PA2HB_CERGO
ID PA2HB_CERGO Reviewed; 137 AA.
AC Q8UVU7;
DT 06-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 25-MAY-2022, entry version 70.
DE RecName: Full=Basic phospholipase A2 homolog Pgo-K49 {ECO:0000303|PubMed:11594738};
DE Short=svPLA2 homolog;
DE Flags: Precursor;
OS Cerrophidion godmani (Porthidium godmani) (Bothrops godmani).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Cerrophidion.
OX NCBI_TaxID=44722;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 17-45, MASS SPECTROMETRY,
RP AND SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=11594738; DOI=10.1006/abbi.2001.2524;
RA Tsai I.-H., Chen Y.-H., Wang Y.-M., Tu M.-C., Tu A.T.;
RT "Purification, sequencing, and phylogenetic analyses of novel Lys-49
RT phospholipases A(2) from the venoms of rattlesnakes and other pit vipers.";
RL Arch. Biochem. Biophys. 394:236-244(2001).
CC -!- FUNCTION: Snake venom phospholipase A2 homolog that lacks enzymatic
CC activity (By similarity). Is myotoxic (By similarity). A model of
CC myotoxic mechanism has been proposed: an apo Lys49-PLA2 is activated by
CC 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:0000250|UniProtKB:Q6JK69}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11594738}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:11594738}.
CC -!- MASS SPECTROMETRY: Mass=13836; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11594738};
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 64, which corresponds to 'Lys-49' in the
CC current nomenclature). {ECO:0000305}.
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DR EMBL; AF374237; AAL39066.1; -; mRNA.
DR AlphaFoldDB; Q8UVU7; -.
DR SMR; Q8UVU7; -.
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:11594738"
FT CHAIN 17..137
FT /note="Basic phospholipase A2 homolog Pgo-K49"
FT /evidence="ECO:0000305|PubMed:11594738"
FT /id="PRO_0000022850"
FT REGION 121..133
FT /note="Important for membrane-damaging activities in
FT eukaryotes and bacteria; heparin-binding"
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT SITE 121
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 124
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 127
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 128
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 130
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 133
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 42..131
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 44..60
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 59..111
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 65..137
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 66..104
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 73..97
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 91..102
FT /evidence="ECO:0000250|UniProtKB:Q90249"
SQ SEQUENCE 137 AA; 15515 MW; 5BD1C46E9B45BEDE CRC64;
MRTLLIVAVL LVGVEGSVYE LGKMILQETG KNAATSYGFY GCNCGVGRRG KPKDATDRCC
FVHKCCYKKL TDCNSKTDRY SYSWKDKTIV CGDNNPCLQE MCECDKAVAI CLRENLNTYN
KKYKIHMKFF CKKPDAC
