PA2HL_VIPAA
ID PA2HL_VIPAA Reviewed; 138 AA.
AC P17935;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 25-MAY-2022, entry version 114.
DE RecName: Full=Basic phospholipase A2 homolog ammodytin L {ECO:0000303|PubMed:2101000, ECO:0000303|PubMed:7662700, ECO:0000303|PubMed:8835336, ECO:0000303|PubMed:8973554, ECO:0000303|PubMed:9219538, ECO:0000303|PubMed:9514950};
DE Short=AMDL {ECO:0000303|PubMed:7662700, ECO:0000303|PubMed:8835336, ECO:0000303|PubMed:8973554};
DE Short=AtnL {ECO:0000303|PubMed:9514950};
DE Short=svPLA2 homolog;
DE Flags: Precursor;
OS Vipera ammodytes ammodytes (Western sand viper).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Viperinae; Vipera.
OX NCBI_TaxID=8705;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION,
RP AND VARIANT SER-71.
RC STRAIN=Northern Balkan; TISSUE=Venom gland;
RX PubMed=2101000; DOI=10.1093/nar/18.15.4601;
RA Pungercar J., Liang N.-S., Strukelj B., Gubensek F.;
RT "Nucleotide sequence of a cDNA encoding ammodytin L.";
RL Nucleic Acids Res. 18:4601-4601(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9219538; DOI=10.1111/j.1432-1033.1997.00772.x;
RA Kordis D., Gubensek F.;
RT "Bov-B long interspersed repeated DNA (LINE) sequences are present in
RT Vipera ammodytes phospholipase A2 genes and in genomes of Viperidae
RT snakes.";
RL Eur. J. Biochem. 246:772-779(1997).
RN [3]
RP PROTEIN SEQUENCE OF 17-138, FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=Northern Balkan; TISSUE=Venom;
RX PubMed=1765075; DOI=10.1111/j.1432-1033.1991.tb16485.x;
RA Krizaj I., Bieber A.L., Ritonja A., Gubensek F.;
RT "The primary structure of ammodytin L, a myotoxic phospholipase A2
RT homologue from Vipera ammodytes venom.";
RL Eur. J. Biochem. 202:1165-1168(1991).
RN [4]
RP FUNCTION.
RX PubMed=7662700; DOI=10.1016/0167-4889(95)00053-u;
RA Incerpi S., de Vito P., Luly P., Rufini S.;
RT "Effect of ammodytin L from Vipera ammodytes on L-6 cells from rat skeletal
RT muscle.";
RL Biochim. Biophys. Acta 1268:137-142(1995).
RN [5]
RP FUNCTION.
RX PubMed=8835336; DOI=10.1016/0041-0101(95)00119-0;
RA Bernardini S., Cannata S., Filoni S., Luly P., Rufini S.;
RT "Effect of ammodytin L from the venom of Vipera ammodytes on Xenopus laevis
RT differentiated muscle fibres and regenerating limbs.";
RL Toxicon 34:81-90(1996).
RN [6]
RP FUNCTION.
RX PubMed=8973554; DOI=10.1042/bj3200467;
RA Rufini S., Cesaroni M.P., Balestro N., Luly P.;
RT "Proliferative effect of ammodytin L from the venom of Vipera ammodytes on
RT 208F rat fibroblasts in culture.";
RL Biochem. J. 320:467-472(1996).
RN [7]
RP FUNCTION.
RX PubMed=9514950; DOI=10.1006/bbrc.1998.8297;
RA Pungercar J., Vucemilo N., Faure G., Bon C., Verheij H.M., Gubensek F.,
RA Krizaj I.;
RT "Ammodytin L, an inactive phospholipase A2 homologue with myotoxicity in
RT mice, binds to the presynaptic acceptor of the beta-neurotoxic ammodytoxin
RT C in Torpedo: an indication for a phospholipase A2 activity-independent
RT mechanism of action of beta-neurotoxins in fish?";
RL Biochem. Biophys. Res. Commun. 244:514-518(1998).
RN [8]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=10653156; DOI=10.1007/s004240000106;
RA Horvat-Znidarsic I., Suput D., Gubensek F.;
RT "The effect of ammodytin L on frog neuromuscular junction.";
RL Pflugers Arch. 439:R102-R103(2000).
