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Potassium channel toxin alpha-KTx 4.1 (TSK4) (Tityustoxin K-alpha) (TsTX-K-alpha) (TyKalpha) (Toxin II-9) (Ts7)

 KAX41_TITSE             Reviewed;          37 AA.
P46114; P08816;
01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
01-NOV-1995, sequence version 1.
22-NOV-2017, entry version 89.
RecName: Full=Potassium channel toxin alpha-KTx 4.1 {ECO:0000303|PubMed:24590385};
AltName: Full=TSK4 {ECO:0000303|PubMed:7509073};
AltName: Full=Tityustoxin K-alpha {ECO:0000303|PubMed:7509073};
Short=TsTX-K-alpha {ECO:0000303|PubMed:7509073};
Short=TyKalpha {ECO:0000305};
AltName: Full=Toxin II-9;
AltName: Full=Ts7 {ECO:0000303|PubMed:24590385};
Tityus serrulatus (Brazilian scorpion).
Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
Scorpiones; Buthida; Buthoidea; Buthidae; Tityus.
NCBI_TaxID=6887;
[1]
PROTEIN SEQUENCE, AND FUNCTION.
TISSUE=Venom;
PubMed=7509073; DOI=10.1073/pnas.91.4.1475;
Rogowski R.S., Krueger B.K., Collins J.H., Blaustein M.P.;
"Tityustoxin K alpha blocks voltage-gated noninactivating K+ channels
and unblocks inactivating K+ channels blocked by alpha-dendrotoxin in
synaptosomes.";
Proc. Natl. Acad. Sci. U.S.A. 91:1475-1479(1994).
[2]
ERRATUM.
Rogowski R.S., Krueger B.K., Collins J.H., Blaustein M.P.;
Proc. Natl. Acad. Sci. U.S.A. 93:12051-12051(1996).
[3]
PROTEIN SEQUENCE OF 1-30, AND SUBCELLULAR LOCATION.
TISSUE=Venom;
Possani L.D., Martin B.M., Svendsen I.;
"The primary structure of noxiustoxin. A K channel blocking peptide,
purified from the venom of the scorpion Centruroides noxius
Hoffmann.";
Carlsberg Res. Commun. 47:285-289(1982).
[4]
PARTIAL PROTEIN SEQUENCE, FUNCTION, AND NOMENCLATURE.
TISSUE=Venom;
PubMed=24590385; DOI=10.3390/toxins6030892;
Cerni F.A., Pucca M.B., Peigneur S., Cremonez C.M., Bordon K.C.,
Tytgat J., Arantes E.C.;
"Electrophysiological characterization of Ts6 and Ts7, K+ channel
toxins isolated through an improved Tityus serrulatus venom
purification procedure.";
Toxins 6:892-913(2014).
[5]
FUNCTION AS KV1.3 CHANNEL BLOCKER, AND MASS SPECTROMETRY.
PubMed=12871837; DOI=10.1038/sj.bjp.0705343;
Rodrigues A.R., Arantes E.C., Monje F., Stuehmer W., Varanda W.A.;
"Tityustoxin-K(alpha) blockade of the voltage-gated potassium channel
Kv1.3.";
Br. J. Pharmacol. 139:1180-1186(2003).
[6]
PHARMACOLOGICAL CHARACTERIZATION.
PubMed=18687312; DOI=10.1016/j.bcp.2008.07.008;
Abdel-Mottaleb Y., Corzo G., Martin-Eauclaire M.F., Satake H.,
Ceard B., Peigneur S., Nambaru P., Bougis P.E., Possani L.D.,
Tytgat J.;
"A common 'hot spot' confers hERG blockade activity to alpha-scorpion
toxins affecting K+ channels.";
Biochem. Pharmacol. 76:805-815(2008).
[7]
STRUCTURE BY NMR, DISULFIDE BONDS, AND MUTAGENESIS OF LYS-27.
PubMed=11352729; DOI=10.1021/bi010173g;
Ellis K.C., Tenenholz T.C., Jerng H., Hayhurst M., Dudlak C.S.,
Gilly W.F., Blaustein M.P., Weber D.J.;
"Interaction of a toxin from the scorpion Tityus serrulatus with a
cloned K+ channel from squid (sqKv1A).";
Biochemistry 40:5942-5953(2001).
