PA2A_BOTJR
ID PA2A_BOTJR Reviewed; 138 AA.
AC Q8AXY1;
DT 16-NOV-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Acidic phospholipase A2 BthA-1;
DE Short=svPLA2;
DE EC=3.1.1.4 {ECO:0000269|PubMed:12167491};
DE AltName: Full=BOJU-III;
DE AltName: Full=BthA-I-PLA2 {ECO:0000303|PubMed:15294287};
DE AltName: Full=Hypotensive phospholipase A2;
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase;
DE Flags: Precursor;
OS Bothrops jararacussu (Jararacussu).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=8726;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=15214498; DOI=10.1023/b:jopc.0000027852.92208.60;
RA Roberto P.G., Kashima S., Marcussi S., Pereira J.O., Astolfi-Filho S.,
RA Nomizo A., Giglio J.R., Fontes M.R., Soares A.M., Franca S.C.;
RT "Cloning and identification of a complete cDNA coding for a bactericidal
RT and antitumoral acidic phospholipase A2 from Bothrops jararacussu venom.";
RL Protein J. 23:273-285(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 17-138, AND FUNCTION.
RC TISSUE=Venom gland;
RX PubMed=15294287; DOI=10.1016/j.pep.2004.05.020;
RA Roberto P.G., Kashima S., Soares A.M., Chioato L., Faca V.M., Fuly A.L.,
RA Astolfi-Filho S., Pereira J.O., Franca S.C.;
RT "Cloning and expression of an acidic platelet aggregation inhibitor
RT phospholipase A2 cDNA from Bothrops jararacussu venom gland.";
RL Protein Expr. Purif. 37:102-108(2004).
RN [3]
RP PROTEIN SEQUENCE OF 17-50, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, TOXIC DOSE, AND CRYSTALLIZATION.
RC TISSUE=Venom;
RX PubMed=12167491; DOI=10.1016/s0006-2952(02)01210-8;
RA Andriao-Escarso S.H., Soares A.M., Fontes M.R., Fuly A.L., Correa F.M.,
RA Rosa J.C., Greene L.J., Giglio J.R.;
RT "Structural and functional characterization of an acidic platelet
RT aggregation inhibitor and hypotensive phospholipase A(2) from Bothrops
RT jararacussu snake venom.";
RL Biochem. Pharmacol. 64:723-732(2002).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 17-138 IN COMPLEX WITH CALCIUM
RP ION, COFACTOR, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=15351695; DOI=10.1016/j.bbrc.2004.08.046;
RA Magro A.J., Murakami M.T., Marcussi S., Soares A.M., Arni R.K.,
RA Fontes M.R.;
RT "Crystal structure of an acidic platelet aggregation inhibitor and
RT hypotensive phospholipase A2 in the monomeric and dimeric states: insights
RT into its oligomeric state.";
RL Biochem. Biophys. Res. Commun. 323:24-31(2004).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 17-138 IN COMPLEX WITH
RP BROMOPHENACYL BROMIDE, DISULFIDE BONDS, AND ACTIVITY REGULATION.
RX PubMed=16301802; DOI=10.1107/s0907444905029598;
RA Magro A.J., Takeda A.A., Soares A.M., Fontes M.R.;
RT "Structure of BthA-I complexed with p-bromophenacyl bromide: possible
RT correlations with lack of pharmacological activity.";
RL Acta Crystallogr. D 61:1670-1677(2005).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (0.97 ANGSTROMS) OF 17-138 IN COMPLEX WITH CALCIUM
RP ION, COFACTOR, AND DISULFIDE BONDS.
