P01525 (NXB4_CERLA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Neurotoxin B-IV
Organism	Cerebratulus lacteus (Milky ribbon worm) (Micrura lactea)
Taxonomic identifier	6221 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Lophotrochozoa › Nemertea › Anopla › Heteronemertea › Cerebratulidae › Cerebratulus

Protein attributes

Sequence length	55 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This toxin increases the excitability of nerves by delaying the inactivation of the voltage-gated sodium channel (Nav). Only acts on some crustacean. Neurotoxin B-IV is more abundant, but 15-fold less toxic than neurotoxin B-II.
Subcellular location	Secreted.
Sequence similarities	Belongs to the worm B-toxin family.

Ontologies

Keywords
Cellular component	Secreted
Molecular function	Ion channel impairing toxin Sodium channel inhibitor Toxin
PTM	Disulfide bond Hydroxylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological_process	pathogenesis Inferred from electronic annotation. Source: InterPro
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	sodium channel inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 55

55

Neurotoxin B-IV

PRO_0000221572

Amino acid modifications

Modified residue

10

1

Hydroxyproline Ref.1

Disulfide bond

12 ↔ 48

Ref.1

Disulfide bond

16 ↔ 52

Ref.1

Disulfide bond

23 ↔ 41

Ref.1

Disulfide bond

26 ↔ 37

Ref.1

Experimental info

Mutagenesis

9

1

Y → F: 5-fold decrease in toxicity. Ref.4

Mutagenesis

13

1

E → A: No change in toxicity. Ref.4

Mutagenesis

13

1

E → Q: No change in toxicity. Ref.4

Mutagenesis

17

1

R → A: Complete loss of toxicity. Ref.4

Mutagenesis

17

1

R → K: Complete loss of toxicity. Ref.4

Mutagenesis

17

1

R → Q: Complete loss of toxicity. Ref.4

Mutagenesis

18 – 19

2

KK → QQ: Very low decrease in toxicity. Ref.5

Mutagenesis

18

1

K → Q: No change in toxicity. Ref.5

Mutagenesis

21

1

D → A: No change in toxicity. Ref.4

Mutagenesis

21

1

D → N: No change in toxicity. Ref.4

Mutagenesis

21

1

D → P: 10-fold decrease in toxicity. Ref.4

Mutagenesis

22

1

L → D: No change in toxicity. Ref.5

Mutagenesis

25

1

R → K: No change in toxicity. Ref.4

Mutagenesis

25

1

R → Q: 400-fold decrease in toxicity. Ref.4

Mutagenesis

29

1

K → N: No change in toxicity. Ref.5

Mutagenesis

30

1

W → F: No change in toxicity. Ref.5

Mutagenesis

30

1

W → S: 41-fold decrease in toxicity. Ref.5

Mutagenesis

30

1

W → Y: 5-fold decrease in toxicity. Ref.5

Mutagenesis

33

1

K → N: No decrease in toxicity. Ref.5

Mutagenesis

34

1

R → A: 80-fold decrease in toxicity. Ref.4

Mutagenesis

34

1

R → K: 8-fold decrease in toxicity. Ref.4

Mutagenesis

34

1

R → Q: 20-fold decrease in toxicity. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

55

Helix Strand Turn

Details...

Turn

7 – 10

4

Helix

11 – 23

13

Helix

28 – 30

3

Helix

34 – 48

15

Turn

49 – 51

3

Sequences

	Sequence		Length	Mass (Da)
	P01525 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: BB76B72E48DB050D	FASTA	55	6,107
	10 20 30 40 50 ASATWGAAYP ACENNCRKKY DLCIRCQGKW AGKRGKCAAH CIIQKNNCKG KCKKE

References

[1]	"Structure and action of heteronemertine polypeptide toxins. Amino acid sequence of Cerebratulus lacteus toxin B-II and revised structure of toxin B-IV." Blumenthal K.M., Keim P.S., Heinrikson R.L., Kem W.R. J. Biol. Chem. 256:9063-9067(1981) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE, SEQUENCE REVISION.
[2]	"Structure and action of heteronemertine polypeptide toxins. Primary structure of Cerebratulus lacteus toxin B-IV." Blumenthal K.M., Kem W.R. J. Biol. Chem. 251:6025-6029(1976) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE.
[3]	"Mutagenesis of Cerebratulus lacteus neurotoxin B-IV identifies NH2-terminal sequences important for biological activity." Howell M.L., Blumenthal K.M. J. Biol. Chem. 266:12884-12888(1991) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS.
[4]	"Role of electrostatic interactions in defining the potency of neurotoxin B-IV from Cerebratulus lacteus." Wen P.H., Blumenthal K.M. J. Biol. Chem. 271:29752-29758(1996) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TYR-9; GLU-13; ARG-17; ASP-21; ARG-25 AND ARG-34.
[5]	"Structure and function of Cerebratulus lacteus neurotoxin B-IV: tryptophan-30 is critical for function while lysines-18, -19, -29, and -33 are not required." Wen P.H., Blumenthal K.M. Biochemistry 36:13435-13440(1997) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF LYS-18; 18-LYS-LYS-19; LEU-22; LYS-29; TRP-30 AND LYS-33.
[6]	"1H-NMR study of neurotoxin B-IV from the marine worm Cerebratulus lacteus. Solution properties, sequence-specific resonance assignments, secondary structure and global fold." Hansen P.E., Kem W.R., Bieber A.L., Norton R.S. Eur. J. Biochem. 210:231-240(1992) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[7]	"Structure of neurotoxin B-IV from the marine worm Cerebratulus lacteus: a helical hairpin cross-linked by disulphide bonding." Barnham K.J., Dyke T.R., Kem W.R., Norton R.S. J. Mol. Biol. 268:886-902(1997) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.

Cross-references

Sequence databases

PIR

NTHNB4. A92340.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1VIB	NMR	-	A	1-55	[»]

ProteinModelPortal

P01525.

SMR

P01525. Positions 1-44.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

Gene3D

1.10.287.120. 1 hit.

InterPro

IPR012497. Neurotoxin_B-IV.
[Graphical view]

Pfam

PF07822. Toxin_13. 1 hit.
[Graphical view]

SUPFAM

SSF57011. Neurotoxin_B-IV. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P01525.

Entry information

Entry name

NXB4_CERLA

Accession

Primary (citable) accession number: P01525

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 1, 2013
This is version 75 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program