LATA_LATGE
ID LATA_LATGE Reviewed; 1368 AA.
AC L7XCU0;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 1.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=Alpha-latrotoxin-Lg1a {ECO:0000305};
DE Short=Alpha-LTX-Lg1a {ECO:0000305};
DE AltName: Full=Alpha-latrotoxin {ECO:0000303|PubMed:23339183};
DE Short=Alpha-LTX {ECO:0000303|PubMed:23339183};
DE Flags: Precursor; Fragment;
OS Latrodectus geometricus (Brown widow spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Entelegynae; Araneoidea; Theridiidae; Latrodectus.
OX NCBI_TaxID=156851;
RN [1] {ECO:0000312|EMBL:AGD80170.1}
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).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=33163957; DOI=10.1016/j.toxcx.2020.100062;
RA Khamtorn P., Rungsa P., Jangpromma N., Klaynongsruang S., Daduang J.,
RA Tessiri T., Daduang S.;
RT "Partial proteomic analysis of brown widow spider (Latrodectus geometricus)
RT venom to determine the biological activities.";
RL Toxicon X 8:100062-100062(2020).
RN [3]
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:33163957}. 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 -!- 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 -!- 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; KC414036; AGD80170.1; -; Genomic_DNA.
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; 5.
DR Pfam; PF13637; Ank_4; 2.
DR Pfam; PF13857; Ank_5; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 20.
DR SUPFAM; SSF48403; SSF48403; 2.
DR PROSITE; PS50088; ANK_REPEAT; 10.
PE 1: Evidence at protein level;
KW ANK repeat; Cleavage on pair of basic residues; Disulfide bond; Exocytosis;
KW G-protein coupled receptor impairing toxin; Membrane; Neurotoxin;
KW Presynaptic neurotoxin; Repeat; Secreted; Target cell membrane;
KW Target membrane; Toxin; Transmembrane.
FT CHAIN <1..1177
FT /note="Alpha-latrotoxin-Lg1a"
FT /evidence="ECO:0000305|PubMed:23339183"
FT /id="PRO_0000455428"
FT PROPEP 1178..>1368
FT /evidence="ECO:0000305"
FT /id="PRO_0000455429"
FT REPEAT 469..500
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 504..533
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 538..568
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 572..601
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 605..635
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REPEAT 639..669
FT /note="ANK 6"
FT /evidence="ECO:0000255"
FT REPEAT 674..704
FT /note="ANK 7"
FT /evidence="ECO:0000255"
FT REPEAT 708..737
FT /note="ANK 8"
FT /evidence="ECO:0000255"
FT REPEAT 741..770
FT /note="ANK 9"
FT /evidence="ECO:0000255"
FT REPEAT 774..803
FT /note="ANK 10"
FT /evidence="ECO:0000255"
FT REPEAT 807..837
FT /note="ANK 11"
FT /evidence="ECO:0000255"
FT REPEAT 841..870
FT /note="ANK 12"
FT /evidence="ECO:0000255"
FT REPEAT 874..903
FT /note="ANK 13"
FT /evidence="ECO:0000255"
FT REPEAT 907..936
FT /note="ANK 14"
FT /evidence="ECO:0000255"
FT REPEAT 953..981
FT /note="ANK 15"
FT /evidence="ECO:0000255"
FT REPEAT 982..1011
FT /note="ANK 16"
FT /evidence="ECO:0000255"
FT REPEAT 1013..1042
FT /note="ANK 17"
FT /evidence="ECO:0000255"
FT REPEAT 1046..1075
FT /note="ANK 18"
FT /evidence="ECO:0000255"
FT REPEAT 1079..1109
FT /note="ANK 19"
FT /evidence="ECO:0000255"
FT REPEAT 1115..1144
FT /note="ANK 20"
FT /evidence="ECO:0000255"
FT REGION 217..236
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 1174..1177
FT /note="Furin-like endopeptidase recognition region"
FT /evidence="ECO:0000250|UniProtKB:P23631"
FT DISULFID 392..1044
FT /evidence="ECO:0000250|UniProtKB:P23631"
FT NON_TER 1
FT /evidence="ECO:0000312|EMBL:AGD80170.1"
FT NON_TER 1368
FT /evidence="ECO:0000312|EMBL:AGD80170.1"
SQ SEQUENCE 1368 AA; 153492 MW; 29398AA9109D20DC CRC64;
NEELTLEEKA EICSELELQQ KYADIASNII GDLSSLPMVG KIVGTIAAAA MTVAHVGSGR
LDIEQTLLGC SDLPFDQIKE ILETRFNEVD RKLESHSAAL EEITKLVDKS ISAVEKTRKQ
MNKRFDEVMK SIQDAKVSPI VSKINNFAKY FDAEKERVRG LKLNDYILKL EEPNGILLHF
KDVRTPKDDS LQSPLFSIIQ ERYAIPKTVD DELAFKVLYA ILYGTQTYVS VMFFLLEQYS
FLANHYYEKG DLEKYDEYFN NLNNVFLDFK SSLVGSGASN NEGLIDNVLQ VLMTVKSNEF
LGLGKNSLEE MLNEKINLFS KIKEEIEGKQ RMTLSETPEN FARISFEKDI TTPIGDWRDS
REVRYAVQYA SETLFSKIGH WSDPVSVRAK ACPTLRMPVD QTRRNVLVFR KFDNSKPQLV
GEITPYQSNF IDIDRDLYNA ASNPDSAVGF MEFKKLISNG ANIRAVFNQG RTVFHAAAKS
GNDKIMIELT FFSKYTDINQ PDKKGYTPIH VAADSGNAGI VNLLIRSGIS VNSKTYNFLQ
TPLHLAAQRG FVATFQRLME SPEININERD KDGFTPLHYA VRGGERILEA FINQAGIDVN
VKSDKGLTPF HLAVIKNDWP VASTLLRSKK IDINAIDENN MTALHYAAIL GFLETTKQLI
NLKEINANAV SSPGLLSALH YAILYKHDDV ALFLLKSSKV NYNLKAFGDI TPLHLAVMQG
RKQVLSEMFN IGININQKTA EKYTPLHLAA MSKYPELVEI LLDQGSNLEA KTITGATPLN
LATFKGKSQA ALILLKDEVN WREPDENGQM PIHGAAMNGL LDVAQAILYL DATVLDIEDK
NLDTPLNLAA QNSHIDMVKY FIDLGAKVNT RNKKGQAPLL AFSKKGNLDM VKYLFDKNAN
VYIADNDGLN FFYYAVRNGH LNIVKYAMSE KDKFEWSTTD NNRSDGCSGE CAISHFAVCD
AVQYDKIEIV KYFVGTLGHY SICSPLHQAA RYGHIHIVKY LVEEEVLSVD GSKPDTPLCY
ASENGHLAVV QYLIRNGAKV NHDCANGMTA IDKAITKNQL QVVQILAENG VDFRRKNRLD
ATPFLTAVAS NSYEIAEYLI REKRQNININ EQNGNKETAL HLAVYYKNLQ MIKLLVKYGI
DENIRNGYDK TALDIARDNK ISSIVEYLQT KSGKFRREYK SSNGEHDLLH ENRISNFTDS
KNLEYQHQHF INADNDASQS FSNTAANQNI DVIGTLLLID VLIRRFSKQG YINNKPDSAS
DGIAQAAALA ITEKFEDILN SLHNKSTEEQ VDFAEVHRKI YAALRSGRNS QVHQVLCSSL
KSISTLKPED IKKLVSVVLS FQSSISLPEV SASAREVYGE TLHLFHES
