MrIA (P01384) Protein Card

General Information
Name MrIA
Alternative name(s) CMrVIB,Mr090,Mr091,Mr10.1,Xen2174,mr10a
Organism Conus marmoreus
Organism region Indo-Pacific
Organism diet molluscivorous
Protein Type Wild type
Protein precursor MrIA precursor (1739)
MrIA precursor (5485)
Notes Targets the norepinephrine transporter. No effect on dopamine or serotonin uptake through DAT and SERT transporters respectively. Inhibited binding of existing NET inhibitors. Higher Na+ concentration improves inhibition. G6A mutation causes significant structural perturbation.(Sharpe et al. 2003)

Classification
Conopeptide class conotoxin
Gene superfamily T superfamily
Cysteine framework X
Pharmacological family chi conotoxin

Sequence
NGVCCGYKLCHOC
Modified residues
positionsymbolname
12O4-Hydroxyproline
Sequence evidence protein level
Average Mass 1408.64
Monoisotopic Mass 1407.52
Isoelectric Point 9.95
Extinction Coefficient [280nm] 1490.00

Activity

IC50: Monoamine transporter

TargetOrganismIC50Ref
NETH. sapiens(Inhibition of norepinephrine uptake. IC50 calculated from reported pIC50. )1.26 µMSharpe,I.A. et al. (2003)
R. norvegicus(Inhibition of norepinephrine uptake. IC50 calculated from reported pIC50. ) 0.62 µMSharpe,I.A. et al. (2003)

