TIA (P01634) Protein Card

General Information
Name TIA
Alternative name(s) T1a,Tu052
Organism Conus tulipa (tulip cone)
Organism region Indo-Pacific
Organism diet piscivorous
Protein Type Wild type
Protein precursor TIA precursor (8074)
TIA precursor (8075)
Notes Full inhibition of the noradrenergic component of rat vas deferens contraction at 10 uM. Inhibited prazosin binding to a1-adrenoreceptors with pIC50 of ~7.5. Alanine mutants N2A, W3A, R4A, L7A, I8A & R12A had reduced binding potency (see "synthetic variants"), whilst other Ala mutants exhibited comparable potency. (Sharpe et al., 2003)

Classification
Conopeptide class conotoxin
Gene superfamily A superfamily
Cysteine framework I
Pharmacological family rho conotoxin

Sequence
FNWRCCLIPACRRNHKKFC(nh2)
Modified residues
positionsymbolname
20nh2C-term amidation
Sequence evidence protein level
Average Mass 2390.89
Monoisotopic Mass 2389.14
Isoelectric Point 12.82
Extinction Coefficient [280nm] 5500.00

Activity

IC50: Adrenoceptors

TargetOrganismIC50AgonistRef
α1A-adrenoceptorH. sapiens18nMBE (20-800 pm)Chen,Z. et al. (2004)
R. norvegicus150nMHEATSharpe,I.A. et al. (2003)
α1B-adrenoceptorH. sapiens2nMBE (20-800 pm)Chen,Z. et al. (2004)
M. auratus124nM125I-HEATSharpe,I.A. et al. (2001)
124nMHEAT (575nM)Sharpe,I.A. et al. (2001)
R. norvegicus70nMHEATSharpe,I.A. et al. (2003)
α1D-adrenoceptorH. sapiens25nMBE (20-800pm)Chen,Z. et al. (2004)
R. norvegicus340nMHEATSharpe,I.A. et al. (2003)

Synthetic variants
TIA[1-5](nh2)CRWNF
TIA[2-19](nh2)CFKKHNRRCAPILCCRWN
TIA[3-19](nh2)CFKKHNRRCAPILCCRW
TIA[4-19](nh2)CFKKHNRRCAPILCCR
TIA[5-19](nh2)CFKKHNRRCAPILCC
[I8A]TIA(nh2)CFKKHNRRCAPALCCRWNF
[L7A]TIA(nh2)CFKKHNRRCAPIACCRWNF
[N2A]TIA(nh2)CFKKHNRRCAPILCCRWAF
[R12A]TIA(nh2)CFKKHNRACAPILCCRWNF
[R4A]TIA(nh2)CFKKHNRRCAPILCCAWNF
[W3A]TIA(nh2)CFKKHNRRCAPILCCRANF

References
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
Sharpe,I.A., Thomas,L., Loughnan,M., Motin,L., Palant,E., Croker,D.E., Alewood,D., Chen,S., Graham,R.M., Alewood,P.F., Adams,D.J. and Lewis,R.J. (2003) Allosteric alpha 1-adrenoreceptor antagonism by the conopeptide rho-TIA J. Biol. Chem. 278:34451-34457
Chen,Z., Rogge,G., Hague,C., Alewood,D., Colless,B., Lewis,R.J. and Minneman,K.P. (2004) Subtype-selective noncompetitive or competitive inhibition of human alpha1-adrenergic receptors by rho-TIA J. Biol. Chem. 279:35326-35333
Lima,V., Mueller,A., Kamikihara,S.Y., Raymundi,V., Alewood,D., Lewis,R.J., Chen,Z., Minneman,K.P. and Pupo,A.S. (2005) Differential antagonism by conotoxin rho-TIA of contractions mediated by distinct alpha1-adrenoceptor subtypes in rat vas deferens, spleen and aorta Eur. J. Pharmacol. 508:183-192
Ragnarsson,L., Wang,C.I., Andersson,A., Fajarningsih,D., Monks,T., Brust,A., Rosengren,K.J. and Lewis,R.J. (2013) Conopeptide ρ-TIA defines a new allosteric site on the extracellular surface of the α1B-adrenoceptor. J. Biol. Chem. 288:1814-1827
Patil, N.A., Karas, J.A., Wade, J.D., Hossain, M.A. and Tailhades, J. (2019) Rapid Photolysis-Mediated Folding of Disulfide-Rich Peptides Chemistry–A European Journal 25:8599-8603
Dutt, M., Dutertre, S., Jin, A.H., Lavergne, V., Alewood, P.F. and Lewis, R.J. (2019) Venomics reveals venom complexity of the piscivorous cone snail, Conus tulipa Marine drugs 17:71

Internal links
Protein Precursor TIA precursor (8074)
TIA precursor (8075)
Nucleic acids
Structure SOLUTION STRUCTURE OF TIA
High-resolution solution NMR structure of the rho-conotoxin TIA

External links
UniProtKB/Swiss-Prot P58811
Ncbi 2LR9_A, P58811

Tools