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CCAP_CONVL
ID   CCAP_CONVL              Reviewed;         207 AA.
AC   E3PQQ8; E3PQQ7;
DT   08-MAR-2011, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2011, sequence version 1.
DT   25-MAY-2022, entry version 24.
DE   RecName: Full=ConoCAP;
DE   Contains:
DE     RecName: Full=ConoCAP-a;
DE     AltName: Full=CCAP-vil;
DE   Contains:
DE     RecName: Full=ConoCAP-b;
DE   Contains:
DE     RecName: Full=ConoCAP-c;
DE   Flags: Precursor;
GN   Name=conoCAP;
OS   Conus villepinii (Villepin's cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Dauciconus.
OX   NCBI_TaxID=257347;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 85-94, SYNTHESIS OF 51-60;
RP   85-94 AND 163-173, FUNCTION, AMIDATION AT GLY-60 AND GLY-173, DISULFIDE
RP   BOND, MASS SPECTROMETRY, AND ALANINE-SCANNING MUTAGENESIS.
RC   TISSUE=Venom, and Venom duct;
RX   PubMed=20923766; DOI=10.1074/jbc.m110.171397;
RA   Moeller C., Melaun C., Castillo C., Diaz M.E., Renzelman C.M., Estrada O.,
RA   Kuch U., Lokey S., Mari F.;
RT   "Functional hypervariability and gene diversity of cardioactive
RT   neuropeptides.";
RL   J. Biol. Chem. 285:40673-40680(2010).
RN   [2]
RP   PROTEIN SEQUENCE OF 85-94, SYNTHESIS OF 85-94, FUNCTION, STRUCTURE BY NMR,
RP   AMIDATION AT ASN-94, DISULFIDE BOND, AND MUTAGENESIS OF CYS-87 AND CYS-92.
RC   TISSUE=Venom;
RX   PubMed=20385188; DOI=10.1016/j.peptides.2010.04.002;
RA   Miloslavina A., Ebert C., Tietze D., Ohlenschlaeger O., Englert C.,
RA   Goerlach M., Imhof D.;
RT   "An unusual peptide from Conus villepinii: synthesis, solution structure,
RT   and cardioactivity.";
RL   Peptides 31:1292-1300(2010).
CC   -!- FUNCTION: [ConoCAP-a]: In contrast to other members of the CCAP family
CC       which are cardio-accelerators, conoCAP-a decreases the heart frequency
CC       in Drosophila larvae (26%), rats and zebrafish embryos. It also reduces
CC       the blood pressure in rats. It decreases systolic calcium in
CC       ventricular cardiac myocytes, indicating that it may act via impairment
CC       of intracellular calcium trafficking.
CC   -!- FUNCTION: [ConoCAP-b]: Synthetic conoCAP-b decreases the heart
CC       frequency of 23% in Drosophila larvae.
CC   -!- FUNCTION: [ConoCAP-c]: Synthetic conoCAP-c decreases the heart
CC       frequency of 12% in Drosophila larvae.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC   -!- MASS SPECTROMETRY: [ConoCAP-a]: Mass=1148.6; Method=MALDI;
CC       Note=Monoisotopic.; Evidence={ECO:0000269|PubMed:20923766};
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DR   EMBL; FN868446; CBM40422.1; -; mRNA.
DR   EMBL; FN868447; CBM40423.1; -; mRNA.
DR   AlphaFoldDB; E3PQQ8; -.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0043655; C:host extracellular space; TAS:UniProtKB.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0044554; P:modulation of heart rate in another organism; IDA:UniProtKB.
DR   GO; GO:0044555; P:negative regulation of heart rate in another organism; IDA:UniProtKB.
PE   1: Evidence at protein level;
KW   Amidation; Cardiotoxin; Cleavage on pair of basic residues;
KW   Direct protein sequencing; Disulfide bond; Secreted; Signal; Toxin.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   PROPEP          22..48
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000405955"
FT   PEPTIDE         51..60
FT                   /note="ConoCAP-b"
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000405956"
FT   PROPEP          63..82
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000405957"
FT   PEPTIDE         85..94
FT                   /note="ConoCAP-a"
FT                   /evidence="ECO:0000269|PubMed:20385188,
FT                   ECO:0000269|PubMed:20923766"
FT                   /id="PRO_0000405958"
FT   PROPEP          98..160
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000405959"
FT   PEPTIDE         163..173
FT                   /note="ConoCAP-c"
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000405960"
FT   PROPEP          177..207
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000405961"
FT   REGION          131..155
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         60
FT                   /note="Glycine amide"
FT                   /evidence="ECO:0000305|PubMed:20923766"
FT   MOD_RES         94
FT                   /note="Asparagine amide"
FT                   /evidence="ECO:0000269|PubMed:20385188"
FT   MOD_RES         173
FT                   /note="Glycine amide"
FT                   /evidence="ECO:0000305|PubMed:20923766"
FT   DISULFID        53..59
FT                   /evidence="ECO:0000305"
FT   DISULFID        87..92
FT   DISULFID        165..171
FT                   /evidence="ECO:0000305"
FT   MUTAGEN         85..86
FT                   /note="Missing: Partial loss of activity of conoCAP-a."
FT   MUTAGEN         85
FT                   /note="P->A: Partial loss of activity of conoCAP-a."
FT   MUTAGEN         85
FT                   /note="Missing: Partial loss of activity of conoCAP-a."
FT   MUTAGEN         86
FT                   /note="F->A: Complete loss of activity of conoCAP-a."
FT   MUTAGEN         87
FT                   /note="C->A: Complete loss of activity of conoCAP-a."
FT                   /evidence="ECO:0000269|PubMed:20385188"
FT   MUTAGEN         88
FT                   /note="N->A: No change of activity of conoCAP-a."
FT   MUTAGEN         89
FT                   /note="S->A: No change of activity of conoCAP-a."
FT   MUTAGEN         90
FT                   /note="F->A: No change of activity of conoCAP-a."
FT   MUTAGEN         91
FT                   /note="G->A: No change of activity of conoCAP-a."
FT   MUTAGEN         92
FT                   /note="C->A: Complete loss of activity of conoCAP-a."
FT                   /evidence="ECO:0000269|PubMed:20385188"
FT   MUTAGEN         93..94
FT                   /note="Missing: No change of activity of conoCAP-a."
FT   MUTAGEN         93
FT                   /note="Y->A: No change of activity of conoCAP-a."
FT   MUTAGEN         94
FT                   /note="N->A: No change of activity of conoCAP-a."
FT   MUTAGEN         94
FT                   /note="Missing: No change of activity of conoCAP-a."
FT   CONFLICT        164
FT                   /note="F -> L (in Ref. 1; CBM40422)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   207 AA;  23089 MW;  18E2D2EE1128C484 CRC64;
     MVSLGHVLFV ILLPVLLPVA ADDPDDQMLS QISLPSSSRS EYDDNDVSKR VFCNGFTGCG
     GRHRDRSRRQ ERYGKRLIPV LAKRPFCNSF GCYNGKRSLS GAGPALSTPV DPSRNNKART
     MARMLDAAAS ARHEQQQQLL QQREQRGLES RDPAASGDLS KRLFCNGYGG CRGGKRTLYS
     PWLERMNEVA DDRSARNALC TRLGWRE
 
 
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