NA245_NEMVE
ID NA245_NEMVE Reviewed; 85 AA.
AC B1NWR7; A7SCE0;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2008, sequence version 1.
DT 25-MAY-2022, entry version 46.
DE RecName: Full=N.vectensis toxin 1 8 {ECO:0000303|PubMed:18538344};
DE Short=Nv1 {ECO:0000303|PubMed:18538344};
DE AltName: Full=Neurotoxin 1-3 {ECO:0000312|EMBL:ABW97333.1};
DE AltName: Full=Neurotoxin 1-6 {ECO:0000312|EMBL:ABW97336.1};
DE AltName: Full=Neurotoxin Nv1-116.45.1 {ECO:0000303|PubMed:18222944};
DE Flags: Precursor;
GN ORFNames=v1g113209;
OS Nematostella vectensis (Starlet sea anemone).
OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC Edwardsiidae; Nematostella.
OX NCBI_TaxID=45351;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Crane Marsh, Neponset River Marsh, Rhode River, and
RC Sippewissett Marsh;
RX PubMed=18222944; DOI=10.1093/molbev/msn021;
RA Moran Y., Weinberger H., Sullivan J.C., Reitzel A.M., Finnerty J.R.,
RA Gurevitz M.;
RT "Concerted evolution of sea anemone neurotoxin genes is revealed through
RT analysis of the Nematostella vectensis genome.";
RL Mol. Biol. Evol. 25:737-747(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CH2 X CH6;
RX PubMed=17615350; DOI=10.1126/science.1139158;
RA Putnam N.H., Srivastava M., Hellsten U., Dirks B., Chapman J., Salamov A.,
RA Terry A., Shapiro H., Lindquist E., Kapitonov V.V., Jurka J.,
RA Genikhovich G., Grigoriev I.V., Lucas S.M., Steele R.E., Finnerty J.R.,
RA Technau U., Martindale M.Q., Rokhsar D.S.;
RT "Sea anemone genome reveals ancestral eumetazoan gene repertoire and
RT genomic organization.";
RL Science 317:86-94(2007).
RN [3]
RP FUNCTION, ALTERNATIVE SPLICING, DEVELOPMENTAL STAGE, AND TOXIC DOSE.
RC STRAIN=Sippewissett Marsh;
RX PubMed=18538344; DOI=10.1016/j.jmb.2008.05.011;
RA Moran Y., Weinberger H., Reitzel A.M., Sullivan J.C., Kahn R., Gordon D.,
RA Finnerty J.R., Gurevitz M.;
RT "Intron retention as a posttranscriptional regulatory mechanism of
RT neurotoxin expression at early life stages of the starlet anemone
RT Nematostella vectensis.";
RL J. Mol. Biol. 380:437-443(2008).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=22048953; DOI=10.1098/rspb.2011.1731;
RA Moran Y., Genikhovich G., Gordon D., Wienkoop S., Zenkert C., Ozbek S.,
RA Technau U., Gurevitz M.;
RT "Neurotoxin localization to ectodermal gland cells uncovers an alternative
RT mechanism of venom delivery in sea anemones.";
RL Proc. R. Soc. B 279:1351-1358(2012).
RN [5]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=29424690; DOI=10.7554/elife.35014;
RA Columbus-Shenkar Y.Y., Sachkova M.Y., Macrander J., Fridrich A.,
RA Modepalli V., Reitzel A.M., Sunagar K., Moran Y.;
RT "Dynamics of venom composition across a complex life cycle.";
RL Elife 7:0-0(2018).
RN [6]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, AND DEVELOPMENTAL STAGE.
RX PubMed=31134275; DOI=10.1093/molbev/msz132;
RA Sachkova M.Y., Singer S.A., Macrander J., Reitzel A.M., Peigneur S.,
RA Tytgat J., Moran Y.;
RT "The birth and death of toxins with distinct functions: a case study in the
RT sea anemone Nematostella.";
RL Mol. Biol. Evol. 36:2001-2012(2019).
CC -!- FUNCTION: Binds to site 3 of voltage-gated sodium channels and inhibits
CC the inactivation process (PubMed:18538344). Is highly active on
CC DmNav1/TipE (drosophila) and is only extremely weakly active on rat
CC Nav1.4-beta-1/SCN4A-SCN1B, and on human Nav1.5-beta-1/SCN5A-beta-1
CC (PubMed:18538344). This reveals high specificity for arthropod over
CC mammalian channels (PubMed:18538344). In vivo, when released into the
CC medium, this recombinant toxin induces impaired swimming, paralysis and
CC death of the crustacean A.nauplii within several hours
CC (PubMed:22048953). Also causes paralysis of cherry shrimps immediately
CC after injection at very low doses (PubMed:29424690). Its effect on
CC zebrafish (D.rerio) larvae is also rapid, since it induces tail
CC twitching accompanied by impaired swimming after 20 minutes and
CC complete paralysis within 45 minutes (PubMed:22048953). It has also
CC been observed to cause death of zebrafish larvae within 1 hour
CC (PubMed:31134275). {ECO:0000269|PubMed:18538344,
CC ECO:0000269|PubMed:22048953, ECO:0000269|PubMed:29424690,
CC ECO:0000269|PubMed:31134275}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18538344}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Intron retention discovered for all transcripts, no
CC experimental confirmation available for this specific sequence.;
CC Name=1;
CC IsoId=B1NWR7-1; Sequence=Displayed;
CC Name=2; Synonyms=truncated;
CC IsoId=B1NWR7-2; Sequence=VSP_039752;
CC -!- TISSUE SPECIFICITY: Expressed in ectodermal glands and in clumps
CC outside of the extodermal layer (PubMed:22048953). Is not expressed in
CC nematocytes (PubMed:22048953). In adult female tissues, shows similar
CC expression levels in mesenteries (gametes-producing tissue), tentacles,
CC pharynx and physa (PubMed:29424690). {ECO:0000269|PubMed:22048953,
CC ECO:0000269|PubMed:29424690}.
