NA1B_ANTXA
ID NA1B_ANTXA Reviewed; 49 AA.
AC P01531; V9GZA1;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 25-MAY-2022, entry version 105.
DE RecName: Full=Delta-actitoxin-Axm1b {ECO:0000303|PubMed:22683676};
DE Short=Delta-AITX-Axm1b {ECO:0000303|PubMed:22683676};
DE AltName: Full=Anthopleurin-B {ECO:0000303|PubMed:6108877};
DE Short=AP-B {ECO:0000303|PubMed:6108877};
DE Short=ApB {ECO:0000303|PubMed:8621610};
OS Anthopleura xanthogrammica (Giant green sea anemone) (Actinia
OS xanthogrammica).
OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC Actiniidae; Anthopleura.
OX NCBI_TaxID=6112;
RN [1]
RP PROTEIN SEQUENCE.
RC TISSUE=Nematoblast;
RX PubMed=4019448; DOI=10.1016/s0021-9258(17)39403-6;
RA Reimer N.S., Yasunobu C.L., Yasunobu K.T., Norton T.R.;
RT "Amino acid sequence of the Anthopleura xanthogrammica heart stimulant,
RT anthopleurin-B.";
RL J. Biol. Chem. 260:8690-8693(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1629194; DOI=10.1016/s0021-9258(19)49663-4;
RA Gallagher M.J., Blumenthal K.M.;
RT "Cloning and expression of wild-type and mutant forms of the cardiotonic
RT polypeptide anthopleurin B.";
RL J. Biol. Chem. 267:13958-13963(1992).
RN [3]
RP PROTEIN SEQUENCE OF 1-28.
RX PubMed=6108877;
RA Norton T.R.;
RT "Cardiotonic polypeptides from Anthopleura xanthogrammica (Brandt) and A.
RT elegantissima (Brandt).";
RL Fed. Proc. 40:21-25(1981).
RN [4]
RP FUNCTION, MUTAGENESIS OF ARG-12 AND LYS-49, AND SITES ARG-12 AND LYS-49.
RX PubMed=8276803; DOI=10.1016/s0021-9258(17)42342-8;
RA Gallagher M.J., Blumenthal K.M.;
RT "Importance of the unique cationic residues arginine 12 and lysine 49 in
RT the activity of the cardiotonic polypeptide anthopleurin B.";
RL J. Biol. Chem. 269:254-259(1994).
RN [5]
RP MUTAGENESIS OF ARG-14 AND LYS-48, AND SITES ARG-14 AND LYS-48.
RX PubMed=8288644; DOI=10.1016/s0021-9258(17)42199-5;
RA Khera P.K., Blumenthal K.M.;
RT "Role of the cationic residues arginine 14 and lysine 48 in the function of
RT the cardiotonic polypeptide anthopleurin B.";
RL J. Biol. Chem. 269:921-925(1994).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF ARG-12; ARG-14; LYS-48 AND LYS-49.
RX PubMed=7612595; DOI=10.1021/bi00027a003;
RA Khera P.K., Benzinger G.R., Lipkind G., Drum C.L., Hanck D.A.,
RA Blumenthal K.M.;
RT "Multiple cationic residues of anthopleurin B that determine high affinity
RT and channel isoform discrimination.";
RL Biochemistry 34:8533-8541(1995).
RN [7]
RP MUTAGENESIS OF ASP-7; ASP-9; HIS-34; LYS-37 AND HIS-39, AND SITES ASP-7;
RP ASP-9; LYS-34; LYS-37 AND LYS-39.
RX PubMed=8639500; DOI=10.1021/bi9528457;
RA Khera P.K., Blumenthal K.M.;
RT "Importance of highly conserved anionic residues and electrostatic
RT interactions in the activity and structure of the cardiotonic polypeptide
RT anthopleurin B.";
RL Biochemistry 35:3503-3507(1996).
RN [8]
RP MUTAGENESIS OF PRO-3; ARG-12; PRO-13; ILE-21; PHE-24; ASN-42 AND LYS-49,
RP AND SITE PRO-13.
