LITD_LATTR
ID LITD_LATTR Reviewed; 1214 AA.
AC Q25338;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 102.
DE RecName: Full=Delta-latroinsectotoxin-Lt1a {ECO:0000305};
DE Short=Delta-LIT-Lt1a {ECO:0000305};
DE AltName: Full=Delta-latroinsectotoxin {ECO:0000303|PubMed:34845192};
DE Short=Delta-LIT {ECO:0000303|PubMed:34845192};
DE Flags: Precursor;
OS Latrodectus tredecimguttatus (Mediterranean black widow spider)
OS (Latrodectus mactans tredecimguttatus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Entelegynae; Araneoidea; Theridiidae; Latrodectus.
OX NCBI_TaxID=6925;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 29-52; 409-420; 481-487;
RP 589-596; 598-617; 771-784; 880-886 AND 891-906, MASS SPECTROMETRY,
RP SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING OF C-TERMINAL, FUNCTION, AND
RP RECOMBINANT EXPRESSION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=8631785; DOI=10.1074/jbc.271.13.7535;
RA Dulubova I.E., Krasnoperov V.G., Khvotchev M.V., Pluzhnikov K.A.,
RA Volkova T.M., Grishin E.V., Vais H., Bell D.R., Usherwood P.N.R.;
RT "Cloning and structure of delta-latroinsectotoxin, a novel insect-specific
RT member of the latrotoxin family: functional expression requires C-terminal
RT truncation.";
RL J. Biol. Chem. 271:7535-7543(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=8651958;
RA Dulubova I.E., Khvoshchev M.V., Krasnoperov V.G., Galkina T.G.,
RA Pluzhnikov K.A., Volkova T.M., Grishin E.V.;
RT "Primary structure of delta-latroinsectotoxin from venom of the Latrodectus
RT mactans tredecimguttatus spider.";
RL Bioorg. Khim. 22:68-73(1996).
RN [3]
RP TOXIC DOSE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=9792186; DOI=10.1016/s0041-0101(98)00162-7;
RA Grishin E.V.;
RT "Black widow spider toxins: the present and the future.";
RL Toxicon 36:1693-1701(1998).
RN [4]
RP SUBUNIT.
RX PubMed=10865132; DOI=10.1016/s0300-9084(00)00199-1;
RA Ashton A.C., Rahman M.A., Volynski K.E., Manser C., Orlova E.V.,
RA Matsushita H., Davletov B.A., van Heel M., Grishin E.V., Ushkaryov Y.A.;
RT "Tetramerisation of alpha-latrotoxin by divalent cations is responsible for
RT toxin-induced non-vesicular release and contributes to the Ca(2+)-dependent
RT vesicular exocytosis from synaptosomes.";
RL Biochimie 82:453-468(2000).
RN [5]
RP STRUCTURE BY ELECTRON MICROSCOPY (4.63 ANGSTROMS) OF 50-928 IN DIMERIC
RP FORM, FUNCTION, RECOMBINANT EXPRESSION, AND SUBUNIT.
RX PubMed=34845192; DOI=10.1038/s41467-021-26562-8;
RA Chen M., Blum D., Engelhard L., Raunser S., Wagner R., Gatsogiannis C.;
RT "Molecular architecture of black widow spider neurotoxins.";
RL Nat. Commun. 12:6956-6956(2021).
CC -!- FUNCTION: Insecticidal presynaptic neurotoxin that induces massive
CC neurotransmitter release at insect (but not vertebrate) neuromuscular
CC junctions. Native toxin forms cation-permeable pores (with high
CC permeability to calcium) in lipid membranes locust muscle membrane and
CC artificial lipid bilayers (PubMed:8631785, PubMed:34845192). May bind
CC to insect neurexin-1 homolog, insect adhesion G protein-coupled
CC receptor L1 homolog, and insect receptor-type tyrosine-protein
CC phosphatase S homolog, and induces neurotransmitter exocytosis both by
CC forming tetrameric pores in membranes and signaling via G protein-
CC coupled receptor (By similarity). Oligomerization is a process
CC independent of divalent cations (PubMed:34845192).
CC {ECO:0000250|UniProtKB:P23631, ECO:0000269|PubMed:34845192,
CC ECO:0000269|PubMed:8631785}.
CC -!- SUBUNIT: Homotetramer in membrane. {ECO:0000269|PubMed:34845192}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8631785,
CC ECO:0000269|PubMed:9792186}. Target cell membrane
CC {ECO:0000269|PubMed:34845192}. Note=Forms a membrane channel in the
CC prey. {ECO:0000305|PubMed:34845192}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:8631785}.
CC -!- DOMAIN: Two helices (H2 and H8) are predicted to insert into membranes
CC and form pores by assembling into tetramers. The helices are contained
CC within a helical bundle domain that undergoes significant
CC conformational changes during pore formation to allow exposure of the
CC transmembrane helices and transition of the toxin from a soluble
CC monomer to a transmembrane tetramer. {ECO:0000269|PubMed:34845192}.
CC -!- MASS SPECTROMETRY: Mass=110916; Mass_error=100; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:8631785};
CC -!- TOXIC DOSE: LD(50) is 60 ug/kg to insect (Galleria mellonella) larvae.
CC {ECO:0000269|PubMed:9792186}.
CC -!- SIMILARITY: Belongs to the cationic peptide 01 (latrotoxin) family. 04
CC (delta-latroinsectotoxin) subfamily. {ECO:0000305}.
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DR EMBL; X92679; CAA63363.1; -; mRNA.
DR PDB; 7PTY; EM; 4.63 A; A=1-1214.
DR PDBsum; 7PTY; -.
DR AlphaFoldDB; Q25338; -.
DR SMR; Q25338; -.
