PA2B1_AGKPI
ID PA2B1_AGKPI Reviewed; 123 AA.
AC P51972;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Basic phospholipase A2 APP-D49;
DE Short=svPLA2;
DE EC=3.1.1.4 {ECO:0000269|PubMed:28633930, ECO:0000269|PubMed:9013608};
DE AltName: Full=App-dimer;
DE AltName: Full=AppP3 {ECO:0000303|PubMed:28633930};
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase;
OS Agkistrodon piscivorus piscivorus (Eastern cottonmouth).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Agkistrodon.
OX NCBI_TaxID=8716;
RN [1]
RP PROTEIN SEQUENCE, SUBCELLULAR LOCATION, AND SUBUNIT.
RC TISSUE=Venom {ECO:0000303|PubMed:8489705};
RX PubMed=8489705; DOI=10.1007/bf01026040;
RA Welches W., Reardon I.M., Heinrikson R.L.;
RT "An examination of structural interactions presumed to be of importance in
RT the stabilization of phospholipase A2 dimers based upon comparative protein
RT sequence analysis of a monomeric and dimeric enzyme from the venom of
RT Agkistrodon p. piscivorus.";
RL J. Protein Chem. 12:187-193(1993).
RN [2] {ECO:0000305}
RP PROTEIN SEQUENCE, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MASS
RP SPECTROMETRY, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom {ECO:0000303|PubMed:28633930};
RX PubMed=28633930; DOI=10.1016/j.toxicon.2017.06.010;
RA Jia Y., Ermolinsky B., Garza A., Provenzano D.;
RT "Phospholipase A2 in the venom of three cottonmouth snakes.";
RL Toxicon 135:84-92(2017).
RN [3]
RP PROTEIN SEQUENCE OF 1-23, SUBUNIT, SUBCELLULAR LOCATION, AND PALMITOYLATION
RP AT LYS-7 AND LYS-10.
RC TISSUE=Venom;
RX PubMed=3403524; DOI=10.1016/s0021-9258(18)37947-x;
RA Cho W., Tomasselli A.G., Heinrikson R.L., Kezdy F.J.;
RT "The chemical basis for interfacial activation of monomeric phospholipases
RT A2. Autocatalytic derivatization of the enzyme by acyl transfer from
RT substrate.";
RL J. Biol. Chem. 263:11237-11241(1988).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=6438084; DOI=10.1016/s0021-9258(18)89822-2;
RA Maraganore J.M., Merutka G., Cho W., Welches W., Kezdy F.J.,
RA Heinrikson R.L.;
RT "A new class of phospholipases A2 with lysine in place of aspartate 49.
RT Functional consequences for calcium and substrate binding.";
RL J. Biol. Chem. 259:13839-13843(1984).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, DISULFIDE BONDS, AND MUTAGENESIS OF GLU-6; LYS-7; LYS-10; LYS-11;
RP LYS-15; LYS-53 AND LYS-60.
RC TISSUE=Venom {ECO:0000303|PubMed:9013608};
RX PubMed=9013608; DOI=10.1074/jbc.272.6.3573;
RA Han S.K., Yoon E.T., Scott D.L., Sigler P.B., Cho W.;
RT "Structural aspects of interfacial adsorption. A crystallographic and site-
RT directed mutagenesis study of the phospholipase A2 from the venom of
RT Agkistrodon piscivorus piscivorus.";
RL J. Biol. Chem. 272:3573-3582(1997).
CC -!- FUNCTION: PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl
CC groups in 3-sn-phosphoglycerides. {ECO:0000269|PubMed:28633930,
CC ECO:0000269|PubMed:6438084}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-
CC glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:15801,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=3.1.1.4;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10035, ECO:0000255|PROSITE-
CC ProRule:PRU10036, ECO:0000269|PubMed:28633930,
CC ECO:0000269|PubMed:9013608};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P14418};
CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000250|UniProtKB:P14418};
CC -!- SUBUNIT: Monomer or homodimer. {ECO:0000269|PubMed:3403524,
CC ECO:0000269|PubMed:8489705}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28633930,
CC ECO:0000269|PubMed:3403524, ECO:0000269|PubMed:6438084,
CC ECO:0000269|PubMed:8489705, ECO:0000269|PubMed:9013608}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:28633930}.
CC -!- PTM: Acylation causes dimerization. {ECO:0000269|PubMed:3403524}.
