NXB4_CERLA
ID NXB4_CERLA Reviewed; 55 AA.
AC P01525;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Neurotoxin B-IV {ECO:0000303|PubMed:7263698, ECO:0000303|PubMed:972152};
OS Cerebratulus lacteus (Milky ribbon worm) (Micrura lactea).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Nemertea; Pilidiophora;
OC Heteronemertea; Lineidae; Cerebratulus.
OX NCBI_TaxID=6221;
RN [1]
RP PROTEIN SEQUENCE, HYDROXYLATION AT PRO-10, AND SEQUENCE REVISION.
RX PubMed=7263698; DOI=10.1016/s0021-9258(19)52508-x;
RA Blumenthal K.M., Keim P.S., Heinrikson R.L., Kem W.R.;
RT "Structure and action of heteronemertine polypeptide toxins. Amino acid
RT sequence of Cerebratulus lacteus toxin B-II and revised structure of toxin
RT B-IV.";
RL J. Biol. Chem. 256:9063-9067(1981).
RN [2]
RP PROTEIN SEQUENCE.
RX PubMed=972152; DOI=10.1016/s0021-9258(17)33054-5;
RA Blumenthal K.M., Kem W.R.;
RT "Structure and action of heteronemertine polypeptide toxins. Primary
RT structure of Cerebratulus lacteus toxin B-IV.";
RL J. Biol. Chem. 251:6025-6029(1976).
RN [3]
RP MUTAGENESIS.
RX PubMed=2071577; DOI=10.1016/s0021-9258(18)98777-6;
RA Howell M.L., Blumenthal K.M.;
RT "Mutagenesis of Cerebratulus lacteus neurotoxin B-IV identifies NH2-
RT terminal sequences important for biological activity.";
RL J. Biol. Chem. 266:12884-12888(1991).
RN [4]
RP MUTAGENESIS OF TYR-9; GLU-13; ARG-17; ASP-21; ARG-25 AND ARG-34.
RX PubMed=8939911; DOI=10.1074/jbc.271.47.29752;
RA Wen P.H., Blumenthal K.M.;
RT "Role of electrostatic interactions in defining the potency of neurotoxin
RT B-IV from Cerebratulus lacteus.";
RL J. Biol. Chem. 271:29752-29758(1996).
RN [5]
RP MUTAGENESIS OF LYS-18; 18-LYS-LYS-19; LEU-22; LYS-29; TRP-30 AND LYS-33.
RX PubMed=9341237; DOI=10.1021/bi970957n;
RA Wen P.H., Blumenthal K.M.;
RT "Structure and function of Cerebratulus lacteus neurotoxin B-IV:
RT tryptophan-30 is critical for function while lysines-18, -19, -29, and -33
RT are not required.";
RL Biochemistry 36:13435-13440(1997).
RN [6]
RP STRUCTURE BY NMR.
RX PubMed=1332861; DOI=10.1111/j.1432-1033.1992.tb17413.x;
RA Hansen P.E., Kem W.R., Bieber A.L., Norton R.S.;
RT "1H-NMR study of neurotoxin B-IV from the marine worm Cerebratulus lacteus.
RT Solution properties, sequence-specific resonance assignments, secondary
RT structure and global fold.";
RL Eur. J. Biochem. 210:231-240(1992).
RN [7]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=9180379; DOI=10.1006/jmbi.1997.0980;
RA Barnham K.J., Dyke T.R., Kem W.R., Norton R.S.;
RT "Structure of neurotoxin B-IV from the marine worm Cerebratulus lacteus: a
RT helical hairpin cross-linked by disulphide bonding.";
RL J. Mol. Biol. 268:886-902(1997).
CC -!- FUNCTION: This toxin increases the excitability of nerves by delaying
CC the inactivation of the voltage-gated sodium channel (Nav). Only acts
CC on some crustacean. Is more abundant, but 15-fold less toxic than
CC neurotoxin B-II.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- DOMAIN: Has the structural arrangement of two alpha-helices stabilized
CC by disulfide bonds (CSalpha/alpha 4(S-S)).
CC {ECO:0000305|PubMed:9180379}.
CC -!- SIMILARITY: Belongs to the worm B-toxin family. {ECO:0000305}.
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DR PIR; A92340; NTHNB4.
DR PDB; 1VIB; NMR; -; A=1-55.
DR PDBsum; 1VIB; -.
DR AlphaFoldDB; P01525; -.
DR SMR; P01525; -.
DR EvolutionaryTrace; P01525; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 1.10.287.120; -; 1.
DR InterPro; IPR012497; Neurotoxin_B-IV.
DR InterPro; IPR036586; Neurotoxin_B-IV-like_sf.
DR Pfam; PF07822; Toxin_13; 1.