RX PubMed=8916901; DOI=10.1021/bi961584d;
RA Kelso G.J., Drum C.L., Hanck D.A., Blumenthal K.M.;
RT "Role for Pro-13 in directing high-affinity binding of anthopleurin B to
RT the voltage-sensitive sodium channel.";
RL Biochemistry 35:14157-14164(1996).
RN [9]
RP MUTAGENESIS OF LEU-18 AND ILE-43, AND SITES LEU-18 AND ILE-43.
RX PubMed=8621610; DOI=10.1074/jbc.271.16.9422;
RA Dias-Kadambi B.L., Drum C.L., Hanck D.A., Blumenthal K.M.;
RT "Leucine 18, a hydrophobic residue essential for high affinity binding of
RT anthopleurin B to the voltage-sensitive sodium channel.";
RL J. Biol. Chem. 271:9422-9428(1996).
RN [10]
RP MUTAGENESIS OF TRP-33 AND TRP-45, AND SITES TRP-33 AND TRP-45.
RX PubMed=8798612; DOI=10.1074/jbc.271.39.23828;
RA Dias-Kadambi B.L., Combs K.A., Drum C.L., Hanck D.A., Blumenthal K.M.;
RT "The role of exposed tryptophan residues in the activity of the cardiotonic
RT polypeptide anthopleurin B.";
RL J. Biol. Chem. 271:23828-23835(1996).
RN [11]
RP FUNCTION ON CHANNEL DOMAIN 1-DOMAIN 4 INTERFACE.
RX PubMed=9306007; DOI=10.1007/s004240050460;
RA Benzinger G.R., Drum C.L., Chen L.Q., Kallen R.G., Hanck D.A., Hanck D.;
RT "Differences in the binding sites of two site-3 sodium channel toxins.";
RL Pflugers Arch. 434:742-749(1997).
RN [12]
RP MUTAGENESIS OF LYS-37; HIS-39 AND TRP-45, AND SITES LYS-37; HIS-39 AND
RP TRP-45.
RX PubMed=9417050; DOI=10.1074/jbc.273.1.80;
RA Benzinger G.R., Kyle J.W., Blumenthal K.M., Hanck D.A.;
RT "A specific interaction between the cardiac sodium channel and site-3 toxin
RT anthopleurin B.";
RL J. Biol. Chem. 273:80-84(1998).
RN [13]
RP MUTAGENESIS OF GLY-10; GLY-15 AND GLY-20, AND SITES GLY-10; GLY-15 AND
RP GLY-20.
RX PubMed=14661964; DOI=10.1021/bi035291d;
RA Seibert A.L., Liu J., Hanck D.A., Blumenthal K.M.;
RT "Arg-14 loop of site 3 anemone toxins: effects of glycine replacement on
RT toxin affinity.";
RL Biochemistry 42:14515-14521(2003).
RN [14]
RP MUTAGENESIS OF ASN-16; THR-17 AND SER-19, AND SITES ASN-16; THR-17 AND
RP SER-19.
RX PubMed=15170345; DOI=10.1021/bi0496135;
RA Seibert A.L., Liu J., Hanck D.A., Blumenthal K.M.;
RT "Role of Asn-16 and Ser-19 in anthopleurin B binding. Implications for the
RT electrostatic nature of Na(V) site 3.";
RL Biochemistry 43:7082-7089(2004).
RN [15]
RP PHOSPHOLIPID-BINDING ACTIVITY.
RX PubMed=15632158; DOI=10.1074/jbc.m412552200;
RA Smith J.J., Alphy S., Seibert A.L., Blumenthal K.M.;
RT "Differential phospholipid binding by site 3 and site 4 toxins.
RT Implications for structural variability between voltage-sensitive sodium
RT channel domains.";
RL J. Biol. Chem. 280:11127-11133(2005).
RN [16]
RP FUNCTION.
RX PubMed=24898004; DOI=10.1124/mol.114.092338;
RA Xiao Y., Blumenthal K., Cummins T.R.;
RT "Gating-pore currents demonstrate selective and specific modulation of
RT individual sodium channel voltage-sensors by biological toxins.";
RL Mol. Pharmacol. 86:159-167(2014).
