UniProtKB - G9I930 (PA2HB_MICTN)
Basic phospholipase A2 homolog MitTx-beta
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 PublicationsMonomer: 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 PublicationMiscellaneous
Caution
GO - Molecular functioni
- calcium ion binding Source: InterPro
- ion channel regulator activity Source: UniProtKB-KW
- phospholipase A2 activity Source: InterPro
- toxin activity Source: UniProtKB-KW
GO - Biological processi
- arachidonic acid secretion Source: InterPro
- lipid catabolic process Source: InterPro
- phospholipid metabolic process Source: InterPro
Keywordsi
Molecular function | Ion channel impairing toxin, Proton-gated sodium channel impairing toxin, Toxin |
Names & Taxonomyi
Protein namesi | Recommended name: Basic phospholipase A2 homolog MitTx-beta1 PublicationShort name: svPLA2 homologCurated |
Organismi | Micrurus tener tener (Texas coral snake) |
Taxonomic identifieri | 1114302 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Lepidosauria › Squamata › Bifurcata › Unidentata › Episquamata › Toxicofera › Serpentes › Colubroidea › Elapidae › Elapinae › Micrurus › |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Keywords - Cellular componenti
SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 30 | 1 PublicationAdd BLAST | 30 | |
ChainiPRO_5000828218 | 31 – 149 | Basic phospholipase A2 homolog MitTx-beta1 PublicationAdd BLAST | 119 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 41 ↔ 100 | 1 PublicationImported | ||
Disulfide bondi | 55 ↔ 148 | 1 PublicationImported | ||
Disulfide bondi | 57 ↔ 73 | 1 PublicationImported | ||
Disulfide bondi | 72 ↔ 130 | 1 PublicationImported | ||
Disulfide bondi | 79 ↔ 123 | 1 PublicationImported | ||
Disulfide bondi | 89 ↔ 116 | 1 PublicationImported | ||
Disulfide bondi | 109 ↔ 121 | 1 PublicationImported |
Keywords - PTMi
Disulfide bondExpressioni
Tissue specificityi
Interactioni
Subunit structurei
Heterodimer of an alpha (Kunitz-type) and a beta (phospholipase A2 homolog) chains; non-covalently-linked.
1 PublicationStructurei
Secondary structure
3D structure databases
SMRi | G9I930 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domaini
Sequence similaritiesi
Keywords - Domaini
SignalFamily and domain databases
CDDi | cd00125, PLA2c, 1 hit |
Gene3Di | 1.20.90.10, 1 hit |
InterProi | View protein in InterPro IPR001211, PLipase_A2 IPR033112, PLipase_A2_Asp_AS IPR016090, PLipase_A2_dom IPR036444, PLipase_A2_dom_sf |
PANTHERi | PTHR11716, PTHR11716, 1 hit |
Pfami | View protein in Pfam PF00068, Phospholip_A2_1, 1 hit |
PRINTSi | PR00389, PHPHLIPASEA2 |
SMARTi | View protein in SMART SM00085, PA2c, 1 hit |
SUPFAMi | SSF48619, SSF48619, 1 hit |
PROSITEi | View protein in PROSITE PS00119, PA2_ASP, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
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
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | JN613326 mRNA Translation: AET85560.1 |
Similar proteinsi
Cross-referencesi
Web resourcesi
Protein Spotlight The poison in pain - Issue 140 of July 2012 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | JN613326 mRNA Translation: AET85560.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4NTW | X-ray | 2.07 | C | 31-148 | [»] | |
4NTX | X-ray | 2.27 | C | 31-148 | [»] | |
4NTY | X-ray | 2.65 | C | 31-148 | [»] | |
SMRi | G9I930 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Family and domain databases
CDDi | cd00125, PLA2c, 1 hit |
Gene3Di | 1.20.90.10, 1 hit |
InterProi | View protein in InterPro IPR001211, PLipase_A2 IPR033112, PLipase_A2_Asp_AS IPR016090, PLipase_A2_dom IPR036444, PLipase_A2_dom_sf |
PANTHERi | PTHR11716, PTHR11716, 1 hit |
Pfami | View protein in Pfam PF00068, Phospholip_A2_1, 1 hit |
PRINTSi | PR00389, PHPHLIPASEA2 |
SMARTi | View protein in SMART SM00085, PA2c, 1 hit |
SUPFAMi | SSF48619, SSF48619, 1 hit |
PROSITEi | View protein in PROSITE PS00119, PA2_ASP, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PA2HB_MICTN | |
Accessioni | G9I930Primary (citable) accession number: G9I930 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 18, 2012 |
Last sequence update: | February 22, 2012 | |
Last modified: | February 23, 2022 | |
This is version 35 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Animal Toxin Annotation Program | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencingDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Protein Spotlight
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries