CTA1A_CONMR
ID CTA1A_CONMR Reviewed; 61 AA.
AC P58808; D6C4H0; Q3YEG8;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2002, sequence version 1.
DT 25-MAY-2022, entry version 79.
DE RecName: Full=Chi-conotoxin MrIA;
DE Short=Chi-MrIA;
DE AltName: Full=Conotoxin MrIA;
DE AltName: Full=Lambda-conotoxin CMrVIB;
DE AltName: Full=Mr10.1;
DE AltName: Full=Xen2174;
DE AltName: Full=mr10a;
DE Flags: Precursor;
OS Conus marmoreus (Marble cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Conus.
OX NCBI_TaxID=42752;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 49-61, SYNTHESIS OF 49-61,
RP MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom duct;
RX PubMed=10900201; DOI=10.1074/jbc.m003619200;
RA McIntosh J.M., Corpuz G.O., Layer R.T., Garrett J.E., Wagstaff J.D.,
RA Bulaj G., Vyazovkina A., Yoshikami D., Cruz L.J., Olivera B.M.;
RT "Isolation and characterization of a novel conus peptide with apparent
RT antinociceptive activity.";
RL J. Biol. Chem. 275:32391-32397(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Luo S., Zhangsun D., Zhang B., Chen X.;
RT "Novel T-superfamily conotoxins, and their coding polynucleotides and
RT use.";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=20363338; DOI=10.1016/j.ympev.2010.03.029;
RA Biggs J.S., Watkins M., Puillandre N., Ownby J.P., Lopez-Vera E.,
RA Christensen S., Moreno K.J., Bernaldez J., Licea-Navarro A., Corneli P.S.,
RA Olivera B.M.;
RT "Evolution of Conus peptide toxins: analysis of Conus californicus Reeve,
RT 1844.";
RL Mol. Phylogenet. Evol. 56:1-12(2010).
RN [4]
RP PROTEIN SEQUENCE OF 49-61, MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=10988292; DOI=10.1074/jbc.m006354200;
RA Balaji R.A., Ohtake A., Sato K., Gopalakrishnakone P., Kini R.M.,
RA Seow K.T., Bay B.-H.;
RT "Lambda-conotoxins, a new family of conotoxins with unique disulfide
RT pattern and protein folding. Isolation and characterization from the venom
RT of Conus marmoreus.";
RL J. Biol. Chem. 275:39516-39522(2000).
RN [5]
RP PROTEIN SEQUENCE OF 49-61, SYNTHESIS OF 49-61, FUNCTION, MASS SPECTROMETRY,
RP STRUCTURE BY NMR OF 49-61, AND DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=11528421; DOI=10.1038/nn0901-902;
RA Sharpe I.A., Gehrmann J., Loughnan M.L., Thomas L., Adams D.A., Atkins A.,
RA Palant E., Craik D.J., Adams D.J., Alewood P.F., Lewis R.J.;
RT "Two new classes of conopeptides inhibit the alpha1-adrenoceptor and
RT noradrenaline transporter.";
RL Nat. Neurosci. 4:902-907(2001).
RN [6]
RP FUNCTION, AND SYNTHESIS OF 49-61.
RX PubMed=12885787; DOI=10.1074/jbc.m213030200;
RA Sharpe I.A., Palant E., Schroeder C.I., Kaye D.M., Adams D.J.,
RA Alewood P.F., Lewis R.J.;
RT "Inhibition of the norepinephrine transporter by the venom peptide chi-
RT MrIA. Site of action, Na+ dependence, and structure-activity
RT relationship.";
RL J. Biol. Chem. 278:40317-40323(2003).
RN [7]
RP FUNCTION.
RX PubMed=12837768; DOI=10.1074/jbc.m213101200;
RA Bryan-Lluka L.J., Bonisch H., Lewis R.J.;
RT "Chi-conopeptide MrIA partially overlaps desipramine and cocaine binding
RT sites on the human norepinephrine transporter.";
RL J. Biol. Chem. 278:40324-40329(2003).
RN [8]
RP FUNCTION.
RX PubMed=16154696; DOI=10.1016/j.pain.2005.08.002;
RA Nielsen C.K., Lewis R.J., Alewood D., Drinkwater R., Palant E.,
RA Patterson M., Yaksh T.L., McCumber D., Smith M.T.;
RT "Anti-allodynic efficacy of the chi-conopeptide, Xen2174, in rats with
RT neuropathic pain.";
RL Pain 118:112-124(2005).