RN [17]
RP REVIEW.
RX PubMed=17092528; DOI=10.1016/j.toxicon.2006.09.017;
RA Hanck D.A., Sheets M.F.;
RT "Site-3 toxins and cardiac sodium channels.";
RL Toxicon 49:181-193(2007).
RN [18]
RP NOMENCLATURE.
RX PubMed=22683676; DOI=10.1016/j.toxicon.2012.05.020;
RA Oliveira J.S., Fuentes-Silva D., King G.F.;
RT "Development of a rational nomenclature for naming peptide and protein
RT toxins from sea anemones.";
RL Toxicon 60:539-550(2012).
RN [19]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=7582896; DOI=10.1016/s0969-2126(01)00214-3;
RA Monks S.A., Pallaghy P.K., Scanlon M.J., Norton R.S.;
RT "Solution structure of the cardiostimulant polypeptide anthopleurin-B and
RT comparison with anthopleurin-A.";
RL Structure 3:791-803(1995).
CC -!- FUNCTION: Binds specifically to voltage-gated sodium channels (Nav)
CC (site 3), thereby delaying their inactivation. This toxin has the
CC highest affinity of all anemone toxins for the mammalian sodium
CC channel, whereas its paralog Anthopleurin-A retains the greatest
CC capacity to discriminate between cardiac (Nav1.5/SCN5A) and neuronal
CC sodium channels (PubMed:8916901). When tested electrophysiologically,
CC this toxin exhibits a high affinity for multiple sodium channels with a
CC 50-fold preference for rat cardiac (Nav1.5/SCN5A) over neuronal
CC channels (0.1 nM versus 5 nM). When tested by ion flux, the affinities
CC are similar and appear to have higher affinity (9 nM versus 22 nM)
CC (PubMed:8276803, PubMed:7612595). The residue Lys-37 of this toxin has
CC been shown to interact with channel Nav1.5 (residue Asp-1612 in rat and
CC Asp-1610 in human), which is located in the DIV S3-S4 linker
CC (corresponding to channel site 3) (PubMed:9417050, PubMed:24898004).
CC Selectively modifies sodium channel inactivation from the open state
CC with little effect on channel activation or on inactivation from closed
CC states (By similarity). Does not display phospholipid-binding
CC activities, suggesting that the domain IV S3-S4 linker is located at
CC the extracellular surface and not buried in the phospholipid bilayer
CC (PubMed:15632158). {ECO:0000250|UniProtKB:P01530,
CC ECO:0000269|PubMed:15632158, ECO:0000269|PubMed:24898004,
CC ECO:0000269|PubMed:7612595, ECO:0000269|PubMed:8276803,
CC ECO:0000269|PubMed:8916901, ECO:0000269|PubMed:9306007,
CC ECO:0000269|PubMed:9417050}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Nematocyst {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the sea anemone sodium channel inhibitory toxin
CC family. Type I subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA27737.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia;
CC URL="https://en.wikipedia.org/wiki/Anthopleurin";
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DR EMBL; M90675; AAA27737.1; ALT_INIT; mRNA.
DR PIR; A92547; NAXAB.
DR PDB; 1APF; NMR; -; A=1-49.
DR PDBsum; 1APF; -.
DR AlphaFoldDB; P01531; -.
DR SMR; P01531; -.
DR EvolutionaryTrace; P01531; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0042151; C:nematocyst; IEA:UniProtKB-SubCell.
DR GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0009966; P:regulation of signal transduction; IEA:InterPro.
DR Gene3D; 2.20.20.10; -; 1.
DR InterPro; IPR000693; Anenome_toxin.
DR InterPro; IPR023355; Myo_ane_neurotoxin_sf.
