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Protein

Kunitz-type neurotoxin MitTx-alpha

Gene
N/A
Organism
Micrurus tener tener (Texas coral snake)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

MitTx, a heteromeric complex between Kunitz- and phospholipase-A2-like proteins, potently, persistently and selectively activates rat and chicken acid-sensing ion channel ASIC1 (PubMed:22094702, PubMed:24507937). Both alternatively spliced rat isoforms ASIC1a and ASIC1b are activated, with a higher potency for ASIC1a (EC(50)=9.4 nM) vs ASIC1b (EC(50)=23 nM) (PubMed:22094702). The rat ASIC3 subtype is also sensitive to the heterodimer, but with a lower potency (EC(50)=830 nM) (PubMed:22094702). On rat ASIC2a, the toxin shows a very weak activation, but produces a remarkable potentiation (>100-fold) of protons when the extracellular pH drops below neutrality (PubMed:22094702). Moderate and weak activations are also observed on the heterotrimers Asic1a-Asic2a and Asic1a-Asic3 (expressed in CHO cells), respectively (PubMed:22094702). The binding sites of the beta subunit of MitTx and the spider psalmotoxin-1 overlap, explaining why these toxins are mutually exclusive (PubMed:22094702. PubMed:24507937). In vivo, the heterodimer elicits robust pain-related behavior in mice by activation of ASIC1 channels on capsaicin-sensitive nerve fibers (PubMed:22094702).2 Publications

Miscellaneous

The heterodimeric toxin does not affect ASIC2b, ASIC4, Asic2a-Asic3 heterotrimer, Kv2.1/KCNB1, Cav3.3/CACNA1I, ENaC alpha/beta/gamma (SCNN1A/SCNN1B/SCNN1G), TRPA1, TRPV1, TRPV3, TRPM8, P2X2/P2RX2, and 5-HT3/HTR3A channels.1 Publication

GO - Molecular functioni

Keywordsi

Molecular functionIon channel impairing toxin, Protease inhibitor, Proton-gated sodium channel impairing toxin, Serine protease inhibitor, Toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Kunitz-type neurotoxin MitTx-alpha1 Publication
OrganismiMicrurus tener tener (Texas coral snake)
Taxonomic identifieri1114302 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiLepidosauriaSquamataBifurcataUnidentataEpisquamataToxicoferaSerpentesColubroideaElapidaeElapinaeMicrurus

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 241 PublicationAdd BLAST24
ChainiPRO_500082821725 – 84Kunitz-type neurotoxin MitTx-alpha1 PublicationAdd BLAST60

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei25Pyrrolidone carboxylic acid1 Publication1
Disulfide bondi31 ↔ 821 PublicationImported
Disulfide bondi41 ↔ 651 PublicationImported
Disulfide bondi57 ↔ 781 PublicationImported

Keywords - PTMi

Disulfide bond, Pyrrolidone carboxylic acid

Expressioni

Tissue specificityi

Expressed by the venom gland.1 Publication

Interactioni

Subunit structurei

Heterodimer of an alpha (Kunitz-type) and a beta (phospholipase A2 homolog) chains; non-covalently-linked.1 Publication

Structurei

Secondary structure

184
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi29 – 32Combined sources4
Beta strandi45 – 51Combined sources7
Turni52 – 55Combined sources4
Beta strandi56 – 62Combined sources7
Beta strandi67 – 69Combined sources3
Beta strandi72 – 74Combined sources3
Helixi75 – 83Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4NTWX-ray2.07B25-84[»]
4NTXX-ray2.27B25-84[»]
4NTYX-ray2.65B25-84[»]
SMRiG9I929.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini31 – 82BPTI/Kunitz inhibitorPROSITE-ProRule annotationAdd BLAST52

Domaini

The toxin-channel complex has a triskelion-like shape with one toxin heterodimer radiating from each ASIC1 subunit. Toxin subunits protrude from the edges of the channel trimer, with each heterodimer interacting almost exclusively with a single subunit.1 Publication

Sequence similaritiesi

Belongs to the venom Kunitz-type family.Curated

Keywords - Domaini

Signal

Family and domain databases

Gene3Di4.10.410.10. 1 hit.
InterProiView protein in InterPro
IPR002223. Kunitz_BPTI.
IPR036880. Kunitz_BPTI_sf.
PfamiView protein in Pfam
PF00014. Kunitz_BPTI. 1 hit.
SMARTiView protein in SMART
SM00131. KU. 1 hit.
SUPFAMiSSF57362. SSF57362. 1 hit.
PROSITEiView protein in PROSITE
PS50279. BPTI_KUNITZ_2. 1 hit.

Sequencei

Sequence statusi: Complete.

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

G9I929-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSGGLLLLL GLLTLCAELT PVSSQIRPAF CYEDPPFFQK CGAFVDSYYF
60 70 80
NRSRITCVHF FYGQCDVNQN HFTTMSECNR VCHG
Length:84
Mass (Da):9,498
Last modified:February 22, 2012 - v1
Checksum:i7D5C274A6ABDA89D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
JN613325 mRNA. Translation: AET85559.1.

Similar proteinsi

Entry informationi

Entry nameiVKTA_MICTN
AccessioniPrimary (citable) accession number: G9I929
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 18, 2012
Last sequence update: February 22, 2012
Last modified: November 22, 2017
This is version 28 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program
Annotation programChordata Protein 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. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  3. SIMILARITY comments
    Index of protein domains and families