COW1_CONBL
ID COW1_CONBL Reviewed; 63 AA.
AC P0C250; A0A0P0CT07;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2018, sequence version 2.
DT 25-MAY-2022, entry version 50.
DE RecName: Full=Contryphan-Lo {ECO:0000303|PubMed:16387709};
DE AltName: Full=Contryphan-Lo1 {ECO:0000305};
DE AltName: Full=Lo959 {ECO:0000303|PubMed:16945451, ECO:0000303|PubMed:24115170};
DE Contains:
DE RecName: Full=Contryphan-Lo Lo902 {ECO:0000303|PubMed:17902199};
DE Flags: Precursor;
OS Conus buxeus loroisii (Cone snail) (Conus loroisii).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Dendroconus.
OX NCBI_TaxID=410709;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C.Lo959;
RG Swine Surveillance;
RL Submitted (SEP-2015) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], MASS SPECTROMETRY, D-AMINO ACID AT TRP-58,
RP AMIDATION AT CYS-62, AND DISULFIDE BOND.
RC TISSUE=Venom, and Venom duct;
RX PubMed=28152596; DOI=10.1021/acs.jproteome.6b00776;
RA Vijayasarathy M., Basheer S.M., Franklin J.B., Balaram P.;
RT "Contryphan genes and mature peptides in the venom of nine cone snail
RT species by transcriptomic and mass spectrometric analysis.";
RL J. Proteome Res. 16:763-772(2017).
RN [3]
RP PROTEIN SEQUENCE OF 55-62, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=16387709; DOI=10.1196/annals.1352.022;
RA Gowd K.H., Sabareesh V., Sudarslal S., Iengar P., Franklin B., Fernando A.,
RA Dewan K., Ramaswami M., Sarma S.P., Sikdar S., Balaram P., Krishnan K.S.;
RT "Novel peptides of therapeutic promise from Indian conidae.";
RL Ann. N. Y. Acad. Sci. 1056:462-473(2005).
RN [4]
RP PROTEIN SEQUENCE OF 55-62, SYNTHESIS, FUNCTION, MASS SPECTROMETRY, D-AMINO
RP ACID AT TRP-58, DISULFIDE BOND, AMIDATION AT CYS-62, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Venom;
RX PubMed=16945451; DOI=10.1016/j.peptides.2006.07.009;
RA Sabareesh V., Gowd K.H., Ramasamy P., Sudarslal S., Krishnan K.S.,
RA Sikdar S.K., Balaram P.;
RT "Characterization of contryphans from Conus loroisii and Conus amadis that
RT target calcium channels.";
RL Peptides 27:2647-2654(2006).
RN [5]
RP PROTEIN SEQUENCE OF 55-62, MASS SPECTROMETRY, SUBCELLULAR LOCATION, D-AMINO
RP ACID AT TRP-58, AND AMIDATION AT CYS-62.
RC TISSUE=Venom;
RX PubMed=17902199; DOI=10.1002/rcm.3225;
RA Thakur S.S., Balaram P.;
RT "Rapid mass spectral identification of contryphans. Detection of
RT characteristic peptide ions by fragmentation of intact disulfide-bonded
RT peptides in crude venom.";
RL Rapid Commun. Mass Spectrom. 21:3420-3426(2007).
RN [6]
RP STRUCTURE BY NMR OF 55-62, SYNTHESIS OF 55-62, DISULFIDE BOND, MUTAGENESIS
RP OF PRO-57, AND CIS-TRANS ISOMERIZATION.
RC TISSUE=Venom;
RX PubMed=24115170; DOI=10.1002/chem.201301722;
RA Sonti R., Gowd K.H., Rao K.N., Ragothama S., Rodriguez A., Perez J.J.,
RA Balaram P.;
RT "Conformational diversity in contryphans from Conus venom: cis-trans
RT isomerisation and aromatic/proline interactions in the 23-membered ring of
RT a 7-residue peptide disulfide loop.";
RL Chemistry 19:15175-15189(2013).
CC -!- FUNCTION: Activates high voltage-activated calcium channels (Cav). This
CC activity is in contrast to other contryphans that inhibit high voltage-
CC gated calcium channels. {ECO:0000269|PubMed:16945451}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16387709,
CC ECO:0000269|PubMed:16945451}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:16387709, ECO:0000305|PubMed:16945451}.
CC -!- DOMAIN: The cysteine framework is C-C. {ECO:0000305}.
CC -!- MASS SPECTROMETRY: [Contryphan-Lo]: Mass=960.1; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:16945451};
CC -!- MASS SPECTROMETRY: [Contryphan-Lo]: Mass=959; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:17902199};
CC -!- MASS SPECTROMETRY: [Contryphan-Lo Lo902]: Mass=902; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:17902199};
CC -!- MASS SPECTROMETRY: [Contryphan-Lo]: Mass=959.35; Method=MALDI;
CC Note=Monoisotopic mass.; Evidence={ECO:0000269|PubMed:28152596};
CC -!- MISCELLANEOUS: Exists in two forms, due to cis-trans isomerization at
CC 56-Cys-Pro-57. {ECO:0000269|PubMed:24115170}.
CC -!- SIMILARITY: Belongs to the O2 superfamily. Contryphan family.
CC {ECO:0000305}.
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DR EMBL; KT713759; ALI96902.1; -; mRNA.
DR PDB; 2M6G; NMR; -; A=55-62.
DR PDB; 2M6H; NMR; -; A=55-62.
DR PDBsum; 2M6G; -.
DR PDBsum; 2M6H; -.
DR AlphaFoldDB; P0C250; -.
DR SMR; P0C250; -.
DR ConoServer; 1272; Contryphan-Lo1.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR004214; Conotoxin.
DR InterPro; IPR011062; Contryphan_CS.
DR Pfam; PF02950; Conotoxin; 1.
DR PROSITE; PS60027; CONTRYPHAN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Calcium channel impairing toxin; D-amino acid;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated calcium channel impairing toxin.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT PROPEP 24..54
FT /evidence="ECO:0000305"
FT /id="PRO_0000445123"
FT PEPTIDE 55..62
FT /note="Contryphan-Lo"
FT /evidence="ECO:0000269|PubMed:16387709,
FT ECO:0000269|PubMed:16945451, ECO:0000269|PubMed:17902199"
FT /id="PRO_0000262670"
FT PEPTIDE 56..62
FT /note="Contryphan-Lo Lo902"
FT /evidence="ECO:0000269|PubMed:17902199"
FT /id="PRO_0000439694"
FT REGION 25..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 58
FT /note="D-tryptophan"
FT /evidence="ECO:0000269|PubMed:16945451,
FT ECO:0000305|PubMed:28152596"
FT MOD_RES 62
FT /note="Cysteine amide"
FT /evidence="ECO:0000269|PubMed:16945451,
FT ECO:0000269|PubMed:28152596"
FT DISULFID 56..62
FT /evidence="ECO:0000269|PubMed:16945451,
FT ECO:0000269|PubMed:24115170, ECO:0000269|PubMed:28152596,
FT ECO:0000312|PDB:2M6G, ECO:0000312|PDB:2M6H"
FT MUTAGEN 57
FT /note="P->V: Abolishes the very slow conformation
FT equilibrium."
FT /evidence="ECO:0000269|PubMed:24115170"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:2M6G"
SQ SEQUENCE 63 AA; 6897 MW; 5FA0BE3C754936B6 CRC64;
MGKLTILVLV AAVLLSTQVM VQGDGDQPAD RNAVRRDDNP GGTRGRFMNI LRRTGCPWDP
WCG