DR PIRSF; PIRSF001905; Anenome_toxin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cardiotoxin; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Nematocyst; Neurotoxin; Secreted; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..49
FT /note="Delta-actitoxin-Axm1b"
FT /evidence="ECO:0000269|PubMed:4019448"
FT /id="PRO_0000221516"
FT REGION 1..7
FT /note="Well-structured region"
FT /evidence="ECO:0000305|PubMed:14661964,
FT ECO:0000305|PubMed:15170345"
FT REGION 8..17
FT /note="Arg-14 loop (non-well-structured region)"
FT /evidence="ECO:0000305|PubMed:14661964,
FT ECO:0000305|PubMed:15170345"
FT REGION 18..49
FT /note="Well-structured region"
FT /evidence="ECO:0000305|PubMed:14661964,
FT ECO:0000305|PubMed:15170345"
FT SITE 7
FT /note="Structurally important"
FT /evidence="ECO:0000305|PubMed:8639500"
FT SITE 9
FT /note="Important for sodium channel affinity and for toxin
FT structure"
FT /evidence="ECO:0000305|PubMed:8639500"
FT SITE 10
FT /note="Important for affinity to sodium channel, probably
FT due to the flexibility this residue gives to the Arg-14
FT loop"
FT /evidence="ECO:0000305|PubMed:14661964"
FT SITE 12
FT /note="Key residue for binding both cardiac and neuronal
FT sodium channels"
FT /evidence="ECO:0000305|PubMed:8276803"
FT SITE 13
FT /note="Important for sodium channel affinity"
FT /evidence="ECO:0000305|PubMed:8916901"
FT SITE 14
FT /note="Not essential for sodium channel affinity"
FT /evidence="ECO:0000305|PubMed:8288644"
FT SITE 15
FT /note="Important for affinity to sodium channel, probably
FT due to the flexibility this residue gives to the Arg-14
FT loop"
FT /evidence="ECO:0000305|PubMed:14661964"
FT SITE 16
FT /note="Binds to sodium channel"
FT /evidence="ECO:0000305|PubMed:15170345"
FT SITE 17
FT /note="Has its side chain oriented away from the channel in
FT the binary complex"
FT /evidence="ECO:0000305|PubMed:15170345"
FT SITE 18
FT /note="Important for high affinity to sodium channel"
FT /evidence="ECO:0000305|PubMed:8621610"
FT SITE 19
FT /note="Binds to sodium channel"
FT /evidence="ECO:0000305|PubMed:15170345"
FT SITE 20
FT /note="Structurally important"
FT /evidence="ECO:0000305|PubMed:14661964"
FT SITE 33
FT /note="Important for channel affinity"
FT /evidence="ECO:0000305|PubMed:8798612"
FT SITE 34
FT /note="Not important for channel affinity and toxin
FT structure"
FT /evidence="ECO:0000305|PubMed:8639500"
FT SITE 37
FT /note="Important for channel affinity (interacts with rat
FT Nav1.5 channel residue Asp-1612)"
FT /evidence="ECO:0000305|PubMed:8639500,
FT ECO:0000305|PubMed:9417050"
FT SITE 39
FT /note="Not important for channel affinity and toxin
FT structure"
FT /evidence="ECO:0000305|PubMed:8639500"
FT SITE 43
FT /note="Structurally important"
FT /evidence="ECO:0000305|PubMed:8621610"
FT SITE 45
FT /note="Does not affect binding, but may affect the
FT stabilization of the cardiac channel open conformation"
FT /evidence="ECO:0000305|PubMed:8798612"
FT SITE 48
FT /note="Binds to sodium channel"
FT /evidence="ECO:0000305|PubMed:8288644"
FT SITE 49
FT /note="Important for most of the cardiac specificity"
FT /evidence="ECO:0000305|PubMed:8276803"
FT DISULFID 4..46
FT /evidence="ECO:0000269|PubMed:7582896"
FT DISULFID 6..36
FT /evidence="ECO:0000269|PubMed:7582896"
FT DISULFID 29..47
FT /evidence="ECO:0000269|PubMed:7582896"
FT MUTAGEN 3
FT /note="P->S: Minor decrease in affinity for sodium channels
FT (4.7-fold on neuronal and 2-fold on cardiac (Nav1.5)
FT channels)."
FT /evidence="ECO:0000269|PubMed:8916901"
FT MUTAGEN 7
FT /note="D->A,N: Incorrect folding or very limited amount of
FT mutant obtained."
