PA2H_BOTNR
ID PA2H_BOTNR Reviewed; 108 AA.
AC P0DUN6;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 1.
DT 25-MAY-2022, entry version 4.
DE RecName: Full=Basic phospholipase A2 homolog BnuTX-I {ECO:0000303|PubMed:26927324};
DE Short=svPLA2 homolog;
DE AltName: Full=Lys49 PLA2-like;
DE Flags: Fragments;
OS Bothrops neuwiedi urutu (Neuwied's lancehead).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=157695;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=26927324; DOI=10.1016/j.toxicon.2016.02.021;
RA Correa E.A., Kayano A.M., Diniz-Sousa R., Setubal S.S., Zanchi F.B.,
RA Zuliani J.P., Matos N.B., Almeida J.R., Resende L.M., Marangoni S.,
RA da Silva S.L., Soares A.M., Calderon L.A.;
RT "Isolation, structural and functional characterization of a new Lys49
RT phospholipase A2 homologue from Bothrops neuwiedi urutu with bactericidal
RT potential.";
RL Toxicon 115:13-21(2016).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that lacks enzymatic
CC inactivity, but induces myotoxicity (PubMed:26927324). Also causes an
CC inflammatory activity that is demonstrated by mice paw edema induction
CC and pro-inflammatory cytokine IL-1 (but not TNF-alpha) elevation
CC (PubMed:26927324). Also shows antimicrobial activity against Gram-
CC positive and Gram-negative bacteria (PubMed:26927324).
CC {ECO:0000269|PubMed:26927324}.
CC -!- SUBUNIT: Probable homodimer; non-covalently-linked (Probable). A model
CC of myotoxic mechanism has been proposed: an apo Lys49-PLA2 is activated
CC by the entrance of a hydrophobic molecule (e.g. fatty acid) at the
CC hydrophobic channel of the protein leading to a reorientation of a
CC monomer (By similarity). This reorientation causes a transition between
CC 'inactive' to 'active' states, causing alignment of C-terminal and
CC membrane-docking sites (MDoS) side-by-side and putting the membrane-
CC disruption sites (MDiS) in the same plane, exposed to solvent and in a
CC symmetric position for both monomers (By similarity). The MDoS region
CC stabilizes the toxin on membrane by the interaction of charged residues
CC with phospholipid head groups (By similarity). Subsequently, the MDiS
CC region destabilizes the membrane with penetration of hydrophobic
CC residues (By similarity). This insertion causes a disorganization of
CC the membrane, allowing an uncontrolled influx of ions (i.e. calcium and
CC sodium), and eventually triggering irreversible intracellular
CC alterations and cell death (By similarity).
CC {ECO:0000250|UniProtKB:I6L8L6, ECO:0000305|PubMed:26927324}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:26927324}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:26927324}.
CC -!- MASS SPECTROMETRY: Mass=13733; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:26927324};
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC K49 sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: Does not bind calcium as one of the calcium-binding sites is
CC lost (Asp->Lys in position 48, which corresponds to 'Lys-49' in the
CC current nomenclature). {ECO:0000305}.
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DR AlphaFoldDB; P0DUN6; -.
DR SMR; P0DUN6; -.
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:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
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.
PE 1: Evidence at protein level;
KW Antibiotic; Antimicrobial; Direct protein sequencing; Disulfide bond;
KW Myotoxin; Secreted; Toxin.
FT CHAIN 1..108
FT /note="Basic phospholipase A2 homolog BnuTX-I"
FT /evidence="ECO:0000269|PubMed:26927324"
FT /id="PRO_0000452897"
FT REGION 96..108
FT /note="Important for membrane-damaging activities in
FT eukaryotes and bacteria; heparin-binding"
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT SITE 96
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 99
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 102
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 103
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 105
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 108
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 26..106
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 28..44
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 43..86
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 49..?
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 50..79
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 66..77
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 72..?
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT NON_CONS 52..53
FT /evidence="ECO:0000305|PubMed:26927324"
FT NON_TER 108
FT /evidence="ECO:0000305|PubMed:26927324"
SQ SEQUENCE 108 AA; 12369 MW; 167CB19DFA99BC16 CRC64;
SLFELGKMIL QETGKNPAKS YGAYGCNCGV LGRGKPKDAT DRCCYVHKCC YKDRYSYSWK
DKTIVCGENN PCLKELCECD KAVAICLREN LGTYNKKYRY HLKPFCKK
