LATA_LATHA
ID LATA_LATHA Reviewed; 1351 AA.
AC G0LXV8;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 2.
DT 25-MAY-2022, entry version 34.
DE RecName: Full=Alpha-latrotoxin-Lh1a {ECO:0000305};
DE Short=Alpha-LTX-Lh1a {ECO:0000305};
DE AltName: Full=Alpha-latrotoxin {ECO:0000303|PubMed:22001442};
DE Short=Alpha-LTX {ECO:0000303|PubMed:22001442};
DE Flags: Precursor; Fragment;
OS Latrodectus hasselti (Redback spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Entelegynae; Araneoidea; Theridiidae; Latrodectus.
OX NCBI_TaxID=256736;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE, FUNCTION,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
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).
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 (By similarity). Induces rapid muscle contracture and
CC loss of twitch tension when added to the isolated and indirectly
CC stimulated chick biventer cervicis nerve-muscle preparation
CC (PubMed:22001442). {ECO:0000250|UniProtKB:P23631,
CC ECO:0000269|PubMed:22001442}.
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:0000250|UniProtKB:P0DJE4}.
CC -!- DEVELOPMENTAL STAGE: Expressed in all life stages examined, including
CC adults, spiderlings and eggs. {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 -!- TOXIC DOSE: LD(50)is 20 ug/kg by subcutaneous injection into mice.
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; FR851877; CCA64564.1; -; Genomic_DNA.
DR AlphaFoldDB; G0LXV8; -.
DR SMR; G0LXV8; -.
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; 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; 3.
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 Disulfide bond; Exocytosis; Membrane; Neurotoxin; Presynaptic neurotoxin;
KW Repeat; Secreted; Signal; Target cell membrane; Target membrane; Toxin;
KW Transmembrane.
FT SIGNAL <1..7
FT /evidence="ECO:0000255"
FT CHAIN 8..1187
FT /note="Alpha-latrotoxin-Lh1a"
FT /id="PRO_5000783570"
FT PROPEP 1188..>1351
FT /evidence="ECO:0000250"
FT /id="PRO_0000415931"
FT REPEAT 446..477
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 478..509
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 513..542
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 547..577
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 581..610
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REPEAT 614..644
FT /note="ANK 6"
FT /evidence="ECO:0000255"
FT REPEAT 648..678
FT /note="ANK 7"
FT /evidence="ECO:0000255"
FT REPEAT 683..711
FT /note="ANK 8"
FT /evidence="ECO:0000255"
FT REPEAT 717..746
FT /note="ANK 9"
FT /evidence="ECO:0000255"
FT REPEAT 750..779
FT /note="ANK 10"
FT /evidence="ECO:0000255"
FT REPEAT 783..812
FT /note="ANK 11"
