UniProt functional annotation for G9I930



	UniProt functional annotation for G9I930

UniProt code: G9I930.

Organism: Micrurus tener tener (Texas coral snake).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; Serpentes; Colubroidea; Elapidae; Elapinae; Micrurus.

Function: 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). {ECO:0000269|PubMed:22094702, ECO:0000269|PubMed:24507937}.

Function: 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. {ECO:0000305|PubMed:22094702}.

Subunit: Heterodimer of an alpha (Kunitz-type) and a beta (phospholipase A2 homolog) chains; non-covalently-linked. {ECO:0000269|PubMed:22094702}.

Subcellular location: Secreted {ECO:0000269|PubMed:22094702}.

Tissue specificity: Expressed by the venom gland. {ECO:0000305|PubMed:22094702}.

Domain: 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. {ECO:0000269|PubMed:24507937}.

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. {ECO:0000305|PubMed:22094702}.

Similarity: Belongs to the phospholipase A2 family. Group I subfamily. K49 sub-subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Micrurus tener tener (Texas coral snake).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; Serpentes; Colubroidea; Elapidae; Elapinae; Micrurus.



Function:		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). {ECO:0000269\|PubMed:22094702, ECO:0000269\|PubMed:24507937}.



Function:		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. {ECO:0000305\|PubMed:22094702}.


Subunit:		Heterodimer of an alpha (Kunitz-type) and a beta (phospholipase A2 homolog) chains; non-covalently-linked. {ECO:0000269\|PubMed:22094702}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:22094702}.
Tissue specificity:		Expressed by the venom gland. {ECO:0000305\|PubMed:22094702}.
Domain:		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. {ECO:0000269\|PubMed:24507937}.
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. {ECO:0000305\|PubMed:22094702}.
Similarity:		Belongs to the phospholipase A2 family. Group I subfamily. K49 sub-subfamily. {ECO:0000305}.