PA2H1_BOTBZ
ID PA2H1_BOTBZ Reviewed; 121 AA.
AC I6L8L6;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2020, sequence version 2.
DT 25-MAY-2022, entry version 51.
DE RecName: Full=Basic phospholipase A2 homolog 2;
DE Short=svPLA2 homolog;
DE AltName: Full=Myotoxin II {ECO:0000303|PubMed:18602430, ECO:0000303|PubMed:22584077};
DE Short=MTX-II {ECO:0000303|PubMed:18602430, ECO:0000303|PubMed:22584077};
OS Bothrops brazili (Brazil'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=157546;
RN [1]
RP PROTEIN SEQUENCE OF 1-49; 51-61; 63-72; 83-98; 105-109 AND 110-117,
RP FUNCTION, MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=18602430; DOI=10.1016/j.peptides.2008.05.021;
RA Costa T.R., Menaldo D.L., Oliveira C.Z., Santos-Filho N.A., Teixeira S.S.,
RA Nomizo A., Fuly A.L., Monteiro M.C., de Souza B.M., Palma M.S.,
RA Stabeli R.G., Sampaio S.V., Soares A.M.;
RT "Myotoxic phospholipases A(2) isolated from Bothrops brazili snake venom
RT and synthetic peptides derived from their C-terminal region: cytotoxic
RT effect on microorganism and tumor cells.";
RL Peptides 29:1645-1656(2008).
RN [2] {ECO:0000312|PDB:4DCF}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS), AND DISULFIDE BONDS.
RX PubMed=22584077; DOI=10.1016/j.ijbiomac.2012.05.006;
RA Ullah A., Souza T.A., Betzel C., Murakami M.T., Arni R.K.;
RT "Crystallographic portrayal of different conformational states of a Lys49
RT phospholipase A homologue: insights into structural determinants for
RT myotoxicity and dimeric configuration.";
RL Int. J. Biol. Macromol. 51:209-214(2012).
RN [3] {ECO:0000312|PDB:4K06}
RP X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS), DISULFIDE BONDS, AND SUBUNIT.
RX PubMed=24145104; DOI=10.1016/j.bbapap.2013.10.009;
RA Fernandes C.A., Comparetti E.J., Borges R.J., Huancahuire-Vega S.,
RA Ponce-Soto L.A., Marangoni S., Soares A.M., Fontes M.R.;
RT "Structural bases for a complete myotoxic mechanism: crystal structures of
RT two non-catalytic phospholipases A2-like from Bothrops brazili venom.";
RL Biochim. Biophys. Acta 1834:2772-2781(2013).
CC -!- FUNCTION: Snake venom phospholipase A2 homolog that lacks enzymatic
CC activity. Is myotoxic and displays edema-inducing activities in mouse
CC paw (PubMed:18602430). Also displays cytotoxic activity against some
CC cell lines, and antimicrobial activities against E.coli, C.albicans and
CC Leishmania (PubMed:18602430). A model of myotoxic mechanism has been
CC proposed: an apo Lys49-PLA2 is activated by the entrance of a
CC hydrophobic molecule (e.g. fatty acid) at the hydrophobic channel of
CC the protein leading to a reorientation of a monomer (PubMed:24145104).
CC This reorientation causes a transition between 'inactive' to 'active'
CC states, causing alignment of C-terminal and membrane-docking sites
CC (MDoS) side-by-side and putting the membrane-disruption sites (MDiS) in
CC the same plane, exposed to solvent and in a symmetric position for both
CC monomers (PubMed:24145104). The MDoS region stabilizes the toxin on
CC membrane by the interaction of charged residues with phospholipid head
CC groups (PubMed:24145104). Subsequently, the MDiS region destabilizes
CC the membrane with penetration of hydrophobic residues
CC (PubMed:24145104). This insertion causes a disorganization of the
CC membrane, allowing an uncontrolled influx of ions (i.e. calcium and
CC sodium), and eventually triggering irreversible intracellular
CC alterations and cell death (PubMed:24145104).
CC {ECO:0000269|PubMed:18602430, ECO:0000305|PubMed:24145104}.