Synthetic variants
Cyclic MrIANGVCCGYKLCHOCAG
MrIA [N1(Abz)](ABZ)GVCCGYKLCHOC(nh2)
MrIA [N1(Bhk)](BHK)GVCCGYKLCHOC(nh2)
MrIA [N1(Cit)](Cit)GVCCGYKLCHOC(nh2)
MrIA [N1(Dmf)](DMF)GVCCGYKLCHOC(nh2)
MrIA [N1(Nle)](Nle)GVCCGYKLCHOC(nh2)
MrIA [N1A]AGVCCGYKLCHOC(nh2)
MrIA [N1D]DGVCCGYKLCHOC(nh2)
MrIA [N1F]FGVCCGYKLCHOC(nh2)
MrIA [N1G]GGVCCGYKLCHOC(nh2)
MrIA [N1I]IGVCCGYKLCHOC(nh2)
MrIA [N1Q]QGVCCGYKLCHOC(nh2)
MrIA [N1R]RGVCCGYKLCHOC(nh2)
MrIA [N1S]SGVCCGYKLCHOC(nh2)
MrIA [N1T]TGVCCGYKLCHOC(nh2)
MrIA [N1Z, C10c]ZGVCCGYKLcHOC(nh2)
MrIA [N1Z, C13c]ZGVCCGYKLCHOc(nh2)
MrIA [N1Z, C4(Hcy), C5(Hcy), C10(Hcy), C13(Hcy)]ZGV(Hcy)(Hcy)GYKL(Hcy)HO(Hcy)(nh2)
MrIA [N1Z, C4c, C13c]ZGVcCGYKLCHOc(nh2)
MrIA [N1Z, C4c, C5c, C10c, C13c]ZGVccGYKLcHOc(nh2)
MrIA [N1Z, C4c]ZGVcCGYKLCHOC(nh2)
MrIA [N1Z, C5c, C10c]ZGVCcGYKLcHOC(nh2)
MrIA [N1Z, Y7(Mty), H11W]ZGVCCG(Mty)KLCWOC(nh2)
MrIA [N1Z, Y7(Mty), L9(Cha), H11W]ZGVCCG(Mty)K(Cha)CWOC(nh2)
MrIA [N1Z,H11(Bta)]ZGVCCGYKLC(BTA)OC(nh2)
MrIA [N1Z,H11(Fla)]ZGVCCGYKLC(FLA)OC(nh2)
MrIA [N1Z,H11(Nal)]ZGVCCGYKLC(Nal)OC(nh2)
MrIA [N1Z,H11(Pya)]ZGVCCGYKLC(PYA)OC(nh2)
MrIA [N1Z,H11E]ZGVCCGYKLCEOC(nh2)
MrIA [N1Z,H11F]ZGVCCGYKLCFOC(nh2)
MrIA [N1Z,H11L]ZGVCCGYKLCLOC(nh2)
MrIA [N1Z,H11P]ZGVCCGYKLCPOC(nh2)
MrIA [N1Z,H11Q]ZGVCCGYKLCQOC(nh2)
MrIA [N1Z,H11R]ZGVCCGYKLCROC(nh2)
MrIA [N1Z,H11W]ZGVCCGYKLCWOC(nh2)
MrIA [N1Z,H11Y]ZGVCCGYKLCYOC(nh2)
MrIA [N1Z,H11h]ZGVCCGYKLChOC(nh2)
MrIA [N1Z,K8(Cit)]ZGVCCGY(Cit)LCHOC(nh2)
MrIA [N1Z,K8(Hly)]ZGVCCGY(HLY)LCHOC(nh2)
MrIA [N1Z,K8(Nle)]ZGVCCGY(Nle)LCHOC(nh2)
MrIA [N1Z,K8(Orn)]ZGVCCGY(Orn)LCHOC(nh2)
MrIA [N1Z,K8E]ZGVCCGYELCHOC(nh2)
MrIA [N1Z,K8I]ZGVCCGYILCHOC(nh2)
MrIA [N1Z,K8L]ZGVCCGYLLCHOC(nh2)
MrIA [N1Z,K8Q]ZGVCCGYQLCHOC(nh2)
MrIA [N1Z,K8R]ZGVCCGYRLCHOC(nh2)
MrIA [N1Z,K8W]ZGVCCGYWLCHOC(nh2)
MrIA [N1Z,K8k]ZGVCCGYkLCHOC(nh2)
MrIA [N1Z,L9(Cha)]ZGVCCGYK(Chg)CHOC(nh2)
MrIA [N1Z,L9(Hle)]ZGVCCGYK(HLE)CHOC(nh2)
MrIA [N1Z,L9(Nle)]ZGVCCGYK(Nle)CHOC(nh2)
MrIA [N1Z,L9I]ZGVCCGYKICHOC(nh2)
MrIA [N1Z,L9P]ZGVCCGYKPCHOC(nh2)
MrIA [N1Z,L9Q]ZGVCCGYKQCHOC(nh2)
MrIA [N1Z,L9R] ZGVCCGYKRCHOC(nh2)
MrIA [N1Z,L9S]ZGVCCGYKSCHOC(nh2)
MrIA [N1Z,L9V]ZGVCCGYKVCHOC(nh2)
MrIA [N1Z,O12(Mey)]ZGVCCGYKLCH(Mty)C(nh2)
MrIA [N1Z,O12(Tic)]ZGVCCGYKLCH(Tic)C(nh2)
MrIA [N1Z,O12D]ZGVCCGYKLCHDC(nh2)
MrIA [N1Z,O12E]ZGVCCGYKLCHEC(nh2)
MrIA [N1Z,O12K]ZGVCCGYKLCHKC(nh2)
MrIA [N1Z,O12P,del13]ZGVCCGYKLCHP
MrIA [N1Z,O12P]ZGVCCGYKLCHPC
MrIA [N1Z,O12Y]ZGVCCGYKLCHYC(nh2)
MrIA [N1Z,Y7(Cha)]ZGVCCG(Cha)KLCHOC(nh2)
MrIA [N1Z,Y7(Dmk)]ZGVCCG(DMF)KLCHOC(nh2)
MrIA [N1Z,Y7(Dpa)]ZGVCCG(DPA)KLCHOC(nh2)
MrIA [N1Z,Y7(Hly)]ZGVCCG(HLY)KLCHOC(nh2)
MrIA [N1Z,Y7(Mty)]ZGVCCG(Mty)KLCHOC(nh2)
MrIA [N1Z,Y7(Thi)]ZGVCCG(THI)KLCHOC(nh2)
MrIA [N1Z,Y7E]ZGVCCGEKLCHOC(nh2)
MrIA [N1Z,Y7F]ZGVCCGFKLCHOC(nh2)
MrIA [N1Z,Y7I]ZGVCCGIKLCHOC(nh2)
MrIA [N1Z,Y7K]ZGVCCGKKLCHOC(nh2)
MrIA [N1Z,Y7L]ZGVCCGLKLCHOC(nh2)
MrIA [N1Z,Y7P]ZGVCCGPKLCHOC(nh2)
MrIA [N1Z,Y7Q]ZGVCCGQKLCHOC(nh2)
MrIA [N1Z,Y7R]ZGVCCGRKLCHOC(nh2)
MrIA [N1Z,Y7S]ZGVCCGSKLCHOC(nh2)
MrIA [N1Z,Y7W]ZGVCCGWKLCHOC(nh2)
MrIA [N1Z,Y7y]ZGVCCGyKLCHOC(nh2)
MrIA [N1Z,del10-13] ZGVCCGYKL
MrIA [N1Z,del11-13]ZGVCCGYKLC
MrIA [N1Z]ZGVCCGYKLCHOC(nh2)
MrIA [N1k]kGVCCGYKLCHOC(nh2)
MrIA [N1n]nGVCCGYKLCHOC(nh2)
MrIA [N1r]rGVCCGYKLCHOC(nh2)
MrIA [O12P]NGVCCGYKLCHPC
MrIA [del1,O12P]GVCCGYKLCHPC
MrIA [del1,Y7Sty]GVCCG(sTy)KLCHOC
MrIA [del1-2]VCCGYKLCHOC
MrIA [del1-4]CGYKLCHOC
MrIA [del1-5]GYKLCHOC
MrIA [del1-6]YKLCHOC
MrIA [del11-13]NGVCCGYKLC
MrIA [del9-13] NGVCCGYK
MrIA [insN_(Hfe)](HFE)NGVCCGYKLCHOC(nh2)
MrIA [insN_GILR,O12P]GILRNGVCCGYKLCHPC
MrIA [insN_ILRGILR,del 6-13]ILRGILRNGVCC(nh2)
MrIA [insN_LR]LRNGVCCGYKLCHOC
MrIA [insN_W]WNGVCCGYKLCHOC(nh2)
MrIA amidatedNGVCCGYKLCHOC(nh2)
MrIA amidated [N1Z,del10-13] ZGVCCGYKL(nh2)
MrIA amidated [O12P] NGVCCGYKLCHPC(nh2)