-!- FUNCTION: Potently blocks Kv1.1/KCNA1 (85%), Kv1.2/KCNA2 (91%),
Kv1.3/KCNA3 (89%), Kv1.6/KCNA6 (94%), and Shaker (97%).
{ECO:0000269|PubMed:12871837, ECO:0000269|PubMed:24590385,
ECO:0000269|PubMed:7509073}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|Ref.3}.
-!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
-!- DOMAIN: Has the structural arrangement of an alpha-helix connected
to a beta-sheet by disulfide bonds (CSalpha/beta).
-!- MASS SPECTROMETRY: Mass=3942; Method=Unknown; Range=1-37;
Evidence={ECO:0000269|PubMed:12871837};
-!- MISCELLANEOUS: Inhibits with low efficiency Kv1.5/KCNA5,
Kv2.1/KCNB1, Kv7.1/KCNQ1 and ERG/KCNH2. Does not inhibit
Kv1.4/KCNA4, Kv3.1/KCNC1, Kv7.2/KCNQ2 (PubMed:24590385) and
ERG1/Kv11.1/KCNH2 (PubMed:18687312). {ECO:0000269|PubMed:18687312,
ECO:0000269|PubMed:24590385}.
-!- SIMILARITY: Belongs to the short scorpion toxin superfamily.
Potassium channel inhibitor family. Alpha-KTx 04 subfamily.
{ECO:0000305}.
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PDB; 1HP2; NMR; -; A=1-37.
PDBsum; 1HP2; -.
ProteinModelPortal; P46114; -.
SMR; P46114; -.
EvolutionaryTrace; P46114; -.
GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
Gene3D; 3.30.30.10; -; 1.
InterPro; IPR036574; Scorpion_toxin-like_sf.
InterPro; IPR001947; Scorpion_toxinS_K_inh.
Pfam; PF00451; Toxin_2; 1.
PRINTS; PR00286; CHARYBDTOXIN.
ProDom; PD003586; Scorpion_toxinS; 1.
SUPFAM; SSF57095; SSF57095; 1.
PROSITE; PS01138; SCORP_SHORT_TOXIN; 1.
1: Evidence at protein level;
3D-structure; Direct protein sequencing; Disulfide bond;
Ion channel impairing toxin; Neurotoxin;
Potassium channel impairing toxin; Secreted; Toxin;
Voltage-gated potassium channel impairing toxin.
PEPTIDE 1 37 Potassium channel toxin alpha-KTx 4.1.
{ECO:0000269|PubMed:7509073}.
/FTId=PRO_0000044923.
REGION 26 33 Interaction with Ca(2+)-activated K(+)
channels. {ECO:0000255}.
SITE 27 27 Basic residue of the functional dyad.
{ECO:0000250}.
SITE 36 36 Aromatic residue of the functional dyad.
{ECO:0000250}.
DISULFID 7 28 {ECO:0000269|PubMed:11352729}.
DISULFID 13 33 {ECO:0000269|PubMed:11352729}.
DISULFID 17 35 {ECO:0000269|PubMed:11352729}.
MUTAGEN 27 27 K->A,E,R: Significant loss of affinity
for squid Kv1A channel.
{ECO:0000269|PubMed:11352729}.
HELIX 10 20 {ECO:0000244|PDB:1HP2}.
STRAND 26 29 {ECO:0000244|PDB:1HP2}.
STRAND 32 35 {ECO:0000244|PDB:1HP2}.