FT /evidence="ECO:0000255"
FT REPEAT 816..846
FT /note="ANK 12"
FT /evidence="ECO:0000255"
FT REPEAT 850..879
FT /note="ANK 13"
FT /evidence="ECO:0000255"
FT REPEAT 883..912
FT /note="ANK 14"
FT /evidence="ECO:0000255"
FT REPEAT 916..945
FT /note="ANK 15"
FT /evidence="ECO:0000255"
FT REPEAT 959..991
FT /note="ANK 16"
FT /evidence="ECO:0000255"
FT REPEAT 992..1019
FT /note="ANK 17"
FT /evidence="ECO:0000255"
FT REPEAT 1023..1052
FT /note="ANK 18"
FT /evidence="ECO:0000255"
FT REPEAT 1056..1085
FT /note="ANK 19"
FT /evidence="ECO:0000255"
FT REPEAT 1089..1119
FT /note="ANK 20"
FT /evidence="ECO:0000255"
FT REPEAT 1125..1154
FT /note="ANK 21"
FT /evidence="ECO:0000255"
FT REPEAT 1158..1187
FT /note="ANK 22"
FT /evidence="ECO:0000255"
FT REGION 4..7
FT /note="Furin-like endopeptidase recognition region"
FT REGION 226..245
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 1184..1187
FT /note="Furin-like endopeptidase recognition region"
FT DISULFID 401..1054
FT /evidence="ECO:0000305"
FT UNSURE 1202
FT /note="Assigned by comparison with orthologs"
FT UNSURE 1215
FT /note="Assigned by comparison with orthologs"
FT NON_TER 1
FT NON_TER 1351
SQ SEQUENCE 1351 AA; 151407 MW; 1200C1B85D42A908 CRC64;
SLVRMRREGE EDLTLEEKAE LCSELELQQK YVDIGSNIIG DLSSLPIVGK IVGTIAAAAM
AVTHVASGRL DIEQTLGGCS DVPFDQIKEI LEERFNEIDR KLESHSAALE EITKLVEKSI
SAVEKTRKQM NKRFDEVMRS IQDAKVSPLV SKINNFARYF DTEKERIRGL KLSDYILKLE
EPNGILLHFK ESRTPRDDSL QAPLFSIIQE RYAVPKSIDD ELAFKVLYAL LYGTQTYVSV
MFFLLEQYSF LANHYYEKGD LEKYDEYFNS LNNVFLDFKS SLVGTGTSNN EGLLDRVLQV
LVTVKNSEFL GLEKNGVNEM LNEKINLFNK IKVEIEGKQR MTLSETPENF AQISFDKDIT
TPIGDWRDGR EVRYAVQYAS ETLFSKISHW SDPVGVREKA CPTLRMPVDQ TRRNILVFRK
FDSSKPQLVG EITPYQSNFI DIDRDLYNTA NNPDSAVGFK EFTKLNYDGA NIRATFEQGR
TVFHAAAKSG NSRIMIGLTF LVKSNELNQP DKKGYTPIHV AADSGNAGIV NLLIQRGVSI
NSKTYNFLQT PLHLAAQRGF VTTFQRLMES PEININERDK DGFTPLHYAV RGGERILEAF
INQIRIDLNA KSNKGLTPFH LAIIKDDWPV ASTLLGSKKV DVNAVDENNM TALHYAAILG
YLETTKQLIN LKEINADVVS SPGLLSALHY AILYKHDDVA SFLLRSSNVN VNLKALGGIT
PLHLAVIQGR TQILSLMFDI GVNIEQQTDE KYTPLHLAAM SKYPELIQIL LDQGSNFEAK
TNSGATPLHL ATFKGKSKAA LILLNNEVNW RDTDENGQMP IHGAAMNGLL DVAQAIISID
ATVLDIKDKN SDTPLNLAAQ KSHIDVIKYF IDQGADINTR NKTGHAPLLA FSKKGNLDMV
KYLFDKNANV YIADNDGINF FYYAVRNGHL NIVKYAMSEK DKFEWSNIDN NRRDECPKEE
CAISHFAVCD AVQFDKIEIV KYFVTTLGNF AICGPLHQAA RYGHLDIEKY LVEEEDLNVD
GSKPDTPLCY ASENGHLAVV QYLVSNGAKV NHDCGNGMTA IDKAITKNHL QVVQFLAANG
VDFRRKNKLG ATPFLTAVSE NAFDIAEYLI RENRQDIDIN EQNVDKETAL HLAVYYKNLQ
MIKLLVKYGI DMTIRNAYDK TALDIATDLK NSNIVEYLKT KSGKFRREYK SSYGEHSLLQ
TNKISSFIDG KNIEHDHPQF INADNESSQL FSDTASNIDV IGPLLLIDVL IRYFSKQGYI
SKESDSASDG ITQAAALSIT EKFEDVLNSL HNESAKEQVD LAEVHGKVYA ALKSGRNSQI
HPILCSSLKS ISTLKPEDME KLGSVIMNSH S
