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G9I929 (IVBMA_MICTN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 10. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Neurotoxin MitTx-alpha
OrganismMicrurus tener tener (Texas coral snake)
Taxonomic identifier1114302 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Lepidosauria › Squamata › Scleroglossa › Serpentes › Colubroidea › Elapidae › Elapinae › Micrurus ›

Protein attributes

Sequence length84 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

This heterodimeric toxin potently activates mouse acid-sensing ion channel ASIC1/ACCN2 expressed in Xenopus oocytes. Both alternatively spliced isoforms ASIC1a and ASIC1b are activated, with a higher potency for ASIC1a (EC50=9.4 nM) vs ASIC1b (EC50=23 nM). The ASIC3/ACCN3 subtype is also sensitive to the heterodimer, but with a lower potency (EC50=830 nM). On ASIC2a/ACCN1, the toxin shows a very weak activation, but produces a remarkable potentiation (>100-fold) of protons when the extracellular pH drops below neutrality. The toxin interacts with the extracellular region of the channel, since responses are only observed in the outside-out configuration. In vivo, the heterodimer elicits robust pain-related behavior in mice by activation of ASIC1/ACCN2 channels on capsaicin-sensitive nerve fibers. Ref.1

Subunit structure

Heterodimer of an alpha and a beta chains. Ref.1

Subcellular location

Secreted.

Tissue specificity

Expressed by the venom gland.

Miscellaneous

This toxin has been studied to probe molecular mechanisms underlying pain sensation. By targeting ASIC1/ACCN2, it reveals an unexpected contribution of this channel to nociception (Ref.1).

The heterodimeric toxin does not affect ASIC2b/ACCN1, ASIC4/ACCN4, Kv2.1/KCNB1, Cav3.3/CACNA1I, ENaC/SCNN1A, TRPA1, TRPV1, TRPV3, TRPM8, P2X2/P2RX2, and 5-HT3/HTR3A channels (Ref.1).

Sequence similarities

Belongs to the venom Kunitz-type family.

Contains 1 BPTI/Kunitz inhibitor domain.

Ontologies

Keywords
   Cellular componentSecreted
   DomainSignal
   Molecular functionIon channel impairing toxin
Neurotoxin
Protease inhibitor
Serine protease inhibitor
Toxin
   PTMDisulfide bond
   Technical termDirect protein sequencing
Gene Ontology (GO)
   Cellular_componentextracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionserine-type endopeptidase inhibitor activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424
Chain25 – 8460Neurotoxin MitTx-alpha
PRO_5000828217

Regions

Domain31 – 8252BPTI/Kunitz inhibitor

Amino acid modifications

Disulfide bond31 ↔ 82 By similarity
Disulfide bond41 ↔ 65 By similarity
Disulfide bond57 ↔ 78 By similarity

Sequences

Sequence LengthMass (Da)Tools
G9I929 [UniParc].

Last modified February 22, 2012. Version 1.
Checksum: 7D5C274A6ABDA89D

FASTA849,498
        10         20         30         40         50         60 
MSSGGLLLLL GLLTLCAELT PVSSQIRPAF CYEDPPFFQK CGAFVDSYYF NRSRITCVHF 

        70         80 
FYGQCDVNQN HFTTMSECNR VCHG

« Hide

References

[1]"A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain."
Bohlen C.J., Chesler A.T., Sharif-Naeini R., Medzihradszky K.F., Zhou S., King D., Sanchez E.E., Burlingame A.L., Basbaum A.I., Julius D.
Nature 479:410-414(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBUNIT, PYROGLUTAMATE FORMATION AT GLN-25.
Tissue: Venom and Venom gland.

Web resources

Protein Spotlight

The poison in pain - Issue 140 of July 2012

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		JN613325 mRNA. Translation: AET85559.1.

3D structure databases

ModBaseSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D4.10.410.10. 1 hit.
InterProIPR002223. Prot_inh_Kunz-m.
[Graphical view]
PfamPF00014. Kunitz_BPTI. 1 hit.
[Graphical view]
SMARTSM00131. KU. 1 hit.
[Graphical view]
SUPFAMSSF57362. Prot_inh_Kunz-m. 1 hit.
PROSITEPS00280. BPTI_KUNITZ_1. False negative.
PS50279. BPTI_KUNITZ_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameIVBMA_MICTN
AccessionPrimary (citable) accession number: G9I929
Entry history
Integrated into UniProtKB/Swiss-Prot: April 18, 2012
Last sequence update: February 22, 2012
Last modified: May 1, 2013
This is version 10 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

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