PA2AA_DABSI
ID PA2AA_DABSI Reviewed; 138 AA.
AC Q7T2R1;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Acidic phospholipase A2 daboiatoxin A chain;
DE Short=DbTx-A;
DE Short=svPLA2;
DE EC=3.1.1.4;
DE AltName: Full=Phospholipase A2 Dsm-a1;
DE AltName: Full=Phospholipase A2 inhibitor;
DE AltName: Full=Phospholipase A2-III;
DE Flags: Precursor;
OS Daboia siamensis (Eastern Russel's viper) (Daboia russelii siamensis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Viperinae; Daboia.
OX NCBI_TaxID=343250;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 17-27, FUNCTION, AND MASS
RP SPECTROMETRY.
RC STRAIN=Myanmar; TISSUE=Venom, and Venom gland;
RX PubMed=17611171; DOI=10.1016/j.bbapap.2007.04.012;
RA Tsai I.-H., Tsai H.-Y., Wang Y.-M., Pe T., Warrell D.-A.;
RT "Venom phospholipases of Russell's vipers from Myanmar and eastern India--
RT cloning, characterization and phylogeographic analysis.";
RL Biochim. Biophys. Acta 1774:1020-1028(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Jia Y.-H., Jin Y., Chen R.-Q., Li D.-S., Wang W.-Y., Xiong Y.-L.;
RT "Biochemical and pharmacological properties of three phospholipase A2s from
RT Vipera russelli siamensis venom.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 17-36, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=7778130; DOI=10.1016/0041-0101(94)00133-s;
RA Thwin M.M., Gopalakrishnakone P., Yuen R., Tan C.H.;
RT "A major lethal factor of the venom of Burmese Russell's viper (Daboia
RT russelli siamensis): isolation, N-terminal sequencing and biological
RT activities of daboiatoxin.";
RL Toxicon 33:63-76(1995).
RN [4]
RP FUNCTION.
RX PubMed=8711753; DOI=10.1016/0041-0101(95)00134-4;
RA Thwin M.M., Gopalakrishnakone P., Yuen R., Tan C.H.;
RT "Synaptosomal binding of 125I-labelled daboiatoxin, a new PLA2 neurotoxin
RT from the venom of Daboia russelli siamensis.";
RL Toxicon 34:183-199(1996).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 17-138, DISULFIDE BOND, SUBUNIT,
RP AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=17505111; DOI=10.1107/s0907444907016204;
RA Gopalan G., Thwin M.M., Gopalakrishnakone P., Swaminathan K.;
RT "Structural and pharmacological comparison of daboiatoxin from Daboia
RT russelli siamensis with viperotoxin F and vipoxin from other vipers.";
RL Acta Crystallogr. D 63:722-729(2007).
CC -!- FUNCTION: Heterodimer (A and B chains): phospholipase A2 that acts as a
CC presynaptic neurotoxin and shows a PLA2 activity of 1377 umol/min/mg.
CC In vivo, induces edema and produces neurotoxic symptoms in mice. Also
CC exhibits indirect hemolysis, a strong myonecrotic activity and
CC cytotoxicity. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-
CC acyl groups in 3-sn-phosphoglycerides.
CC -!- FUNCTION: Monomer: Snake venom phospholipase A2 (PLA2) that shows a
CC PLA2 activity of 578 umol/min/mg.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-
CC glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:15801,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=3.1.1.4;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10035, ECO:0000255|PROSITE-
CC ProRule:PRU10036};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 1 Ca(2+) ion. {ECO:0000250};
CC -!- SUBUNIT: Heterodimer of A and B chain; non-covalently linked. The
CC acidic protein (B chain) has phospholipase A2 activity and the A chain
CC weakly inhibits the B chain enzymatic activity but potentiates its
CC lethal potency. {ECO:0000269|PubMed:17505111}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7778130}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:7778130}.
