Potently blocks voltage-gated potassium channels Kv1.1/KCNA1 (IC(50)=7-11 nM) and Kv1.3/KCNA3 (IC(50)=11-29 pM) (PubMed:9359871, PubMed:24676092, PubMed:15498765). Also mildly blocks intermediate (IK) conductance calcium-activated potassium channels (KCa3.1/KCNN4) and ERG1/Kv11.1/KCNH2 (PubMed:18687312, PubMed:15498765). Shows ability to suppress proliferation of lymphocytes, which are known to be sensitive to Kv1.3/KCNA3 homotetrameric channel block (PubMed:24676092). Expressed by the venom gland. Has the structural arrangement of an alpha-helix connected to a beta-sheet by disulfide bonds (CSalpha/beta). The lower affinity for Kv1.1/KCNA1 is due to HsTX1 inability to come close to the pore domain, which prevents the pore-inserting lysine (Lys-23) from making proper contacts with the tyrosine carbonyls in the selectivity filter of the channel. Amidated (PubMed:9359871). The amidated toxin shows 5-fold more affinity for Kv1.3/KCNA3 than the synthetic carboxylated form (PubMed:9359871). Some analogs of this peptide are potential candidate for treatment of autoimmune diseases through block of Kv1.3/KCNA3. Does not block Kv1.2/KCNA2 potassium channels (PubMed:15498765). Does not induce hemolysis (PubMed:24676092). PEGylation of HsTX1[R14A] enhances its circulating half-life in rats, reduces its affinity but not its selectivity for Kv1.3/KCNA3, and dramatically reduces its adsorption to inert surfaces. PEG-HsTX1[R14A] is equipotent to HsTX1[R14A] in preferential inhibition of human and rat CCR7(-) effector memory T lymphocytes (TEM) proliferation, leaving CCR7(+) naive and central memory T cells able to proliferate. It reduces inflammation in an active delayed-type hypersensitivity model and in the pristane-induced arthritis (PIA) model of rheumatoid arthritis (RA). Importantly, a single subcutaneous dose of PEG-HsTX1[R14A] reduces inflammation in PIA for a longer period of time than the non-PEGylated HsTX1[R14A]. Together, these data indicate that HsTX1[R14A] and PEG-HsTX1[R14A] are effective in a model of RA and are therefore potential therapeutics for TEM cell-mediated autoimmune diseases. Belongs to the short scorpion toxin superfamily. Potassium channel inhibitor family. Alpha-KTx 06 subfamily.