CONII_CONST
ID CONII_CONST Reviewed; 123 AA.
AC P0CB20;
DT 28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 1.
DT 03-AUG-2022, entry version 34.
DE RecName: Full=Con-ikot-ikot;
DE Flags: Precursor;
OS Conus striatus (Striated cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Pionoconus.
OX NCBI_TaxID=6493;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 38-64, FUNCTION,
RP SUBCELLULAR LOCATION, AND MASS SPECTROMETRY.
RC TISSUE=Venom, and Venom gland;
RX PubMed=19481459; DOI=10.1016/j.cub.2009.05.017;
RA Walker C.S., Jensen S., Ellison M., Matta J.A., Lee W.Y., Imperial J.S.,
RA Duclos N., Brockie P.J., Madsen D.M., Isaac J.T., Olivera B., Maricq A.V.;
RT "A novel Conus snail polypeptide causes excitotoxicity by blocking
RT desensitization of AMPA receptors.";
RL Curr. Biol. 19:900-908(2009).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 38-123 IN COMPLEX WITH AMPA
RP RECEPTOR GRIA2, DISULFIDE BOND, SUBUNIT, AND FUNCTION.
RX PubMed=25103405; DOI=10.1126/science.1258409;
RA Chen L., Durr K.L., Gouaux E.;
RT "X-ray structures of AMPA receptor-cone snail toxin complexes illuminate
RT activation mechanism.";
RL Science 345:1021-1026(2014).
CC -!- FUNCTION: Potently and selectively blocks the desensitization of
CC ionotropic glutamate AMPA receptor (GRIA1, GRIA2, GRIA3 and GRIA4). Can
CC also open already desensitized GRIA1 receptors. Binds to a different
CC site than does the drug cyclothiazide (PubMed:19481459). The toxin acts
CC like a straightjacket on the ligand-binding domain (LBD) 'gating ring'
CC of the receptor, restraining the domains via both intra- and interdimer
CC cross-links such that agonist-induced closure of the LBD 'clamshells'
CC is transduced into an irislike expansion of the gating ring
CC (PubMed:25103405). Application of the toxin to hippocampal slices
CC causes a large and rapid increase in resting AMPAR-mediated current
CC leading to neuronal death (PubMed:19481459).
CC {ECO:0000269|PubMed:19481459, ECO:0000269|PubMed:25103405}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000269|PubMed:25103405}.
CC -!- INTERACTION:
CC P0CB20; P0CB20: -; NbExp=3; IntAct=EBI-16116011, EBI-16116011;
CC P0CB20; P19491-2: Gria2; Xeno; NbExp=2; IntAct=EBI-16116011, EBI-15817825;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19481459}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct. {ECO:0000305}.
CC -!- DOMAIN: The cysteine framework is CC-CC-C-C-C-CC-C-C-C-C.
CC {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=9443; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:19481459};
CC -!- MASS SPECTROMETRY: Mass=18868; Method=MALDI; Note=Dimer.;
CC Evidence={ECO:0000269|PubMed:19481459};
CC -!- MISCELLANEOUS: Ikot-ikot is a Filipino word that translates to
CC 'spinning around' or 'turning around', a reference to the swimming
CC phenotype observed in fish injected with the toxin.
CC {ECO:0000305|PubMed:19481459}.
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DR PDB; 4U5B; X-ray; 3.50 A; E/F=38-123.
DR PDB; 4U5C; X-ray; 3.69 A; E/F=38-123.
DR PDB; 4U5D; X-ray; 3.58 A; E/F=38-123.
DR PDB; 4U5E; X-ray; 3.51 A; E/F=38-123.
DR PDB; 4U5F; X-ray; 3.70 A; E/F=38-123.
DR PDB; 4U5G; X-ray; 2.20 A; A/B=38-123.
DR PDB; 4U5H; X-ray; 1.58 A; A/B/C/D/E/F/G/H=38-123.
DR PDBsum; 4U5B; -.
DR PDBsum; 4U5C; -.
DR PDBsum; 4U5D; -.
DR PDBsum; 4U5E; -.
DR PDBsum; 4U5F; -.
DR PDBsum; 4U5G; -.
DR PDBsum; 4U5H; -.
DR AlphaFoldDB; P0CB20; -.
DR SMR; P0CB20; -.
DR DIP; DIP-61686N; -.
DR IntAct; P0CB20; 1.
DR TCDB; 8.B.40.1.1; the conotoxin con-ikot-ikot/conopressin/conophysin/conodipine (ccccc) family.
DR PRIDE; P0CB20; -.
DR ConoServer; 3890; Con-ikot-ikot precursor.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0035792; C:host cell postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Ionotropic glutamate receptor inhibitor;
KW Neurotoxin; Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..37
FT /evidence="ECO:0000269|PubMed:19481459"
FT /id="PRO_0000381162"
FT CHAIN 38..123
FT /note="Con-ikot-ikot"
FT /id="PRO_0000381163"
FT SITE 74
FT /note="Interaction with glutamate receptor 2 (GRIA2)"
FT /evidence="ECO:0000269|PubMed:25103405"
FT SITE 85
FT /note="Interaction with glutamate receptor 2 (GRIA2)"
FT /evidence="ECO:0000269|PubMed:25103405"
FT SITE 112
FT /note="Interaction with glutamate receptor 2 (GRIA2)"
FT /evidence="ECO:0000269|PubMed:25103405"
FT DISULFID 43
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:25103405"
FT DISULFID 44
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:25103405"
FT DISULFID 49..80
FT /evidence="ECO:0000269|PubMed:25103405"
FT DISULFID 50..89
FT /evidence="ECO:0000269|PubMed:25103405"
FT DISULFID 57..72
FT /evidence="ECO:0000269|PubMed:25103405"
FT DISULFID 90..118
FT /evidence="ECO:0000269|PubMed:25103405"
FT DISULFID 96..113
FT /evidence="ECO:0000269|PubMed:25103405"
FT DISULFID 122
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:25103405"
FT HELIX 43..58
FT /evidence="ECO:0007829|PDB:4U5H"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:4U5H"
FT HELIX 65..80
FT /evidence="ECO:0007829|PDB:4U5H"
FT TURN 85..87
FT /evidence="ECO:0007829|PDB:4U5H"
FT HELIX 91..100
FT /evidence="ECO:0007829|PDB:4U5H"
FT HELIX 106..113
FT /evidence="ECO:0007829|PDB:4U5H"
SQ SEQUENCE 123 AA; 13635 MW; 61F0E44BDE2191D1 CRC64;
MAMNMSMTLC MFVMVVVAAT VIDSTQLQEP DLSRMRRSGP ADCCRMKECC TDRVNECLQR
YSGREDKFVS FCYQEATVTC GSFNEIVGCC YGYQMCMIRV VKPNSLSGAH EACKTVSCGN
PCA
