PA2HD_CALRH
ID PA2HD_CALRH Reviewed; 137 AA.
AC Q9PVF4;
DT 13-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 86.
DE RecName: Full=Basic phospholipase A2 homolog W6D49 {ECO:0000305|PubMed:11054123};
DE Short=svPLA2 homolog;
DE AltName: Full=Inactive basic phospholipase A2 W6D49 {ECO:0000303|PubMed:11054123};
DE Short=CRV-W6D49 {ECO:0000303|PubMed:11054123};
DE Short=svPLA2;
DE Flags: Precursor;
OS Calloselasma rhodostoma (Malayan pit viper) (Agkistrodon rhodostoma).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Calloselasma.
OX NCBI_TaxID=8717;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, MASS SPECTROMETRY,
RP SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=11054123; DOI=10.1046/j.1432-1327.2000.01766.x;
RA Tsai I.-H., Wang Y.-M., Au L.-C., Ko T.-P., Chen Y.-H., Chu Y.-F.;
RT "Phospholipases A2 from Callosellasma rhodostoma venom gland. Cloning and
RT sequencing of 10 of the cDNAs, three-dimensional modelling and chemical
RT modification of the major isozyme.";
RL Eur. J. Biochem. 267:6684-6691(2000).
CC -!- FUNCTION: Snake venom phospholipase A2 homolog that lacks enzymatic
CC activity. Shows myotoxin activities and displays edema-inducing
CC activities (PubMed:11054123). 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:11054123}.
CC -!- ACTIVITY REGULATION: Heparin reduces its edema-inducing activity
CC (PubMed:11054123). {ECO:0000269|PubMed:11054123}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11054123}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11054123}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:11054123}.
CC -!- MASS SPECTROMETRY: Mass=13674; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11054123};
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
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DR EMBL; AF104065; AAF03249.1; -; mRNA.
DR AlphaFoldDB; Q9PVF4; -.
DR SMR; Q9PVF4; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
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:UniProtKB-KW.
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 Disulfide bond; Heparin-binding; Lipid degradation; Lipid metabolism;
KW Myotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:11054123"
FT CHAIN 17..137
FT /note="Basic phospholipase A2 homolog W6D49"
FT /evidence="ECO:0000269|PubMed:11054123"
FT /id="PRO_0000022780"
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 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:P81165"
FT DISULFID 44..60
FT /evidence="ECO:0000250|UniProtKB:P81165"
FT DISULFID 59..111
FT /evidence="ECO:0000250|UniProtKB:P81165"
FT DISULFID 65..137
FT /evidence="ECO:0000250|UniProtKB:P81165"
FT DISULFID 66..104
FT /evidence="ECO:0000250|UniProtKB:P81165"
FT DISULFID 73..97
FT /evidence="ECO:0000250|UniProtKB:P81165"
FT DISULFID 91..102
FT /evidence="ECO:0000250|UniProtKB:P81165"
SQ SEQUENCE 137 AA; 15457 MW; 8F5FE6C04573B631 CRC64;
MRTLWILAVL LVSVDGSMFN LWKMIMVMTG KEATKNYGMY GCNCGPMKRG KPKDATDQCC
ADHDCCYKKL TDCDPKKESY SYKFEKGEIL CGETNPCLNQ ACECDKAVAT CFRDNLDTYN
KKQQFNTGIF CSKAKAC
