Reviewed, UniProtKB/Swiss-Prot P00608 (PA22_NOTSC)

Names and origin

Protein names	Recommended name:     Phospholipase A2     EC=3.1.1.4 Alternative name(s):     Notexin     Phosphatidylcholine 2-acylhydrolase
Organism	Notechis scutatus scutatus (Mainland tiger snake) (Common tiger snake)
Taxonomic identifier	70142 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Lepidosauria › Squamata › Scleroglossa › Serpentes › Colubroidea › Elapidae › Acanthophiinae › Notechis

Protein attributes

Sequence length	119 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Inhibits neuromuscular transmission by blocking acetylcholine release from the nerve termini. Acts presynaptically. Is directly toxic to skeletal muscle upon local application in vivo (dystrophic effect).
Catalytic activity	Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.
Cofactor	Binds 1 calcium ion per subunit.
Subunit structure	Monomer.
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Toxic dose	LD50 is 0.025 mg/kg by intravenous injection.
Miscellaneous	Activity and lethal neurotoxicity are lost upon modification with p-bromophenacyl bromide.
Sequence similarities	Belongs to the phospholipase A2 family. Group I subfamily.

Ontologies

Keywords
Biological process	Lipid degradation
Cellular component	Secreted
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Neurotoxin Presynaptic neurotoxin Toxin
PTM	Disulfide bond
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW phospholipid metabolic process Inferred from electronic annotation. Source: InterPro synaptic transmission Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell presynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW 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

Chain

1 – 119

119

Phospholipase A2

PRO_0000161675

Sites

Active site

48

1

Ref.3 Ref.5

Active site

93

1

Ref.3

Metal binding

28

1

Calcium; via carbonyl oxygen

Metal binding

30

1

Calcium; via carbonyl oxygen

Metal binding

32

1

Calcium; via carbonyl oxygen

Metal binding

49

1

Calcium

Amino acid modifications

Disulfide bond

11 ↔ 71

Disulfide bond

27 ↔ 118

Disulfide bond

29 ↔ 45

Disulfide bond

44 ↔ 99

Disulfide bond

51 ↔ 92

Disulfide bond

60 ↔ 85

Disulfide bond

78 ↔ 90

Natural variations

Natural variant

16

1

K → R in variant S.

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

119

Helix Strand Turn

Details...

Helix

2 – 12

11

Turn

13 – 15

3

Helix

19 – 22

4

Beta strand

23 – 25

3

Turn

26 – 28

3

Beta strand

29 – 31

3

Helix

40 – 57

18

Beta strand

69 – 72

4

Beta strand

75 – 78

4

Beta strand

81 – 83

3

Helix

84 – 102

19

Helix

107 – 109

3

Helix

114 – 117

4

Sequences

	Sequence		Length	Mass (Da)
	P00608-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 23D8BF780221D852	FASTA	119	13,593
	10 20 30 40 50 60 NLVQFSYLIQ CANHGKRPTW HYMDYGCYCG AGGSGTPVDE LDRCCKIHDD CYDEAGKKGC 70 80 90 100 110 FPKMSAYDYY CGENGPYCRN IKKKCLRFVC DCDVEAAFCF AKAPYNNANW NIDTKKRCQ

References

[1]	"Amino acid sequence of a presynaptic neurotoxin from the venom of Notechis scutatus scutatus (Australian tiger snake)." Halpert J., Eaker D. J. Biol. Chem. 250:6990-6997(1975) [PubMed: 1158892] [Abstract] Cited for: PROTEIN SEQUENCE. Tissue: Venom.
[2]	"On the purification of notexin. Isolation of a single amino acid variant from the venom of Notechis scutatus scutatus." Chwetzoff S., Mollier P., Bouet F., Rowan E.G., Harvey A.L., Menez A. FEBS Lett. 261:226-230(1990) [PubMed: 2155818] [Abstract] Cited for: PROTEIN SEQUENCE (NOTEXIN-S). Tissue: Venom.
[3]	"The role of phospholipase activity in the action of a presynaptic neurotoxin from the venom of Notechis scutatus scutatus (Australian tiger snake)." Halpert J., Eaker D., Karlsson E. FEBS Lett. 61:72-76(1976) [PubMed: 1245225] [Abstract] Cited for: ACTIVE SITE.
[4]	"Tryptophan 110, a residue involved in the toxic activity but not in the enzymatic activity of notexin." Mollier P., Chwetzoff S., Bouet F., Harvey A.L., Menez A. Eur. J. Biochem. 185:263-270(1989) [PubMed: 2583182] [Abstract] Cited for: INVOLVEMENT OF TRP-110 IN TOXICITY.
[5]	"The three-dimensional structure of notexin, a presynaptic neurotoxic phospholipase A2 at 2.0-A resolution." Westerlund B., Nordlund P., Uhlim U., Eaker D., Eklund H. FEBS Lett. 301:159-164(1992) [PubMed: 1568473] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).

Cross-references

Sequence databases

PIR

PSNOAT. A00749.
PSNOAS. S08258.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AE7	X-ray	2.00	A	1-119	[»]

ModBase

Search...

Phylogenomic databases

HOVERGEN

P00608.

Enzyme and pathway databases

BRENDA

3.1.1.4. 292759.

Family and domain databases

InterPro

IPR016090. Phospholipase_A2.
IPR013090. Phospholipase_A2_AS.
IPR001211. Phospholipase_A2_euk.
[Graphical view]

Gene3D

G3DSA:1.20.90.10. Phospholipase_A2. 1 hit.

PANTHER

PTHR11716. Phospholipase_A2. 1 hit.

Pfam

PF00068. Phospholip_A2_1. 1 hit.
[Graphical view]

PRINTS

PR00389. PHPHLIPASEA2.

ProDom

PD000303. PhospholipaseA2. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00085. PA2c. 1 hit.
[Graphical view]

PROSITE

PS00119. PA2_ASP. 1 hit.
PS00118. PA2_HIS. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

PA22_NOTSC

Accession

Primary (citable) accession number: P00608

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	June 16, 2009
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)