ID PA2HB_AGKPL Reviewed; 137 AA. AC C0HKC2; DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot. DT 25-OCT-2017, sequence version 1. DT 26-FEB-2020, entry version 6. DE RecName: Full=Basic phospholipase A2 homolog APL-K49 {ECO:0000303|PubMed:28633930}; DE Short=svPLA2 homolog {ECO:0000250|UniProtKB:P04361}; DE AltName: Full=AplP2 {ECO:0000303|PubMed:28633930}; DE Flags: Precursor; OS Agkistrodon piscivorus leucostoma (Western cottonmouth) (Acontias OS leucostoma). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; OC Serpentes; Colubroidea; Viperidae; Crotalinae; Agkistrodon. OX NCBI_TaxID=459671; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Venom gland; RX PubMed=18502463; DOI=10.1016/j.toxicon.2008.03.028; RA Jia Y., Cantu B.A., Sanchez E.E., Perez J.C.; RT "Complementary DNA sequencing and identification of mRNAs from the venomous RT gland of Agkistrodon piscivorus leucostoma."; RL Toxicon 51:1457-1466(2008). RN [2] RP PROTEIN SEQUENCE OF 17-32, FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION. RC TISSUE=Venom; 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). CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that lacks enzymatic CC activity. Is myotoxic and displays edema-inducing activities (By CC similarity). A model of myotoxic mechanism has been proposed: an apo CC Lys49-PLA2 is activated by the entrance of a hydrophobic molecule (e.g. CC fatty acid) at the hydrophobic channel of the protein leading to a CC reorientation of a monomer (By similarity). This reorientation causes a CC transition between 'inactive' to 'active' states, causing alignment of CC C-terminal and membrane-docking sites (MDoS) side-by-side and putting CC the membrane-disruption sites (MDiS) in the same plane, exposed to CC solvent and in a symmetric position for both monomers (By similarity). CC The MDoS region stabilizes the toxin on membrane by the interaction of CC charged residues with phospholipid head groups (By similarity). CC Subsequently, the MDiS region destabilizes the membrane with CC penetration of hydrophobic residues (By similarity). This insertion CC causes a disorganization of the membrane, allowing an uncontrolled CC influx of ions (i.e. calcium and sodium), and eventually triggering CC irreversible intracellular alterations and cell death (By similarity). CC {ECO:0000250|UniProtKB:I6L8L6, ECO:0000269|PubMed:28633930}. CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:28633930}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28633930}. CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. CC {ECO:0000305|PubMed:18502463}. 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 ligands 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; EV854871; -; NOT_ANNOTATED_CDS; mRNA. DR SMR; C0HKC2; -. 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: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 Direct protein sequencing; Disulfide bond; Myotoxin; Secreted; Signal; KW Toxin. FT SIGNAL 1..16 FT /evidence="ECO:0000269|PubMed:28633930" FT CHAIN 17..137 FT /note="Basic phospholipase A2 homolog APL-K49" FT /evidence="ECO:0000305|PubMed:28633930" FT /id="PRO_0000442173" 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:0000250|UniProtKB:Q90249" FT DISULFID 44..60 FT /evidence="ECO:0000250|UniProtKB:Q90249" FT DISULFID 59..111 FT /evidence="ECO:0000250|UniProtKB:Q90249" FT DISULFID 65..137 FT /evidence="ECO:0000250|UniProtKB:Q90249" FT DISULFID 66..104 FT /evidence="ECO:0000250|UniProtKB:Q90249" FT DISULFID 73..97 FT /evidence="ECO:0000250|UniProtKB:Q90249" FT DISULFID 91..102 FT /evidence="ECO:0000250|UniProtKB:Q90249" SQ SEQUENCE 137 AA; 15713 MW; 3D8FC7C0E4B5AA8D CRC64; MRTLWIVALL LVGVEGSVLE LGKMILQETG KNAITSYGSY GCNCGWGHRG QPKDATDRCC FVHKCCYKKL TDCNHKTDRY SYSWKNKAII CEEKNPCLKE MCECDKAVAI CLRENLDTYN KKYKAYFKLK CKKPDTC //