P30288 (TOG4A_AGEAP) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Omega-agatoxin-Aa4a Short name=Omega-AGTX-Aa4a Alternative name(s): Omega-agatoxin IVA Short name=Omega-Aga-IVA Omega-agatoxin-4A
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	48 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Omega-agatoxins inhibit neuronal voltage-gated calcium channels. This toxin acts by modifying the gating of the high voltage activated P-type Cav2.1/CACNA1A channel. Is a potent blocker in both insect and mammalian central neurons. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7
Subcellular location	Secreted Ref.1.
Tissue specificity	Expressed by the venom gland. Ref.1
Domain	The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.
Miscellaneous	This toxin is a diagnostic ligand for P-type channels Ca2.1/CACNA1A in the mammalian brain. The binding site for this toxin has been localized in part to the extracellular S3-S4 loop in repeat IV of the alpha1 subunit of mammalian Cav2.1/CACNA1A channels, which is proximal to the S4 sensor domain.
Sequence similarities	Belongs to the plectoxin superfamily. Type IV omega-agatoxin family.

Ontologies

Keywords
Cellular component	Secreted
Domain	Knottin
Molecular function	Calcium channel inhibitor Ion channel impairing toxin Neurotoxin Presynaptic neurotoxin Toxin
PTM	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
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 48

48

Omega-agatoxin-Aa4a

PRO_0000087610

Amino acid modifications

Disulfide bond

4 ↔ 20

Ref.2 Ref.8 Ref.9

Disulfide bond

12 ↔ 25

Ref.2 Ref.8 Ref.9

Disulfide bond

19 ↔ 36

Ref.2 Ref.8 Ref.9

Disulfide bond

27 ↔ 34

Ref.2 Ref.8 Ref.9

Secondary structure

1

.

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.

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48

Helix Strand Turn

Details...

Beta strand

3 – 5

3

Beta strand

7 – 11

5

Beta strand

20 – 22

3

Beta strand

24 – 26

3

Beta strand

29 – 33

5

Beta strand

35 – 38

4

Turn

41 – 44

4

Turn

45 – 47

3

Sequences

	Sequence		Length	Mass (Da)
	P30288 [UniParc]. Last modified April 1, 1993. Version 1. Checksum: 945054B55EAE81FD	FASTA	48	5,210
	10 20 30 40 KKKCIAKDYG RCKWGGTPCC RGRGCICSIM GTNCECKPRL IMEGLGLA

References

[1]	"P-type calcium channels blocked by the spider toxin omega-Aga-IVA." Mintz I.M., Venema V.J., Swiderek K.M., Lee T.D., Bean B.P., Adams M.E. Nature 355:827-829(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, TOXIN TARGET. Tissue: Venom.
[2]	"Synthesis of omega-agatoxin IVA and its related peptides." Nishio H., Kumagaye K.Y., Kubo S., Chen Y.N., Momiyama A., Takahashi T., Kimura T., Sakakibara S. Biochem. Biophys. Res. Commun. 196:1447-1453(1993) [PubMed] [Europe PMC] [Abstract] Cited for: SYNTHESIS, FUNCTION, DISULFIDE BONDS.
[3]	"Omega AGA toxin IVA blocks high-voltage-activated calcium channel currents in cultured pars intercerebralis neurosecretory cells of adult locusta migratoria." Bickmeyer U., Rossler W., Wiegand H. Neurosci. Lett. 181:113-116(1994) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TOXIN TARGET.
[4]	"Alteration of P-type calcium channel gating by the spider toxin omega-Aga-IVA." McDonough S.I., Mintz I.M., Bean B.P. Biophys. J. 72:2117-2128(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"Ca2+ currents in central insect neurons: electrophysiological and pharmacological properties." Wicher D., Penzlin H. J. Neurophysiol. 77:186-199(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"A hot spot for the interaction of gating modifier toxins with voltage-dependent ion channels." Winterfield J.R., Swartz K.J. J. Gen. Physiol. 116:637-644(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Discovery and structure of a potent and highly specific blocker of insect calcium channels." Wang X.-H., Connor M., Wilson D., Wilson H.I., Nicholson G.M., Smith R., Shaw D., Mackay J.P., Alewood P.F., Christie M.J., King G.F. J. Biol. Chem. 276:40306-40312(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TOXIN TARGET.
[8]	"Three-dimensional solution structure of the calcium channel antagonist omega-agatoxin IVA: consensus molecular folding of calcium channel blockers." Kim J.I., Konishi S., Iwai H., Kohno T., Gouda H., Shimada I., Sato K., Arata Y. J. Mol. Biol. 250:659-671(1995) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.
[9]	"Structure-activity relationships for P-type calcium channel-selective omega-agatoxins." Reily M.D., Holub K.E., Gray W.R., Norris T.M., Adams M.E. Nat. Struct. Biol. 1:853-856(1994) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.

Cross-references

Sequence databases

PIR

S20256.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IVA	NMR	-	A	1-48	[»]
1OAV	NMR	-	A	1-48	[»]
1OAW	NMR	-	A	1-48	[»]

ProteinModelPortal

P30288.

SMR

P30288. Positions 1-48.

ModBase

Search...

Protein family/group databases

TCDB

8.B.6.2.1. Ca2+ channel-targeting spider toxin (CST) family.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

ArachnoServer

AS000182. omega-agatoxin-Aa4a.

Family and domain databases

InterPro

IPR004169. Spidertoxin.
[Graphical view]

Pfam

PF02819. Toxin_9. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P30288.

Entry information

Entry name

TOG4A_AGEAP

Accession

Primary (citable) accession number: P30288

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	April 1, 1993
Last modified:	April 3, 2013
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program