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Protein

Delta-actitoxin-Axm1b

Gene
N/A
Organism
Anthopleura xanthogrammica (Giant green sea anemone) (Actinia xanthogrammica)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Binds specifically to voltage-gated sodium channels (Nav) (site 3), thereby delaying their inactivation. This toxin has the highest affinity of all anemone toxins for the mammalian sodium channel, whereas its paralog Anthopleurin-A retains the greatest capacity to discriminate between cardiac (Nav1.5/SCN5A) and neuronal sodium channels (PubMed:8916901). When tested electrophysiologically, this toxin exhibits a high affinity for multiple sodium channels with a 50-fold preference for rat cardiac (Nav1.5/SCN5A) over neuronal channels (0.1 nM versus 5 nM). When tested by ion flux, the affinities are similar and appear to have higher affinity (9 nM versus 22 nM) (PubMed:8276803, PubMed:7612595). The residue Lys-37 of this toxin has been shown to interact with channel Nav1.5 (residue Asp-1612 in rat and Asp-1610 in human), which is located in the DIV S3-S4 linker (corresponding to channel site 3) (PubMed:9417050, PubMed:24898004). Selectively modifies sodium channel inactivation from the open state with little effect on channel activation or on inactivation from closed states (By similarity). Does not display phospholipid-binding activities, suggesting that the domain IV S3-S4 linker is located at the extracellular surface and not buried in the phospholipid bilayer (PubMed:15632158).By similarity7 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei7Structurally important1 Publication1
Sitei9Important for sodium channel affinity and for toxin structure1 Publication1
Sitei10Important for affinity to sodium channel, probably due to the flexibility this residue gives to the Arg-14 loop1 Publication1
Sitei12Key residue for binding both cardiac and neuronal sodium channels1 Publication1
Sitei13Important for sodium channel affinity1 Publication1
Sitei14Not essential for sodium channel affinity1 Publication1
Sitei15Important for affinity to sodium channel, probably due to the flexibility this residue gives to the Arg-14 loop1 Publication1
Sitei16Binds to sodium channel1 Publication1
Sitei17Has its side chain oriented away from the channel in the binary complex1 Publication1
Sitei18Important for high affinity to sodium channel1 Publication1
Sitei19Binds to sodium channel1 Publication1
Sitei20Structurally important1 Publication1
Sitei33Important for channel affinity1 Publication1
Sitei34Not important for channel affinity and toxin structure1 Publication1
Sitei37Important for channel affinity (interacts with rat Nav1.5 channel residue Asp-1612)2 Publications1
Sitei39Not important for channel affinity and toxin structure1 Publication1
Sitei43Structurally important1 Publication1
Sitei45Does not affect binding, but may affect the stabilization of the cardiac channel open conformation1 Publication1
Sitei48Binds to sodium channel1 Publication1
Sitei49Important for most of the cardiac specificity1 Publication1

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cardiotoxin, Ion channel impairing toxin, Neurotoxin, Toxin, Voltage-gated sodium channel impairing toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Delta-actitoxin-Axm1b1 Publication
Short name:
Delta-AITX-Axm1b1 Publication
Alternative name(s):
Anthopleurin-B1 Publication
Short name:
AP-B1 Publication
Short name:
ApB1 Publication
OrganismiAnthopleura xanthogrammica (Giant green sea anemone) (Actinia xanthogrammica)
Taxonomic identifieri6112 [NCBI]
Taxonomic lineageiEukaryotaMetazoaCnidariaAnthozoaHexacoralliaActiniariaNynantheaeActiniidaeAnthopleura

