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Protein

Alpha-cobratoxin

Gene
N/A
Organism
Naja kaouthia (Monocled cobra) (Naja siamensis)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Monomer: binds with high affinity to muscular (alpha-1-beta-1-gamma-delta (CHRNA1/CHRNB1/CHRNG/CHRND) nAChR) (IC50=4.5 nM on Torpedo californica membranes) and neuronal alpha-7/CHRNA7 nicotinic acetylcholine receptors (IC50=105 nM).2 Publications
Homodimer: binds with high affinity (but lower than the monomeric form) to muscular (IC50=9.7 nM) and with low affinity to neuronal alpha-7/CHRNA7 nAChRs (IC50=1370 nM) (PubMed:22223648). However, it acquires (compared to the monomeric form) the capacity to block alpha-3/beta-2 (CHRNA3/CHRNB2) nAChRs (PubMed:18381281).2 Publications
Heterodimer with cytotoxin 3 (AC P01446): is slightly more active than the homodimer in inhibiting alpha-7 nAChR and is considerably more active in blocking the alpha-3-beta-2 nAChR.1 Publication

Miscellaneous

The monomeric form has no effect on alpha-3/beta-2 (CHRNA3/CHRNB2) nAChR (PubMed:18381281). It does not show any blockade of the nicotine-evoked release of dopamine (PubMed:9840221) and does not affect ACh release.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei23Binds to Torpedo AChR1 Publication1
Sitei25Binds to both neuronal alpha-7 and Torpedo AChRs2 Publications1
Sitei27Binds to both neuronal alpha-7 and Torpedo AChRs2 Publications1
Sitei28Binds to alpha-7 AChR1 Publication1
Sitei29Binds to both neuronal alpha-7 and Torpedo AChRs2 Publications1
Sitei33Binds to both neuronal alpha-7 and Torpedo AChRs2 Publications1
Sitei35Binds to alpha-7 AChR1 Publication1
Sitei36Binds to both neuronal alpha-7 and Torpedo AChRs2 Publications1
Sitei49Binds to Torpedo AChR1 Publication1
Sitei65Binds to both neuronal alpha-7 and Torpedo AChRs2 Publications1

GO - Biological processi

Keywordsi

Molecular functionAcetylcholine receptor inhibiting toxin, Ion channel impairing toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-cobratoxin7 Publications
Short name:
Alpha-CbT1 Publication
Short name:
alpha-CT2 Publications
Short name:
alpha-Cbtx6 Publications
Alternative name(s):
Alpha-elapitoxin-Nk2aCurated
Short name:
Alpha-EPTX-Nk2aCurated
Long neurotoxin 1
Siamensis 31 Publication
OrganismiNaja kaouthia (Monocled cobra) (Naja siamensis)
Taxonomic identifieri8649 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiLepidosauriaSquamataBifurcataUnidentataEpisquamataToxicoferaSerpentesColubroideaElapidaeElapinaeNaja

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi23K → E: 2-fold and 28-fold decrease in affinity for Torpedo AChRs. 1 Publication1
Mutagenesisi25W → A: 11-fold decrease in affinity for Torpedo AChRs and 6-fold decrease in affinity for neuronal alpha-7 AChR. 2 Publications1
Mutagenesisi27D → R: 31-fold decrease in affinity for Torpedo AChRs and 50-fold decrease in affinity for neuronal alpha-7 AChR. 2 Publications1
Mutagenesisi28A → G: 5-fold decrease in affinity for neuronal alpha-7 AChR. 1 Publication1
Mutagenesisi29F → A: 12-fold decrease in affinity for Torpedo AChRs and 74-fold decrease in affinity for neuronal alpha-7 AChR. 2 Publications1
Mutagenesisi33R → E: 767-fold decrease in affinity for Torpedo AChRs and 339-fold decrease in affinity for neuronal alpha-7 AChR. 2 Publications1
Mutagenesisi35K → A: 11-fold decrease in affinity for neuronal alpha-7 AChR. 1 Publication1
Mutagenesisi36R → A: 16-fold decrease in affinity for Torpedo AChRs. 2 Publications1
Mutagenesisi49K → E: 3-fold and 53-fold decrease in affinity for Torpedo AChRs. 1 Publication1
Mutagenesisi65F → A: 7-fold decrease in affinity for Torpedo AChRs and 15-fold decrease in affinity for neuronal alpha-7 AChR. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000935541 – 71Alpha-cobratoxin1 PublicationAdd BLAST71