References
Lovelace,E.S., Armishaw,C.J., Colgrave,M.L., Wahlstrom,M.E., Alewood,P.F., Daly,N.L. and Craik,D.J. (2006) Cyclic MrIA: a stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter J. Med. Chem. 49:6561-6568
Sharpe,I.A., Gehrmann,J., Loughnan,M.L., Thomas,L., Adams,D.A., Atkins,A., Palant,E., Craik,D.J., Adams,D.J., Alewood,P.F. and Lewis,R.J. (2001) Two new classes of conopeptides inhibit the alpha1-adrenoceptor and noradrenaline transporter Nat. Neurosci. 4:902-907
McIntosh,J.M., Corpuz,G.O., Layer,R.T., Garrett,J.E., Wagstaff,J.D., Bulaj,G., Vyazovkina,A., Yoshikami,D., Cruz,L.J. and Olivera,B.M. (2000) Isolation and characterization of a novel conus peptide with apparent antinociceptive activity J. Biol. Chem. 275:32391-32397
Sharpe,I.A., Palant,E., Schroeder,C.I., Kaye,D.M., Adams,D.J., Alewood,P.F. and Lewis,R.J. (2003) Inhibition of the norepinephrine transporter by the venom peptide chi-MrIA. Site of action, Na+ dependence, and structure-activity relationship J. Biol. Chem. 278:40317-40323
Dutertre,S., Jin,A.H., Kaas,Q., Jones,A., Alewood,P.F. and Lewis,R.J. (2013) Deep venomics reveals the mechanism for expanded peptide diversity in cone snail venom. Mol. Cell Proteomics 12:312-329
Ziegman, R., Brust, A., Jha, P., Cardoso, F.C., Lewis, R.J. and Alewood, P.F. (2019) ‘Messy’Processing of χ-conotoxin MrIA Generates Homologues with Reduced hNET Potency Marine drugs 17:165

Internal links
Protein Precursor MrIA precursor (1739)
MrIA precursor (5485)
Nucleic acids
Structure SOLUTION STRUCTURE OF MRIA

External links
Ncbi 2J15_A

Tools