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Protein

Rho-conotoxin TIA

Gene
N/A
Organism
Conus tulipa (Fish-hunting cone snail) (Tulip cone)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Allosteric inhibitor of alpha-1B adrenergic receptors (ADRA1B). Binds to an allosteric modulatory site on transmembrane helix 6 and 7 at the base of extracellular loop 3 of ADRA1B (PubMed:23184947). Also weekly inhibits alpha-1A (ADRA1A) and alpha-1D (ADRA1D) adrenergic receptors in a competive manner (PubMed:15194691). Potently inhibits contractions of vas deferens, spleen and aorta in response to noradrenaline (PubMed:15680270).5 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor impairing toxin, Toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Rho-conotoxin TIA
Short name:
Rho-TIA
OrganismiConus tulipa (Fish-hunting cone snail) (Tulip cone)
Taxonomic identifieri6495 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Organism-specific databases

ConoServeri1634. TIA.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Pharmaceutical usei

Is under preclinical trial by Xenome.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi40 – 401N → A: Little loss in inhibition. 1 Publication
Mutagenesisi41 – 411W → A: Important loss in inhibition. 1 Publication
Mutagenesisi42 – 421R → A: Most important loss in inhibition. 1 Publication
Mutagenesisi45 – 451L → A: Little loss in inhibition. 1 Publication
Mutagenesisi46 – 461I → A: Important loss in inhibition, and change from non-competitive to competitive antagonist of alpha-1B receptor subtype. 2 Publications
Mutagenesisi50 – 501R → A: Little loss in inhibition. 1 Publication
Mutagenesisi56 – 561F → A or N: Selectivity increase for alpha-1B subtype. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1616Sequence analysisAdd
BLAST
Propeptidei17 – 38221 PublicationPRO_0000404204Add
BLAST
Peptidei39 – 5719Rho-conotoxin TIAPRO_0000044510Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi43 ↔ 49
Disulfide bondi44 ↔ 57
Modified residuei57 – 571Cysteine amide1 Publication

Keywords - PTMi

Amidation, Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom duct.

Structurei

Secondary structure

1
58
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi42 – 454Combined sources
Helixi47 – 504Combined sources
Helixi54 – 563Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IENNMR-A39-57[»]
2LR9NMR-A39-57[»]
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP58811.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni40 – 423Interacts with ADRA1B

Domaini

The cysteine framework is I (CC-C-C). Alpha4/7 pattern.

Sequence similaritiesi

Belongs to the conotoxin A superfamily.Curated

Keywords - Domaini

Signal

Family and domain databases

InterProiIPR009958. Conotoxin_a-typ.
[Graphical view]
PfamiPF07365. Toxin_8. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P58811-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFTVFLLVVL ATTGVSFTLD RASDGGNAVA KKSDVTARFN WRCCLIPACR

RNHKKFCG
Length:58
Mass (Da):6,395
Last modified:February 8, 2011 - v2
Checksum:iEAA3234432D865A6
GO

Sequence cautioni

The sequence ADN79119.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Mass spectrometryi

Molecular mass is 2390.15 Da from positions 1 - 19. Determined by ESI. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
GQ981400 mRNA. Translation: ADN79119.1. Different initiation.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
GQ981400 mRNA. Translation: ADN79119.1. Different initiation.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IENNMR-A39-57[»]
2LR9NMR-A39-57[»]
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri1634. TIA.

Miscellaneous databases

EvolutionaryTraceiP58811.

Family and domain databases

InterProiIPR009958. Conotoxin_a-typ.
[Graphical view]
PfamiPF07365. Toxin_8. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Superfamily, scaffold and functions: review and phylogenetic classification of conotoxins."
    Puillandre N., Olivera B.M.
    Submitted (SEP-2009) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Two new classes of conopeptides inhibit the alpha1-adrenoceptor and noradrenaline transporter."
    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., Lewis R.J.
    Nat. Neurosci. 4:902-907(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 39-57, FUNCTION, STRUCTURE BY NMR OF 39-57, AMIDATION AT CYS-57, DISULFIDE BONDS, SYNTHESIS OF 39-57, MASS SPECTROMETRY.
    Tissue: Venom.
  3. Cited for: FUNCTION, SYNTHESIS OF 39-57, MUTAGENESIS OF ASN-40; TRP-41; ARG-42; LEU-45; ILE-46 AND ARG-50.
  4. "Subtype-selective noncompetitive or competitive inhibition of human alpha1-adrenergic receptors by rho-TIA."
    Chen Z., Rogge G., Hague C., Alewood D., Colless B., Lewis R.J., Minneman K.P.
    J. Biol. Chem. 279:35326-35333(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF ILE-46 AND PHE-56.
  5. "Differential antagonism by conotoxin rho-TIA of contractions mediated by distinct alpha1-adrenoceptor subtypes in rat vas deferens, spleen and aorta."
    Lima V., Mueller A., Kamikihara S.Y., Raymundi V., Alewood D., Lewis R.J., Chen Z., Minneman K.P., Pupo A.S.
    Eur. J. Pharmacol. 508:183-192(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Conopeptide rho-TIA defines a new allosteric site on the extracellular surface of the alpha1B-adrenoceptor."
    Ragnarsson L., Wang C.I., Andersson A., Fajarningsih D., Monks T., Brust A., Rosengren K.J., Lewis R.J.
    J. Biol. Chem. 288:1814-1827(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, STRUCTURE BY NMR OF 39-57, INTERACTING REGION OF 40-42 WITH ADRA1B, DISULFIDE BONDS.

Entry informationi

Entry nameiCA1A_CONTU
AccessioniPrimary (citable) accession number: P58811
Secondary accession number(s): E2DEK8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: February 8, 2011
Last modified: January 7, 2015
This is version 58 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Miscellaneous

Has no effect on alpha-2 adrenergic receptors (ADRA2) (PubMed:11528421, PubMed:12824165).2 Publications

Keywords - Technical termi

3D-structure, Direct protein sequencing, Pharmaceutical

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.