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nematocyst, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3P → S: Minor decrease in affinity for sodium channels (4.7-fold on neuronal and 2-fold on cardiac (Nav1.5) channels). 1 Publication1
Mutagenesisi7D → A or N: Incorrect folding or very limited amount of mutant obtained. 1 Publication1
Mutagenesisi7D → K: Incorrect folding; when associated with D-37. 1 Publication1
Mutagenesisi7D → N: Small decrease in affinity (4-6-fold), and very limited amount of mutant obtained. 1 Publication1
Mutagenesisi9D → A: Major decrease in affinity for both cardiac (Nav1.5) (300-fold) and neuronal (100-fold) channels. 1 Publication1
Mutagenesisi9D → N: Decrease in affinity for both cardiac (Nav1.5) (10-fold) and neuronal (8-fold) channels. 1 Publication1
Mutagenesisi10G → A: Decrease in affinity for both cardiac (Nav1.5) (15-fold) and neuronal (450-fold) channels, as well as a 30-fold increase in discrimination for Nav1.5. Decrease in affinity for cardiac (Nav1.5) (600-fold); when associated with A-15. Not correctly folded; when associated with A-20. 1 Publication1
Mutagenesisi12R → A: Major decrease in affinity for both cardiac (Nav1.5) and neuronal sodium channels. 1 Publication1
Mutagenesisi12R → K: Minor effect on toxicity. 1 Publication1
Mutagenesisi12R → S: Minor effect on toxicity. Decrease in affinity for both cardiac (Nav1.5) (5-fold) and neuronal (37-fold) channels; when associated with Q-49 (tested by ion flux studies). Loss of discrimination between cardiac and neuronal channels; when associated with Val-13 and Q-49. 3 Publications1
Mutagenesisi13P → V: Decrease in affinity for both cardiac (Nav1.5) (9-fold) and neuronal channels (9-fold). Loss of discrimination between cardiac and neuronal channels; when associated with S-12 and Q-49. 1 Publication1
Mutagenesisi14R → A: Minor effect on toxicity. 1 Publication1
Mutagenesisi14R → K: Minor effect on toxicity. 1 Publication1
Mutagenesisi14R → Q: Minor effect on toxicity. Decrease in affinity for both cardiac (Nav1.5) (56-fold) and neuronal (72-fold) channels; when associated with S-12 (tested by ion flux studies). Decrease in affinity for both cardiac (Nav1.5) (13-fold) and neuronal (27-fold) channels; when associated with A-48 (tested by ion flux studies). 2 Publications1
Mutagenesisi15G → A: Decrease in affinity for both cardiac (Nav1.5) (13-fold) and neuronal (600-fold) channels, as well as a 50-fold increase in discrimination for Nav1.5. Decrease in affinity for cardiac (Nav1.5) (600-fold); when associated with A-10. 1 Publication1
Mutagenesisi16N → A: Decrease in affinity for cardiac (Nav1.5) (8-fold) channels. 1 Publication1
Mutagenesisi16N → D: Decrease in affinity for both cardiac (Nav1.5) (500-fold) and neuronal (3600-fold) channels. 1 Publication1
Mutagenesisi16N → R: Decrease in affinity for both cardiac (Nav1.5) (5-fold) and neuronal (56-fold) channels. 1 Publication1
Mutagenesisi17T → A or D: No change in activity. 1 Publication1
Mutagenesisi18L → A: Major decrease in affinity for both cardiac (Nav1.5) (330-fold) and neuronal (34-fold) channels, as well as a 9.5-fold decrease in discrimination for Nav1.5. 1 Publication1
Mutagenesisi18L → V: Decrease in affinity for both cardiac (Nav1.5) and neuronal channels. 1 Publication1
Mutagenesisi19S → A: Decrease in affinity for cardiac (Nav1.5) (5.6-fold) channels. 1 Publication1
Mutagenesisi19S → D: Major decrease in affinity for both cardiac (Nav1.5) (85-fold) and neuronal (653-fold) channels. 1 Publication1
Mutagenesisi19S → R: Decrease in affinity for both cardiac (Nav1.5) (5.7-fold) and neuronal (27-fold) channels. 1 Publication1
Mutagenesisi20G → A: Incorrect folding. Incorrect folding; when associated with A-10. 1 Publication1
Mutagenesisi21I → T: Minor decrease in affinity for sodium channels (2.2-fold on neuronal and 2.9-fold on cardiac (Nav1.5) channels). 1 Publication1
Mutagenesisi24F → L: Minor decrease in affinity for sodium channels (4.8-fold on neuronal and 2.4-fold on cardiac (Nav1.5) channels). 1 Publication1
Mutagenesisi33W → A: No mutant obtained. 1 Publication1
Mutagenesisi33W → F: Major decrease in affinity for both cardiac (Nav1.5) (31-fold) and neuronal (50-fold) channels (tested by ion flux studies). This mutant is the first ApB mutant that displays a significantly altered association rate (K(on)). 1 Publication1
Mutagenesisi33W → S: No mutant obtained. 1 Publication1
Mutagenesisi33W → Y: Minor decrease in affinity for both cardiac (Nav1.5) (5.6-fold) and neuronal (5-fold) channels. 1 Publication1
Mutagenesisi34H → A: Minor decrease in affinity. 1 Publication1
Mutagenesisi37K → A: Decrease in affinity for both cardiac (Nav1.5) (11-fold) and neuronal (7-fold) channels. 1 Publication1
Mutagenesisi37K → A: Decrease in affinity for cardiac (Nav1.5) channels (13-fold) (with decrease in K(on) and increase in K(off)). 1 Publication1
Mutagenesisi37K → D: Incorrect folding; when associated with K-7. 1 Publication1
Mutagenesisi39H → A: No change in activity. 1 Publication1
Mutagenesisi39H → A: Small decrease in affinity for cardiac (Nav1.5) channels (1.1-fold) (with increase in both K(on) and K(off)). 1 Publication1
Mutagenesisi42N → T: Minor decrease in affinity for sodium channels (1.1-fold on neuronal and 3.4-fold on cardiac (Nav1.5) channels). 1 Publication1
Mutagenesisi43I → A, G or F: Incorrect folding. 1 Publication1
Mutagenesisi43I → L or V: Small decrease in apparent binding affinity for both neuronal and cardiac (Nav1.5) channels (tested by ion flux studies). 1 Publication1
Mutagenesisi45W → A: Minor decrease in affinity for both cardiac (Nav1.5) (7.7-fold) and neuronal (4-fold) channels (tested by ion flux studies). 1 Publication1
Mutagenesisi45W → F: Minor decrease in affinity for both cardiac (Nav1.5) (2-4-fold) (with decrease in K(on) and increase in K(off)) and neuronal (5-fold) channels (tested by ion flux studies). 2 Publications1
Mutagenesisi45W → S: Minor decrease in affinity for both cardiac (Nav1.5) (3.3-fold) and neuronal (7-fold) channels (tested by ion flux studies). 1 Publication1
Mutagenesisi48K → A: Minor effect on toxicity. Decrease in affinity for both cardiac (Nav1.5) (13-fold) and neuronal (27-fold) channels; when associated with Q-14 (tested by ion flux studies). 2 Publications1
Mutagenesisi48K → Q: Minor effect on toxicity. 1 Publication1
Mutagenesisi48K → R: Minor effect on toxicity. 1 Publication1
Mutagenesisi49K → A: Minor effect on toxicity. 1 Publication1
Mutagenesisi49K → Q: Minor effect on toxicity. Decrease in affinity for both cardiac (Nav1.5) (5-fold) and neuronal (37-fold) channels; when associated with S-12 (tested by ion flux studies). Loss of discrimination between cardiac and neuronal channels; when associated with S-12 and V-13. 3 Publications1
Mutagenesisi49K → R: Minor effect on toxicity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002215161 – 49Delta-actitoxin-Axm1b1 PublicationAdd BLAST49