FT /evidence="ECO:0000269|PubMed:8639500"
FT MUTAGEN 7
FT /note="D->K: Incorrect folding; when associated with D-37."
FT /evidence="ECO:0000269|PubMed:8639500"
FT MUTAGEN 7
FT /note="D->N: Small decrease in affinity (4-6-fold), and
FT very limited amount of mutant obtained."
FT /evidence="ECO:0000269|PubMed:8639500"
FT MUTAGEN 9
FT /note="D->A: Major decrease in affinity for both cardiac
FT (Nav1.5) (300-fold) and neuronal (100-fold) channels."
FT /evidence="ECO:0000269|PubMed:8639500"
FT MUTAGEN 9
FT /note="D->N: Decrease in affinity for both cardiac (Nav1.5)
FT (10-fold) and neuronal (8-fold) channels."
FT /evidence="ECO:0000269|PubMed:8639500"
FT MUTAGEN 10
FT /note="G->A: Decrease in affinity for both cardiac (Nav1.5)
FT (15-fold) and neuronal (450-fold) channels, as well as a
FT 30-fold increase in discrimination for Nav1.5. Decrease in
FT affinity for cardiac (Nav1.5) (600-fold); when associated
FT with A-15. Not correctly folded; when associated with A-
FT 20."
FT /evidence="ECO:0000269|PubMed:14661964"
FT MUTAGEN 12
FT /note="R->A: Major decrease in affinity for both cardiac
FT (Nav1.5) and neuronal sodium channels."
FT /evidence="ECO:0000269|PubMed:8276803"
FT MUTAGEN 12
FT /note="R->K: Minor effect on toxicity."
FT /evidence="ECO:0000269|PubMed:8276803"
FT MUTAGEN 12
FT /note="R->S: Minor effect on toxicity. Decrease in affinity
FT for both cardiac (Nav1.5) (5-fold) and neuronal (37-fold)
FT channels; when associated with Q-49 (tested by ion flux
FT studies). Loss of discrimination between cardiac and
FT neuronal channels; when associated with Val-13 and Q-49."
FT /evidence="ECO:0000269|PubMed:7612595,
FT ECO:0000269|PubMed:8276803, ECO:0000269|PubMed:8916901"
FT MUTAGEN 13
FT /note="P->V: Decrease in affinity for both cardiac (Nav1.5)
FT (9-fold) and neuronal channels (9-fold). Loss of
FT discrimination between cardiac and neuronal channels; when
FT associated with S-12 and Q-49."
FT /evidence="ECO:0000269|PubMed:8916901"
FT MUTAGEN 14
FT /note="R->A: Minor effect on toxicity."
FT /evidence="ECO:0000269|PubMed:8288644"
FT MUTAGEN 14
FT /note="R->K: Minor effect on toxicity."
FT /evidence="ECO:0000269|PubMed:8288644"
FT MUTAGEN 14
FT /note="R->Q: Minor effect on toxicity. Decrease in affinity
FT for both cardiac (Nav1.5) (56-fold) and neuronal (72-fold)
FT channels; when associated with S-12 (tested by ion flux
FT studies). Decrease in affinity for both cardiac (Nav1.5)
FT (13-fold) and neuronal (27-fold) channels; when associated
FT with A-48 (tested by ion flux studies)."
FT /evidence="ECO:0000269|PubMed:7612595,
FT ECO:0000269|PubMed:8288644"
FT MUTAGEN 15
FT /note="G->A: Decrease in affinity for both cardiac (Nav1.5)
FT (13-fold) and neuronal (600-fold) channels, as well as a
FT 50-fold increase in discrimination for Nav1.5. Decrease in
FT affinity for cardiac (Nav1.5) (600-fold); when associated
FT with A-10."
FT /evidence="ECO:0000269|PubMed:14661964"
FT MUTAGEN 16
FT /note="N->A: Decrease in affinity for cardiac (Nav1.5) (8-
FT fold) channels."
FT /evidence="ECO:0000269|PubMed:15170345"
FT MUTAGEN 16
FT /note="N->D: Decrease in affinity for both cardiac (Nav1.5)
FT (500-fold) and neuronal (3600-fold) channels."
