PA2B6_CRODO
ID PA2B6_CRODO Reviewed; 122 AA.
AC P0CAS2;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Phospholipase A2 crotoxin basic chain;
DE Short=CB;
DE Short=Crotoxin-B;
DE Short=svPLA2;
DE EC=3.1.1.4;
DE AltName: Full=CdcolF6a;
DE Short=F6a;
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase;
OS Crotalus durissus collilineatus (Brazilian rattlesnake).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Crotalus.
OX NCBI_TaxID=221569;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUBUNIT, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=17203389; DOI=10.1007/s10930-006-9063-y;
RA Ponce-Soto L.A., Lomonte B., Rodrigues-Simioni L., Novello J.C.,
RA Marangoni S.;
RT "Biological and structural characterization of crotoxin and new isoform of
RT crotoxin B PLA(2) (F6a) from Crotalus durissus collilineatus snake venom.";
RL Protein J. 26:221-230(2007).
RN [2]
RP PROTEIN SEQUENCE OF 1-60, AND VARIANTS LYS-15 AND PHE-20.
RC TISSUE=Venom {ECO:0000303|Ref.2};
RA Oliveira I., Boldrini-Franca J., Bordon K., Cardoso I., Pucca M.,
RA Carone S., Zoccal K., Frantz F., Faccioli L., Sampaio S., Rosa J.,
RA Arantes E.;
RT "Proteome of Crotalus durissus collilineatus venoms: analysis of individual
RT variations.";
RL Submitted (JUN-2016) to UniProtKB.
RN [3]
RP FUNCTION.
RX PubMed=16003952; DOI=10.1007/s10930-004-1517-5;
RA Toyama M.H., Toyama D.O., Joazeiro P.P., Carneiro E.M., Beriam L.O.,
RA Marangoni L.S., Boschero A.C.;
RT "Biological and structural characterization of a new PLA2 from the Crotalus
RT durissus collilineatus venom.";
RL Protein J. 24:103-112(2005).
RN [4]
RP FUNCTION.
RX PubMed=17915277; DOI=10.1016/j.toxicon.2007.08.007;
RA Gutierrez J.M., Ponce-Soto L.A., Marangoni S., Lomonte B.;
RT "Systemic and local myotoxicity induced by snake venom group II
RT phospholipases A2: comparison between crotoxin, crotoxin B and a Lys49 PLA2
RT homologue.";
RL Toxicon 51:80-92(2008).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=19851009; DOI=10.1107/s1744309109032631;
RA Salvador G.H., Fernandes C.A., Correa L.C., Santos-Filho N.A., Soares A.M.,
RA Fontes M.R.;
RT "Crystallization and preliminary X-ray diffraction analysis of crotoxin B
RT from Crotalus durissus collilineatus venom.";
RL Acta Crystallogr. F 65:1011-1013(2009).
CC -!- FUNCTION: Heterodimer CA-CB: Crotoxin is a potent presynaptic
CC neurotoxin that possesses phospholipase A2 (PLA2) activity and exerts a
CC lethal action by blocking neuromuscular transmission (PubMed:17203389,
CC PubMed:16003952). It consists of a non-covalent association of a basic
CC and weakly toxic PLA2 subunit (CB), with a small acidic, non-enzymatic
CC and non-toxic subunit (CA also named crotapotin). The complex acts by
CC binding to a specific 48-kDa protein (R48) receptor located on
CC presynaptic membranes, forming a transient ternary complex CA-CB-R48,
CC followed by dissociation of the CA-CB complex and release of the CA
CC subunit. At equilibrium, only the CB subunits remain associated with
CC the specific crotoxin receptor. In addition to neurotoxicity, crotoxin
CC has been found to exert nephrotoxicity, and cardiovascular toxicity.
CC Moreover, anti-inflammatory, immunomodulatory, anti-tumor and analgesic
CC effects of crotoxin have also been reported (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:16003952,
CC ECO:0000269|PubMed:17203389}.
CC -!- FUNCTION: Monomer CB: The basic subunit of crotoxin is a snake venom
CC phospholipase A2 (PLA2) that exhibits weak neurotoxicity
CC (PubMed:17203389, PubMed:16003952) and strong anticoagulant effects by
CC binding to factor Xa (F10) and inhibiting the prothrombinase activity
CC (By similarity). In addition, it exerts myotoxicity (PubMed:17203389,
CC PubMed:16003952, PubMed:17915277), nephrotoxicity, and cardiovascular
CC toxicity as well as anti-inflammatory, immunomodulatory, anti-tumor and
CC analgesic effects (By similarity). Also shows a strong antimicrobial
CC activity against X.axonopodis passiforae (Gram-negative) which is
CC completely dependent on the enzymatic activity (PubMed:16003952). PLA2
CC catalyzes the calcium-dependent hydrolysis of the 2- acyl groups in 3-
CC sn-phosphoglycerides. {ECO:0000250, ECO:0000269|PubMed:16003952,
CC ECO:0000269|PubMed:17203389, ECO:0000269|PubMed:17915277}.
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 one acidic (CA also named crotapotin) and one
CC basic (CB) subunits; non-covalently linked.
CC {ECO:0000269|PubMed:17203389}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- MASS SPECTROMETRY: Mass=14943.14; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:17203389};
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR AlphaFoldDB; P0CAS2; -.
DR SMR; P0CAS2; -.
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: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 Calcium; Direct protein sequencing; Disulfide bond; Hydrolase;
KW Lipid degradation; Lipid metabolism; Metal-binding; Neurotoxin;
KW Presynaptic neurotoxin; Secreted; Toxin.
FT CHAIN 1..122
FT /note="Phospholipase A2 crotoxin basic chain"
FT /id="PRO_0000376919"
FT ACT_SITE 47
FT /evidence="ECO:0000250|UniProtKB:P62022"
FT ACT_SITE 89
FT /evidence="ECO:0000250|UniProtKB:P62022"
FT BINDING 27
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P62022"
FT BINDING 29
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P62022"
FT BINDING 31
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P62022"
FT BINDING 48
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P62022"
FT DISULFID 26..115
FT /evidence="ECO:0000250|UniProtKB:P62022"
FT DISULFID 28..44
FT /evidence="ECO:0000250|UniProtKB:P62022"
FT DISULFID 43..95
FT /evidence="ECO:0000250|UniProtKB:P62022"
FT DISULFID 49..122
FT /evidence="ECO:0000250|UniProtKB:P62022"
FT DISULFID 50..88
FT /evidence="ECO:0000250|UniProtKB:P62022"
FT DISULFID 57..81
FT /evidence="ECO:0000250|UniProtKB:P62022"
FT DISULFID 75..86
FT /evidence="ECO:0000250|UniProtKB:P62022"
FT VARIANT 15
FT /note="R -> K"
FT /evidence="ECO:0000269|Ref.2"
FT VARIANT 20
FT /note="P -> F"
FT /evidence="ECO:0000269|Ref.2"
SQ SEQUENCE 122 AA; 14264 MW; ABD31823D4E2EBFD CRC64;
HLLQFNKMIK FETRRNAIPP YAFYGCYCGW GGRGRPKDAT DRCCFVHDCC YGKLAKCNTK
WDFYRYSLKS GYITCGKGTW CEEQICECDR VAAECLRRSL STYRYGYMIY PDSRCRGPSE
TC
