O16A_CONPU
ID O16A_CONPU Reviewed; 81 AA.
AC P58913;
DT 26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 26-JUL-2002, sequence version 1.
DT 25-MAY-2022, entry version 74.
DE RecName: Full=Delta-conotoxin PVIA {ECO:0000303|PubMed:7711013};
DE AltName: Full=Lockjaw peptide {ECO:0000303|PubMed:7711013};
DE Flags: Precursor;
OS Conus purpurascens (Purple cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Chelyconus.
OX NCBI_TaxID=41690;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 52-80, SYNTHESIS OF 52-80,
RP HYDROXYLATION AT PRO-57 AND PRO-65, MASS SPECTROMETRY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Venom, and Venom duct;
RX PubMed=7711013; DOI=10.1021/bi00015a002;
RA Shon K.-J., Grilley M.M., Marsh M., Yoshikami D., Hall A.R., Kurz B.,
RA Gray W.R., Imperial J.S., Hillyard D.R., Olivera B.M.;
RT "Purification, characterization, synthesis, and cloning of the lockjaw
RT peptide from Conus purpurascens venom.";
RL Biochemistry 34:4913-4918(1995).
RN [2]
RP PROTEIN SEQUENCE OF 52-80, AND SYNTHESIS OF 52-80.
RX PubMed=12074021; DOI=10.1038/381148a0;
RA Terlau H., Shon K.-J., Grilley M.M., Stocker M., Stuehmer W., Olivera B.M.;
RT "Strategy for rapid immobilization of prey by a fish-hunting marine
RT snail.";
RL Nature 381:148-151(1996).
RN [3]
RP FUNCTION.
RX PubMed=10627583; DOI=10.1523/jneurosci.20-01-00076.2000;
RA Safo P., Rosenbaum T., Shcherbatko A., Choi D.-Y., Han E.,
RA Toledo-Aral J.J., Olivera B.M., Brehm P., Mandel G.;
RT "Distinction among neuronal subtypes of voltage-activated sodium channels
RT by mu-conotoxin PIIIA.";
RL J. Neurosci. 20:76-80(2000).
RN [4]
RP SYNTHESIS OF 52-80, AMIDATION AT GLY-80, AND MUTAGENESIS OF THR-59; PHE-60;
RP ILE-63 AND LYS-64.
RX PubMed=11683628; DOI=10.1021/bi010683a;
RA Bulaj G., DeLaCruz R., Azimi-Zonooz A., West P., Watkins M., Yoshikami D.,
RA Olivera B.M.;
RT "Delta-conotoxin structure/function through a cladistic analysis.";
RL Biochemistry 40:13201-13208(2001).
CC -!- FUNCTION: Delta-conotoxins bind to site 6 of voltage-gated sodium
CC channels (Nav) and inhibit the inactivation process. This toxin shows
CC weak effects on rNav1.2/SCN2A (EC(50)=2.9 uM), rNav1.4/SCN4A
CC (EC(50)=5.2 uM), hNav1.7/SCN9A (EC(50)=1.9 uM) and rNav1.7/SCN9A
CC (EC(50)=6.4 uM) (PubMed:10627583). In vivo, this toxin shows different
CC effects. In mice, injection of this toxin causes hyperactivity, rapid
CC running, limb extension, and death. In fish, the peptide elicites
CC spurts of rapid swimming, with twisted motions, quivering fins and the
CC lockjaw extended mouth syndrome. Rigid paralysis and death are observed
CC at higher doses. In mollusks, this peptide is inactive. Injection of
CC this peptide together with the kappa-conotoxin PVIIA causes the sudden
CC tetanus of prey (STOP) syndrome, which is a single, lethal 'fin-pop' in
CC envenomed fish. {ECO:0000269|PubMed:10627583,
CC ECO:0000269|PubMed:12074021}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7711013}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:7711013}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000250|UniProtKB:P56714}.
CC -!- DOMAIN: The cysteine framework is VI/VII (C-C-CC-C-C). {ECO:0000305}.
CC -!- PTM: The difference between delta-conotoxin PVIA and [deamido]-delta-
CC conotoxin PVIA lies in the state of amidation of Gly-80.
CC -!- MASS SPECTROMETRY: Mass=2997.3; Method=Unknown;
CC Evidence={ECO:0000269|PubMed:7711013};
CC -!- SIMILARITY: Belongs to the conotoxin O1 superfamily. {ECO:0000305}.
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DR PIR; A58651; A58651.
DR AlphaFoldDB; P58913; -.
DR SMR; P58913; -.
DR ConoServer; 1563; PVIA precursor.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR004214; Conotoxin.
DR InterPro; IPR012322; Conotoxin_d-typ_CS.
DR Pfam; PF02950; Conotoxin; 1.
DR PROSITE; PS60005; DELTA_CONOTOXIN; 1.
PE 1: Evidence at protein level;
KW Amidation; Cleavage on pair of basic residues; Direct protein sequencing;
KW Disulfide bond; Hydroxylation; Ion channel impairing toxin; Knottin;
KW Neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..49
FT /evidence="ECO:0000269|PubMed:7711013"
FT /id="PRO_0000034898"
FT PEPTIDE 52..80
FT /note="Delta-conotoxin PVIA"
FT /evidence="ECO:0000269|PubMed:7711013"
FT /id="PRO_0000034899"
FT MOD_RES 57
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000269|PubMed:7711013"
FT MOD_RES 65
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000269|PubMed:7711013"
FT MOD_RES 80
FT /note="Glycine amide; in form delta-conotoxin PVIA"
FT /evidence="ECO:0000269|PubMed:11683628"
FT DISULFID 54..69
FT /evidence="ECO:0000250|UniProtKB:P56714"
FT DISULFID 61..73
FT /evidence="ECO:0000250|UniProtKB:P56714"
FT DISULFID 68..78
FT /evidence="ECO:0000250|UniProtKB:P56714"
FT MUTAGEN 59
FT /note="T->A: No loss of activity."
FT /evidence="ECO:0000269|PubMed:11683628"
FT MUTAGEN 60
FT /note="F->A: Loss of biological activity. However,
FT coinjection of this mutant protects against the wild-type
FT conotoxin, suggesting that the mutant binds competitively
FT to the wild-type conotoxin ligand site. Such a protective
FT effect does not occur for all physiological targets."
FT /evidence="ECO:0000269|PubMed:11683628"
FT MUTAGEN 63
FT /note="I->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11683628"
FT MUTAGEN 64
FT /note="K->A: No loss of activity."
FT /evidence="ECO:0000269|PubMed:11683628"
SQ SEQUENCE 81 AA; 8945 MW; ACCFE9E1C65ABFEC CRC64;
MKLTCVMIVA VLFLTAWTFV TADDSKNGLE NHFWKARDEM KNREASKLDK KEACYAPGTF
CGIKPGLCCS EFCLPGVCFG G