RN [9]
RP STRUCTURE BY NMR OF 49-61, SYNTHESIS OF 49-61, DISULFIDE BONDS, AND
RP HYDROXYLATION AT PRO-60.
RX PubMed=15931669; DOI=10.1002/bip.20302;
RA Nilsson K.P.R., Lovelace E.S., Caesar C.E., Tynngard N., Alewood P.F.,
RA Johansson H.M., Sharpe I.A., Lewis R.J., Daly N.L., Craik D.J.;
RT "Solution structure of chi-conopeptide MrIA, a modulator of the human
RT norepinephrine transporter.";
RL Biopolymers 80:815-823(2005).
RN [10]
RP PHARMACEUTICAL.
RX PubMed=21839105; DOI=10.1016/j.toxicon.2011.07.012;
RA Lewis R.J.;
RT "Discovery and development of the chi-conopeptide class of analgesic
RT peptides.";
RL Toxicon 59:524-528(2012).
CC -!- FUNCTION: Chi-conotoxins inhibit the neuronal noradrenaline transporter
CC (NET/SLC6A2). {ECO:0000269|PubMed:11528421,
CC ECO:0000269|PubMed:12837768, ECO:0000269|PubMed:12885787,
CC ECO:0000269|PubMed:16154696}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10900201,
CC ECO:0000269|PubMed:10988292}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:10900201, ECO:0000305|PubMed:10988292}.
CC -!- DOMAIN: The cysteine framework is X (CC-CX[hydroxyPro]C).
CC {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=1408.5; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:10900201};
CC -!- MASS SPECTROMETRY: Mass=1408.97; Mass_error=0.09; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:10988292};
CC -!- MASS SPECTROMETRY: Mass=1408.53; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11528421};
CC -!- PHARMACEUTICAL: Is under phase II clinical trial by Xenome under the
CC name Xen2174. This structural analog of MrIA was developed to overcome
CC the relatively poor chemical stability of Mr1A in solution. Used to
CC treat neuropathic pain.
CC -!- MISCELLANEOUS: Exists in two forms, due to cis-trans isomerization at
CC 59-His-Hyp-60.
CC -!- MISCELLANEOUS: This toxin does not produce effects on the activity of
CC the dopamine transporter (DAT/SLC6A3) and the serotonin transporter
CC (SERT/SLC6A4). {ECO:0000305|PubMed:12885787}.
CC -!- SIMILARITY: Belongs to the conotoxin T superfamily. {ECO:0000305}.
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DR EMBL; DQ141145; AAZ85410.1; -; mRNA.
DR EMBL; FJ959112; ADB93082.1; -; Genomic_DNA.
DR EMBL; GQ981407; ADN79126.1; -; mRNA.
DR PDB; 2EW4; NMR; -; A=49-61.
DR PDB; 2J15; NMR; -; A=49-61.
DR PDBsum; 2EW4; -.
DR PDBsum; 2J15; -.
DR AlphaFoldDB; P58808; -.
DR SMR; P58808; -.
DR TCDB; 8.B.4.2.1; the conotoxin t (conotoxin t) family.
DR ConoServer; 1739; MrIA precursor.
DR EvolutionaryTrace; P58808; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR031565; T-conotoxin.
DR Pfam; PF16981; Chi-conotoxin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Hydroxylation;
KW Neurotoxin; Pharmaceutical; Secreted; Signal; Toxin.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..48
FT /evidence="ECO:0000269|PubMed:10900201,
FT ECO:0000269|PubMed:10988292, ECO:0000269|PubMed:11528421"
FT /id="PRO_0000035081"
FT PEPTIDE 49..61
FT /note="Chi-conotoxin MrIA"
FT /id="PRO_0000035082"
FT MOD_RES 60
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000269|PubMed:15931669"
FT DISULFID 52..61
FT DISULFID 53..58
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:2EW4"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:2EW4"
SQ SEQUENCE 61 AA; 6499 MW; F4DE5B5A97EB8DBA CRC64;
MRCLPVLIIL LLLTASAPGV VVLPKTEDDV PMSSVYGNGK SILRGILRNG VCCGYKLCHP
C