SEQUENCE 37 AA; 3948 MW; 639B98A977335929 CRC64;
VFINAKCRGS PECLPKCKEA IGKAAGKCMN GKCKCYP


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Pathways :
WP1003: Ovarian Infertility Genes
WP1047: TNF-alpha NF-kB Signaling Pathway
WP1120: Ovarian Infertility Genes
WP1163: TNF-alpha NF-kB Signaling Pathway
WP1209: EBV LMP1 signaling
WP1224: EBV LMP1 signaling
WP1225: estrogen signalling
WP1340: Ovarian Infertility Genes
WP1369: TNF-alpha NF-kB Signaling Pathway
WP1434: Osteopontin Signaling
WP1487: TNF-alpha and mucus production in lung epythelium
WP1531: Vitamin D synthesis
WP1566: Citrate cycle (TCA cycle)
WP1571: EBV LMP1 signaling
WP1584: Type II diabetes mellitus
WP1614: 1- and 2-Methylnaphthalene degradation
WP1618: alpha-Linolenic acid metabolism
WP1655: Geraniol degradation
WP1772: Apoptosis Modulation and Signaling
WP1835: Interferon alpha/beta signaling
WP1904: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
WP1963: The effect of Glucocorticoids on target gene expression
WP210: Cytoplasmic Ribosomal Proteins
WP2100: AhR pathway
WP215: noncanonical wnt pathway

Related Genes :
[ADAMTS7] A disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAM-TS 7) (ADAM-TS7) (ADAMTS-7) (EC 3.4.24.-) (COMPase)
[] Potassium channel toxin alpha-KTx 6.1 (PiTX-K-gamma) (Potassium channel-blocking toxin 1) (Pi-1) (Pi1)
[hipA b1507 JW1500] Serine/threonine-protein kinase toxin HipA (Ser/Thr-protein kinase HipA) (EC 2.7.11.1) (Toxin HipA)
[] Potassium channel toxin gamma-KTx 2.1 (Neurotoxin BeKm-1) (BeKm1)
[] Potassium channel toxin alpha-KTx 23.1 (Toxin Vm24) (Toxin alpha-KTx 21.1)
[] Potassium channel toxin TsTXK-beta (Potassium channel toxin beta-KTx 1) (Tityustoxin K-beta) (TsTX K beta) (TsTX-K beta) (TsTXKbeta) (Ts8) (TsK2)
[mqsR ygiU b3022 JW2990] mRNA interferase toxin MqsR (EC 3.1.-.-) (Endoribonuclease MqsR) (Motility quorum-sensing regulator MqsR) (Toxin MqsR)
[yafQ b0225 JW0215] mRNA interferase toxin YafQ (EC 3.1.-.-) (Endoribonuclease YafQ) (Toxin YafQ)
[Adamts7] A disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAM-TS 7) (ADAM-TS7) (ADAMTS-7) (EC 3.4.24.-) (COMPase)
[] Potassium channel toxin alpha-KTx 6.2 (Maurotoxin) (MTX)
[] Ts19 (Potassium channel toxin beta-Ktx 2) [Cleaved into: Ts19 fragment I (Potassium channel toxin beta-Ktx 2-1); Ts19 fragment II (Ts19 Frag-II) (Potassium channel toxin beta-Ktx 2-2); Ts19 fragment III (Ts19 Frag-III)]
[KCNMA1 KCNMA SLO] Calcium-activated potassium channel subunit alpha-1 (BK channel) (BKCA alpha) (Calcium-activated potassium channel, subfamily M subunit alpha-1) (K(VCA)alpha) (KCa1.1) (Maxi K channel) (MaxiK) (Slo-alpha) (Slo1) (Slowpoke homolog) (Slo homolog) (hSlo)
[iaaA spt ybiK b0828 JW0812] Isoaspartyl peptidase (EC 3.4.19.5) (Beta-aspartyl-peptidase) (EcAIII) (Isoaspartyl dipeptidase) [Cleaved into: Isoaspartyl peptidase subunit alpha; Isoaspartyl peptidase subunit beta]
[KCNA2] Potassium voltage-gated channel subfamily A member 2 (NGK1) (Voltage-gated K(+) channel HuKIV) (Voltage-gated potassium channel HBK5) (Voltage-gated potassium channel subunit Kv1.2)
