (PubMed:26817841). Shows inhibitory
CC activity against Gram-positive bacteria such as S.aureus, B.subtilis,
CC and M.luteus as well as methicillin-resistant S.aureus (MIC=0.1-20 uM)
CC (PubMed:26817841). Does not act on bacteria by disrupting membranes
CC (PubMed:26817841). Also moderately inhibits Kv1.1/KCNA1 (25.2%
CC inhibition at 1 uM), Kv1.2/KCNA2 (30.5% inhibition at 1 uM), and
CC Kv1.3/KCNA3 potassium channels (IC(50)=510.2 nM, 61% inhibition at 1
CC uM) (PubMed:26817841). Inhibits potassium channels by interacting with
CC the pore region (PubMed:26817841). Does not show hemolytic activity
CC (PubMed:27128943). In vitro, dose-dependently decreases the production
CC of Hepatitis B virus (HBV) DNA and HBV viral proteins in both culture
CC medium and cell lysate (PubMed:27128943). {ECO:0000269|PubMed:26817841,
CC ECO:0000269|PubMed:27128943}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:24129506}.
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:26817841}.
CC -!- MISCELLANEOUS: Has no inhibitory activity against Gram-negative
CC bacteria (PubMed:26817841). Shows very weak inhibition of the potassium
CC currents mediated by the Kv11.1/KCNH2/ERG1 (11.6%), KCa3.1/KCNN4/IK/SK4
CC (3.9%), KCa2.3/KCNN3/SK3 (7%), Kv7/KCNQ (5.9%), when tested at 1 uM
CC (PubMed:26817841). {ECO:0000269|PubMed:26817841}.
CC -!- SIMILARITY: Belongs to the invertebrate defensin family. Type 2
CC subfamily. {ECO:0000305}.
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DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; 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 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 Antibiotic; Antimicrobial;
KW Calcium-activated potassium channel impairing toxin; Defensin;
KW Disulfide bond; Immunity; Innate immunity; Ion channel impairing toxin;
KW Neurotoxin; Potassium channel impairing toxin; Secreted; Signal; Toxin;
KW Voltage-gated potassium channel impairing toxin.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..62
FT /note="Defensin BmKDfsin4"
FT /evidence="ECO:0000305|PubMed:24129506"
FT /id="PRO_0000455528"
FT SITE 37
FT /note="Key residue in interaction with Kv1.3/KCNA3"
FT /evidence="ECO:0000269|PubMed:26817841"
FT SITE 43
FT /note="Key residue in interaction with Kv1.3/KCNA3"
FT /evidence="ECO:0000269|PubMed:26817841"
FT DISULFID 28..49
FT /evidence="ECO:0000250|UniProtKB:A0A384E0Y8"
FT DISULFID 35..57
FT /evidence="ECO:0000250|UniProtKB:A0A384E0Y8"
FT DISULFID 39..59
FT /evidence="ECO:0000250|UniProtKB:A0A384E0Y8"
FT MUTAGEN 37
FT /note="K->A: Important decrease in ability to block
FT Kv1.3/KCNA3 potassium channel."
FT /evidence="ECO:0000269|PubMed:26817841"
FT MUTAGEN 43
FT /note="R->A: Important decrease in ability to block
FT Kv1.3/KCNA3 potassium channel."
FT /evidence="ECO:0000269|PubMed:26817841"
FT MUTAGEN 44
FT /note="R->A: Moderate decrease in abmility to block
FT Kv1.3/KCNA3 potassium channel."
FT /evidence="ECO:0000269|PubMed:26817841"
FT MUTAGEN 45
FT /note="R->A: Moderate decrease in ability to block
FT Kv1.3/KCNA3 potassium channel."
FT /evidence="ECO:0000269|PubMed:26817841"
FT MUTAGEN 61
FT /note="R->A: Moderate decrease in ability to block
FT Kv1.3/KCNA3 potassium channel."
FT /evidence="ECO:0000269|PubMed:26817841"
SQ SEQUENCE 62 AA; 7074 MW; 6FFEC316F4DFD529 CRC64;
MKTIVLLFVL ALVFCTLEMG IVEAGFGCPF NQGQCHKHCQ SIRRRGGYCD GFLKQRCVCY
RK
