ID   CYHEL_AFREN             Reviewed;          30 AA.
AC   C0HLP6;
DT   07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT   02-JUN-2021, sequence version 2.
DT   25-MAY-2022, entry version 5.
DE   RecName: Full=Cyclotide hyen-L {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 cytotoxic activity against HUVEC cells (LC(50)= 2.26
CC       uM) and various cancer cells including HeLa (LC(50)= 3.48 uM), MCF-7
CC       and K562 (PubMed:32414842). Displays very weak 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=3087.4; 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   AlphaFoldDB; C0HLP6; -.
DR   SMR; C0HLP6; -.
DR   GO; GO:0051715; P:cytolysis in another organism; IDA:UniProtKB.
DR   GO; GO:0006952; P:defense response; 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   Direct protein sequencing; Disulfide bond; Knottin; Plant defense.
FT   PEPTIDE         1..30
FT                   /note="Cyclotide hyen-L"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00395"
FT                   /id="PRO_0000450768"
FT   DISULFID        4..21
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00395,
FT                   ECO:0000269|PubMed:32414842"
FT   DISULFID        8..23
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00395,
FT                   ECO:0000269|PubMed:32414842"
FT   DISULFID        13..28
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:B1NRQ8"
SQ   SEQUENCE   30 AA;  3114 MW;  B6F6DAD562656937 CRC64;
     GIPCAESCVY IPCTVTALLG CSCSDKVCYN