PA2H_DEIAC
ID PA2H_DEIAC Reviewed; 138 AA.
AC O57385; Q8UVZ5;
DT 06-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 25-MAY-2022, entry version 96.
DE RecName: Full=Basic phospholipase A2 homolog acutohaemolysin {ECO:0000303|PubMed:10930841, ECO:0000303|PubMed:12871974};
DE Short=svPLA2 homolog;
DE AltName: Full=Dac-K49 {ECO:0000303|PubMed:11594738};
DE Flags: Precursor;
OS Deinagkistrodon acutus (Hundred-pace snake) (Agkistrodon acutus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Deinagkistrodon.
OX NCBI_TaxID=36307;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=10084123; DOI=10.1016/s1050-3862(98)00033-3;
RA Fan C.Y., Qian Y.C., Yang S.L., Gong Y.;
RT "cDNA cloning and sequence analysis of Lys-49 phospholipase A2 from
RT Agkistrodon acutus.";
RL Genet. Anal. 15:15-18(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=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).
RN [3]
RP PROTEIN SEQUENCE OF 17-27, SUBUNIT, MASS SPECTROMETRY, CRYSTALLIZATION, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=10930841; DOI=10.1107/s0907444900005643;
RA Huang Q.-Q., Zhu X.-Y., Li N., Deng W.-H., Chen T.-B., Rao P.-F.,
RA Teng M.-K., Niu L.-W.;
RT "Characterization, crystallization and preliminary X-ray diffraction
RT analysis of acutohaemolysin, a haemolytic toxin from Agkistrodon acutus
RT venom.";
RL Acta Crystallogr. D 56:907-911(2000).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (0.85 ANGSTROMS) OF 17-138, SUBUNIT, AND DISULFIDE
RP BONDS.
RC TISSUE=Venom;
RX PubMed=12871974; DOI=10.1074/jbc.m305210200;
RA Liu Q., Huang Q.-Q., Teng M.-K., Weeks C.M., Jelsch C., Zhang R.,
RA Niu L.-W.;
RT "The crystal structure of a novel, inactive, lysine 49 PLA2 from
RT Agkistrodon acutus venom: an ultrahigh resolution, AB initio structure
RT determination.";
RL J. Biol. Chem. 278:41400-41408(2003).
CC -!- FUNCTION: Snake venom phospholipase A2 homolog that lacks enzymatic
CC activity (PubMed:10930841). Is myotoxic (By similarity). Has a strong
CC indirect hemolytic activity and anticoagulant activity
CC (PubMed:10930841). A model of myotoxic mechanism has been proposed: an
CC apo Lys49-PLA2 is activated by the entrance of a hydrophobic molecule
CC (e.g. fatty acid) at the hydrophobic channel of the protein leading to
CC a reorientation of a monomer (By similarity). This reorientation causes
CC a transition between 'inactive' to 'active' states, causing alignment
CC of C-terminal and membrane-docking sites (MDoS) side-by-side and
CC putting the membrane-disruption sites (MDiS) in the same plane, exposed
CC to solvent and in a symmetric position for both monomers (By
CC similarity). The MDoS region stabilizes the toxin on membrane by the
CC interaction of charged residues with phospholipid head groups (By
CC similarity). Subsequently, the MDiS region destabilizes the membrane
CC 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:10930841}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:10930841,
CC ECO:0000269|PubMed:12871974}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10930841}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:10930841}.
CC -!- MASS SPECTROMETRY: Mass=13938; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:10930841};
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; AJ223188; CAA11159.1; -; mRNA.
DR EMBL; AF269132; AAL36975.1; -; mRNA.
DR PDB; 1MC2; X-ray; 0.85 A; A=17-138.
DR PDB; 1MG6; X-ray; 1.60 A; A=17-138.
DR PDBsum; 1MC2; -.
DR PDBsum; 1MG6; -.
DR AlphaFoldDB; O57385; -.
DR SMR; O57385; -.
DR EvolutionaryTrace; O57385; -.
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 3D-structure; Direct protein sequencing; Disulfide bond; Myotoxin;
KW Secreted; Signal; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:10930841"
FT CHAIN 17..138
FT /note="Basic phospholipase A2 homolog acutohaemolysin"
FT /id="PRO_0000022774"
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 133
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 42..131
FT /evidence="ECO:0000269|PubMed:12871974,
FT ECO:0007744|PDB:1MC2, ECO:0007744|PDB:1MG6"
FT DISULFID 44..60
FT /evidence="ECO:0000269|PubMed:12871974,
FT ECO:0007744|PDB:1MC2, ECO:0007744|PDB:1MG6"
FT DISULFID 59..111
FT /evidence="ECO:0000269|PubMed:12871974,
FT ECO:0007744|PDB:1MC2, ECO:0007744|PDB:1MG6"
FT DISULFID 65..138
FT /evidence="ECO:0000269|PubMed:12871974,
FT ECO:0007744|PDB:1MC2, ECO:0007744|PDB:1MG6"
FT DISULFID 66..104
FT /evidence="ECO:0000269|PubMed:12871974,
FT ECO:0007744|PDB:1MC2, ECO:0007744|PDB:1MG6"
FT DISULFID 73..97
FT /evidence="ECO:0000269|PubMed:12871974,
FT ECO:0007744|PDB:1MC2, ECO:0007744|PDB:1MG6"
FT DISULFID 91..102
FT /evidence="ECO:0000269|PubMed:12871974,
FT ECO:0007744|PDB:1MC2, ECO:0007744|PDB:1MG6"
FT CONFLICT 130
FT /note="S -> L (in Ref. 2; AAL36975)"
FT /evidence="ECO:0000305"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:1MC2"
FT HELIX 33..37
FT /evidence="ECO:0007829|PDB:1MC2"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:1MC2"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:1MC2"
FT HELIX 55..67
FT /evidence="ECO:0007829|PDB:1MC2"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:1MC2"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:1MC2"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:1MC2"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:1MC2"
FT HELIX 96..114
FT /evidence="ECO:0007829|PDB:1MC2"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:1MC2"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:1MC2"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:1MC2"
SQ SEQUENCE 138 AA; 15777 MW; 1353CD8C8F54DA99 CRC64;
MRALWIVAVL LVGVEGSLFE LGKMIWQETG KNPVKNYGLY GCNCGVGGRG EPLDATDRCC
FVHKCCYKKL TDCDSKKDRY SYKWKNKAIV CGKNQPCMQE MCECDKAFAI CLRENLDTYN
KSFRYHLKPS CKKTSEQC
