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Protein

Basic phospholipase A2 homolog MitTx-beta

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

Heterodimer: 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 toxin 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
Monomer: does not have phospholipase A2 activity but may maintain some lipid-binding character from its PLA2 lineage, which could aid in effecting neuronal depolarization.1 Publication

Miscellaneous

The heterodimeric toxin does not affect ASIC2b, ASIC4, 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

GO - Biological processi

Keywordsi

Molecular functionIon channel impairing toxin, Proton-gated sodium channel impairing toxin, Toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Basic phospholipase A2 homolog MitTx-beta1 Publication
Short name:
svPLA2 homologCurated
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 – 301 PublicationAdd BLAST30
ChainiPRO_500082821831 – 149Basic phospholipase A2 homolog MitTx-beta1 PublicationAdd BLAST119

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi41 ↔ 1001 PublicationImported
Disulfide bondi55 ↔ 1481 PublicationImported
Disulfide bondi57 ↔ 731 PublicationImported
Disulfide bondi72 ↔ 1301 PublicationImported
Disulfide bondi79 ↔ 1231 PublicationImported
Disulfide bondi89 ↔ 1161 PublicationImported
Disulfide bondi109 ↔ 1211 PublicationImported

Keywords - PTMi

Disulfide bond

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

1149
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi32 – 40Combined sources9
Helixi47 – 49Combined sources3
Turni50 – 52Combined sources3
Turni54 – 56Combined sources3
Helixi68 – 87Combined sources20
Turni91 – 93Combined sources3
Helixi104 – 106Combined sources3
Helixi115 – 133Combined sources19
Helixi138 – 140Combined sources3
Helixi145 – 147Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4NTWX-ray2.07C31-148[»]
4NTXX-ray2.27C31-148[»]
4NTYX-ray2.65C31-148[»]
ProteinModelPortaliG9I930.
SMRiG9I930.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

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

Keywords - Domaini

Signal

Family and domain databases

CDDicd00125. PLA2c. 1 hit.
Gene3Di1.20.90.10. 1 hit.
InterProiView protein in InterPro
IPR001211. PLipase_A2.
IPR033112. PLipase_A2_Asp_AS.
IPR016090. PLipase_A2_dom.
IPR036444. PLipase_A2_dom_sf.
PANTHERiPTHR11716. PTHR11716. 1 hit.
PfamiView protein in Pfam
PF00068. Phospholip_A2_1. 1 hit.
PRINTSiPR00389. PHPHLIPASEA2.
SMARTiView protein in SMART
SM00085. PA2c. 1 hit.
SUPFAMiSSF48619. SSF48619. 1 hit.
PROSITEiView protein in PROSITE
PS00119. PA2_ASP. 1 hit.

Sequencei

Sequence statusi: Complete.

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

G9I930-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDKMNPAHLL VLAAVCVSLL GASSIPPQAL NLNQFRLMIK CTNDRVWADF
60 70 80 90 100
VDYGCYCVAR DSNTPVDDLD RCCQAQKQCY DEAVKVHGCK PLVMFYSFEC
110 120 130 140
RYLASDLDCS GNNTKCRNFV CNCDRTATLC ILTATYNRNN HKIDPSRCQ
Length:149
Mass (Da):16,793
Last modified:February 22, 2012 - v1
Checksum:i4CF027CBCA751BE4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
JN613326 mRNA. Translation: AET85560.1.

Similar proteinsi

Entry informationi

Entry nameiPA2HB_MICTN
AccessioniPrimary (citable) accession number: G9I930
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 18, 2012
Last sequence update: February 22, 2012
Last modified: October 25, 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

Caution

Does not bind calcium as one of the calcium-binding sites is lost (Asp->Lys in position 77, which corresponds to 'Lys-49' in the current nomenclature).Curated

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