CC -!- MASS SPECTROMETRY: Mass=13607; Method=Electrospray; Note=in Dsm-a1.;
CC Evidence={ECO:0000269|PubMed:17611171};
CC -!- MASS SPECTROMETRY: Mass=13812; Method=Electrospray; Note=in Dsm-a1'
CC which has only its protein sequence AA 17-27 sequenced.;
CC Evidence={ECO:0000269|PubMed:17611171};
CC -!- TOXIC DOSE: Monomer: DbTx-A alone is non-lethal, even at doses as high
CC as 2 ug/g. {ECO:0000269|PubMed:17505111}.
CC -!- TOXIC DOSE: Heterodimer (A and B chains): LD(50) is estimated to be
CC about 0.1 ug/g by intraperitoneal injection into mice.
CC {ECO:0000269|PubMed:17505111}.
CC -!- MISCELLANEOUS: Does not provoke hemorrhage.
CC {ECO:0000305|PubMed:7778130}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
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DR EMBL; AY303800; AAP58959.1; -; mRNA.
DR EMBL; DQ090655; AAZ53177.1; -; mRNA.
DR PDB; 2H4C; X-ray; 2.60 A; A/C/E/G=17-138.
DR PDBsum; 2H4C; -.
DR AlphaFoldDB; Q7T2R1; -.
DR SMR; Q7T2R1; -.
DR EvolutionaryTrace; Q7T2R1; -.
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:UniProtKB-EC.
DR GO; GO:0019834; F:phospholipase A2 inhibitor activity; IEA:UniProtKB-KW.
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:UniProtKB-KW.
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; Calcium; Direct protein sequencing; Disulfide bond;
KW Hydrolase; Lipid degradation; Lipid metabolism; Metal-binding; Myotoxin;
KW Neurotoxin; Phospholipase A2 inhibitor; Presynaptic neurotoxin; Secreted;
KW Signal; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:17611171,
FT ECO:0000269|PubMed:7778130"
FT CHAIN 17..138
FT /note="Acidic phospholipase A2 daboiatoxin A chain"
FT /id="PRO_0000419222"
FT ACT_SITE 63
FT /evidence="ECO:0000250"
FT ACT_SITE 105
FT /evidence="ECO:0000250"
FT BINDING 43
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 45
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 47
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 64
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT DISULFID 42..131
FT /evidence="ECO:0000269|PubMed:17505111"
FT DISULFID 44..60
FT /evidence="ECO:0000269|PubMed:17505111"
FT DISULFID 59..111
FT /evidence="ECO:0000269|PubMed:17505111"
FT DISULFID 65..138
FT /evidence="ECO:0000250"
FT DISULFID 66..104
FT /evidence="ECO:0000269|PubMed:17505111"
FT DISULFID 73..97
FT /evidence="ECO:0000269|PubMed:17505111"
FT DISULFID 91..102
FT /evidence="ECO:0000269|PubMed:17505111"
FT HELIX 18..25
FT /evidence="ECO:0007829|PDB:2H4C"
FT TURN 26..28
FT /evidence="ECO:0007829|PDB:2H4C"
FT TURN 34..39
FT /evidence="ECO:0007829|PDB:2H4C"
FT TURN 41..44
FT /evidence="ECO:0007829|PDB:2H4C"
FT HELIX 55..69
FT /evidence="ECO:0007829|PDB:2H4C"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:2H4C"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:2H4C"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:2H4C"
FT HELIX 98..111
FT /evidence="ECO:0007829|PDB:2H4C"
FT TURN 112..118
FT /evidence="ECO:0007829|PDB:2H4C"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:2H4C"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:2H4C"
SQ SEQUENCE 138 AA; 15395 MW; 36BC84C66C7B9B5C CRC64;
MRTLWIMAVC LIGVEGNFFQ FAEMIVKMTG KEAVHSYAIY GCYCGWGGQG KPQDATDRCC
FVHDCCYGTV NDCNPKMATY SYSFENGDIV CGDNNLCLKT VCECDRAAAI CLGQNVNTYD
KNYENYAISH CTEESEQC