FT /evidence="ECO:0000269|PubMed:15170345"
FT MUTAGEN 16
FT /note="N->R: Decrease in affinity for both cardiac (Nav1.5)
FT (5-fold) and neuronal (56-fold) channels."
FT /evidence="ECO:0000269|PubMed:15170345"
FT MUTAGEN 17
FT /note="T->A,D: No change in activity."
FT /evidence="ECO:0000269|PubMed:15170345"
FT MUTAGEN 18
FT /note="L->A: Major decrease in affinity for both cardiac
FT (Nav1.5) (330-fold) and neuronal (34-fold) channels, as
FT well as a 9.5-fold decrease in discrimination for Nav1.5."
FT /evidence="ECO:0000269|PubMed:8621610"
FT MUTAGEN 18
FT /note="L->V: Decrease in affinity for both cardiac (Nav1.5)
FT and neuronal channels."
FT /evidence="ECO:0000269|PubMed:8621610"
FT MUTAGEN 19
FT /note="S->A: Decrease in affinity for cardiac (Nav1.5)
FT (5.6-fold) channels."
FT /evidence="ECO:0000269|PubMed:15170345"
FT MUTAGEN 19
FT /note="S->D: Major decrease in affinity for both cardiac
FT (Nav1.5) (85-fold) and neuronal (653-fold) channels."
FT /evidence="ECO:0000269|PubMed:15170345"
FT MUTAGEN 19
FT /note="S->R: Decrease in affinity for both cardiac (Nav1.5)
FT (5.7-fold) and neuronal (27-fold) channels."
FT /evidence="ECO:0000269|PubMed:15170345"
FT MUTAGEN 20
FT /note="G->A: Incorrect folding. Incorrect folding; when
FT associated with A-10."
FT /evidence="ECO:0000269|PubMed:14661964"
FT MUTAGEN 21
FT /note="I->T: Minor decrease in affinity for sodium channels
FT (2.2-fold on neuronal and 2.9-fold on cardiac (Nav1.5)
FT channels)."
FT /evidence="ECO:0000269|PubMed:8916901"
FT MUTAGEN 24
FT /note="F->L: Minor decrease in affinity for sodium channels
FT (4.8-fold on neuronal and 2.4-fold on cardiac (Nav1.5)
FT channels)."
FT /evidence="ECO:0000269|PubMed:8916901"
FT MUTAGEN 33
FT /note="W->A: No mutant obtained."
FT /evidence="ECO:0000269|PubMed:8798612"
FT MUTAGEN 33
FT /note="W->F: Major decrease in affinity for both cardiac
FT (Nav1.5) (31-fold) and neuronal (50-fold) channels (tested
FT by ion flux studies). This mutant is the first ApB mutant
FT that displays a significantly altered association rate
FT (K(on))."
FT /evidence="ECO:0000269|PubMed:8798612"
FT MUTAGEN 33
FT /note="W->S: No mutant obtained."
FT /evidence="ECO:0000269|PubMed:8798612"
FT MUTAGEN 33
FT /note="W->Y: Minor decrease in affinity for both cardiac
FT (Nav1.5) (5.6-fold) and neuronal (5-fold) channels."
FT /evidence="ECO:0000269|PubMed:8798612"
FT MUTAGEN 34
FT /note="H->A: Minor decrease in affinity."
FT /evidence="ECO:0000269|PubMed:8639500"
FT MUTAGEN 37
FT /note="K->A: Decrease in affinity for both cardiac (Nav1.5)
FT (11-fold) and neuronal (7-fold) channels."
FT /evidence="ECO:0000269|PubMed:8639500"
FT MUTAGEN 37
FT /note="K->A: Decrease in affinity for cardiac (Nav1.5)
FT channels (13-fold) (with decrease in K(on) and increase in
FT K(off))."
FT /evidence="ECO:0000269|PubMed:9417050"
FT MUTAGEN 37
FT /note="K->D: Incorrect folding; when associated with K-7."
