PA2HP_PROMU
ID PA2HP_PROMU Reviewed; 138 AA.
AC Q2PWA3;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 1.
DT 25-MAY-2022, entry version 62.
DE RecName: Full=Basic phospholipase A2 homolog promutoxin {ECO:0000303|PubMed:16793192};
DE Short=svPLA2 homolog;
DE Flags: Precursor;
OS Protobothrops mucrosquamatus (Taiwan habu) (Trimeresurus mucrosquamatus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Protobothrops.
OX NCBI_TaxID=103944;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 17-46, FUNCTION, SUBUNIT,
RP MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=16793192; DOI=10.1016/j.biochi.2006.05.003;
RA Wei J.-F., Li T., Wei X.-L., Sun Q.-Y., Yang F.-M., Chen Q.-Y., Wang W.-Y.,
RA Xiong Y.-L., He S.-H.;
RT "Purification, characterization and cytokine release function of a novel
RT Arg-49 phospholipase A(2) from the venom of Protobothrops mucrosquamatus.";
RL Biochimie 88:1331-1342(2006).
CC -!- FUNCTION: Snake venom phospholipase A2 homolog that lacks enzymatic
CC activity. Exhibits potent myotoxicity causing myonecrosis and edema in
CC the gastrocnemius muscle of mice (PubMed:16793192). Is also able to
CC stimulate the release of IL12 (IL12A-IL12B), TNF-alpha (TNF), IL6 and
CC IL1-beta (IL1B) from human monocytes, and induce IL2, TNFalpha and IL6
CC release from T-cells (PubMed:16793192). A model of myotoxic mechanism
CC has been 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:16793192}.
CC -!- SUBUNIT: Homodimer; non-covalently linked.
CC {ECO:0000250|UniProtKB:I6L8L6, ECO:0000269|PubMed:16793192}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16793192}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:16793192}.
CC -!- MASS SPECTROMETRY: Mass=13656; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:16793192};
CC -!- MISCELLANEOUS: Fails to induce platelet aggregation, and has little
CC effect on the ADP-induced platelet aggregation. Does not show
CC hemorrhagic activity (PubMed:16793192). {ECO:0000305|PubMed:16793192}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC R49 sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: Does not bind calcium as one of the calcium-binding sites is
CC lost (Asp->Arg in position 64, which corresponds to 'Arg-49' in the
CC current nomenclature). {ECO:0000305}.
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DR EMBL; DQ299948; ABC02868.1; -; mRNA.
DR AlphaFoldDB; Q2PWA3; -.
DR SMR; Q2PWA3; -.
DR PRIDE; Q2PWA3; -.
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: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 Direct protein sequencing; Disulfide bond; Myotoxin; Secreted; Signal;
KW Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:16793192"
FT CHAIN 17..138
FT /note="Basic phospholipase A2 homolog promutoxin"
FT /id="PRO_0000419213"
FT REGION 122..133
FT /note="Important for membrane-damaging activities in
FT eukaryotes and bacteria; heparin-binding"
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT SITE 122
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 125
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 128
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 129
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 131
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 42..132
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT DISULFID 44..60
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT DISULFID 59..112
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT DISULFID 65..138
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT DISULFID 66..105
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT DISULFID 73..98
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT DISULFID 91..103
FT /evidence="ECO:0000250|UniProtKB:P24605"
SQ SEQUENCE 138 AA; 15443 MW; C218367908B7F140 CRC64;
MRTLWIMAVL LLGVEGSVIE LGKMVFQETG KNPVKNYGLY GCNCGVGKRG KPVDATDSCC
FVHRCCYKKV TGCDPKKDRY SYSWENKAIV CGEKNPPCLK QVCECDKAVA ICLRENLGTY
DKKHRVTMKF LCKAPESC
