LITA_LATTR
ID LITA_LATTR Reviewed; 1411 AA.
AC Q02989;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Alpha-latroinsectotoxin-Lt1a {ECO:0000305};
DE Short=Alpha-LIT-Lt1a {ECO:0000305};
DE AltName: Full=Alpha-latroinsectotoxin {ECO:0000303|PubMed:8477689};
DE Short=Alpha-LIT {ECO:0000303|PubMed:8477689};
DE Flags: Precursor; Fragment;
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], AND PROTEIN SEQUENCE OF 36-48; 153-164;
RP 196-207; 335-341; 352-365; 377-386; 397-402; 441-453; 455-461; 466-472;
RP 485-488; 523-529; 566-572; 704-707; 722-730; 782-791; 831-845; 971-990;
RP 996-1010; 1018-1039; 1077-1090; 1123-1130; 1148-1154; 1157-1162 AND
RP 1165-1168.
RC TISSUE=Venom gland;
RX PubMed=8477689; DOI=10.1111/j.1432-1033.1993.tb17741.x;
RA Kiyatkin N.N.I., Dulubova I.I.E., Grishin E.V.;
RT "Cloning and structural analysis of (alpha)-latroinsectotoxin cDNA:
RT abundance of ankyrin-like repeats.";
RL Eur. J. Biochem. 213:121-127(1993).
RN [2]
RP TOXIC DOSE.
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 [3]
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 [4]
RP FUNCTION.
RX PubMed=17764656; DOI=10.1016/j.bbamem.2007.07.004;
RA Shatursky O.Y., Volkova T.M., Himmelreich N.H., Grishin E.V.;
RT "The geometry of the ionic channel lumen formed by alpha-latroinsectotoxin
RT from black widow spider venom in the bilayer lipid membranes.";
RL Biochim. Biophys. Acta 1768:2757-2763(2007).
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 (By similarity). May bind to insect neurexin-
CC 1 homolog, insect adhesion G protein-coupled receptor L1 homolog, and
CC insect receptor-type tyrosine-protein phosphatase S homolog, and
CC induces neurotransmitter exocytosis both by forming tetrameric pores in
CC membranes and signaling via G protein-coupled receptor (By similarity).
CC Oligomerization is a process independent of divalent cations (By
CC similarity). The toxin forms channels with 0.55-0.58 nm entrance
CC diameter and a relatively small conductance in planar phospholipid
CC membranes (PubMed:17764656). {ECO:0000250|UniProtKB:P23631,
CC ECO:0000250|UniProtKB:Q25338, ECO:0000269|PubMed:17764656}.
CC -!- SUBUNIT: Homotetramer in membranes. {ECO:0000269|PubMed:10865132}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:10865132}. Target
CC cell membrane {ECO:0000305|PubMed:10865132}. Note=Forms a membrane
CC channel in the prey. {ECO:0000305|PubMed:10865132}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:8477689}.
CC -!- DOMAIN: The H8 helix is predicted to insert into membranes and form
CC pores by assembling into tetramers. The helix is contained within a
CC helical bundle domain that undergoes significant conformational changes
CC during pore formation to allow exposure of the H8 transmembrane helix
CC and transition of the toxin from a soluble monomer to a transmembrane
CC tetramer. {ECO:0000250|UniProtKB:Q9XZC0}.
CC -!- TOXIC DOSE: LD(50) is 15 ug/kg to insect (Galleria mellonella) larvae.
CC {ECO:0000269|PubMed:9792186}.
CC -!- SIMILARITY: Belongs to the cationic peptide 01 (latrotoxin) family. 02
CC (alpha-latroinsectotoxin) subfamily. {ECO:0000305}.
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DR EMBL; Z14086; CAA78464.1; -; mRNA.
DR PIR; S30355; S30355.
DR AlphaFoldDB; Q02989; -.
DR SMR; Q02989; -.
DR TCDB; 1.C.63.1.2; the Alpha-latrotoxin (latrotoxin) family.
DR PRIDE; Q02989; -.
DR ArachnoServer; AS000062; alpha-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; -; 4.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR Pfam; PF00023; Ank; 1.
DR Pfam; PF12796; Ank_2; 6.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 20.
DR SUPFAM; SSF48403; SSF48403; 2.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 10.
PE 1: Evidence at protein level;
KW ANK repeat; Cleavage on pair of basic residues; Direct protein sequencing;
KW Exocytosis; Membrane; Neurotoxin; Presynaptic neurotoxin; Repeat; Secreted;
KW Target cell membrane; Target membrane; Toxin; Transmembrane.