[Kcnma1 Kcnma] Calcium-activated potassium channel subunit alpha-1 (BK channel) (BKCA alpha) (Calcium-activated potassium channel, subfamily M subunit alpha-1) (K(VCA)alpha) (KCa1.1) (Maxi K channel) (MaxiK) (Slo-alpha) (Slo1) (mSlo1) (Slowpoke homolog) (Slo homolog) (mSlo)
[KCNMA1 KCNMA] Calcium-activated potassium channel subunit alpha-1 (BK channel) (BKCA alpha) (Calcium-activated potassium channel, subfamily M subunit alpha-1) (K(VCA)alpha) (KCa1.1) (Maxi K channel) (MaxiK) (Slo-alpha) (Slo1) (Slowpoke homolog) (RbSlo) (Slo homolog)
[KCNMA1 KCNMA] Calcium-activated potassium channel subunit alpha-1 (BK channel) (BKCA alpha) (Calcium-activated potassium channel, subfamily M subunit alpha-1) (K(VCA)alpha) (KCa1.1) (Maxi K channel) (MaxiK) (Slo-alpha) (Slo1) (Slowpoke homolog) (Slo homolog) (cSlo)
[Kcnma1 Kcnma] Calcium-activated potassium channel subunit alpha-1 (BK channel) (BKCA alpha) (Calcium-activated potassium channel, subfamily M subunit alpha-1) (K(VCA)alpha) (KCa1.1) (Maxi K channel) (MaxiK) (Slo-alpha) (Slo1) (Slowpoke homolog) (Slo homolog)
[KCNMA1 KCNMA] Calcium-activated potassium channel subunit alpha-1 (BK channel) (BKCA alpha) (Calcium-activated potassium channel, subfamily M subunit alpha-1) (K(VCA)alpha) (KCa1.1) (Maxi K channel) (MaxiK) (Slo-alpha) (Slo1) (Slowpoke homolog) (Slo homolog) (Fragment)
[KCNMA1 KCNMA] Calcium-activated potassium channel subunit alpha-1 (BK channel) (BKCA alpha) (Calcium-activated potassium channel, subfamily M subunit alpha-1) (K(VCA)alpha) (KCa1.1) (Maxi K channel) (MaxiK) (Slo-alpha) (Slo1) (Slowpoke homolog) (Slo homolog) (bSlo)
[KCNMA1 KCNMA] Calcium-activated potassium channel subunit alpha-1 (BK channel) (BKCA alpha) (Calcium-activated potassium channel, subfamily M subunit alpha-1) (K(VCA)alpha) (KCa1.1) (Maxi K channel) (MaxiK) (Slo-alpha) (Slo1) (Slowpoke homolog) (Slo homolog) (Fragment)
[KCNMA1 KCNMA] Calcium-activated potassium channel subunit alpha-1 (BK channel) (BKCA alpha) (Calcium-activated potassium channel, subfamily M subunit alpha-1) (K(VCA)alpha) (KCa1.1) (Maxi K channel) (MaxiK) (Slo-alpha) (Slo1) (Slowpoke homolog) (Slo homolog) (Fragment)
[kcnma1 kcnma xslo] Calcium-activated potassium channel subunit alpha-1 (BK channel) (BKCA alpha) (Calcium-activated potassium channel, subfamily M subunit alpha-1) (K(VCA)alpha) (KCa1.1) (Maxi K channel) (MaxiK) (Slo-alpha) (Slo1) (Slowpoke homolog) (Slo homolog) (xSlo)
[] Potassium channel toxin alpha-KTx 1.1 (ChTX-Lq1) (ChTx-a) (Charybdotoxin) (CTX) (ChTX)
[Adamts7] A disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAM-TS 7) (ADAM-TS7) (ADAMTS-7) (EC 3.4.24.-) (COMPase)
[] Potassium channel toxin alpha-KTx 3.6 (BmKTX)
[aqpZ bniP b0875 JW0859] Aquaporin Z (Bacterial nodulin-like intrinsic protein)
[Kcna2] Potassium voltage-gated channel subfamily A member 2 (RAK) (RBK2) (RCK5) (Voltage-gated potassium channel subunit Kv1.2)
[ATP1A3] Sodium/potassium-transporting ATPase subunit alpha-3 (Na(+)/K(+) ATPase alpha-3 subunit) (EC 7.2.2.13) (Na(+)/K(+) ATPase alpha(III) subunit) (Sodium pump subunit alpha-3)
[Atp1a2] Sodium/potassium-transporting ATPase subunit alpha-2 (Na(+)/K(+) ATPase alpha-2 subunit) (EC 7.2.2.13) (Na(+)/K(+) ATPase alpha(+) subunit) (Sodium pump subunit alpha-2)

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