P61409 (AF2_GRARO) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Kappa-theraphotoxin-Gr2c Short name=Kappa-TRTX-Gr2c Alternative name(s): GsAF II Short name=GsAFII Mechanotoxin-alpha
Organism	Grammostola rosea (Chilean rose tarantula) (Grammostola spatulata)
Taxonomic identifier	432528 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Chelicerata › Arachnida › Araneae › Mygalomorphae › Theraphosidae › Grammostola

Protein attributes

Sequence length	81 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	Inhibits sodium channels Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.4/SCN4A, Nav1.6/SCN8A, Nav1.7/SCN9A, potassium channels Kv11.1/KCNH2, as well as high-voltage-gated calcium channels Cav1.2/CACNA1C. Also blocks mechanosensitive ion channels (also named stretch-activated channels or SACs) and the hypotonic cell swelling induced calcium increase associated with the activation of such channels. It can thus be useful in treating cardiac ventricular disturbances. Also induces analgesia in mammals. This analgesia is probably mediated by a non-opioid receptor related mechanism. Ref.1 Ref.2 Ref.3 Ref.4
Subcellular location	Secreted Ref.2 Ref.3.
Tissue specificity	Expressed by the venom gland. Ref.2 Ref.3
Domain	The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin By similarity.
Miscellaneous	This toxin does not have effect on sodium channels Nav1.3/SCN3A (IC50=24 µM) and Nav1.5/SCN5A (IC50>40 µM), and potassium channels Kv1.1/KCNA1, Kv1.4/KCNA4, Kv11.2/KCNH6 and Kv11.3/KCNH7 (IC50>200 µM) (Ref.4).
Sequence similarities	Belongs to the phrixotoxin family.
Mass spectrometry	Molecular mass is 3979.9 Da from positions 51 - 81. Determined by ESI. Ref.2 Ref.3 Molecular mass is 3980.0 Da from positions 51 - 81. Ref.4

Ontologies

Keywords
Cellular component	Secreted
Domain	Knottin Signal
Molecular function	Calcium channel inhibitor Ion channel impairing toxin Potassium channel inhibitor Sodium channel inhibitor Toxin
PTM	Disulfide bond
Technical term	Direct protein sequencing
Gene Ontology (GO)
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium channel inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW potassium channel inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW 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
	Signal peptide	1 – 19	19	Potential
	Propeptide	20 – 50	31			PRO_0000414298
	Peptide	51 – 81	31	Kappa-theraphotoxin-Gr2c Ref.1 Ref.2 Ref.3 Ref.4		PRO_0000045016
Amino acid modifications
	Disulfide bond	52 ↔ 66		By similarity
	Disulfide bond	59 ↔ 71		By similarity
	Disulfide bond	65 ↔ 75		By similarity
Experimental info
	Sequence conflict	81	1	Missing AA sequence Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P61409 [UniParc]. Last modified December 14, 2011. Version 2. Checksum: 8BD59C517DAA704C	FASTA	81	9,679
	10 20 30 40 50 60 MKAFFVILGL ALLCAYSFAL EEQDQLSLRN DLLTVMFAEN SELTPETEER YCQKWMWTCD 70 80 EERKCCEGLV CRLWCKKKIE W

References

[1]	"Characterization of voltage-dependent calcium channel blocking peptides from the venom of the tarantula Grammostola rosea." Ono S., Kimura T., Kubo T. Toxicon 58:265-276(2011) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 51-81, FUNCTION. Tissue: Venom and Venom gland.
[2]	"Analgesic peptides from venom of Grammostola spatulata and use thereof." Lampe R.A. Patent number US5877026, 02-MAR-1999 Cited for: PROTEIN SEQUENCE OF 51-81, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MASS SPECTROMETRY. Tissue: Venom.
[3]	"Antiarrhythmic peptide from venom of spider Grammostola spatulata." Lampe R.A. Patent number US5968838, 19-OCT-1999 Cited for: PROTEIN SEQUENCE OF 51-81, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MASS SPECTROMETRY. Tissue: Venom.
[4]	"Target promiscuity and heterogeneous effects of tarantula venom peptides affecting Na+ and K+ ion channels." Redaelli E., Cassulini R.R., Silva D.F., Clement H., Schiavon E., Zamudio F.Z., Odell G., Arcangeli A., Clare J.J., Alagon A., de la Vega R.C., Possani L.D., Wanke E. J. Biol. Chem. 285:4130-4142(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 51-81, MASS SPECTROMETRY, FUNCTION, TOXIN TARGET.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB612242 mRNA. Translation: BAK55734.1.
3D structure databases
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
ArachnoServer	AS000027. kappa-theraphotoxin-Gr2c.
Family and domain databases
ProtoNet	Search...

Entry information

Entry name

AF2_GRARO

Accession

Primary (citable) accession number: P61409
Secondary accession number(s): F8WQV7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 24, 2004
Last sequence update:	December 14, 2011
Last modified:	March 6, 2013
This is version 33 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program