P59888 (IPTXI_PANIM) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Imperatoxin-1 Alternative name(s): Imperatoxin I Short name=IpTxi Imperatoxin inhibitor Cleaved into the following 2 chains: Imperatoxin-1 large subunit EC=3.1.1.4 Alternative name(s): Imperatoxin I large subunit Imperatoxin-1 small subunit Alternative name(s): Imperatoxin I small subunit
Organism	Pandinus imperator (Emperor scorpion)
Taxonomic identifier	55084 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Arthropoda › Chelicerata › Arachnida › Scorpiones › Iurida › Scorpionoidea › Scorpionidae › Scorpioninae › Pandinus

Protein attributes

Sequence length	167 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	Phosholipase toxin, which may catalyze the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Inhibits both skeletal (RYR1) and cardiac (RYR2) ryanodine receptors (calcium release channels). Probably blocks ryanodine receptors by generating a lipid product. Ref.1
Catalytic activity	Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.
Subunit structure	Heterodimer composed of a small subunit and a large subunit linked by a disulfide bridge. Ref.1
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Sequence similarities	Belongs to the phospholipase A2 family.
Caution	In contrast to other phospholipases, it lacks the typical Asp active site (Asp->Glu in position 93).

Ontologies

Keywords
Biological process	Lipid degradation
Cellular component	Secreted
Domain	Signal
Ligand	Calcium Metal-binding
Molecular function	Calcium channel inhibitor Hydrolase Ionic channel inhibitor Neurotoxin Toxin
PTM	Disulfide bond Zymogen
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW phospholipid metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium channel inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: InterPro phospholipase A2 activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – ?		Potential
	Propeptide	? – 31		Potential		PRO_0000022988
	Chain	32 – 135	104	Imperatoxin-1 large subunit		PRO_0000022989
	Propeptide	136 – 140	5			PRO_0000022990
	Chain	141 – 167	27	Imperatoxin-1 small subunit		PRO_0000022991
Sites
	Active site	64	1	By similarity
	Metal binding	38	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	40	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	42	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	65	1	Calcium By similarity
Amino acid modifications
	Disulfide bond	39 ↔ 61		By similarity
	Disulfide bond	60 ↔ 99		By similarity
	Disulfide bond	67 ↔ 92		By similarity
	Disulfide bond	90 ↔ 127		By similarity
	Disulfide bond	132 ↔ 144		Interchain (between large and small chains) Probable
Experimental info
	Mutagenesis	144	1	C → M or A: Does not affect the binding of ryanodine to cardiac ryanodine receptor. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P59888 [UniParc]. Last modified September 26, 2003. Version 1. Checksum: 027420BFB033B18E	FASTA	167	18,664
	10 20 30 40 50 60 MHTPKHAIQR ISKEEMEFFE GRCERMGEAD ETMWGTKWCG SGNEATDISE LGYWSNLDSC 70 80 90 100 110 120 CRTHDHCDNI PSGQTKYGLT NEGKYTMMNC KCETAFEQCL RNVTGGMEGP AAGFVRKTYF 130 140 150 160 DLYGNGCYNV QCPSQRRLAR SEECPDGVAT YTGEAGYGAW AINKLNG

References

[1]

"The mechanism of inhibition of ryanodine receptor channels by imperatoxin I, a heterodimeric protein from the scorpion Pandinus imperator." Zamudio F.Z., Conde R., Arevalo C., Becerril B., Martin B.M., Valdivia H.H., Possani L.D. J. Biol. Chem. 272:11886-11894(1997) [PubMed: 9115249] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 32-135 AND 141-167, HETERODIMERIZATION, FUNCTION, MUTAGENESIS OF CYS-144. Tissue: Venom and Venom gland.

[2]

"Scorpion toxins targeted against the sarcoplasmic reticulum Ca(2+)-release channel of skeletal and cardiac muscle." Valdivia H.H., Kirby M.S., Lederer W.J., Coronado R. Proc. Natl. Acad. Sci. U.S.A. 89:12185-12189(1992) [PubMed: 1334561] [Abstract] Cited for: IDENTIFICATION.

Cross-references

3D structure databases
ProteinModelPortal	P59888.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR016090. PLipase_A2. IPR013090. PLipase_A2_AS. IPR001211. PLipase_A2_euk. [Graphical view]
Gene3D	G3DSA:1.20.90.10. Phospholipase_A2. 1 hit.
PANTHER	PTHR12253. Phospholipase_A2_met. 1 hit.
Pfam	PF05826. Phospholip_A2_2. 1 hit. [Graphical view]
SUPFAM	SSF48619. PhospholipaseA2. 1 hit.
PROSITE	PS00119. PA2_ASP. False negative. PS00118. PA2_HIS. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

IPTXI_PANIM

Accession

Primary (citable) accession number: P59888

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	September 26, 2003
Last modified:	November 16, 2011
This is version 51 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program