KAX6L_UROYA
ID KAX6L_UROYA Reviewed; 62 AA.
AC P0DL37; A0A0A0PP69;
DT 01-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2014, sequence version 1.
DT 25-MAY-2022, entry version 20.
DE RecName: Full=Potassium channel toxin alpha-KTx 6.21 {ECO:0000303|PubMed:24723491};
DE AltName: Full=Urotoxin {ECO:0000303|PubMed:24723491, ECO:0000303|PubMed:31881193};
DE Short=Uro {ECO:0000303|PubMed:31881193};
DE Flags: Precursor;
OS Urodacus yaschenkoi (Inland robust scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Iurida; Scorpionoidea; Scorpionidae; Urodacinae; Urodacus.
OX NCBI_TaxID=1273102;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 25-43, FUNCTION, MASS
RP SPECTROMETRY, AMIDATION AT VAL-61, 3D-STRUCTURE MODELING IN INTERACTION
RP WITH KV1.1/KCNA1 AND KV1.2/KCNA2, MOLECULAR DYNAMICS SIMULATIONS, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=24723491; DOI=10.1124/mol.113.090183;
RA Luna-Ramirez K., Bartok A., Restano-Cassulini R., Quintero-Hernandez V.,
RA Coronas F.I.V., Christensen J., Wright C.E., Panyi G., Possani L.D.;
RT "Structure, molecular modeling, and function of the novel potassium channel
RT blocker urotoxin isolated from the venom of the Australian scorpion
RT Urodacus yaschenkoi.";
RL Mol. Pharmacol. 86:28-41(2014).
RN [2]
RP STRUCTURE BY NMR OF 25-61, FUNCTION, DISULFIDE BONDS, RECOMBINANT
RP EXPRESSION, AND MUTAGENESIS OF THR-43 AND LYS-49.
RX PubMed=31881193; DOI=10.1016/j.bcp.2019.113782;
RA Luna-Ramirez K., Csoti A., McArthur J.R., Chin Y.K.Y., Anangi R.,
RA Najera R.D.C., Possani L.D., King G.F., Panyi G., Yu H., Adams D.J.,
RA Finol-Urdaneta R.K.;
RT "Structural basis of the potency and selectivity of Urotoxin, a potent Kv1
RT blocker from scorpion venom.";
RL Biochem. Pharmacol. 174:113782-113782(2020).
CC -!- FUNCTION: Reversible blocker of voltage-gated potassium channels with
CC fast binding and unbinding kinetics (PubMed:24723491, PubMed:31881193).
CC Has highest activity on human voltage-gated potassium channel
CC Kv1.2/KCNA2 channels (IC(50)=0.11-0.16 nM), whereas its affinity for
CC other channels tested was in the nanomolar range (hKv1.1/KCNA1,
CC IC(50)=253 nM; hKv1.3/KCNA3, IC(50)=91 nM; and hKCa3.1/KCNN4, IC(50)=70
CC nM) (PubMed:24723491, PubMed:31881193). {ECO:0000269|PubMed:24723491,
CC ECO:0000269|PubMed:31881193}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24723491}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:24723491}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to
CC antiparallel beta-sheets by disulfide bonds (CS-alpha/beta).
CC {ECO:0000305}.
CC -!- PTM: C-terminal amidation is important for activity. There is a 50-70-
CC fold decrease in ability to inhibit Kv1.2/KCNA2 when the toxin is not
CC amidated. This decrease may be explained by a 23-fold slower
CC association rate (k(on)) together with a 2-fold faster dissociation
CC rate (k(off)). {ECO:0000269|PubMed:31881193}.
CC -!- MASS SPECTROMETRY: Mass=4012.75; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:24723491};
CC -!- MISCELLANEOUS: Has no effect on hKv1.4/KCNA4, hKv1.5/KCNA5, ether-a-go-
CC go-related gene type 1 (hERG1), and ether-a-go-go-like (hELK2)
CC channels. {ECO:0000305|PubMed:24723491}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 06 subfamily. {ECO:0000305}.
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DR EMBL; KC818423; AHJ59315.1; -; mRNA.
DR PDB; 6MZT; NMR; -; A=25-61.
DR PDBsum; 6MZT; -.
DR AlphaFoldDB; P0DL37; -.
DR SMR; P0DL37; -.
DR TCDB; 8.B.8.1.7; the Alpha-ktx15 scorpion toxin (Alpha-ktx15) family.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.30.10; -; 1.
DR InterPro; IPR036574; Scorpion_toxin-like_sf.
DR InterPro; IPR001947; Scorpion_toxinS_K_inh.
DR Pfam; PF00451; Toxin_2; 1.
DR PRINTS; PR00286; CHARYBDTOXIN.
DR SUPFAM; SSF57095; SSF57095; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Potassium channel impairing toxin;
KW Secreted; Signal; Toxin.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:24723491"
FT PEPTIDE 25..61
FT /note="Potassium channel toxin alpha-KTx 6.21"
FT /evidence="ECO:0000269|PubMed:24723491"
FT /id="PRO_0000430422"
FT SITE 49
FT /note="Pharmacophore, responsible of Kv1 potassium channel
FT pore occlusion"
FT /evidence="ECO:0000269|PubMed:31881193"
FT MOD_RES 61
FT /note="Valine amide"
FT /evidence="ECO:0000269|PubMed:24723491"
FT DISULFID 29..50
FT /evidence="ECO:0000269|PubMed:31881193,
FT ECO:0007744|PDB:6MZT"
FT DISULFID 35..55
FT /evidence="ECO:0000269|PubMed:31881193,
FT ECO:0007744|PDB:6MZT"
FT DISULFID 39..57
FT /evidence="ECO:0000269|PubMed:31881193,
FT ECO:0007744|PDB:6MZT"
FT DISULFID 45..60
FT /evidence="ECO:0000269|PubMed:31881193,
FT ECO:0007744|PDB:6MZT"
FT MUTAGEN 43
FT /note="T->Q: 30-fold decrease in ability to inhibit
FT Kv1.1/KCNA1, and no change in ability to inhibit both
FT Kv1.2/KCNA2 and Kv1.3/KCNA3 potassium channels."
FT /evidence="ECO:0000269|PubMed:31881193"
FT MUTAGEN 49
FT /note="K->A: Very important decrease in ability to inhibit
FT Kv1.2/KCNA2 potassium channel, and important decrease in
FT ability to inhibit both Kv1.1/KCNA1 and Kv1.3/KCNA3
FT potassium channels."
FT /evidence="ECO:0000269|PubMed:31881193"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:6MZT"
FT HELIX 33..42
FT /evidence="ECO:0007829|PDB:6MZT"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:6MZT"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:6MZT"
SQ SEQUENCE 62 AA; 6793 MW; 0BB389DFF032AC2F CRC64;
MNAKLIYLLL VVTTMMLTFD TTQAGDIKCS GTRQCWGPCK KQTTCTNSKC MNGKCKCYGC
VG