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi3 ↔ 20In monomer, partialCombined sources6 Publications
Disulfide bondi3Interchain (with C-20) (in homodimer), partialCombined sources1 Publication
Disulfide bondi14 ↔ 41Combined sources7 Publications
Disulfide bondi20Interchain (with C-3) (in homodimer), partialCombined sources1 Publication
Disulfide bondi26 ↔ 30Combined sources7 Publications
Disulfide bondi45 ↔ 56Combined sources7 Publications
Disulfide bondi57 ↔ 62Combined sources7 Publications

Post-translational modificationi

The disulfide bond Cys26-Cys30 is not necessary for toxin activity, since reduction and alkylation of this bond does not decrease the inhibitory activity against alpha-7 nAChR, but surprisingly enhances the inhibitory activity against alpha-3-beta-2.1 Publication

Keywords - PTMi

Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom gland.Curated

Interactioni

Subunit structurei

Monomer, homo- or heterodimer with cytotoxins 1 (P60305), 2 (AC P01445), and 3 (AC P01446); disulfide-linked.8 Publications

Structurei

Secondary structure

171
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 10Combined sources5
Beta strandi19 – 25Combined sources7
Turni27 – 29Combined sources3
Helixi30 – 33Combined sources4
Beta strandi36 – 44Combined sources9
Beta strandi52 – 57Combined sources6
Beta strandi59 – 63Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CTXX-ray2.80A1-71[»]
1LXGNMR-A1-71[»]
1LXHNMR-A1-71[»]
1YI5X-ray4.20F/G/H/I/J1-71[»]
4AEAX-ray1.94A/B1-71[»]
ProteinModelPortaliP01391.
SMRiP01391.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01391.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

HOVERGENiHBG006553.

Family and domain databases

CDDicd00206. snake_toxin. 1 hit.
InterProiView protein in InterPro
IPR003571. Snake_3FTx.
IPR018354. Snake_toxin_con_site.
PROSITEiView protein in PROSITE
PS00272. SNAKE_TOXIN. 1 hit.

Sequencei

Sequence statusi: Complete.

P01391-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
IRCFITPDIT SKDCPNGHVC YTKTWCDAFC SIRGKRVDLG CAATCPTVKT
60 70
GVDIQCCSTD NCNPFPTRKR P
Length:71
Mass (Da):7,831
Last modified:July 21, 1986 - v1
Checksum:i6F07ADD885E9AC33
GO

Sequence databases

PIRiA01662. N2NJ1S.

Cross-referencesi

Sequence databases

PIRiA01662. N2NJ1S.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CTXX-ray2.80A1-71[»]
1LXGNMR-A1-71[»]
1LXHNMR-A1-71[»]
1YI5X-ray4.20F/G/H/I/J1-71[»]
4AEAX-ray1.94A/B1-71[»]
ProteinModelPortaliP01391.
SMRiP01391.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

HOVERGENiHBG006553.

Miscellaneous databases

EvolutionaryTraceiP01391.

Family and domain databases

CDDicd00206. snake_toxin. 1 hit.
InterProiView protein in InterPro
IPR003571. Snake_3FTx.
IPR018354. Snake_toxin_con_site.
PROSITEiView protein in PROSITE
PS00272. SNAKE_TOXIN. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry namei3L21_NAJKA
AccessioniPrimary (citable) accession number: P01391
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: April 12, 2017
This is version 110 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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.