TIA (P01634) Protein Card

General Information
Name TIA
Alternative name(s) T1a
Organism Conus tulipa (tulip cone)
Organism region Indo-Pacific
Organism diet piscivorous
Protein Type Wild type
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]FNWRC(nh2)
TIA[2-19]NWRCCLIPACRRNHKKFC(nh2)
TIA[3-19]WRCCLIPACRRNHKKFC(nh2)
TIA[4-19]RCCLIPACRRNHKKFC(nh2)
TIA[5-19]CCLIPACRRNHKKFC(nh2)
[I8A]TIAFNWRCCLAPACRRNHKKFC(nh2)
[L7A]TIAFNWRCCAIPACRRNHKKFC(nh2)
[N2A]TIAFAWRCCLIPACRRNHKKFC(nh2)
[R12A]TIAFNWRCCLIPACARNHKKFC(nh2)
[R4A]TIAFNWACCLIPACRRNHKKFC(nh2)
[W3A]TIAFNARCCLIPACRRNHKKFC(nh2)

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

Internal links
Nucleic acids
Structure SOLUTION STRUCTURE OF TIA
High-resolution solution NMR structure of the rho-conotoxin TIA

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

Tools