PA2H_LACMU
ID PA2H_LACMU Reviewed; 120 AA.
AC P0DUN7;
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 LmutTX {ECO:0000303|PubMed:29067765};
DE Short=svPLA2 homolog;
DE AltName: Full=LmmV toxin {ECO:0000303|PubMed:29067765};
DE AltName: Full=Lys49 PLA2-like;
OS Lachesis muta muta (Bushmaster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Lachesis.
OX NCBI_TaxID=8753;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY,
RP SYNTHESIS, AND 3D-STRUCTURE MODELING.
RC TISSUE=Venom;
RX PubMed=29067765; DOI=10.1111/bcpt.12921;
RA Diniz-Sousa R., Caldeira C.A.S., Kayano A.M., Paloschi M.V., Pimenta D.C.,
RA Simoes-Silva R., Ferreira A.S., Zanchi F.B., Matos N.B., Grabner F.P.,
RA Calderon L.A., Zuliani J.P., Soares A.M.;
RT "Identification of the molecular determinants of the antibacterial activity
RT of LmutTX, a Lys49 phospholipase A2 homologue isolated from Lachesis muta
RT muta snake venom (Linnaeus, 1766).";
RL Basic Clin. Pharmacol. Toxicol. 122:413-423(2018).
CC -!- FUNCTION: Snake venom phospholipase A2 homolog that lacks enzymatic
CC activity (PubMed:29067765). Shows moderate cytotoxicity against C2C12
CC myotubes (activity above 200 ug/mL) (PubMed:29067765). Also shows
CC antibacterial activity against both Gram-positive and Gram-negative
CC bacteria (PubMed:29067765). 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 (By similarity).
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 (By similarity). The MDoS region stabilizes the toxin on
CC membrane by the interaction of charged residues with phospholipid head
CC groups (By similarity). Subsequently, the MDiS region destabilizes the
CC membrane with penetration of hydrophobic residues (By similarity). This
CC insertion causes a disorganization of the membrane, allowing an
CC uncontrolled influx of ions (i.e. calcium and sodium), and eventually
CC triggering irreversible intracellular alterations and cell death (By
CC similarity). {ECO:0000250|UniProtKB:I6L8L6,
CC ECO:0000269|PubMed:29067765}.
CC -!- SUBUNIT: Monomer. {ECO:0000305|PubMed:29067765}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:29067765}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:29067765}.
CC -!- MASS SPECTROMETRY: Mass=13889; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:29067765};
CC -!- MISCELLANEOUS: This protein corresponds to 0.8% of the venom protein
CC content. {ECO:0000269|PubMed:29067765}.
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; P0DUN7; -.
DR SMR; P0DUN7; -.
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..120
FT /note="Basic phospholipase A2 homolog LmutTX"
FT /evidence="ECO:0000269|PubMed:29067765"
FT /id="PRO_0000452898"
FT DISULFID 26..114
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 28..44
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 43..95
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 49..120
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 50..88
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 57..81
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 75..86
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
SQ SEQUENCE 120 AA; 13538 MW; 5B894F3B5E9D749A CRC64;
SLVELGKMIL QETGKNPVTS YGAYGCNCGV LGSGKPKDAT DRCCYVHKCC YKKLTDCDPK
KDRYSYSWKD KTIVCGENNS CLKELCECDK AVAICLRENL DTYNKKYNYL KPFCKKADPC
