CA1A_CONTU
ID CA1A_CONTU Reviewed; 58 AA.
AC P58811; E2DEK8;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 08-FEB-2011, sequence version 2.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Rho-conotoxin TIA {ECO:0000303|PubMed:11528421};
DE Short=Rho-TIA {ECO:0000303|PubMed:11528421};
DE Flags: Precursor;
OS Conus tulipa (Fish-hunting cone snail) (Tulip cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Gastridium.
OX NCBI_TaxID=6495;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Puillandre N., Olivera B.M.;
RT "Superfamily, scaffold and functions: review and phylogenetic
RT classification of conotoxins.";
RL Submitted (SEP-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 39-57, FUNCTION, STRUCTURE BY NMR OF 39-57, AMIDATION
RP AT CYS-57, DISULFIDE BONDS, SYNTHESIS OF 39-57, MASS SPECTROMETRY, AND
RP SUBCELLULAR LOCATION.
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 [3]
RP FUNCTION, SYNTHESIS OF 39-57, AND MUTAGENESIS OF ASN-40; TRP-41; ARG-42;
RP LEU-45; ILE-46 AND ARG-50.
RX PubMed=12824165; DOI=10.1074/jbc.m305410200;
RA Sharpe I.A., Thomas L., Loughnan M.L., Motin L., Palant E., Croker D.E.,
RA Alewood D., Chen S., Graham R.M., Alewood P.F., Adams D.J., Lewis R.J.;
RT "Allosteric alpha 1-adrenoreceptor antagonism by the conopeptide rho-TIA.";
RL J. Biol. Chem. 278:34451-34457(2003).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF ILE-46 AND PHE-56.
RX PubMed=15194691; DOI=10.1074/jbc.m403703200;
RA Chen Z., Rogge G., Hague C., Alewood D., Colless B., Lewis R.J.,
RA Minneman K.P.;
RT "Subtype-selective noncompetitive or competitive inhibition of human
RT alpha1-adrenergic receptors by rho-TIA.";
RL J. Biol. Chem. 279:35326-35333(2004).
RN [5]
RP FUNCTION.
RX PubMed=15680270; DOI=10.1016/j.ejphar.2004.12.011;
RA Lima V., Mueller A., Kamikihara S.Y., Raymundi V., Alewood D., Lewis R.J.,
RA Chen Z., Minneman K.P., Pupo A.S.;
RT "Differential antagonism by conotoxin rho-TIA of contractions mediated by
RT distinct alpha1-adrenoceptor subtypes in rat vas deferens, spleen and
RT aorta.";
RL Eur. J. Pharmacol. 508:183-192(2005).
RN [6]
RP FUNCTION, STRUCTURE BY NMR OF 39-57, INTERACTING REGION OF 40-42 WITH
RP ADRA1B, AND DISULFIDE BONDS.
RX PubMed=23184947; DOI=10.1074/jbc.m112.430785;
RA Ragnarsson L., Wang C.I., Andersson A., Fajarningsih D., Monks T.,
RA Brust A., Rosengren K.J., Lewis R.J.;
RT "Conopeptide rho-TIA defines a new allosteric site on the extracellular
RT surface of the alpha1B-adrenoceptor.";
RL J. Biol. Chem. 288:1814-1827(2013).
CC -!- FUNCTION: Allosteric inhibitor of alpha-1B adrenergic receptors
CC (ADRA1B). Binds to an allosteric modulatory site on transmembrane helix
CC 6 and 7 at the base of extracellular loop 3 of ADRA1B
CC (PubMed:23184947). Also weekly inhibits alpha-1A (ADRA1A) and alpha-1D
CC (ADRA1D) adrenergic receptors in a competive manner (PubMed:15194691).
CC Potently inhibits contractions of vas deferens, spleen and aorta in
CC response to noradrenaline (PubMed:15680270). May also inhibits
CC nicotinic acetylcholine receptors with a possible distinct nAChR
CC binding mode from other alpha-conotoxins, due to a different three
CC residue motif (lacks the Ser-Xaa-Pro motif) (By similarity).
