COW2_CONVC
ID COW2_CONVC Reviewed; 63 AA.
AC W4VSA0; A0A1U7Q1X1;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 19-MAR-2014, sequence version 1.
DT 25-MAY-2022, entry version 22.
DE RecName: Full=Contryphan-Vc2 {ECO:0000303|PubMed:24505301, ECO:0000303|PubMed:28216409};
DE AltName: Full=[D-Trp3]-contryphan-Vc2 {ECO:0000303|PubMed:28216409};
DE Flags: Precursor;
OS Conus victoriae (Queen Victoria cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Cylinder.
OX NCBI_TaxID=319920;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=24505301; DOI=10.1371/journal.pone.0087648;
RA Robinson S.D., Safavi-Hemami H., McIntosh L.D., Purcell A.W., Norton R.S.,
RA Papenfuss A.T.;
RT "Diversity of conotoxin gene superfamilies in the venomous snail, Conus
RT victoriae.";
RL PLoS ONE 9:E87648-E87648(2014).
RN [2]
RP STRUCTURE BY NMR OF 56-63 ([D-TRP3]-CONTRYPHAN-VC2), SYNTHESIS OF 56-63
RP (D-TRP; L-TRP AND L-ALA), MUTAGENESIS OF TRP-58, DISULFIDE BOND, BIOASSAY,
RP FUNCTION, AMIDATION AT CYS-62, AND CIS-TRANS ISOMERIZATION.
RX PubMed=28216409; DOI=10.1016/j.toxicon.2017.02.012;
RA Drane S.B., Robinson S.D., MacRaild C.A., Chhabra S., Chittoor B.,
RA Morales R.A., Leung E.W., Belgi A., Espino S.S., Olivera B.M.,
RA Robinson A.J., Chalmers D.K., Norton R.S.;
RT "Structure and activity of contryphan-Vc2: importance of the D-amino acid
RT residue.";
RL Toxicon 129:113-122(2017).
CC -!- FUNCTION: Its target is unknown, but this toxin may modulate voltage-
CC activated calcium channels (Cav) or calcium-dependent potassium
CC channels (KCa). {ECO:0000250|UniProtKB:P0C248,
CC ECO:0000250|UniProtKB:P0C250, ECO:0000250|UniProtKB:P62903,
CC ECO:0000250|UniProtKB:P83047}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:24505301}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:24505301}.
CC -!- DOMAIN: The cysteine framework is C-C. {ECO:0000305}.
CC -!- PTM: D-chirality of Trp-58 ('Trp-3' in the mature Contryphan-Vc2
CC peptide) seems to be only protective against proteolytic degradation,
CC since [L-Trp3]-contryphan-Vc2 is degraded by trypsin within 4 hours,
CC while [D-Trp3]-contryphan-Vc2 is not affected and the toxicity of both
CC [D-Trp3]- and [L-Trp3]-contryphan-Vc2 is similar when intractranially
CC injected into mice (PubMed:28216409). It is also noteworthy that
CC neither [D-Trp3]- nor [L-Trp3]-contryphan-Vc2 is susceptible to
CC cleavage by pepsin or alpha-chymotrypsin over the 4 hours duration of
CC the assay (PubMed:28216409). {ECO:0000269|PubMed:28216409}.
CC -!- MISCELLANEOUS: Exists in two forms, due to cis-trans isomerization at
CC 59-Thr-Pro-60. The trans conformation is the major form, with a
CC cis:trans ratio of 1:5. {ECO:0000269|PubMed:28216409}.
CC -!- SIMILARITY: Belongs to the O2 superfamily. Contryphan family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Biological Magnetic Resonance Data Bank;
CC URL="http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=30152";
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DR EMBL; GAIH01000060; JAB84657.1; -; mRNA.
DR PDB; 5L34; NMR; -; A=56-62.
DR PDBsum; 5L34; -.
DR AlphaFoldDB; W4VSA0; -.
DR SMR; W4VSA0; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR004214; Conotoxin.
DR Pfam; PF02950; Conotoxin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; D-amino acid; Disulfide bond; Lipid-binding;
KW Neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT PROPEP 24..55
FT /evidence="ECO:0000305"
FT /id="PRO_0000445138"
FT PEPTIDE 56..62
FT /note="Contryphan-Vc2"
FT /evidence="ECO:0000305|PubMed:28216409"
FT /id="PRO_5004850815"
FT SITE 58
FT /note="Key residue for activity; D- or L-amino acid at this
FT position is not important"
FT /evidence="ECO:0000269|PubMed:28216409"
FT MOD_RES 58
FT /note="D-tryptophan"
FT /evidence="ECO:0000250|UniProtKB:P58786"
FT MOD_RES 62
FT /note="Cysteine amide"
FT /evidence="ECO:0000305|PubMed:28216409"
FT DISULFID 56..62
FT /evidence="ECO:0000269|PubMed:28216409,
FT ECO:0000312|PDB:5L34"
FT MUTAGEN 58
FT /note="W->A: Loss of activity when intracranially injected
FT into mice."
FT /evidence="ECO:0000269|PubMed:28216409"
SQ SEQUENCE 63 AA; 6901 MW; C7516B393BBF121B CRC64;
MGKLTILFLV AAALLSTQVM VQGDGDQPAD RDAVPRDDNP AGTIEKFMNL LRQVRCRWTP
VCG