RN [9]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=11005629; DOI=10.1007/s004240000022;
RA Frangez R., Krizaj I., Gubensek F., Suput D.;
RT "Effects of ammodytin L on miniature and endplate potentials in
RT neuromuscular junction of frog m.cutaneus pectoris.";
RL Pflugers Arch. 440:R101-R102(2000).
RN [10]
RP FUNCTION, TOXIC DOSE, AND MUTAGENESIS OF HIS-43; LEU-46; ASN-48 AND SER-64.
RC TISSUE=Venom;
RX PubMed=17927217; DOI=10.1021/bi701304e;
RA Petan T., Krizaj I., Pungercar J.;
RT "Restoration of enzymatic activity in a Ser-49 phospholipase A2 homologue
RT decreases its Ca(2+)-independent membrane-damaging activity and increases
RT its toxicity.";
RL Biochemistry 46:12795-12809(2007).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 17-138, AND DISULFIDE BOND.
RA Turk D., Guncar G., Krizaj I.;
RT "Crystal structure of ammodytin L.";
RL Submitted (JUN-2008) to the PDB data bank.
CC -!- FUNCTION: Snake venom phospholipase A2 homolog that lacks enzymatic
CC activity.Snake venom phospholipase A2 homolog that Is very active in
CC inducing myonecrosis in vivo and shows a potent calcium-independent
CC membrane-damaging activity in vitro, most probably by binding and
CC incorporating in the membrane. Also acts as a presynaptic neurotoxin. A
CC model of myotoxic mechanism has been proposed: an apo Lys49-PLA2 is
CC activated by the entrance of a hydrophobic molecule (e.g. fatty acid)
CC at the hydrophobic channel of the protein leading to a reorientation of
CC a monomer (By similarity). This reorientation causes a transition
CC between 'inactive' to 'active' states, causing alignment of C-terminal
CC and membrane-docking sites (MDoS) side-by-side and putting the
CC membrane-disruption sites (MDiS) in the same plane, exposed to solvent
CC and in a symmetric position for both monomers (By similarity). The MDoS
CC region stabilizes the toxin on membrane by the interaction of charged
CC residues with phospholipid head groups (By similarity). Subsequently,
CC the MDiS region destabilizes the membrane with penetration of
CC hydrophobic residues (By similarity). This insertion causes a
CC disorganization of the membrane, allowing an uncontrolled influx of
CC ions (i.e. calcium and sodium), and eventually triggering irreversible
CC intracellular alterations and cell death (By similarity).
CC {ECO:0000250|UniProtKB:I6L8L6, ECO:0000269|PubMed:10653156,
CC ECO:0000269|PubMed:11005629, ECO:0000269|PubMed:1765075,
CC ECO:0000269|PubMed:17927217, ECO:0000269|PubMed:7662700,
CC ECO:0000269|PubMed:8835336, ECO:0000269|PubMed:8973554,
CC ECO:0000269|PubMed:9514950}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1765075,
CC ECO:0000269|PubMed:2101000}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:1765075, ECO:0000305|PubMed:2101000}.
CC -!- TOXIC DOSE: Is not lethal to mice even at 10 mg/kg.
CC {ECO:0000269|PubMed:17927217}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC S49 sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: Does not bind calcium as one of the calcium-binding sites is
CC lost (Asp->Ser in position 64, which corresponds to 'Ser-49' in the
CC current nomenclature). {ECO:0000305}.
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DR EMBL; X53036; CAA37208.1; -; mRNA.
DR EMBL; X84017; CAA58839.1; -; Genomic_DNA.
DR PIR; S10992; S10992.
DR PDB; 3DIH; X-ray; 2.60 A; A=17-138.
DR PDBsum; 3DIH; -.
DR AlphaFoldDB; P17935; -.
DR SMR; P17935; -.
DR EvolutionaryTrace; P17935; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004623; F:phospholipase A2 activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0050482; P:arachidonic acid secretion; IEA:InterPro.
DR GO; GO:0016042; P:lipid catabolic process; IEA:InterPro.
DR GO; GO:0006644; P:phospholipid metabolic process; IEA:InterPro.
