LATA_STEGR
ID LATA_STEGR Reviewed; 1400 AA.
AC L7X8P2;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 1.
DT 03-AUG-2022, entry version 33.
DE RecName: Full=Alpha-latrotoxin-Sg1a {ECO:0000305};
DE Short=Alpha-LTX-Sg1a {ECO:0000305};
DE AltName: Full=Alpha-latrotoxin {ECO:0000303|PubMed:23339183};
DE Short=Alpha-LTX {ECO:0000303|PubMed:23339183};
DE Flags: Precursor;
OS Steatoda grossa (False black widow).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Entelegynae; Araneoidea; Theridiidae; Steatoda.
OX NCBI_TaxID=256750;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=23339183; DOI=10.1093/molbev/mst011;
RA Garb J.E., Hayashi C.Y.;
RT "Molecular evolution of alpha-latrotoxin, the exceptionally potent
RT vertebrate neurotoxin in black widow spider venom.";
RL Mol. Biol. Evol. 30:999-1014(2013).
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:0000250|UniProtKB:P23631}. 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:0000250|UniProtKB:P0DJE4}.
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 -!- MISCELLANEOUS: Is the main neurotoxin responsible for the human
CC envenomation syndrome known as latrodectism that results from bites by
CC Latrodectus species.
CC -!- SIMILARITY: Belongs to the cationic peptide 01 (latrotoxin) family. 03
CC (alpha-latrotoxin) subfamily. {ECO:0000305}.
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DR EMBL; KC414039; AGD80173.1; -; Genomic_DNA.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C: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; 2.
DR Pfam; PF12796; Ank_2; 5.
DR Pfam; PF13637; Ank_4; 1.
DR Pfam; PF13857; Ank_5; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 19.
DR SUPFAM; SSF48403; SSF48403; 3.
DR PROSITE; PS50297; ANK_REP_REGION; 11.
DR PROSITE; PS50088; ANK_REPEAT; 13.
PE 3: Inferred from homology;
KW ANK repeat; Exocytosis; Membrane; Neurotoxin; Presynaptic neurotoxin;
KW Repeat; Secreted; Signal; Target cell membrane; Target membrane; Toxin.
FT SIGNAL 1..20
FT /evidence="ECO:0000250|UniProtKB:P23631"
FT CHAIN 21..1197
FT /note="Alpha-latrotoxin-Sg1a"
FT /id="PRO_0000455432"
FT PROPEP 1198..1400
FT /evidence="ECO:0000305"
FT /id="PRO_0000455433"
FT REPEAT 490..520
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 524..553
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 558..588
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 592..621
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 625..655
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REPEAT 659..689
FT /note="ANK 6"
FT /evidence="ECO:0000255"
FT REPEAT 694..726
FT /note="ANK 7"
FT /evidence="ECO:0000255"
FT REPEAT 728..757
FT /note="ANK 8"
FT /evidence="ECO:0000255"
FT REPEAT 761..790