CC -!- DEVELOPMENTAL STAGE: Is detected in unfertilized eggs (at protein
CC level) (PubMed:29424690, PubMed:31134275). Is also detected in late
CC planulae, primary polyps and adults (both females and males) (at
CC protein level) (PubMed:22048953, PubMed:29424690). Nv1 is transcribed
CC throughout the complete life cycle and is found at multiple
CC developmental stages including unfertilized eggs, blastulae, gastrulae,
CC early planulae, planulae, metamorphosing planulae, primary polyps,
CC juvenile polyps (2 and 4 months old), adult males, and adult females,
CC with highest levels in juvenile polyps and adults (PubMed:18538344,
CC PubMed:29424690). Importantly, Nv1 transcripts are not spliced in the
CC embryo and planula due to intron retention and therefore Nv1 can be
CC considered purely an adult toxin (PubMed:18538344).
CC {ECO:0000269|PubMed:18538344, ECO:0000269|PubMed:22048953,
CC ECO:0000269|PubMed:29424690, ECO:0000269|PubMed:31134275}.
CC -!- TOXIC DOSE: PD(50) is 76 nmol/kg into blowfly larvae.
CC {ECO:0000269|PubMed:18538344}.
CC -!- MISCELLANEOUS: Nv1 toxin seems to be encoded by 8 different genes. 4 of
CC them code for identical precursors, whereas 4 others code for very
CC similar precursors. In the genome draft, 6 additional loci are also
CC correlated to Nv1 toxin, but they are not predicted to be functional
CC genes. This high similarity may be explained by concerted evolution.
CC -!- MISCELLANEOUS: The primary structure of the mature peptide is identical
CC in 9 entries (AC B1NWS4, AC B1NWS1, AC B1NWR6, AC P0CH90, AC P0CH46, AC
CC B1NWS8, AC A7SCE5, AC B1NWR7 and AC P0CH45). Additional information can
CC be found in entry AC B1NWS4. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 2]: Due to an intron retention observed only in
CC early life stages (embryo and planula). {ECO:0000305}.
CC -!- MISCELLANEOUS: Has no activity on the rat brain channel Nav1.2a-beta-
CC 1/SCN2A-SCN1B. {ECO:0000269|PubMed:18538344}.
CC -!- SIMILARITY: Belongs to the sea anemone sodium channel inhibitory toxin
CC family. Type II subfamily. {ECO:0000305}.
CC -!- CAUTION: This toxin precursor is identical to three other precursors
CC (AC B1NWR6, AC B1NWS4 and AC P0CH46). AC B1NWR6 shows 8 variants that
CC could also be associated with this gene. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EDO38676.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; EU124454; ABW97333.1; -; Genomic_DNA.
DR EMBL; EU124457; ABW97336.1; -; Genomic_DNA.
DR EMBL; DS469622; EDO38676.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_001630733.1; XM_001630683.1.
DR RefSeq; XP_001630735.1; XM_001630685.1.
DR RefSeq; XP_001630737.1; XM_001630687.1.
DR RefSeq; XP_001630739.1; XM_001630689.1.
DR AlphaFoldDB; B1NWR7; -.
DR SMR; B1NWR7; -.
DR HOGENOM; CLU_2944416_0_0_1; -.
DR PhylomeDB; B1NWR7; -.
DR Proteomes; UP000001593; Unassembled WGS sequence.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 2.20.20.10; -; 1.
DR InterPro; IPR023355; Myo_ane_neurotoxin_sf.
PE 1: Evidence at protein level;
KW Alternative splicing; Cleavage on pair of basic residues; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Reference proteome; Secreted;
KW Signal; Toxin; Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..36
FT /evidence="ECO:0000305"
FT /id="PRO_0000398320"
FT CHAIN 39..85
FT /note="N.vectensis toxin 1 8"
FT /evidence="ECO:0000305|PubMed:18538344"
FT /id="PRO_5000319661"
FT DISULFID 42..82
FT /evidence="ECO:0000250|UniProtKB:P19651"
FT DISULFID 44..72
FT /evidence="ECO:0000250|UniProtKB:P19651"
FT DISULFID 65..83
FT /evidence="ECO:0000250|UniProtKB:P19651"
FT VAR_SEQ 23..85
FT /note="RDMMSDDELDFHLSKRGIPCACDSDGPDIRSASLSGIVWMGSCPSGWKKCKS
FT YYSIVADCCNQ -> K (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_039752"
SQ SEQUENCE 85 AA; 9268 MW; 26673B8F76FA1099 CRC64;
MASFKIVIVC LALLVAVACA RRRDMMSDDE LDFHLSKRGI PCACDSDGPD IRSASLSGIV
WMGSCPSGWK KCKSYYSIVA DCCNQ