FT /evidence="ECO:0000269|PubMed:8639500"
FT MUTAGEN 39
FT /note="H->A: No change in activity."
FT /evidence="ECO:0000269|PubMed:8639500"
FT MUTAGEN 39
FT /note="H->A: Small decrease in affinity for cardiac
FT (Nav1.5) channels (1.1-fold) (with increase in both K(on)
FT and K(off))."
FT /evidence="ECO:0000269|PubMed:9417050"
FT MUTAGEN 42
FT /note="N->T: Minor decrease in affinity for sodium channels
FT (1.1-fold on neuronal and 3.4-fold on cardiac (Nav1.5)
FT channels)."
FT /evidence="ECO:0000269|PubMed:8916901"
FT MUTAGEN 43
FT /note="I->A,G,F: Incorrect folding."
FT /evidence="ECO:0000269|PubMed:8621610"
FT MUTAGEN 43
FT /note="I->L,V: Small decrease in apparent binding affinity
FT for both neuronal and cardiac (Nav1.5) channels (tested by
FT ion flux studies)."
FT /evidence="ECO:0000269|PubMed:8621610"
FT MUTAGEN 45
FT /note="W->A: Minor decrease in affinity for both cardiac
FT (Nav1.5) (7.7-fold) and neuronal (4-fold) channels (tested
FT by ion flux studies)."
FT /evidence="ECO:0000269|PubMed:8798612"
FT MUTAGEN 45
FT /note="W->F: Minor decrease in affinity for both cardiac
FT (Nav1.5) (2-4-fold) (with decrease in K(on) and increase in
FT K(off)) and neuronal (5-fold) channels (tested by ion flux
FT studies)."
FT /evidence="ECO:0000269|PubMed:8798612,
FT ECO:0000269|PubMed:9417050"
FT MUTAGEN 45
FT /note="W->S: Minor decrease in affinity for both cardiac
FT (Nav1.5) (3.3-fold) and neuronal (7-fold) channels (tested
FT by ion flux studies)."
FT /evidence="ECO:0000269|PubMed:8798612"
FT MUTAGEN 48
FT /note="K->A: Minor effect on toxicity. Decrease in affinity
FT for both cardiac (Nav1.5) (13-fold) and neuronal (27-fold)
FT channels; when associated with Q-14 (tested by ion flux
FT studies)."
FT /evidence="ECO:0000269|PubMed:7612595,
FT ECO:0000269|PubMed:8288644"
FT MUTAGEN 48
FT /note="K->Q: Minor effect on toxicity."
FT /evidence="ECO:0000269|PubMed:8288644"
FT MUTAGEN 48
FT /note="K->R: Minor effect on toxicity."
FT /evidence="ECO:0000269|PubMed:8288644"
FT MUTAGEN 49
FT /note="K->A: Minor effect on toxicity."
FT /evidence="ECO:0000269|PubMed:8276803"
FT MUTAGEN 49
FT /note="K->Q: Minor effect on toxicity. Decrease in affinity
FT for both cardiac (Nav1.5) (5-fold) and neuronal (37-fold)
FT channels; when associated with S-12 (tested by ion flux
FT studies). Loss of discrimination between cardiac and
FT neuronal channels; when associated with S-12 and V-13."
FT /evidence="ECO:0000269|PubMed:7612595,
FT ECO:0000269|PubMed:8276803, ECO:0000269|PubMed:8916901"
FT MUTAGEN 49
FT /note="K->R: Minor effect on toxicity."
FT /evidence="ECO:0000269|PubMed:8276803"
FT CONFLICT 12..13
FT /note="RP -> PN (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 25
FT /note="Y -> A (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT TURN 14..17
FT /evidence="ECO:0007829|PDB:1APF"
FT STRAND 20..23
FT /evidence="ECO:0007829|PDB:1APF"
FT STRAND 42..47
FT /evidence="ECO:0007829|PDB:1APF"
SQ SEQUENCE 49 AA; 5274 MW; 7BD237179065AE90 CRC64;
GVPCLCDSDG PRPRGNTLSG ILWFYPSGCP SGWHNCKAHG PNIGWCCKK
