PV21_POMMA
ID PV21_POMMA Reviewed; 565 AA.
AC P0DQO9;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 07-APR-2021, sequence version 1.
DT 25-MAY-2022, entry version 4.
DE RecName: Full=Perivitellin-2 67 kDa subunit {ECO:0000303|PubMed:29506476};
DE Short=PmPV2 67 kDa subunit {ECO:0000305};
DE Short=PmPV2-67 {ECO:0000303|PubMed:30980073, ECO:0000303|PubMed:32446810};
DE AltName: Full=PV2 MACPF 'A' toxic subunit {ECO:0000303|PubMed:32446810};
DE AltName: Full=Pma_3499_0.31 {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:P0C8G6}.
CC -!- TOXIC DOSE: LD(50) is 250 ug/kg by intraperitoneal injection into mice.
CC {ECO:0000269|PubMed:32446810}.
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DR AlphaFoldDB; P0DQO9; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; 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; IPR020864; MACPF.
DR InterPro; IPR020863; MACPF_CS.
DR Pfam; PF01823; MACPF; 1.
DR SMART; SM00457; MACPF; 1.
DR PROSITE; PS00279; MACPF_1; 1.
DR PROSITE; PS51412; MACPF_2; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Enterotoxin; Hemagglutinin; Lipoprotein; Membrane;
KW Neurotoxin; Secreted; Signal; Storage protein; Target cell membrane;
KW Target membrane; Toxin.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..565
FT /note="Perivitellin-2 67 kDa subunit"
FT /evidence="ECO:0000305|PubMed:29506476,
FT ECO:0000305|PubMed:30980073"
FT /id="PRO_0000452119"
FT DOMAIN 27..340
FT /note="MACPF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00745"
FT REGION 387..565
FT /note="Invertebrate MACPF Accessory Domain (IMAD)"
FT /evidence="ECO:0000305|PubMed:32446810"
FT DISULFID 398
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:32446810"
SQ SEQUENCE 565 AA; 62355 MW; D294FECC2EBD24A6 CRC64;
MSQLRWWVVS QVLLLIAICS LDHSEGARVC PKIVPGLDKL RVGVDITKLD LLPLFDLGDN
GFRSAVADYT CDRGQTAVVD GESFDVPDQV DSVVIESSGQ QTSSVTTIKS ESQISQALSI
SAGISVETAK AGFSSSASYA EMQEAITKYG RTVSQMSAVY TTCSANLSPN LLLGQNPLQT
LSRLPSDFTA DTQGYYDFIK TYGTHYFNKG KLGGMFLFTS ETDMSYFQNK NSQQIEATVK
ATFASILSTE TGGSSDESKE VIEFKESSLI TSKFFGGQTN LAADGLTKWQ PTIAKLPYFM
SGTLSTISSL IADTTKRASM ELAVKNYLLK AKVANLDRLT YIRLNSWSVG HNELRDLSAQ
LQNLKTKTIF SDADEKLLQS IEDQVSVPAW FSDRTTFCFR STAVGSADQC NGQSTNTLCA
EPNRYTQQYM DKTYLGDTGC RLVWKISTTE STDWFKSVKV NFRWYPTWSP CACGPVGTPF
TISAPANSWT QDYLDVTNPK FGECMLQWMI EVPPTATLWA KNLEFCIDFT CGKKKQCVDA
NQWTEPYLDI SAHEACGMSW ALIAK
