LATA_LATMA
ID LATA_LATMA Reviewed; 202 AA.
AC P0DJE4;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 1.
DT 25-MAY-2022, entry version 28.
DE RecName: Full=Alpha-latrotoxin-Lm1a {ECO:0000305};
DE Short=Alpha-LTX-Lm1a {ECO:0000305};
DE AltName: Full=Alpha-latrotoxin {ECO:0000303|PubMed:22001442};
DE Short=Alpha-LTX {ECO:0000303|PubMed:22001442};
DE Flags: Fragments;
OS Latrodectus mactans (Black widow spider) (Aranea mactans).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Entelegynae; Araneoidea; Theridiidae; Latrodectus.
OX NCBI_TaxID=6924;
RN [1]
RP PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Venom;
RX PubMed=22001442; DOI=10.1016/j.bcp.2011.09.024;
RA Graudins A., Little M.J., Pineda S.S., Hains P.G., King G.F., Broady K.W.,
RA Nicholson G.M.;
RT "Cloning and activity of a novel alpha-latrotoxin from red-back spider
RT venom.";
RL Biochem. Pharmacol. 83:170-183(2012).
RN [2]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=34632517; DOI=10.1093/jme/tjab168;
RA Torres S.L., Landeros A., Penhallegon E.J., Salazar K., Porter L.M.;
RT "Expression of brown and southern black widow spider (Araneae: Theridiidae)
RT latrotoxins is tissue- and life stage-specific for alpha-latroinsectotoxins
RT and delta-latroinsectotoxins and is ubiquitous for alpha-latrotoxins.";
RL J. Med. Entomol. 59:184-191(2022).
CC -!- FUNCTION: Presynaptic neurotoxin that causes massive release of
CC neurotransmitters from vertebrate (but not invertebrate) nerve
CC terminals and endocrine cells via a complex mechanism involving
CC activation of receptor(s) and toxin insertion into the plasma membrane
CC with subsequent pore formation. Binds to neurexin-1-alpha (NRXN1) in a
CC calcium dependent manner, adhesion G protein-coupled receptor L1
CC (ADGRL1, also termed latrophilin-1 and calcium-independent receptor of
CC latrotoxin (CIRL)), and receptor-type tyrosine-protein phosphatase S
CC (PTPRS), also termed PTP sigma. NRXN1 and PTPRS are suggested to
CC provide a platform for binding and subsequent pore formation events. In
CC contrast, binding to ADGRL1 does not involve oligomerization and
CC channel formation, but direct downstream stimulation of the synaptic
CC fusion machinery. {ECO:0000250|UniProtKB:P23631}.
CC -!- SUBUNIT: Homotetramer in membranes. {ECO:0000250|UniProtKB:P23631}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22001442}. Target
CC cell membrane {ECO:0000250|UniProtKB:P23631}. Note=Forms a membrane
CC channel in the prey. {ECO:0000250|UniProtKB:P23631}.
CC -!- TISSUE SPECIFICITY: Expressed in venom gland, cephalothorax, and
CC abdomen tissues from both males and females.
CC {ECO:0000269|PubMed:34632517}.
CC -!- DEVELOPMENTAL STAGE: Expressed in all life stages examined, including
CC adults, spiderlings and eggs. {ECO:0000269|PubMed:34632517}.
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 -!- PTM: Processed by furin-like proteases at both the N- and C-termini.
CC {ECO:0000250}.
CC -!- PTM: Contains 1 disulfide bond. {ECO:0000250|UniProtKB:P23631}.
CC -!- MISCELLANEOUS: Is the main neurotoxin responsible for the human
CC envenomation syndrome known as latrodectism that results from bites by
CC Latrodectus species.
CC -!- MISCELLANEOUS: Iso and Leu residues are assigned by comparison with
CC orthologs.
CC -!- SIMILARITY: Belongs to the cationic peptide 01 (latrotoxin) family. 03
CC (alpha-latrotoxin) subfamily. {ECO:0000305}.
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DR AlphaFoldDB; P0DJE4; -.
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; -; 1.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR SUPFAM; SSF48403; SSF48403; 1.
PE 1: Evidence at protein level;
KW ANK repeat; Direct protein sequencing; Disulfide bond; Exocytosis;
KW Membrane; Neurotoxin; Presynaptic neurotoxin; Repeat; Secreted;
KW Target cell membrane; Target membrane; Toxin; Transmembrane.
FT CHAIN <1..>202
FT /note="Alpha-latrotoxin-Lm1a"
FT /id="PRO_0000415933"
FT REPEAT 95..>109
FT /note="ANK 1"
FT /evidence="ECO:0000255, ECO:0000305"
FT REPEAT <110..120
FT /note="ANK 2"
FT /evidence="ECO:0000255, ECO:0000305"
FT REPEAT <122..>132
FT /note="ANK 3"
FT /evidence="ECO:0000255, ECO:0000305"
FT REPEAT <133..138
FT /note="ANK 4"
FT /evidence="ECO:0000255, ECO:0000305"
FT REPEAT 142..161
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REPEAT <163..>170
FT /note="ANK 6"
FT /evidence="ECO:0000255, ECO:0000305"
FT REPEAT <171..182
FT /note="ANK 7"
FT /evidence="ECO:0000255, ECO:0000305"
FT REPEAT 184..>184
FT /note="ANK 8"
FT /evidence="ECO:0000255, ECO:0000305"
FT REPEAT <185..191
FT /note="ANK 9"
FT /evidence="ECO:0000255, ECO:0000305"
FT REPEAT <193..>202
FT /note="ANK 10"
FT /evidence="ECO:0000255, ECO:0000305"
FT REGION 175..181
FT /note="4C4.1 epitope"
FT /evidence="ECO:0000250"
FT NON_CONS 19..20
FT /evidence="ECO:0000305"
FT NON_CONS 38..39
FT /evidence="ECO:0000305"
FT NON_CONS 53..54
FT /evidence="ECO:0000305"
FT NON_CONS 70..71
FT /evidence="ECO:0000305"
FT NON_CONS 80..81
FT /evidence="ECO:0000305"
FT NON_CONS 93..94
FT /evidence="ECO:0000305"
FT NON_CONS 109..110
FT /evidence="ECO:0000305"
FT NON_CONS 121..122
FT /evidence="ECO:0000305"
FT NON_CONS 132..133
FT /evidence="ECO:0000305"
FT NON_CONS 141..142
FT /evidence="ECO:0000305"
FT NON_CONS 150..151
FT /evidence="ECO:0000305"
FT NON_CONS 162..163
FT /evidence="ECO:0000305"
FT NON_CONS 170..171
FT /evidence="ECO:0000305"
FT NON_CONS 184..185
FT /evidence="ECO:0000305"
FT NON_CONS 192..193
FT /evidence="ECO:0000305"
FT NON_TER 1
FT NON_TER 202
SQ SEQUENCE 202 AA; 22054 MW; C5DD6D960F465095 CRC64;
IVGTIAAAAM TVTHVASGRL NDYILKLEEP NGILLHFKAP LFSIIQEGYA VPKSSLVGTG
TSNNEGLLDR NGVDEMLNEK YAVQYASETL FSKDLYNAAS NPDSAVGFKL MESPEININE
RNDWPVASTL LRSSNVNVNL KNSDTPLNLA YFIDQGADIN TRNGHLNIVK YLVEEEDLSV
DGSKYGIDMT IRTALDIATD LK
