PA2H1_AGKCL
ID PA2H1_AGKCL Reviewed; 137 AA.
AC P49121;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 25-MAY-2022, entry version 106.
DE RecName: Full=Basic phospholipase A2 homolog MT1 {ECO:0000305|PubMed:8579368};
DE Short=svPLA2 homolog;
DE AltName: Full=ACL myotoxin {ECO:0000303|PubMed:8579368, ECO:0000303|PubMed:9920492};
DE Flags: Precursor;
OS Agkistrodon contortrix laticinctus (Broad-banded copperhead) (Agkistrodon
OS mokasen laticinctus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Agkistrodon.
OX NCBI_TaxID=37195;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 17-36, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=8579368; DOI=10.1006/abbi.1996.0042;
RA de Araujo H.S.S., White S.P., Ownby C.L.;
RT "cDNA cloning and sequence analysis of a lysine-49 phospholipase A2
RT myotoxin from Agkistrodon contortrix laticinctus snake venom.";
RL Arch. Biochem. Biophys. 326:21-30(1996).
RN [2]
RP FUNCTION, SUBUNIT, AND ACTIVITY REGULATION.
RC TISSUE=Venom;
RX PubMed=9920492; DOI=10.1016/s0041-0101(98)00183-4;
RA Melo P.A., Ownby C.L.;
RT "Ability of wedelolactone, heparin, and para-bromophenacyl bromide to
RT antagonize the myotoxic effects of two crotaline venoms and their PLA2
RT myotoxins.";
RL Toxicon 37:199-215(1999).
RN [3] {ECO:0000312|PDB:1S8G, ECO:0000312|PDB:1S8H, ECO:0000312|PDB:1S8I}
RP X-RAY CRYSTALLOGRAPHY (1.61 ANGSTROMS) OF 17-137 IN COMPLEX WITH FATTY
RP ACID, AND DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=15596433; DOI=10.1074/jbc.m410588200;
RA Ambrosio A.L.B., Nonato M.C., de Araujo H.S.S., Arni R., Ward R.J.,
RA Ownby C.L., de Souza D.H.F., Garratt R.C.;
RT "A molecular mechanism for Lys49-phospholipase A2 activity based on ligand-
RT induced conformational change.";
RL J. Biol. Chem. 280:7326-7335(2005).
CC -!- FUNCTION: Snake venom phospholipase A2 homolog that lacks enzymatic
CC activity. Has myotoxic activities (PubMed:9920492). A model of myotoxic
CC mechanism has been proposed: an apo Lys49-PLA2 is activated by the
CC entrance of a hydrophobic molecule (e.g. fatty acid) at the hydrophobic
CC channel of the protein leading to a reorientation of a monomer (By
CC similarity). This reorientation causes a transition between 'inactive'
CC to 'active' states, causing alignment of C-terminal and membrane-
CC docking sites (MDoS) side-by-side and putting the membrane-disruption
CC sites (MDiS) in the same plane, exposed to solvent and in a symmetric
CC position for both monomers (By similarity). The MDoS region stabilizes
CC the toxin on membrane by the interaction of charged residues with
CC phospholipid head groups (By similarity). Subsequently, the MDiS region
CC destabilizes the membrane with penetration of hydrophobic residues (By
CC similarity). This insertion causes a disorganization of the membrane,
CC allowing an uncontrolled influx of ions (i.e. calcium and sodium), and
CC eventually triggering irreversible intracellular alterations and cell
CC death (By similarity). {ECO:0000250|UniProtKB:I6L8L6,
CC ECO:0000269|PubMed:9920492}.
CC -!- ACTIVITY REGULATION: Heparin and wedelolactone inhibit the myotoxic
CC activity (PubMed:9920492). The PLA2 inhibitor, para-bromophenacyl
CC bromide (BPB), inhibits the myotoxic activity (PubMed:9920492).
CC {ECO:0000269|PubMed:9920492}.
CC -!- SUBUNIT: Binds to heparin (PubMed:9920492).
CC {ECO:0000269|PubMed:9920492}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8579368}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:8579368}.
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; U21335; AAC59887.1; -; mRNA.
DR PIR; S68429; S68429.
DR PDB; 1S8G; X-ray; 2.30 A; A=17-137.
DR PDB; 1S8H; X-ray; 1.80 A; A=17-137.
DR PDB; 1S8I; X-ray; 1.61 A; A=17-137.
DR PDBsum; 1S8G; -.
DR PDBsum; 1S8H; -.
DR PDBsum; 1S8I; -.
DR AlphaFoldDB; P49121; -.
DR SMR; P49121; -.
DR EvolutionaryTrace; P49121; -.
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: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; Heparin-binding;
KW Myotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:8579368"
FT CHAIN 17..137
FT /note="Basic phospholipase A2 homolog MT1"
FT /id="PRO_0000022775"
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 DISULFID 42..131
FT /evidence="ECO:0000269|PubMed:15596433,
FT ECO:0007744|PDB:1S8G, ECO:0007744|PDB:1S8H,
FT ECO:0007744|PDB:1S8I"
FT DISULFID 44..60
FT /evidence="ECO:0000269|PubMed:15596433,
FT ECO:0007744|PDB:1S8G, ECO:0007744|PDB:1S8H,
FT ECO:0007744|PDB:1S8I"
FT DISULFID 59..111
FT /evidence="ECO:0000269|PubMed:15596433,
FT ECO:0007744|PDB:1S8G, ECO:0007744|PDB:1S8H,
FT ECO:0007744|PDB:1S8I"
FT DISULFID 65..137
FT /evidence="ECO:0000269|PubMed:15596433,
FT ECO:0007744|PDB:1S8G, ECO:0007744|PDB:1S8H,
FT ECO:0007744|PDB:1S8I"
FT DISULFID 66..104
FT /evidence="ECO:0000269|PubMed:15596433,
FT ECO:0007744|PDB:1S8G, ECO:0007744|PDB:1S8H,
FT ECO:0007744|PDB:1S8I"
FT DISULFID 73..97
FT /evidence="ECO:0000269|PubMed:15596433,
FT ECO:0007744|PDB:1S8G, ECO:0007744|PDB:1S8H,
FT ECO:0007744|PDB:1S8I"
FT DISULFID 91..102
FT /evidence="ECO:0000269|PubMed:15596433,
FT ECO:0007744|PDB:1S8G, ECO:0007744|PDB:1S8H,
FT ECO:0007744|PDB:1S8I"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:1S8I"
FT HELIX 33..37
FT /evidence="ECO:0007829|PDB:1S8I"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:1S8I"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:1S8I"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:1S8G"
FT HELIX 55..68
FT /evidence="ECO:0007829|PDB:1S8I"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:1S8I"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:1S8I"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:1S8I"
FT HELIX 96..114
FT /evidence="ECO:0007829|PDB:1S8I"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:1S8I"
FT HELIX 121..124
FT /evidence="ECO:0007829|PDB:1S8I"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:1S8I"
SQ SEQUENCE 137 AA; 15775 MW; 8537C670E4AFAA86 CRC64;
MRTLWIVALL LVGVEGSLLE LGKMILQETG KNAITSYGSY GCNCGWGHRG QPKDATDRCC
FVHKCCYKKL TDCNHKTDRY SYSWKNKAII CEEKNPCLKE MCECDKAVAI CLRENLDTYN
KKYKAYFKFK CKKPETC