DR CDD; cd00125; PLA2c; 1.
DR Gene3D; 1.20.90.10; -; 1.
DR InterPro; IPR001211; PLipase_A2.
DR InterPro; IPR033112; PLipase_A2_Asp_AS.
DR InterPro; IPR016090; PLipase_A2_dom.
DR InterPro; IPR036444; PLipase_A2_dom_sf.
DR InterPro; IPR033113; PLipase_A2_His_AS.
DR PANTHER; PTHR11716; PTHR11716; 1.
DR Pfam; PF00068; Phospholip_A2_1; 1.
DR PRINTS; PR00389; PHPHLIPASEA2.
DR SMART; SM00085; PA2c; 1.
DR SUPFAM; SSF48619; SSF48619; 1.
DR PROSITE; PS00119; PA2_ASP; 1.
DR PROSITE; PS00118; PA2_HIS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Myotoxin;
KW Neurotoxin; Presynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:1765075"
FT CHAIN 17..138
FT /note="Basic phospholipase A2 homolog ammodytin L"
FT /evidence="ECO:0000269|PubMed:1765075"
FT /id="PRO_0000022974"
FT REGION 121..133
FT /note="Important for membrane-damaging activities in
FT eukaryotes and bacteria; heparin-binding"
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT DISULFID 42..131
FT /evidence="ECO:0000269|Ref.11, ECO:0007744|PDB:3DIH"
FT DISULFID 44..60
FT /evidence="ECO:0000269|Ref.11, ECO:0007744|PDB:3DIH"
FT DISULFID 59..111
FT /evidence="ECO:0000269|Ref.11, ECO:0007744|PDB:3DIH"
FT DISULFID 65..138
FT /evidence="ECO:0000269|Ref.11, ECO:0007744|PDB:3DIH"
FT DISULFID 66..104
FT /evidence="ECO:0000269|Ref.11, ECO:0007744|PDB:3DIH"
FT DISULFID 73..97
FT /evidence="ECO:0000269|Ref.11, ECO:0007744|PDB:3DIH"
FT DISULFID 91..102
FT /evidence="ECO:0000269|Ref.11, ECO:0007744|PDB:3DIH"
FT VARIANT 71
FT /note="P -> S (in minor variant)"
FT /evidence="ECO:0000269|PubMed:2101000"
FT MUTAGEN 43
FT /note="H->Y: Enzymatically active in presence of calcium
FT with increased toxicity; when associated with V-46 or W-46;
FT G-48 and D-64."
FT /evidence="ECO:0000269|PubMed:17927217"
FT MUTAGEN 46
FT /note="L->V,W: Enzymatically active in presence of calcium
FT with increased toxicity; when associated with Y-43; G-48
FT and D-64."
FT /evidence="ECO:0000269|PubMed:17927217"
FT MUTAGEN 48
FT /note="N->G: Enzymatically active in presence of calcium
FT with increased toxicity; when associated with Y-43; V-46 or
FT W-46; and D-64."
FT /evidence="ECO:0000269|PubMed:17927217"
FT MUTAGEN 64
FT /note="S->D: Enzymatically active in presence of calcium
FT with increased toxicity; when associated with Y-43; V-46 or
FT W-46; and G-48."
FT /evidence="ECO:0000269|PubMed:17927217"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:3DIH"
FT HELIX 33..37
FT /evidence="ECO:0007829|PDB:3DIH"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:3DIH"
FT HELIX 55..68
FT /evidence="ECO:0007829|PDB:3DIH"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:3DIH"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:3DIH"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:3DIH"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:3DIH"
FT HELIX 96..114
FT /evidence="ECO:0007829|PDB:3DIH"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:3DIH"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:3DIH"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:3DIH"
SQ SEQUENCE 138 AA; 15636 MW; D8F15B1C87231F79 CRC64;
MRILWIVAVC LIGVEGSVIE FGKMIQEETD KNPLTSYSFY GCHCGLGNKG KPKDATDRCC
FVHSCCYAKL PDCSPKTNRY EYHRENGAIV CGSSTPCKKQ ICECDRAAAI CFRENLKTYN
KKYKVYLRFK CKGVSEKC
