ID   CYHED_AFREN             Reviewed;          30 AA.
AC   C0HLN8;
DT   07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT   07-OCT-2020, sequence version 1.
DT   03-AUG-2022, entry version 6.
DE   RecName: Full=Cyclotide hyen-D {ECO:0000303|PubMed:32414842};
OS   Afrohybanthus enneaspermus (Spade flower) (Viola enneasperma).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   rosids; fabids; Malpighiales; Violaceae; Afrohybanthus.
OX   NCBI_TaxID=212266 {ECO:0000303|PubMed:32414842};
RN   [1] {ECO:0000305}
RP   PROTEIN SEQUENCE, MASS SPECTROMETRY, FUNCTION, TISSUE SPECIFICITY, DOMAIN,
RP   AND DISULFIDE BONDS.
RX   PubMed=32414842; DOI=10.1074/jbc.ra120.012627;
RA   Du Q., Chan L.Y., Gilding E.K., Henriques S.T., Condon N.D., Ravipati A.S.,
RA   Kaas Q., Huang Y.H., Craik D.J.;
RT   "Discovery and mechanistic studies of cytotoxic cyclotides from the
RT   medicinal herb Hybanthus enneaspermus.";
RL   J. Biol. Chem. 295:10911-10925(2020).
CC   -!- FUNCTION: Probably participates in a plant defense mechanism (By
CC       similarity). Has strong cytotoxic activity against HUVEC cells (LC(50)=
CC       0.58 uM) and various cancer cells including HeLa (LC(50)= 0.48 uM),
CC       MCF-7 and K562 (PubMed:32414842). Also displays some hemolytic activity
CC       (PubMed:32414842). Binds to and induces leakage in phospholipd
CC       membranes, particularly ones containing 1-palmitoyl-2-
CC       oleophosphatidylethanolamine (POPE) (PubMed:32414842).
CC       {ECO:0000255|PROSITE-ProRule:PRU00395, ECO:0000269|PubMed:32414842}.
CC   -!- TISSUE SPECIFICITY: Detected in stems (at protein level).
CC       {ECO:0000269|PubMed:32414842}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin. {ECO:0000305}.
CC   -!- PTM: This is a cyclic peptide. {ECO:0000255|PROSITE-ProRule:PRU00395}.
CC   -!- MASS SPECTROMETRY: Mass=3154.5; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:32414842};
CC   -!- SIMILARITY: Belongs to the cyclotide family. Bracelet subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00395}.
CC   -!- CAUTION: This peptide is cyclic. The start position was chosen by
CC       similarity to Oak1 (kalata B1) for which the DNA sequence is known.
CC       {ECO:0000255|PROSITE-ProRule:PRU00395}.
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DR   PDB; 7RIH; X-ray; 1.35 A; B=1-30.
DR   PDB; 7RII; X-ray; 1.22 A; A=1-30.
DR   PDB; 7RIJ; X-ray; 1.30 A; A=1-30.
DR   PDB; 7RN3; NMR; -; A=1-30.
DR   PDBsum; 7RIH; -.
DR   PDBsum; 7RII; -.
DR   PDBsum; 7RIJ; -.
DR   PDBsum; 7RN3; -.
DR   AlphaFoldDB; C0HLN8; -.
DR   SMR; C0HLN8; -.
DR   GO; GO:0051715; P:cytolysis in another organism; IDA:UniProtKB.
DR   GO; GO:0006952; P:defense response; IDA:UniProtKB.
DR   GO; GO:0044179; P:hemolysis in another organism; IDA:UniProtKB.
DR   InterPro; IPR005535; Cyclotide.
DR   InterPro; IPR012323; Cyclotide_bracelet_CS.
DR   InterPro; IPR036146; Cyclotide_sf.
DR   Pfam; PF03784; Cyclotide; 1.
DR   PIRSF; PIRSF037891; Cycloviolacin; 1.
DR   SUPFAM; SSF57038; SSF57038; 1.
DR   PROSITE; PS51052; CYCLOTIDE; 1.
DR   PROSITE; PS60008; CYCLOTIDE_BRACELET; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Disulfide bond; Knottin;
KW   Plant defense.
FT   PEPTIDE         1..30
FT                   /note="Cyclotide hyen-D"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00395"
FT                   /id="PRO_0000450760"
FT   DISULFID        4..20
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00395,
FT                   ECO:0000269|PubMed:32414842"
FT   DISULFID        8..22
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00395,
FT                   ECO:0000269|PubMed:32414842"
FT   DISULFID        13..27
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00395,
FT                   ECO:0000269|PubMed:32414842"
FT   CROSSLNK        1..30
FT                   /note="Cyclopeptide (Gly-Asn)"
FT                   /evidence="ECO:0000250|UniProtKB:C0HKI7"
FT   STRAND          2..7
FT                   /evidence="ECO:0007829|PDB:7RII"
FT   STRAND          9..11
FT                   /evidence="ECO:0007829|PDB:7RII"
FT   HELIX           14..18
FT                   /evidence="ECO:0007829|PDB:7RII"
FT   STRAND          21..23
FT                   /evidence="ECO:0007829|PDB:7RII"
FT   STRAND          26..29
FT                   /evidence="ECO:0007829|PDB:7RII"
SQ   SEQUENCE   30 AA;  3180 MW;  B24D7A52EF3D1639 CRC64;
     GFPCGESCVY IPCFTAAIGC SCKSKVCYKN