CC {ECO:0000250|UniProtKB:Q2I2R8, ECO:0000269|PubMed:11528421,
CC ECO:0000269|PubMed:12824165, ECO:0000269|PubMed:15194691,
CC ECO:0000269|PubMed:15680270, ECO:0000269|PubMed:23184947}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11528421}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:11528421}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=2390.15; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11528421};
CC -!- MISCELLANEOUS: Has no effect on alpha-2 adrenergic receptors (ADRA2)
CC (PubMed:11528421, PubMed:12824165). {ECO:0000305|PubMed:11528421,
CC ECO:0000305|PubMed:12824165}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ADN79119.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; GQ981400; ADN79119.1; ALT_INIT; mRNA.
DR PDB; 1IEN; NMR; -; A=39-57.
DR PDB; 2LR9; NMR; -; A=39-57.
DR PDBsum; 1IEN; -.
DR PDBsum; 2LR9; -.
DR AlphaFoldDB; P58811; -.
DR BMRB; P58811; -.
DR SMR; P58811; -.
DR TCDB; 8.B.32.1.9; the nicotinic acetylcholine receptor-targeting alpha-conotoxin (a-conotoxin) family.
DR EvolutionaryTrace; P58811; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0035792; C:host cell postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR009958; Conotoxin_a-typ.
DR Pfam; PF07365; Toxin_8; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylcholine receptor inhibiting toxin; Amidation;
KW Direct protein sequencing; Disulfide bond;
KW G-protein coupled receptor impairing toxin; Neurotoxin;
KW Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT PROPEP 17..38
FT /evidence="ECO:0000269|PubMed:11528421"
FT /id="PRO_0000404204"
FT PEPTIDE 39..57
FT /note="Rho-conotoxin TIA"
FT /evidence="ECO:0000269|PubMed:11528421"
FT /id="PRO_0000044510"
FT REGION 40..42
FT /note="Interaction with ADRA1B"
FT REGION 45..47
FT /note="Lacks the Ser-Xaa-Pro motif that is crucial for
FT potent interaction with nAChR"
FT /evidence="ECO:0000305"
FT MOD_RES 57
FT /note="Cysteine amide"
FT /evidence="ECO:0000269|PubMed:11528421"
FT DISULFID 43..49
FT /evidence="ECO:0000269|PubMed:11528421,
FT ECO:0000269|PubMed:23184947, ECO:0000312|PDB:1IEN,
FT ECO:0000312|PDB:2LR9"
FT DISULFID 44..57
FT /evidence="ECO:0000269|PubMed:11528421,
FT ECO:0000269|PubMed:23184947, ECO:0000312|PDB:1IEN,
FT ECO:0000312|PDB:2LR9"
FT MUTAGEN 40
FT /note="N->A: Little loss in inhibition."
FT /evidence="ECO:0000269|PubMed:12824165"
FT MUTAGEN 41
FT /note="W->A: Important loss in inhibition."
FT /evidence="ECO:0000269|PubMed:12824165"
FT MUTAGEN 42
FT /note="R->A: Most important loss in inhibition."
FT /evidence="ECO:0000269|PubMed:12824165"
FT MUTAGEN 45
FT /note="L->A: Little loss in inhibition."
FT /evidence="ECO:0000269|PubMed:12824165"
FT MUTAGEN 46
FT /note="I->A: Important loss in inhibition, and change from
FT non-competitive to competitive antagonist of alpha-1B
FT receptor subtype."
FT /evidence="ECO:0000269|PubMed:12824165,
FT ECO:0000269|PubMed:15194691"
FT MUTAGEN 50
FT /note="R->A: Little loss in inhibition."
FT /evidence="ECO:0000269|PubMed:12824165"
FT MUTAGEN 56
FT /note="F->A,N: Selectivity increase for alpha-1B subtype."
FT /evidence="ECO:0000269|PubMed:15194691"
FT HELIX 42..45
FT /evidence="ECO:0007829|PDB:1IEN"
FT HELIX 47..50
FT /evidence="ECO:0007829|PDB:1IEN"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:1IEN"
SQ SEQUENCE 58 AA; 6395 MW; EAA3234432D865A6 CRC64;
MFTVFLLVVL ATTGVSFTLD RASDGGNAVA KKSDVTARFN WRCCLIPACR RNHKKFCG
