P37045 (TOG4B_AGEAP) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Omega-agatoxin-Aa4b Short name=Omega-AGTX-Aa4b Alternative name(s): Omega-agatoxin IVB Short name=Omega-Aga-IVB Omega-agatoxin IVC Short name=Omega-Aga-IVC Omega-agatoxin tsukuba Short name=Omega-Aga-TK Short name=Omega-agatoxin-TK Omega-agatoxin-4B
Organism	Agelenopsis aperta (North American funnel-web spider) (Agelenopsis gertschi)
Taxonomic identifier	6908 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Chelicerata › Arachnida › Araneae › Araneomorphae › Entelegynae › RTA clade › Agelenidae › Agelenopsis

Protein attributes

Sequence length	83 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Antagonist of voltage-gated Cav2.1/CACNA1A (P-type) calcium channels. Paralyzes insect by blocking neuromuscular transmission. Ref.2
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Domain	The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.
Post-translational modification	The toxin with D-Ser (named omega-aga IVC) is 80-90 fold more potent than that with L-Ser (omega-aga IVB) against Cav2.1/CACNA1A (P-type) channels in rat cerebellar Purkinje neurons and is more resistant to proteases. The epimerization is done by the venom peptide isomerase heterodimer.
Sequence similarities	Belongs to the plectoxin superfamily. Type IV omega-agatoxin family.

Ontologies

Keywords
Cellular component	Secreted
Domain	Knottin Signal
Molecular function	Calcium channel inhibitor Ion channel impairing toxin Neurotoxin Presynaptic neurotoxin Toxin
PTM	D-amino acid Disulfide bond
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological_process	pathogenesis Inferred from electronic annotation. Source: InterPro
Cellular_component	other organism presynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	calcium channel inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW sodium channel inhibitor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Propeptide

21 – 35

15

By similarity

PRO_0000035490

Chain

36 – 83

48

Omega-agatoxin-Aa4b

PRO_0000035491

Amino acid modifications

Modified residue

81

1

D-serine (Ser); by venom peptide isomerase Ref.4 Ref.5 Ref.6

Disulfide bond

39 ↔ 55

Ref.2 Ref.4 Ref.7 Ref.8

Disulfide bond

47 ↔ 60

Ref.2 Ref.4 Ref.7 Ref.8

Disulfide bond

54 ↔ 71

Ref.2 Ref.4 Ref.7 Ref.8

Disulfide bond

62 ↔ 69

Ref.2 Ref.4 Ref.7 Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

83

Helix Strand Turn

Details...

Beta strand

49 – 51

3

Turn

55 – 57

3

Beta strand

60 – 62

3

Beta strand

64 – 71

8

Turn

76 – 79

4

Sequences

	Sequence		Length	Mass (Da)
	P37045 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: 826F5C7E2FDD3CDE	FASTA	83	9,167
	10 20 30 40 50 60 MKLCMTLLIT AIAVVTFVVA TQEESAEFNE VEESREDNCI AEDYGKCTWG GTKCCRGRPC 70 80 RCSMIGTNCE CTPRLIMEGL SFA

References

[1]	Heck S.D., Siok C.J., Krapcho K.J. Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure and properties of omega-agatoxin IVB, a new antagonist of P-type calcium channels." Adams M.E., Mintz I.M., Reily M.D., Thanabal V., Bean B.P. Mol. Pharmacol. 44:681-688(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 36-83, FUNCTION, STRUCTURE BY NMR OF 36-83, DISULFIDE BONDS. Tissue: Venom.
[3]	"A novel peptide from funnel web spider venom, omega-Aga-TK, selectively blocks, P-type calcium channels." Teramoto T., Kuwada M., Niidome T., Sawada K., Nishizawa Y., Katayama K. Biochem. Biophys. Res. Commun. 196:134-140(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 36-83. Tissue: Venom.
[4]	"Disulfide bond assignment of omega-agatoxins IVB and IVC: discovery of a D-serine residue in omega-agatoxin IVB." Heck S.D., Kelbaugh P.R., Kelly M.E., Thadeio P.F., Saccomano N.A., Stroh J.G., Volkmann R.A. J. Am. Chem. Soc. 116:10426-10436(1994) Cited for: DISULFIDE BONDS, D-AMINO ACID AT SER-81.
[5]	"Functional consequences of posttranslational isomerization of Ser46 in a calcium channel toxin." Heck S.D., Siok C.J., Krapcho K.J., Kelbaugh P.R., Thadeio P.F., Welch M.J., Williams R.D., Ganong A.H., Kelly M.E., Lanzetti A.J. Science 266:1065-1068(1994) [PubMed] [Europe PMC] [Abstract] Cited for: D-AMINO ACID AT SER-81, CHARACTERIZATION OF D- AND L- FORMS.
[6]	"Omega-agatoxin-TK containing D-serine at position 46, but not synthetic omega-[L-Ser46]agatoxin-TK, exerts blockade of P-type calcium channels in cerebellar Purkinje neurons." Kuwada M., Teramoto T., Kumagaye K.Y., Nakajima K., Watanabe T., Kawai T., Kawakami Y., Niidome T., Sawada K., Nishizawa Y. Mol. Pharmacol. 46:587-593(1994) [PubMed] [Europe PMC] [Abstract] Cited for: D-AMINO ACID AT SER-81, CHARACTERIZATION OF D- AND L- FORMS.
[7]	"Sequential assignment and structure determination of spider toxin omega-Aga-IVB." Yu H., Rosen M.K., Saccomano N.A., Phillips D., Volkmann R.A., Schreiber S.L. Biochemistry 32:13123-13129(1993) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 36-83, DISULFIDE BONDS.
[8]	"The solution structure of omega-Aga-IVB, a P-type calcium channel antagonist from venom of the funnel web spider, Agelenopsis aperta." Reily M.D., Thanabal V., Adams M.E. J. Biomol. NMR 5:122-132(1995) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 36-83, DISULFIDE BONDS.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U15925 mRNA. Translation: AAA57116.1.

PIR

A44664.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AGG	NMR	-	A	36-83	[»]
1OMA	NMR	-	A	36-83	[»]
1OMB	NMR	-	A	36-83	[»]

ProteinModelPortal

P37045.

SMR

P37045. Positions 36-83.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

ArachnoServer

AS000183. omega-agatoxin-Aa4b.

Family and domain databases

Gene3D

4.10.40.10. 1 hit.

InterPro

IPR008017. Atracotoxin_delta.
IPR004169. Spidertoxin.
[Graphical view]

Pfam

PF02819. Toxin_9. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P37045.

Entry information

Entry name

TOG4B_AGEAP

Accession

Primary (citable) accession number: P37045

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	February 1, 1996
Last modified:	May 29, 2013
This is version 78 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program