CC -!- SUBUNIT: Homodimer; non-covalently linked (probable alternative/compact
CC dimer conformation in solution). {ECO:0000269|PubMed:22584077,
CC ECO:0000269|PubMed:24145104}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18602430}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:18602430}.
CC -!- MASS SPECTROMETRY: Mass=13965.5; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:18602430};
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 PDB; 4DCF; X-ray; 2.70 A; A/B/C/D=1-121.
DR PDB; 4K06; X-ray; 2.08 A; A/B=1-121.
DR PDBsum; 4DCF; -.
DR PDBsum; 4K06; -.
DR AlphaFoldDB; I6L8L6; -.
DR SMR; I6L8L6; -.
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.
DR PROSITE; PS00119; PA2_ASP; 1.
DR PROSITE; PS00118; PA2_HIS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Direct protein sequencing;
KW Disulfide bond; Myotoxin; Secreted; Toxin.
FT CHAIN 1..121
FT /note="Basic phospholipase A2 homolog 2"
FT /evidence="ECO:0000269|PubMed:18602430"
FT /id="PRO_0000449045"
FT REGION 105..117
FT /note="Important for membrane-damaging activities in
FT eukaryotes and bacteria; heparin-binding"
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT SITE 105
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000269|PubMed:24145104"
FT SITE 108
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000269|PubMed:24145104"
FT SITE 111
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000269|PubMed:24145104"
FT SITE 112
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000269|PubMed:24145104"
FT SITE 114
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000269|PubMed:24145104"
FT SITE 117
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000269|PubMed:24145104"
FT DISULFID 26..115
FT /evidence="ECO:0000269|PubMed:22584077,
FT ECO:0000269|PubMed:24145104, ECO:0007744|PDB:4DCF,
FT ECO:0007744|PDB:4K06"
FT DISULFID 28..44
FT /evidence="ECO:0000269|PubMed:22584077,
FT ECO:0000269|PubMed:24145104, ECO:0007744|PDB:4DCF,
FT ECO:0007744|PDB:4K06"
FT DISULFID 43..95
FT /evidence="ECO:0000269|PubMed:22584077,
FT ECO:0000269|PubMed:24145104, ECO:0007744|PDB:4DCF,
FT ECO:0007744|PDB:4K06"
FT DISULFID 49..121
FT /evidence="ECO:0000269|PubMed:22584077,
FT ECO:0000269|PubMed:24145104, ECO:0007744|PDB:4DCF,
FT ECO:0007744|PDB:4K06"
FT DISULFID 50..88
FT /evidence="ECO:0000269|PubMed:22584077,
FT ECO:0000269|PubMed:24145104, ECO:0007744|PDB:4DCF,
FT ECO:0007744|PDB:4K06"
FT DISULFID 57..81
FT /evidence="ECO:0000269|PubMed:22584077,
FT ECO:0000269|PubMed:24145104, ECO:0007744|PDB:4DCF,
FT ECO:0007744|PDB:4K06"
FT DISULFID 75..86
FT /evidence="ECO:0000269|PubMed:22584077,
FT ECO:0000269|PubMed:24145104, ECO:0007744|PDB:4DCF,
FT ECO:0007744|PDB:4K06"
FT CONFLICT 114
FT /note="F -> L (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 2..13
FT /evidence="ECO:0007829|PDB:4K06"
FT HELIX 17..21
FT /evidence="ECO:0007829|PDB:4K06"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:4K06"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:4K06"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:4K06"
FT HELIX 39..52
FT /evidence="ECO:0007829|PDB:4K06"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:4K06"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:4K06"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:4K06"
FT HELIX 80..98
FT /evidence="ECO:0007829|PDB:4K06"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:4K06"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:4K06"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:4K06"
SQ SEQUENCE 121 AA; 13691 MW; 3B8FBB1D59B402E2 CRC64;
SLFQLGKMIL QETGKNPAAS YGAYGCNCGV LGRGKPKDAT DRCCYVHKCC KKKLTGCDPK
KDRYSYSWKD KTIVCGENNP CLKELCECDK AVAICLRENL NTYNKKYRYH LKPFCKKADP
C