CC -!- MASS SPECTROMETRY: Mass=13988.67; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:28633930};
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
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DR PIR; B53872; B53872.
DR PDB; 1VAP; X-ray; 1.60 A; A/B=1-123.
DR PDBsum; 1VAP; -.
DR AlphaFoldDB; P51972; -.
DR BMRB; P51972; -.
DR SMR; P51972; -.
DR EvolutionaryTrace; P51972; -.
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:UniProtKB-EC.
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 3D-structure; Calcium; Direct protein sequencing; Disulfide bond;
KW Hydrolase; Lipid degradation; Lipid metabolism; Lipoprotein; Metal-binding;
KW Palmitate; Secreted.
FT CHAIN 1..123
FT /note="Basic phospholipase A2 APP-D49"
FT /evidence="ECO:0000269|PubMed:28633930,
FT ECO:0000269|PubMed:8489705"
FT /id="PRO_0000161605"
FT ACT_SITE 47
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10035"
FT ACT_SITE 89
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10036"
FT BINDING 27
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P14418"
FT BINDING 29
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P14418"
FT BINDING 31
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P14418"
FT BINDING 48
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P14418"
FT LIPID 7
FT /note="N6-palmitoyl lysine"
FT /evidence="ECO:0000269|PubMed:3403524"
FT LIPID 10
FT /note="N6-palmitoyl lysine"
FT /evidence="ECO:0000269|PubMed:3403524"
FT DISULFID 26..116
FT /evidence="ECO:0000269|PubMed:9013608,
FT ECO:0007744|PDB:1VAP"
FT DISULFID 28..44
FT /evidence="ECO:0000269|PubMed:9013608,
FT ECO:0007744|PDB:1VAP"
FT DISULFID 43..95
FT /evidence="ECO:0000269|PubMed:9013608,
FT ECO:0007744|PDB:1VAP"
FT DISULFID 49..123
FT /evidence="ECO:0000269|PubMed:9013608,
FT ECO:0007744|PDB:1VAP"
FT DISULFID 50..88
FT /evidence="ECO:0000269|PubMed:9013608,
FT ECO:0007744|PDB:1VAP"
FT DISULFID 57..81
FT /evidence="ECO:0000269|PubMed:9013608,
FT ECO:0007744|PDB:1VAP"
FT DISULFID 75..86
FT /evidence="ECO:0000269|PubMed:9013608,
FT ECO:0007744|PDB:1VAP"
FT MUTAGEN 6
FT /note="E->R: 75% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:9013608"
FT MUTAGEN 7
FT /note="K->E: 95% decrease in catalytic efficiency. 500-fold
FT decrease in catalytic efficiency; when associated with E-
FT 10."
FT /evidence="ECO:0000269|PubMed:9013608"
FT MUTAGEN 10
FT /note="K->E: 95% decrease in catalytic efficiency. 500-fold
FT decrease in catalytic efficiency; when associated with E-
FT 7."
FT /evidence="ECO:0000269|PubMed:9013608"
FT MUTAGEN 11
FT /note="K->E: 75% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:9013608"
FT MUTAGEN 15
FT /note="K->E: 60% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:9013608"
FT MUTAGEN 53
FT /note="K->E: No effect on catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:9013608"
FT MUTAGEN 60
FT /note="K->E: No effect on catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:9013608"
FT HELIX 2..13
FT /evidence="ECO:0007829|PDB:1VAP"
FT HELIX 17..20
FT /evidence="ECO:0007829|PDB:1VAP"
FT STRAND 21..24
FT /evidence="ECO:0007829|PDB:1VAP"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:1VAP"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:1VAP"
FT HELIX 39..52
FT /evidence="ECO:0007829|PDB:1VAP"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:1VAP"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:1VAP"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:1VAP"
FT HELIX 80..98
FT /evidence="ECO:0007829|PDB:1VAP"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:1VAP"
FT HELIX 105..108
FT /evidence="ECO:0007829|PDB:1VAP"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:1VAP"
SQ SEQUENCE 123 AA; 13989 MW; C39986552D990D72 CRC64;
NLFQFEKLIK KMTGKSGMLW YSAYGCYCGW GGQGRPKDAT DRCCFVHDCC YGKVTGCNPK
MDIYTYSVDN GNIVCGGTNP CKKQICECDR AAAICFRDNL KTYDSKTYWK YPKKNCKEES
EPC
