ID   PV22_POMMA              Reviewed;         286 AA.
AC   P0DQP0;
DT   07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT   07-APR-2021, sequence version 1.
DT   25-MAY-2022, entry version 5.
DE   RecName: Full=Perivitellin-2 31 kDa subunit {ECO:0000303|PubMed:29506476};
DE            Short=PmPV2 31 kDa subunit {ECO:0000305};
DE            Short=PmPV2-31 {ECO:0000303|PubMed:30980073, ECO:0000303|PubMed:32446810};
DE   AltName: Full=PV2 tachylectin 'B' delivery subunit {ECO:0000303|PubMed:32446810};
DE   AltName: Full=Pma_3499_0.54 {ECO:0000303|PubMed:30980073};
DE   AltName: Full=Pore forming toxin {ECO:0000303|PubMed:32446810};
DE            Short=PFT {ECO:0000303|PubMed:32446810};
DE   Flags: Precursor;
OS   Pomacea maculata (Giant applesnail).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Architaenioglossa; Ampullarioidea; Ampullariidae; Pomacea.
OX   NCBI_TaxID=1245466;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Albumen gland;
RX   PubMed=29506476; DOI=10.1186/s12864-018-4553-9;
RA   Ip J.C.H., Mu H., Chen Q., Sun J., Ituarte S., Heras H., Van Bocxlaer B.,
RA   Ganmanee M., Huang X., Qiu J.W.;
RT   "AmpuBase: a transcriptome database for eight species of apple snails
RT   (Gastropoda: Ampullariidae).";
RL   BMC Genomics 19:179-179(2018).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=30980073; DOI=10.1093/molbev/msz084;
RA   Sun J., Mu H., Ip J.C.H., Li R., Xu T., Accorsi A., Sanchez Alvarado A.,
RA   Ross E., Lan Y., Sun Y., Castro-Vazquez A., Vega I.A., Heras H.,
RA   Ituarte S., Van Bocxlaer B., Hayes K.A., Cowie R.H., Zhao Z., Zhang Y.,
RA   Qian P.Y., Qiu J.W.;
RT   "Signatures of divergence, invasiveness, and terrestrialization revealed by
RT   four apple snail genomes.";
RL   Mol. Biol. Evol. 36:1507-1520(2019).
RN   [3]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=32231667; DOI=10.3389/fimmu.2020.00428;
RA   Giglio M.L., Ituarte S., Ibanez A.E., Dreon M.S., Prieto E.,
RA   Fernandez P.E., Heras H.;
RT   "Novel role for animal innate immune molecules: enterotoxic activity of a
RT   snail egg MACPF-toxin.";
RL   Front. Immunol. 11:428-428(2020).
RN   [4]
RP   FUNCTION, TOXIC DOSE, SUBCELLULAR LOCATION, SUBUNIT, DISULFIDE BOND, AND
RP   3D-STRUCTURE MODELING.
RX   PubMed=32446810; DOI=10.1016/j.jsb.2020.107531;
RA   Giglio M.L., Ituarte S., Milesi V., Dreon M.S., Brola T.R., Caramelo J.,
RA   Ip J.C.H., Mate S., Qiu J.W., Otero L.H., Heras H.;
RT   "Exaptation of two ancient immune proteins into a new dimeric pore-forming
RT   toxin in snails.";
RL   J. Struct. Biol. 211:107531-107531(2020).
