UniProt functional annotation for P60514



	UniProt functional annotation for P60514

UniProt code: P60514.

Organism: Psalmopoeus cambridgei (Trinidad chevron tarantula).

Taxonomy: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae; Mygalomorphae; Theraphosidae; Psalmopoeus.

Function: This toxin is a gating modifier that acts principally as an inhibitor on ASIC1a (ASIC isoform 2) and a potentiator on ASIC1b (ASIC isoform 3) (PubMed:10829030, PubMed:15955877, PubMed:21036899). This toxin potently and selectively inhibits rat, mouse and human ASIC1a (IC(50)=0.35-3.7 nM) (PubMed:10829030, PubMed:15955877, PubMed:21715637, PubMed:26248594, PubMed:21825095). The blockade is rapidly reversible (PubMed:10829030, PubMed:28320941). The toxin acts by shifting its steady-state desensitization to more alkaline pH (0.27 pH unit) (PubMed:15955877, PubMed:16505147). At higher concentrations, it potentiates rat and human ASIC1b and activates chicken ASIC1 by stabilizing the open state of these subtypes (PubMed:16505147, PubMed:21036899, PubMed:19185346, PubMed:24262969, PubMed:22842900). The toxin binds most tightly to the open and the desensitized states of ASIC1a (promoting desensitization), whereas it binds most tightly to the open state of ASIC1b (promoting opening) (PubMed:16505147). The toxin also inhibits mouse ASIC1a-ASIC2b (IC(50)=2.64 nM) and rat ASIC1a-ASIC2a (PubMed:21715637, PubMed:27277303). It binds to the extracellular domain at subunit interfaces in the acidic pocket with the majority of contacts on the thumb domain of the channel (PubMed:21825095, PubMed:22842900, PubMed:22760635). It is also noteworthy that calcium competes with the toxin, probably by inhibiting binding of the toxin to the channel (PubMed:15955877). {ECO:0000269|PubMed:10829030, ECO:0000269|PubMed:15955877, ECO:0000269|PubMed:16505147, ECO:0000269|PubMed:19185346, ECO:0000269|PubMed:21036899, ECO:0000269|PubMed:21715637, ECO:0000269|PubMed:21825095, ECO:0000269|PubMed:22760635, ECO:0000269|PubMed:22842900, ECO:0000269|PubMed:24262969, ECO:0000269|PubMed:26248594, ECO:0000269|PubMed:27277303, ECO:0000269|PubMed:28320941}.

Subcellular location: Secreted {ECO:0000269|PubMed:10829030}.

Tissue specificity: Expressed by the venom gland. {ECO:0000305|PubMed:10829030}.

Domain: The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin. {ECO:0000269|PubMed:12824480, ECO:0000269|PubMed:21825095, ECO:0000269|PubMed:22760635, ECO:0000269|PubMed:22842900}.

Mass spectrometry: Mass=4689.25; Method=MALDI; Evidence={ECO:0000269|PubMed:10829030};

Mass spectrometry: Mass=4690; Method=MALDI; Evidence={ECO:0000269|PubMed:12824480};

Pharmaceutical: This toxin has been shown to be neuroprotective in both rodent and porcine models of cerebral ischemia when administered 30 minutes prior to induction of stroke (PubMed:28457973). In addition, a single dose of this toxin (1 ng/kg, i.c.v. 2 h post stroke) does indeed provide substantial neuronal and functional protection in ischemic stroke in conscious hypertensive rats (PubMed:26320544). {ECO:0000269|PubMed:26320544, ECO:0000269|PubMed:28457973}.

Miscellaneous: This peptide is present at only 0.4% abundance in P.cambridgei venom. {ECO:0000269|PubMed:26320544}.

Miscellaneous: Does not act on rat and mouse ASIC1a-ASIC2a (PubMed:10829030, PubMed:21715637). Does not act on rat ASIC1a-ASIC3 (PubMed:10829030). {ECO:0000269|PubMed:10829030, ECO:0000269|PubMed:21715637}.