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi4 ↔ 461 Publication
Disulfide bondi6 ↔ 361 Publication
Disulfide bondi29 ↔ 471 Publication

Keywords - PTMi

Disulfide bond

Structurei

Secondary structure

149
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni14 – 17Combined sources4
Beta strandi20 – 23Combined sources4
Beta strandi42 – 47Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1APFNMR-A1-49[»]
ProteinModelPortaliP01531.
SMRiP01531.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01531.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 7Well-structured region2 Publications7
Regioni8 – 17Arg-14 loop (non-well-structured region)2 Publications10
Regioni18 – 49Well-structured region2 PublicationsAdd BLAST32

Sequence similaritiesi

Family and domain databases

Gene3Di2.20.20.10. 1 hit.
InterProiIPR000693. Anenome_toxin.
IPR023355. Myo_neuro_toxin.
[Graphical view]
PfamiPF00706. Toxin_4. 1 hit.
[Graphical view]
PIRSFiPIRSF001905. Anenome_toxin. 1 hit.

Sequencei

Sequence statusi: Complete.

P01531-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40 
GVPCLCDSDG PRPRGNTLSG ILWFYPSGCP SGWHNCKAHG PNIGWCCKK
Length:49
Mass (Da):5,274
Last modified:January 1, 1988 - v1
Checksum:i7BD237179065AE90
GO

Sequence cautioni

The sequence AAA27737 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti12 – 13RP → PN AA sequence (PubMed:6108877).Curated2
Sequence conflicti25Y → A AA sequence (PubMed:6108877).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M90675 mRNA. Translation: AAA27737.1. Different initiation.
PIRiA92547. NAXAB.

Cross-referencesi

Web resourcesi

Wikipedia

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M90675 mRNA. Translation: AAA27737.1. Different initiation.
PIRiA92547. NAXAB.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1APFNMR-A1-49[»]
ProteinModelPortaliP01531.
SMRiP01531.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP01531.

Family and domain databases

Gene3Di2.20.20.10. 1 hit.
InterProiIPR000693. Anenome_toxin.
IPR023355. Myo_neuro_toxin.
[Graphical view]
PfamiPF00706. Toxin_4. 1 hit.
[Graphical view]
PIRSFiPIRSF001905. Anenome_toxin. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiNA1B_ANTXA
AccessioniPrimary (citable) accession number: P01531
Secondary accession number(s): V9GZA1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 1, 1988
Last modified: November 2, 2016
This is version 94 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing

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.