UniProtKB - P17935 (PA2HL_VIPAA)
Basic phospholipase A2 homolog ammodytin L
Functioni
Snake venom phospholipase A2 homolog that lacks enzymatic activity.Snake venom phospholipase A2 homolog that Is very active in inducing myonecrosis in vivo and shows a potent calcium-independent membrane-damaging activity in vitro, most probably by binding and incorporating in the membrane. Also acts as a presynaptic neurotoxin. A model of myotoxic mechanism has been proposed: an apo Lys49-PLA2 is activated by the entrance of a hydrophobic molecule (e.g. fatty acid) at the hydrophobic channel of the protein leading to a reorientation of a monomer (By similarity).
This reorientation causes a transition between 'inactive' to 'active' states, causing alignment of C-terminal and membrane-docking sites (MDoS) side-by-side and putting the membrane-disruption sites (MDiS) in the same plane, exposed to solvent and in a symmetric position for both monomers (By similarity).
The MDoS region stabilizes the toxin on membrane by the interaction of charged residues with phospholipid head groups (By similarity).
Subsequently, the MDiS region destabilizes the membrane with penetration of hydrophobic residues (By similarity).
This insertion causes a disorganization of the membrane, allowing an uncontrolled influx of ions (i.e. calcium and sodium), and eventually triggering irreversible intracellular alterations and cell death (By similarity).
By similarity8 PublicationsCaution
GO - Molecular functioni
- calcium ion binding Source: InterPro
- phospholipase A2 activity Source: InterPro
- toxin activity Source: UniProtKB-KW
GO - Biological processi
- arachidonic acid secretion Source: InterPro
- lipid catabolic process Source: InterPro
- phospholipid metabolic process Source: InterPro
Keywordsi
Molecular function | Myotoxin, Neurotoxin, Presynaptic neurotoxin, Toxin |
Names & Taxonomyi
Protein namesi | Recommended name: Basic phospholipase A2 homolog ammodytin L6 PublicationsShort name: AMDL3 Publications Short name: AtnL1 Publication Short name: svPLA2 homolog |
Organismi | Vipera ammodytes ammodytes (Western sand viper) |
Taxonomic identifieri | 8705 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Lepidosauria › Squamata › Bifurcata › Unidentata › Episquamata › Toxicofera › Serpentes › Colubroidea › Viperidae › Viperinae › Vipera › |
Subcellular locationi
Extracellular region or secreted
- Secreted 2 Publications
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Keywords - Cellular componenti
SecretedPathology & Biotechi
Toxic dosei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 43 | H → Y: Enzymatically active in presence of calcium with increased toxicity; when associated with V-46 or W-46; G-48 and D-64. 1 Publication | 1 | |
Mutagenesisi | 46 | L → V or W: Enzymatically active in presence of calcium with increased toxicity; when associated with Y-43; G-48 and D-64. 1 Publication | 1 | |
Mutagenesisi | 48 | N → G: Enzymatically active in presence of calcium with increased toxicity; when associated with Y-43; V-46 or W-46; and D-64. 1 Publication | 1 | |
Mutagenesisi | 64 | S → D: Enzymatically active in presence of calcium with increased toxicity; when associated with Y-43; V-46 or W-46; and G-48. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 16 | 1 PublicationAdd BLAST | 16 | |
ChainiPRO_0000022974 | 17 – 138 | Basic phospholipase A2 homolog ammodytin L1 PublicationAdd BLAST | 122 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 42 ↔ 131 | Combined sources1 Publication | ||
Disulfide bondi | 44 ↔ 60 | Combined sources1 Publication | ||
Disulfide bondi | 59 ↔ 111 | Combined sources1 Publication | ||
Disulfide bondi | 65 ↔ 138 | Combined sources1 Publication | ||
Disulfide bondi | 66 ↔ 104 | Combined sources1 Publication | ||
Disulfide bondi | 73 ↔ 97 | Combined sources1 Publication | ||
Disulfide bondi | 91 ↔ 102 | Combined sources1 Publication |
Keywords - PTMi
Disulfide bondExpressioni
Tissue specificityi
Structurei
Secondary structure
3D structure databases
SMRi | P17935 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P17935 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 121 – 133 | Important for membrane-damaging activities in eukaryotes and bacteria; heparin-bindingBy similarityAdd BLAST | 13 |
Sequence similaritiesi
Keywords - Domaini
SignalFamily and domain databases
CDDi | cd00125, PLA2c, 1 hit |
Gene3Di | 1.20.90.10, 1 hit |
InterProi | View protein in InterPro IPR001211, PLipase_A2 IPR033112, PLipase_A2_Asp_AS IPR016090, PLipase_A2_dom IPR036444, PLipase_A2_dom_sf IPR033113, PLipase_A2_His_AS |
PANTHERi | PTHR11716, PTHR11716, 1 hit |
Pfami | View protein in Pfam PF00068, Phospholip_A2_1, 1 hit |
PRINTSi | PR00389, PHPHLIPASEA2 |
SMARTi | View protein in SMART SM00085, PA2c, 1 hit |
SUPFAMi | SSF48619, SSF48619, 1 hit |
PROSITEi | View protein in PROSITE PS00119, PA2_ASP, 1 hit PS00118, PA2_HIS, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MRILWIVAVC LIGVEGSVIE FGKMIQEETD KNPLTSYSFY GCHCGLGNKG
60 70 80 90 100
KPKDATDRCC FVHSCCYAKL PDCSPKTNRY EYHRENGAIV CGSSTPCKKQ
110 120 130
ICECDRAAAI CFRENLKTYN KKYKVYLRFK CKGVSEKC
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 71 | P → S in minor variant. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X53036 mRNA Translation: CAA37208.1 X84017 Genomic DNA Translation: CAA58839.1 |
PIRi | S10992 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X53036 mRNA Translation: CAA37208.1 X84017 Genomic DNA Translation: CAA58839.1 |
PIRi | S10992 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3DIH | X-ray | 2.60 | A | 17-138 | [»] | |
SMRi | P17935 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P17935 |
Family and domain databases
CDDi | cd00125, PLA2c, 1 hit |
Gene3Di | 1.20.90.10, 1 hit |
InterProi | View protein in InterPro IPR001211, PLipase_A2 IPR033112, PLipase_A2_Asp_AS IPR016090, PLipase_A2_dom IPR036444, PLipase_A2_dom_sf IPR033113, PLipase_A2_His_AS |
PANTHERi | PTHR11716, PTHR11716, 1 hit |
Pfami | View protein in Pfam PF00068, Phospholip_A2_1, 1 hit |
PRINTSi | PR00389, PHPHLIPASEA2 |
SMARTi | View protein in SMART SM00085, PA2c, 1 hit |
SUPFAMi | SSF48619, SSF48619, 1 hit |
PROSITEi | View protein in PROSITE PS00119, PA2_ASP, 1 hit PS00118, PA2_HIS, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PA2HL_VIPAA | |
Accessioni | P17935Primary (citable) accession number: P17935 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1990 |
Last sequence update: | November 1, 1990 | |
Last modified: | June 2, 2021 | |
This is version 113 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Animal Toxin Annotation Program | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencingDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families