CC   -!- FUNCTION: The egg defensive protein perivitellin-2 is a pore-forming
CC       two-subunit glycoprotein that affects both the nervous and digestive
CC       systems of mammals (PubMed:32231667, PubMed:32446810). In addition, it
CC       is a source of both structural and energetic molecules during embryonic
CC       development (By similarity). The tachylectin subunit (31 kDa) binds
CC       target membranes while the MACPF subunit (67 kDa) disrupts lipid
CC       bilayers forming large pores (inner diameter of about 5.6 nm) altering
CC       the plasma membrance conductance (PubMed:32446810). Both in vivo and in
CC       vitro, the protein shows wide pH range stability and is resistant to
CC       enzymatic proteolysis from gastrointestinal environments
CC       (PubMed:32231667). It is cytotoxic to both epithelial and immune cells
CC       from the digestive system of mammals (PubMed:32231667). It induces
CC       enterocyte death by a lytic mechanism and disrupts enterocyte
CC       monolayers in a dose-dependent manner (PubMed:32231667). After oral
CC       administration to mice, it binds enterocytes and induces large dose-
CC       dependent morphological changes on their small intestine mucosa,
CC       reducing the absorptive surface (PubMed:32231667). Additionally, it is
CC       detected in the Peyer's patches where it activates lymphoid follicles
CC       and triggers apoptosis (PubMed:32231667). The toxin can also traverse
CC       the intestinal barrier and induce oral adaptive immunity with evidence
CC       of circulating antibody response (PubMed:32231667). The toxin also
CC       shows hemagglutination properties thanks to the tachylectin subunit,
CC       but has no hemolytic activity (PubMed:32446810). In addition to
CC       enterotoxin activity, the toxin also acts as a neurotoxin, since an
CC       intraperitoneal injection can induce paralysis of the mice rear limbs,
CC       followed by death (PubMed:32446810). {ECO:0000250|UniProtKB:P0C8G6,
CC       ECO:0000269|PubMed:32231667, ECO:0000269|PubMed:32446810}.
CC   -!- SUBUNIT: Perivitellin-2 is a dimer of heterodimers held together head-
CC       to-tail by non-covalent forces. The heterodimer is composed of the
CC       tachylectin subunit (31 kDa) and the MACPF subunit (67 kDa) that are
CC       disulfide-linked. {ECO:0000269|PubMed:32446810}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Target cell membrane
CC       {ECO:0000269|PubMed:32231667, ECO:0000269|PubMed:32446810}.
CC   -!- TISSUE SPECIFICITY: Produced by albumen secretory cells. Found in
CC       developing eggs. {ECO:0000305|PubMed:29506476}.
CC   -!- PTM: PV2 is a very high density lipoprotein (VHDL). It contains 3.75%
CC       of lipids. The major lipid classes are free sterols and phospholipids
CC       and also have significant quantities of energy-providing
CC       triacylglycerides and free fatty acids. {ECO:0000250|UniProtKB:P0C8G7}.
CC   -!- TOXIC DOSE: LD(50) is 250 ug/kg by intraperitoneal injection into mice.
CC       {ECO:0000269|PubMed:32446810}.
CC   -!- SIMILARITY: Belongs to the tectonin family. {ECO:0000305}.
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DR   AlphaFoldDB; P0DQP0; -.
DR   SMR; P0DQP0; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR   GO; GO:0045735; F:nutrient reservoir activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR006624; Beta-propeller_rpt_TECPR.
DR   Pfam; PF19193; Tectonin; 2.
DR   SMART; SM00706; TECPR; 3.
PE   1: Evidence at protein level;
KW   Disulfide bond; Enterotoxin; Glycoprotein; Hemagglutinin; Lectin;
KW   Lipoprotein; Membrane; Neurotoxin; Secreted; Signal; Storage protein;
KW   Target cell membrane; Target membrane; Toxin.
FT   SIGNAL          1..30
FT                   /evidence="ECO:0000255"
FT   CHAIN           31..286
FT                   /note="Perivitellin-2 31 kDa subunit"
FT                   /evidence="ECO:0000305|PubMed:29506476,
FT                   ECO:0000305|PubMed:30980073"
FT                   /id="PRO_0000452120"
FT   CARBOHYD        101
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        161
FT                   /note="Interchain"
FT                   /evidence="ECO:0000269|PubMed:32446810"
SQ   SEQUENCE   286 AA;  31562 MW;  A276EC0049810F2C CRC64;
     MVKKIHFVME RHASIVAFLL AVLALTESQA FTSVKLPRDE HWPYNYVSVG PAGVWAVNRQ
     NKLFYRTGTY GDNANMGSGW QFKQDGVGQV DVGKDKVGYI NLSGGSLFRI EGISQANPVG
     GTPKSWEWWT KYIGMSLRED TRFSSRIENQ NKVLTFTFRT CFWASRITNW CFADSSYTET
     VTAGGSGTWI TKSQLKYKSG TFGNPDTEGG DWILVDSGSF QHVSSGSGVV LAVRSNGELV
     QRTGITCSLP QGTGWTSMLN SMSRVDTYGT VAWAVDTAGD LYFINL