FT PROPEP <1..35
FT /evidence="ECO:0000305|PubMed:8477689"
FT /id="PRO_0000001616"
FT CHAIN 36..1195
FT /note="Alpha-latroinsectotoxin-Lt1a"
FT /evidence="ECO:0000305"
FT /id="PRO_0000001617"
FT PROPEP 1196..1411
FT /evidence="ECO:0000305"
FT /id="PRO_0000391355"
FT REPEAT 462..495
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 499..528
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 533..562
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 567..597
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 601..630
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REPEAT 634..663
FT /note="ANK 6"
FT /evidence="ECO:0000255"
FT REPEAT 667..697
FT /note="ANK 7"
FT /evidence="ECO:0000255"
FT REPEAT 702..732
FT /note="ANK 8"
FT /evidence="ECO:0000255"
FT REPEAT 736..765
FT /note="ANK 9"
FT /evidence="ECO:0000255"
FT REPEAT 769..798
FT /note="ANK 10"
FT /evidence="ECO:0000255"
FT REPEAT 802..831
FT /note="ANK 11"
FT /evidence="ECO:0000255"
FT REPEAT 835..864
FT /note="ANK 12"
FT /evidence="ECO:0000255"
FT REPEAT 869..898
FT /note="ANK 13"
FT /evidence="ECO:0000255"
FT REPEAT 902..931
FT /note="ANK 14"
FT /evidence="ECO:0000255"
FT REPEAT 935..965
FT /note="ANK 15"
FT /evidence="ECO:0000255"
FT REPEAT 968..999
FT /note="ANK 16"
FT /evidence="ECO:0000255"
FT REPEAT 1000..1029
FT /note="ANK 17"
FT /evidence="ECO:0000255"
FT REPEAT 1080..1109
FT /note="ANK 18"
FT /evidence="ECO:0000255"
FT REPEAT 1112..1142
FT /note="ANK 19"
FT /evidence="ECO:0000255"
FT REPEAT 1146..1175
FT /note="ANK 20"
FT /evidence="ECO:0000255"
FT REPEAT 1331..1361
FT /note="ANK 21"
FT /evidence="ECO:0000255"
FT REGION 245..264
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"
FT REGION 1230..1254
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1230..1245
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT NON_TER 1
SQ SEQUENCE 1411 AA; 157806 MW; B9001D1A5B0B7EF2 CRC64;
ACSSPEVSIF HFFVYAGSFV KNFKKMKGSS AISKREMSRA DQCKLLAYTA VGYETVGNVA
ADIASIEGAN LVAAPVAAGG HLGKGLTDAA MIAMDCSSIP FEEIKEILNK EFKEMGRKLD
KNTEALEHVS KLVSKTLSTV EKIRVEMREG FKLVIETIEN IATKEIVFDI NKIVQYFNNE
RENINSRQKE EFVAKLQEPA PGNFLLYLRN SRTSESGTLY SLLFRIIDQE LAIPNNAGDN
NAIQALYALF YGTETFISIM FYLVKQYSYL AEYHYQKGNL EEFNTNFDHM KIVFQDFKFS
LIGINQNTKP LVDEVLNVLN NVKNKSFIRN VQNKLFYDLM KQTESLLELK KEIANMELPI
IDETPRLSIS ISFKERSDDK PVDTPLLKWD KGKEVKYAIQ FEQDGKFSKI SSWSKPVTVQ
HLACPFISVD KDRRNRLIFR QFGDQIPELV GTLRGSQVEF RDIHRDLYNA AQVPYAREAL
SISRTLIQNG ANVSETFELG RGAIHAAASA GNYDVGELLL NKDINLLEKA DKNGYTPLHI
AADSNKNDFV MFLIGNNADV NVRTKSDLFT PLHLAARRDL TDVTQTLIDI TEIDLNAQDK
SGFTPLHLSI SSTSETAAIL IRNTNAVINI KSKVGLTPLH LATLQNNLSV SKLLAGKGAY
LNDGDANGMT PLHYAAMTGN LEMVDFLLNQ QYININAATK EKKWTPLHLA ILFKKNDVAE
RLLSDENLNI RLETNGGINP LHLASATGNK QLVIELLAKN ADVTRLTSKG FSALHLGIIG
KNEEIPFFLV EKGANVNDKT NSGVTPLHFA AGLGKANIFR LLLSRGADIK AEDINSQMPI
HEAVSNGHLE IVRILIEKDP SLMNVKNIRN EYPFYLAVEK RYKDIFDYFV SKDANVNEVD
HNGNTLLHLF SSTGELEVVQ FLMQNGANFR LKNNERKTFF DLAIENGRLN IVAFAVEKNK
VNLQAAHRGK TILYHAICDS AKYDKIEIVK YFIEKLNESE CNPLHEAAAY AHLDLVKYFV
QERGINPAEF NEENQASPFC ITIHGAPCGY SLDCDTPDRL EVVEYLSDKI PDINGKCDVQ
ENTPITVAIF ANKVSILNYL VGIGADPNQQ VDGDPPLYIA ARQGRFEIVR CLIEVHKVDI
NTRNKERFTA LHAAARNDFM DVVKYLVRQG ADVNAKGIDD LRPIDIAGEK AKAYLQSSRF
LRSGHSFQSN EIDSFGNTIH GISMSARTND KLTQQISSKG TRSDSNSTEG KMHSENVHVR
SIDVNGALLL LDFMIRVFAS KKTNFAPYGS RIKTRSAAEA QAEALIMTER FENLLSGLIG
DPIPDSIDFS NVHSKIYKAI MSGRRSVISE MLCSFAEEYS KLNHESIKQL LSEFETLTTT
KASEIHIEES VPYAPFEICE LKVNSNVSQI K