DR SUPFAM; SSF57011; SSF57011; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Hydroxylation;
KW Ion channel impairing toxin; Secreted; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..55
FT /note="Neurotoxin B-IV"
FT /evidence="ECO:0000269|PubMed:7263698,
FT ECO:0000269|PubMed:972152"
FT /id="PRO_0000221572"
FT MOD_RES 10
FT /note="Hydroxyproline"
FT /evidence="ECO:0000269|PubMed:7263698"
FT DISULFID 12..52
FT /evidence="ECO:0000269|PubMed:9180379,
FT ECO:0007744|PDB:1VIB"
FT DISULFID 16..48
FT /evidence="ECO:0000269|PubMed:9180379,
FT ECO:0007744|PDB:1VIB"
FT DISULFID 23..41
FT /evidence="ECO:0000269|PubMed:9180379,
FT ECO:0007744|PDB:1VIB"
FT DISULFID 26..37
FT /evidence="ECO:0000269|PubMed:9180379,
FT ECO:0007744|PDB:1VIB"
FT MUTAGEN 9
FT /note="Y->F: 5-fold decrease in toxicity."
FT /evidence="ECO:0000269|PubMed:8939911"
FT MUTAGEN 13
FT /note="E->A: No change in toxicity."
FT /evidence="ECO:0000269|PubMed:8939911"
FT MUTAGEN 13
FT /note="E->Q: No change in toxicity."
FT /evidence="ECO:0000269|PubMed:8939911"
FT MUTAGEN 17
FT /note="R->A: Complete loss of toxicity."
FT /evidence="ECO:0000269|PubMed:8939911"
FT MUTAGEN 17
FT /note="R->K: Complete loss of toxicity."
FT /evidence="ECO:0000269|PubMed:8939911"
FT MUTAGEN 17
FT /note="R->Q: Complete loss of toxicity."
FT /evidence="ECO:0000269|PubMed:8939911"
FT MUTAGEN 18..19
FT /note="KK->QQ: Very low decrease in toxicity."
FT /evidence="ECO:0000269|PubMed:9341237"
FT MUTAGEN 18
FT /note="K->Q: No change in toxicity."
FT /evidence="ECO:0000269|PubMed:9341237"
FT MUTAGEN 21
FT /note="D->A: No change in toxicity."
FT /evidence="ECO:0000269|PubMed:8939911"
FT MUTAGEN 21
FT /note="D->N: No change in toxicity."
FT /evidence="ECO:0000269|PubMed:8939911"
FT MUTAGEN 21
FT /note="D->P: 10-fold decrease in toxicity."
FT /evidence="ECO:0000269|PubMed:8939911"
FT MUTAGEN 22
FT /note="L->D: No change in toxicity."
FT /evidence="ECO:0000269|PubMed:9341237"
FT MUTAGEN 25
FT /note="R->K: No change in toxicity."
FT /evidence="ECO:0000269|PubMed:8939911"
FT MUTAGEN 25
FT /note="R->Q: 400-fold decrease in toxicity."
FT /evidence="ECO:0000269|PubMed:8939911"
FT MUTAGEN 29
FT /note="K->N: No change in toxicity."
FT /evidence="ECO:0000269|PubMed:9341237"
FT MUTAGEN 30
FT /note="W->F: No change in toxicity."
FT /evidence="ECO:0000269|PubMed:9341237"
FT MUTAGEN 30
FT /note="W->S: 41-fold decrease in toxicity."
FT /evidence="ECO:0000269|PubMed:9341237"
FT MUTAGEN 30
FT /note="W->Y: 5-fold decrease in toxicity."
FT /evidence="ECO:0000269|PubMed:9341237"
FT MUTAGEN 33
FT /note="K->N: No decrease in toxicity."
FT /evidence="ECO:0000269|PubMed:9341237"
FT MUTAGEN 34
FT /note="R->A: 80-fold decrease in toxicity."
FT /evidence="ECO:0000269|PubMed:8939911"
FT MUTAGEN 34
FT /note="R->K: 8-fold decrease in toxicity."
FT /evidence="ECO:0000269|PubMed:8939911"
FT MUTAGEN 34
FT /note="R->Q: 20-fold decrease in toxicity."
FT /evidence="ECO:0000269|PubMed:8939911"
FT TURN 7..10
FT /evidence="ECO:0007829|PDB:1VIB"
FT HELIX 11..23
FT /evidence="ECO:0007829|PDB:1VIB"
FT HELIX 28..30
FT /evidence="ECO:0007829|PDB:1VIB"
FT HELIX 34..48
FT /evidence="ECO:0007829|PDB:1VIB"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:1VIB"
SQ SEQUENCE 55 AA; 6107 MW; BB76B72E48DB050D CRC64;
ASATWGAAYP ACENNCRKKY DLCIRCQGKW AGKRGKCAAH CIIQKNNCKG KCKKE