FT /note="ANK 9"
FT /evidence="ECO:0000255"
FT REPEAT 794..823
FT /note="ANK 10"
FT /evidence="ECO:0000255"
FT REPEAT 827..856
FT /note="ANK 11"
FT /evidence="ECO:0000255"
FT REPEAT 861..890
FT /note="ANK 12"
FT /evidence="ECO:0000255"
FT REPEAT 894..923
FT /note="ANK 13"
FT /evidence="ECO:0000255"
FT REPEAT 927..957
FT /note="ANK 14"
FT /evidence="ECO:0000255"
FT REPEAT 969..1001
FT /note="ANK 15"
FT /evidence="ECO:0000255"
FT REPEAT 1002..1031
FT /note="ANK 16"
FT /evidence="ECO:0000255"
FT REPEAT 1033..1062
FT /note="ANK 17"
FT /evidence="ECO:0000255"
FT REPEAT 1066..1095
FT /note="ANK 18"
FT /evidence="ECO:0000255"
FT REPEAT 1099..1129
FT /note="ANK 19"
FT /evidence="ECO:0000255"
FT REPEAT 1135..1164
FT /note="ANK 20"
FT /evidence="ECO:0000255"
FT REPEAT 1168..1197
FT /note="ANK 21"
FT /evidence="ECO:0000255"
FT REGION 17..20
FT /note="Furin-like endopeptidase recognition region"
FT /evidence="ECO:0000250|UniProtKB:P23631"
FT REGION 238..257
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 1194..1197
FT /note="Furin-like endopeptidase recognition region"
FT /evidence="ECO:0000250|UniProtKB:P23631"
SQ SEQUENCE 1400 AA; 156398 MW; 941B23DF7F54C918 CRC64;
MSAVEEIYQY TMNSSARLKR EDVELSLEEK AEICSELELQ QKSTDIAANI IGDISSLPIV
GKIVGTMAAA MMAIAHVGSG ALDIQQTLLG CSDLPFDEIK EIMEQKFNEI DRKLDSHSKA
LEEITKLAEK TLSSVEKTRK QMNKRFDEVL ESIKNTNIAP IVSKISNFGR YFDXEAERIR
GLNLNDYVAK LEEEKGILYY LRESRTPKGD GLHAPLLIII NEGYAIPASI NDELAFKALD
ALLYGTQTYV SVMFFLLEQY SFLANYYYGK GELDIYNKYF DSITNIFLDF KSSLVGSGGS
DSAALLESVL QVLVAVKSKE FLKFLEMDVV VMLNEKISLF SKIKEDVDGK ERITSSLTPE
NYVHISFEKD IPTPFGDWKE DKEVRYAVQY ESETLFSKVS HWSNPITVRG KACPTLRMPV
DQNRKSILVF RKFENRKPQL VGSVSPYQSN FIDIDRDLYN AAGNPDLDVG HXEVVKLVAN
GANIKAPFEQ GRTALHAAAE SGNAKVMFGL VLXSLGDLNK PDKNGFTAIH AAADKGNAGI
VNLLIDYSAS VNVKTYRTLQ TPLHLAARRG FKRTFDRLLE SPDININEKD KDGFTPLHSA
VLGGKEIVKA FINQPGTDIN AKSEKGLTPF HLAIINDDWP VAETLLTSES LQVNANDENN
NTPLHYAVML GHLEIMKKLI NLSQVNVNAV SIPNLWSALH YAIFFKRDDV TLELLKILKV
DKDLQSLGGI TPLHLAVSLG RKTVVSEMVR IGINLEQKTT EDFTPLHLAA MSKYPEIVTF
LIDQGSNMEA KTANGATPLL LATLKGREQA SMILLGNEVN FRAVDKDGQM PIHGAAMNGM
LEIAREIINL EPSIVAAQNN NLDTPLNLAA QHLHPEMVKF LVGRKADINT KNKDGNAPLL
AFSKMGNLDM IKFLISNGAD VYIADNDGLN FFYYAVRHGH LNIIKYAMSE RKFTWSTPDN
NRRRECPNEE CAISHFAVCD AIQYGKINVV KYFVGTLQHF SICRPLITAA MYGQLDIVKY
LVEEEELNVN VAKPGTPLCH AAENGYLDVV KYLVENGXEI NRDCVRGETA IDMAISKNHI
NVVRYLVKKG ADLRRRNALG STPFFTAVSS NSLDIARYFI NEKIGDIDIN EQNEKGESAL
HLAVYYRNLQ MVKLLVENGI NVGIRNAIGK TALEIARDAR FSRIVEYLNT KSRRFRKGFQ
ILRNAQGYPH MNMISNFIGS KNIEHDHQRF LNSDVEESKT FLNSPSFQNI DVIGTLLLVD
VLIRYFTKQG YINEENDSAS DEGVQAAALE ITENFENFLN VFDDTPKEQV DLTEVHRKVY
AALKSGRKSQ IHQVLCSSLK SVSKLEPAEI ETLVSELLNL QSSFPLTKFP PSTAEAFENS
LHILGESCLN SEWSPSLMLM