Similarity: Belongs to the psalmotoxin-1 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Psalmopoeus cambridgei (Trinidad chevron tarantula).
Taxonomy:		Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae; Mygalomorphae; Theraphosidae; Psalmopoeus.



Function:		This toxin is a gating modifier that acts principally as an inhibitor on ASIC1a (ASIC isoform 2) and a potentiator on ASIC1b (ASIC isoform 3) (PubMed:10829030, PubMed:15955877, PubMed:21036899). This toxin potently and selectively inhibits rat, mouse and human ASIC1a (IC(50)=0.35-3.7 nM) (PubMed:10829030, PubMed:15955877, PubMed:21715637, PubMed:26248594, PubMed:21825095). The blockade is rapidly reversible (PubMed:10829030, PubMed:28320941). The toxin acts by shifting its steady-state desensitization to more alkaline pH (0.27 pH unit) (PubMed:15955877, PubMed:16505147). At higher concentrations, it potentiates rat and human ASIC1b and activates chicken ASIC1 by stabilizing the open state of these subtypes (PubMed:16505147, PubMed:21036899, PubMed:19185346, PubMed:24262969, PubMed:22842900). The toxin binds most tightly to the open and the desensitized states of ASIC1a (promoting desensitization), whereas it binds most tightly to the open state of ASIC1b (promoting opening) (PubMed:16505147). The toxin also inhibits mouse ASIC1a-ASIC2b (IC(50)=2.64 nM) and rat ASIC1a-ASIC2a (PubMed:21715637, PubMed:27277303). It binds to the extracellular domain at subunit interfaces in the acidic pocket with the majority of contacts on the thumb domain of the channel (PubMed:21825095, PubMed:22842900, PubMed:22760635). It is also noteworthy that calcium competes with the toxin, probably by inhibiting binding of the toxin to the channel (PubMed:15955877). {ECO:0000269\|PubMed:10829030, ECO:0000269\|PubMed:15955877, ECO:0000269\|PubMed:16505147, ECO:0000269\|PubMed:19185346, ECO:0000269\|PubMed:21036899, ECO:0000269\|PubMed:21715637, ECO:0000269\|PubMed:21825095, ECO:0000269\|PubMed:22760635, ECO:0000269\|PubMed:22842900, ECO:0000269\|PubMed:24262969, ECO:0000269\|PubMed:26248594, ECO:0000269\|PubMed:27277303, ECO:0000269\|PubMed:28320941}.


Subcellular location:		Secreted {ECO:0000269\|PubMed:10829030}.
Tissue specificity:		Expressed by the venom gland. {ECO:0000305\|PubMed:10829030}.
Domain:		The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin. {ECO:0000269\|PubMed:12824480, ECO:0000269\|PubMed:21825095, ECO:0000269\|PubMed:22760635, ECO:0000269\|PubMed:22842900}.
Mass spectrometry:		Mass=4689.25; Method=MALDI; Evidence={ECO:0000269\|PubMed:10829030};
Mass spectrometry:		Mass=4690; Method=MALDI; Evidence={ECO:0000269\|PubMed:12824480};
Pharmaceutical:		This toxin has been shown to be neuroprotective in both rodent and porcine models of cerebral ischemia when administered 30 minutes prior to induction of stroke (PubMed:28457973). In addition, a single dose of this toxin (1 ng/kg, i.c.v. 2 h post stroke) does indeed provide substantial neuronal and functional protection in ischemic stroke in conscious hypertensive rats (PubMed:26320544). {ECO:0000269\|PubMed:26320544, ECO:0000269\|PubMed:28457973}.
Miscellaneous:		This peptide is present at only 0.4% abundance in P.cambridgei venom. {ECO:0000269\|PubMed:26320544}.
Miscellaneous:		Does not act on rat and mouse ASIC1a-ASIC2a (PubMed:10829030, PubMed:21715637). Does not act on rat ASIC1a-ASIC3 (PubMed:10829030). {ECO:0000269\|PubMed:10829030, ECO:0000269\|PubMed:21715637}.
Similarity:		Belongs to the psalmotoxin-1 family. {ECO:0000305}.