DR ArachnoServer; AS000063; delta-Latroinsectotoxin-Lt1a.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR Gene3D; 1.25.40.20; -; 5.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR Pfam; PF12796; Ank_2; 4.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 13.
DR SUPFAM; SSF48403; SSF48403; 2.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 6.
PE 1: Evidence at protein level;
KW 3D-structure; ANK repeat; Cleavage on pair of basic residues;
KW Direct protein sequencing; Exocytosis; Membrane; Neurotoxin;
KW Presynaptic neurotoxin; Repeat; Secreted; Signal; Target cell membrane;
KW Target membrane; Toxin; Transmembrane.
FT SIGNAL 1..?
FT PROPEP ?..28
FT /evidence="ECO:0000305|PubMed:8631785"
FT /id="PRO_0000001618"
FT CHAIN 29..1019
FT /note="Delta-latroinsectotoxin-Lt1a"
FT /evidence="ECO:0000305|PubMed:8631785"
FT /id="PRO_0000001619"
FT PROPEP 1020..1214
FT /note="C-terminal domain cleavage is required for toxin
FT activation"
FT /evidence="ECO:0000305|PubMed:34845192"
FT /id="PRO_0000001620"
FT REPEAT 464..497
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 501..532
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 536..565
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 570..600
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 604..633
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REPEAT 637..666
FT /note="ANK 6"
FT /evidence="ECO:0000255"
FT REPEAT 670..699
FT /note="ANK 7"
FT /evidence="ECO:0000255"
FT REPEAT 706..734
FT /note="ANK 8"
FT /evidence="ECO:0000255"
FT REPEAT 740..769
FT /note="ANK 9"
FT /evidence="ECO:0000255"
FT REPEAT 773..802
FT /note="ANK 10"
FT /evidence="ECO:0000255"
FT REPEAT 806..835
FT /note="ANK 11"
FT /evidence="ECO:0000255"
FT REPEAT 839..868
FT /note="ANK 12"
FT /evidence="ECO:0000255"
FT REPEAT 872..901
FT /note="ANK 13"
FT /evidence="ECO:0000255"
FT REPEAT 906..936
FT /note="ANK 14"
FT /evidence="ECO:0000255"
FT REPEAT 966..994
FT /note="ANK 15"
FT /evidence="ECO:0000255"
FT REGION 64..89
FT /note="Helix H2 is the probable transmembrane region of the
FT tetrameric pore inserted in the target cell membrane"
FT /evidence="ECO:0000250|UniProtKB:Q9XZC0"
FT REGION 250..269
FT /note="Helix H8 is the probable transmembrane region of the
FT tetrameric pore inserted in the target cell membrane"
FT /evidence="ECO:0000250|UniProtKB:Q9XZC0"
SQ SEQUENCE 1214 AA; 135822 MW; 9311438814E49169 CRC64;
MHSKELQTIS AAVARKAVPN TMVIRLKRDE EDGEMTLEER QAQCKAIEYS NSVFGMIADV
ANDIGSIPVI GEVVGIVTAP IAIVSHITSA GLDIASTALD CDDIPFDEIK EILEERFNEI
DRKLDKNTAA LEEVSKLVSK TFVTVEKTRN EMNENFKLVL ETIESKEIKS IVFKINDFKK
FFEKERQRIK GLPKDRYVAK LLEQKGILGS LKEVREPSGN SLSSALNELL DKNNNYAIPK
VVDDNKAFQA LYALFYGTQT YAAVMFFLLE QHSYLADYYY QKGDDVNFNA EFNNVAIIFD
DFKSSLTGGD DGLIDNVIEV LNTVKALPFI KNADSKLYRE LVTRTKALET LKNQIKTTDL
PLIDDIPETL SQVNFPNDEN QLPTPIGNWV DGVEVRYAVQ YESKGMYSKF SEWSEPFTVQ
GNACPTIKVR VDPKKRNRLI FRKFNSGKPQ FAGTMTHSQT NFKDIHRDLY DAALNINKLK
AVDEATTLIE KGADIEAKFD NDRSAMHAVA YRGNNKIALR FLLKNQSIDI ELKDKNGFTP
LHIAAEAGQA GFVKLLINHG ADVNAKTSKT NLTPLHLATR SGFSKTVRNL LESPNIKVNE
KEDDGFTPLH TAVMSTYMVV DALLNHPDID KNAQSTSGLT PFHLAIINES QEVAESLVES
NADLNIQDVN HMAPIHFAAS MGSIKMLRYL ISIKDKVSIN SVTENNNWTP LHFAIYFKKE
DAAKELLKQD DINLTIVADG NLTVLHLAVS TGQINIIKEL LKRGSNIEEK TGEGYTSLHI
AAMRKEPEIA VVLIENGADI EARSADNLTP LHSAAKIGRK STVLYLLEKG ADIGAKTADG
STALHLAVSG RKMKTVETLL NKGANLKEYD NNKYLPIHKA IINDDLDMVR LFLEKDPSLK
DDETEEGRTS IMLIVQKLLL ELYNYFINNY AETLDEEALF NRLDEQGKLE LAYIFHNKEG
DAKEAVKPTI LVTIKLMEYC LKKLREESGA PEGSFDSPSS KQCISTFSED EMFRRTLPEI
VKETNSRYLP LKGFSRSLNK FLPSLKFAES KNSYRSENFV SNIDSNGALL LLDVFIRKFT
NEKYNLTGKE AVPYLEAKAS SLRIASKFEE LLTEVKGIPA GELINMAEVS SNIHKAIASG
KPVSKVLCSY LDTFSELNSQ QMEELVNTYL STKPSVITSA SADYQKLPNL LTATCLEPER
MAQLIDVHQK MFLR