RX PubMed=16376474; DOI=10.1016/j.biochi.2005.10.014;
RA Murakami M.T., Gabdoulkhakov A., Genov N., Cintra A.C.O., Betzel C.,
RA Arni R.K.;
RT "Insights into metal ion binding in phospholipases A2: ultra high-
RT resolution crystal structures of an acidic phospholipase A2 in the Ca2+
RT free and bound states.";
RL Biochimie 88:543-549(2006).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that displays edema-
CC inducing activities (activity that is inhibited by EDTA and
CC dexamethasone), inhibits phospholipid-dependent collagen/ADP-induced
CC platelet aggregation, possess hypotensive as well as anticoagulant
CC activities. In addition, this enzyme shows bactericidal activity
CC against E.coli and S.aureus. PLA2 catalyzes the calcium-dependent
CC hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.
CC {ECO:0000269|PubMed:12167491, ECO:0000269|PubMed:15214498,
CC ECO:0000269|PubMed:15294287}.
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, ECO:0000269|PubMed:12167491};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000305|PubMed:15351695, ECO:0000305|PubMed:16376474};
CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000305|PubMed:15351695,
CC ECO:0000305|PubMed:16376474};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA and bromophenacyl bromide (BPB).
CC {ECO:0000269|PubMed:15214498, ECO:0000269|PubMed:16301802}.
CC -!- SUBUNIT: Homodimer; non-covalently linked.
CC {ECO:0000269|PubMed:15214498, ECO:0000269|PubMed:15351695,
CC ECO:0000269|PubMed:16376474}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12167491,
CC ECO:0000269|PubMed:15214498}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:12167491, ECO:0000305|PubMed:15214498}.
CC -!- TOXIC DOSE: LD(50) is 25 mg/kg by intraperitoneal injection into mice.
CC {ECO:0000269|PubMed:12167491}.
CC -!- TOXIC DOSE: LD(50) is 7.5 mg/kg by intravenous injection into mice.
CC {ECO:0000269|PubMed:12167491}.
CC -!- TOXIC DOSE: LD(50) is 0.5 mg/kg by intracerebroventricular injection.
CC {ECO:0000269|PubMed:12167491}.
CC -!- MISCELLANEOUS: This enzyme has been found to be not myotoxic, not
CC cytotoxic, not hemorrhagic and not lethal.
CC {ECO:0000305|PubMed:12167491}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
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DR EMBL; AY145836; AAN37410.1; -; mRNA.
DR PDB; 1U73; X-ray; 1.90 A; A/B=17-138.
DR PDB; 1UMV; X-ray; 1.79 A; X=17-138.
DR PDB; 1Z76; X-ray; 1.85 A; A/B=17-138.
DR PDB; 1ZL7; X-ray; 1.60 A; A=17-138.
DR PDB; 1ZLB; X-ray; 0.97 A; A=17-138.
DR PDBsum; 1U73; -.
DR PDBsum; 1UMV; -.
DR PDBsum; 1Z76; -.
DR PDBsum; 1ZL7; -.
DR PDBsum; 1ZLB; -.
DR AlphaFoldDB; Q8AXY1; -.
DR SMR; Q8AXY1; -.
DR EvolutionaryTrace; Q8AXY1; -.
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:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0050482; P:arachidonic acid secretion; IEA:InterPro.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006644; P:phospholipid metabolic process; IEA:InterPro.
DR GO; GO:0008217; P:regulation of blood pressure; IEA:UniProtKB-KW.
