COW_CONAA
ID COW_CONAA Reviewed; 63 AA.
AC P0C248; A0A0P0CKR5;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2018, sequence version 2.
DT 25-MAY-2022, entry version 45.
DE RecName: Full=Contryphan-Am {ECO:0000303|PubMed:16387709};
DE AltName: Full=Am975 {ECO:0000303|PubMed:16945451, ECO:0000303|PubMed:17902199};
DE AltName: Full=Bromocontryphan Ama1055 {ECO:0000303|PubMed:31203793};
DE AltName: Full=Contryphan Am976 {ECO:0000303|PubMed:30593932};
DE AltName: Full=Contryphan Ama976 {ECO:0000303|PubMed:31203793};
DE Contains:
DE RecName: Full=Contryphan-Am Ama919 {ECO:0000303|PubMed:31203793};
DE Short=Contryphan 919 {ECO:0000303|PubMed:31203793};
DE AltName: Full=Contryphan-Am Am918 {ECO:0000303|PubMed:17902199};
DE Flags: Precursor;
OS Conus amadis (Amadis cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Leptoconus.
OX NCBI_TaxID=198732;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C.Am975;
RG Swine Surveillance;
RL Submitted (SEP-2015) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=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 NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION BY MASS SPECTROMETRY,
RP HYDROXYLATION AT PRO-57, AND AMIDATION AT CYS-62.
RC TISSUE=Venom, and Venom duct;
RX PubMed=30593932; DOI=10.1016/j.jprot.2018.12.028;
RA Vijayasarathy M., Balaram P.;
RT "Cone snail prolyl-4-hydroxylase alpha-subunit sequences derived from
RT transcriptomic data and mass spectrometric analysis of variable proline
RT hydroxylation in C. amadis venom.";
RL J. Proteomics 194:37-48(2019).
RN [4]
RP PROTEIN SEQUENCE OF 55-62, AND SUBCELLULAR LOCATION.
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 [5]
RP PROTEIN SEQUENCE OF 55-62, SYNTHESIS OF 55-62, FUNCTION, MASS SPECTROMETRY,
RP SUBCELLULAR LOCATION, HYDROXYLATION AT PRO-57, D-AMINO ACID AT TRP-58,
RP DISULFIDE BOND, AND AMIDATION AT CYS-62.
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 [6]
RP PROTEIN SEQUENCE OF 55-62, MASS SPECTROMETRY, SUBCELLULAR LOCATION,
RP HYDROXYLATION AT PRO-57, D-AMINO 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 [7]
RP PROTEIN SEQUENCE OF 55-62, SUBCELLULAR LOCATION, HYDROXYLATION AT PRO-57,
RP BROMINATION AT TRP-61, AMIDATION AT CYS-62, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=31203793; DOI=10.2174/0929866526666190614144006;
RA Rajesh R.P., Franklin J.B., Badsha I., Arjun P., Jain R.P., Vignesh M.S.,
RA Kannan R.R.;
RT "Proteome based de novo sequencing of novel conotoxins from marine
RT molluscivorous cone snail Conus amadis and neurological activities of its
RT natural venom in zebrafish model.";
RL Protein Pept. Lett. 26:819-833(2019).
CC -!- FUNCTION: Inhibits high voltage-activated calcium channels (Cav).
CC {ECO:0000269|PubMed:16945451}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16387709,
CC ECO:0000269|PubMed:16945451, ECO:0000269|PubMed:17902199}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:16387709, ECO:0000305|PubMed:16945451,
CC ECO:0000305|PubMed:17902199}.
CC -!- DOMAIN: The cysteine framework is C-C. {ECO:0000305}.
CC -!- MASS SPECTROMETRY: [Contryphan-Am]: Mass=976.5; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:16945451};
CC -!- MASS SPECTROMETRY: [Contryphan-Am]: Mass=975; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:17902199};
CC -!- MASS SPECTROMETRY: [Contryphan-Am Ama919]: Mass=918; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:17902199};
CC -!- MASS SPECTROMETRY: [Contryphan-Am Ama919]: Mass=919.2; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:31203793};
CC -!- MASS SPECTROMETRY: Mass=1054.1; Method=MALDI; Note=in the brominated
CC form (Ama1054).; Evidence={ECO:0000269|PubMed:31203793};
CC -!- MISCELLANEOUS: Three forms of this peptide have been described. Am918
CC is 7 residues long and is hydroxylated and amidated; Am975 is 8
CC residues long and is also hydroxylated and amidated, while Ama1054 is
CC only different from Am975 by an additional Trp bromination. An amidated
CC peptide of 8 residues with identical sequence but without hydrolation
CC is described in Conus buxeus loroisii venom (AC P0C250).
CC {ECO:0000305|PubMed:16945451, ECO:0000305|PubMed:17902199,
CC ECO:0000305|PubMed:31203793}.
CC -!- MISCELLANEOUS: Exists in two forms, due to cis-trans isomerization
CC (possibly at 56-Cys-hydroxyPro-57). The cis conformation is the major
CC form. {ECO:0000250|UniProtKB:P58787, ECO:0000269|PubMed:30593932}.
CC -!- SIMILARITY: Belongs to the O2 superfamily. Contryphan family.
CC {ECO:0000305}.
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DR EMBL; KT713755; ALI96898.1; -; mRNA.
DR AlphaFoldDB; P0C248; -.
DR ConoServer; 1270; Contryphan-Am.
DR ConoServer; 8373; Contryphan-Am precursor.
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 Amidation; Bromination; Calcium channel impairing toxin; D-amino acid;
KW Direct protein sequencing; Disulfide bond; Hydroxylation;
KW Ion channel impairing toxin; 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_0000445122"
FT PEPTIDE 55..62
FT /note="Contryphan-Am"
FT /evidence="ECO:0000269|PubMed:16387709,
FT ECO:0000269|PubMed:16945451, ECO:0000269|PubMed:17902199,
FT ECO:0000269|PubMed:31203793"
FT /id="PRO_0000262668"
FT PEPTIDE 56..62
FT /note="Contryphan-Am Ama919"
FT /evidence="ECO:0000269|PubMed:17902199,
FT ECO:0000269|PubMed:31203793"
FT /id="PRO_0000439692"
FT REGION 23..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 57
FT /note="4-hydroxyproline; in Ama919, Ama976 and Ama1055"
FT /evidence="ECO:0000269|PubMed:16945451,
FT ECO:0000269|PubMed:17902199, ECO:0000269|PubMed:30593932,
FT ECO:0000269|PubMed:31203793"
FT MOD_RES 58
FT /note="D-tryptophan"
FT /evidence="ECO:0000269|PubMed:16945451,
FT ECO:0000269|PubMed:17902199"
FT MOD_RES 61
FT /note="6'-bromotryptophan; partial; in Ama1055"
FT /evidence="ECO:0000269|PubMed:31203793"
FT MOD_RES 62
FT /note="Cysteine amide; in Ama919, Ama976 and Ama1055"
FT /evidence="ECO:0000269|PubMed:16945451,
FT ECO:0000269|PubMed:17902199, ECO:0000269|PubMed:31203793"
FT DISULFID 56..62
FT /evidence="ECO:0000269|PubMed:16945451,
FT ECO:0000305|PubMed:17902199, ECO:0000305|PubMed:31203793"
SQ SEQUENCE 63 AA; 6730 MW; 0542F1F008740D66 CRC64;
MGKLTILVLV AAALLSTQVM VQGDGDQPAD RDAVPRDDNP SGMSGKFMNV LRRAGCPWDP
WCG
