PA2HB_CALRH
ID PA2HB_CALRH Reviewed; 138 AA.
AC Q9PVF3;
DT 13-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 75.
DE RecName: Full=Basic phospholipase A2 homolog G6K49;
DE Short=svPLA2 homolog;
DE AltName: Full=CRV/TMV/DAV-K49;
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].
RC TISSUE=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 (PLA2) that lacks enzymatic
CC activity. Displays myotoxic activities (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:Q2PWA3}.
CC -!- SUBUNIT: Homodimer; non-covalently linked.
CC {ECO:0000250|UniProtKB:Q2PWA3}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:11054123}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:11054123}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF104066; AAF03250.1; -; mRNA.
DR AlphaFoldDB; Q9PVF3; -.
DR SMR; Q9PVF3; -.
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 2: Evidence at transcript level;
KW Disulfide bond; Myotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..138
FT /note="Basic phospholipase A2 homolog G6K49"
FT /id="PRO_0000022782"
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:Q90249"
FT DISULFID 44..60
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 59..112
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 65..138
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 66..105
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 73..98
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 91..103
FT /evidence="ECO:0000250|UniProtKB:Q90249"
SQ SEQUENCE 138 AA; 15466 MW; FC5A9CAE313E5AB4 CRC64;
MRTLWIMAVL LLGVEGSLIE LGKMIFQETG KNPVKNYGLY GCNCGVGNRG KPVDATDRCC
FVHKCCYKKV TGCDPKKDRY SYSWENKAIV CGEKNPPCLK QVCECDKAVA ICLRENLGTY
DKKHRVTVKF LCKAPESC