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; Antibiotic; Antimicrobial;
KW Blood coagulation cascade inhibiting toxin; Calcium;
KW Direct protein sequencing; Disulfide bond; Hemostasis impairing toxin;
KW Hydrolase; Hypotensive agent; Lipid degradation; Lipid metabolism;
KW Metal-binding; Platelet aggregation inhibiting toxin; Secreted; Signal;
KW Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:12167491"
FT CHAIN 17..138
FT /note="Acidic phospholipase A2 BthA-1"
FT /id="PRO_0000413804"
FT ACT_SITE 63
FT /evidence="ECO:0000305|PubMed:16376474"
FT ACT_SITE 105
FT /evidence="ECO:0000305|PubMed:16376474"
FT BINDING 43
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:15351695,
FT ECO:0000269|PubMed:16376474, ECO:0007744|PDB:1UMV,
FT ECO:0007744|PDB:1ZL7"
FT BINDING 47
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:15351695,
FT ECO:0000269|PubMed:16376474, ECO:0007744|PDB:1UMV,
FT ECO:0007744|PDB:1ZL7"
FT BINDING 48
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:15351695,
FT ECO:0000269|PubMed:16376474, ECO:0007744|PDB:1UMV,
FT ECO:0007744|PDB:1ZL7"
FT BINDING 64
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:15351695,
FT ECO:0000269|PubMed:16376474, ECO:0007744|PDB:1UMV,
FT ECO:0007744|PDB:1ZL7"
FT DISULFID 42..131
FT /evidence="ECO:0000269|PubMed:15351695,
FT ECO:0000269|PubMed:16301802, ECO:0000269|PubMed:16376474,
FT ECO:0007744|PDB:1UMV, ECO:0007744|PDB:1Z76,
FT ECO:0007744|PDB:1ZL7"
FT DISULFID 44..60
FT /evidence="ECO:0000269|PubMed:15351695,
FT ECO:0000269|PubMed:16301802, ECO:0000269|PubMed:16376474,
FT ECO:0007744|PDB:1UMV, ECO:0007744|PDB:1Z76,
FT ECO:0007744|PDB:1ZL7"
FT DISULFID 59..111
FT /evidence="ECO:0000269|PubMed:15351695,
FT ECO:0000269|PubMed:16301802, ECO:0000269|PubMed:16376474,
FT ECO:0007744|PDB:1UMV, ECO:0007744|PDB:1Z76,
FT ECO:0007744|PDB:1ZL7"
FT DISULFID 65..138
FT /evidence="ECO:0000269|PubMed:15351695,
FT ECO:0000269|PubMed:16301802, ECO:0000269|PubMed:16376474,
FT ECO:0007744|PDB:1UMV, ECO:0007744|PDB:1Z76,
FT ECO:0007744|PDB:1ZL7"
FT DISULFID 66..104
FT /evidence="ECO:0000269|PubMed:15351695,
FT ECO:0000269|PubMed:16301802, ECO:0000269|PubMed:16376474,
FT ECO:0007744|PDB:1UMV, ECO:0007744|PDB:1Z76,
FT ECO:0007744|PDB:1ZL7"
FT DISULFID 73..97
FT /evidence="ECO:0000269|PubMed:15351695,
FT ECO:0000269|PubMed:16301802, ECO:0000269|PubMed:16376474,
FT ECO:0007744|PDB:1UMV, ECO:0007744|PDB:1Z76,
FT ECO:0007744|PDB:1ZL7"
FT DISULFID 91..102
FT /evidence="ECO:0000269|PubMed:15351695,
FT ECO:0000269|PubMed:16301802, ECO:0000269|PubMed:16376474,
FT ECO:0007744|PDB:1UMV, ECO:0007744|PDB:1Z76,
FT ECO:0007744|PDB:1ZL7"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:1ZLB"
FT HELIX 33..38
FT /evidence="ECO:0007829|PDB:1ZLB"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:1ZLB"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:1ZLB"
FT HELIX 55..68
FT /evidence="ECO:0007829|PDB:1ZLB"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:1ZLB"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:1ZLB"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:1ZLB"
FT HELIX 96..114
FT /evidence="ECO:0007829|PDB:1ZLB"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:1ZLB"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:1ZLB"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:1ZLB"
SQ SEQUENCE 138 AA; 15456 MW; 513647907BFD0F4E CRC64;
MRTLWIMAVL LVGVEGSLWQ FGKMINYVMG ESGVLQYLSY GCYCGLGGQG QPTDATDRCC
FVHDCCYGKV TGCDPKIDSY TYSKKNGDVV CGGDDPCKKQ ICECDRVATT CFRDNKDTYD
IKYWFYGAKN CQEKSEPC
