LATA_LATPL
ID LATA_LATPL Reviewed; 1361 AA.
AC L7XDS4;
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-Lp1a {ECO:0000305};
DE Short=Alpha-LTX-Lp1a {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 pallidus (White widow spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Entelegynae; Araneoidea; Theridiidae; Latrodectus.
OX NCBI_TaxID=256741;
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; KC414038; AGD80172.1; -; 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; 3.
DR PROSITE; PS50297; ANK_REP_REGION; 8.
DR PROSITE; PS50088; ANK_REPEAT; 11.
PE 3: Inferred from homology;
KW ANK repeat; Cleavage on pair of basic residues; Disulfide bond; Exocytosis;
KW Membrane; Neurotoxin; Presynaptic neurotoxin; Repeat; Secreted;
KW Target cell membrane; Target membrane; Toxin; Transmembrane.
FT CHAIN 1..1179
FT /note="Alpha-latrotoxin-Lp1a"
FT /id="PRO_0000455430"
FT PROPEP 1180..>1361
FT /evidence="ECO:0000305"
FT /id="PRO_0000455431"
FT REPEAT 470..501
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 505..534
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 539..569
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 573..602
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 606..636
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REPEAT 640..670
FT /note="ANK 6"
FT /evidence="ECO:0000255"
FT REPEAT 675..703
FT /note="ANK 7"
FT /evidence="ECO:0000255"
FT REPEAT 709..738
FT /note="ANK 8"
FT /evidence="ECO:0000255"
FT REPEAT 742..771
FT /note="ANK 9"
FT /evidence="ECO:0000255"
FT REPEAT 775..804
FT /note="ANK 10"
FT /evidence="ECO:0000255"
FT REPEAT 808..838
FT /note="ANK 11"
FT /evidence="ECO:0000255"
FT REPEAT 842..871
FT /note="ANK 12"
FT /evidence="ECO:0000255"
FT REPEAT 875..904
FT /note="ANK 13"
FT /evidence="ECO:0000255"
FT REPEAT 908..937
FT /note="ANK 14"
FT /evidence="ECO:0000255"
FT REPEAT 951..983
FT /note="ANK 15"
FT /evidence="ECO:0000255"
FT REPEAT 984..1013
FT /note="ANK 16"
FT /evidence="ECO:0000255"
FT REPEAT 1015..1044
FT /note="ANK 17"
FT /evidence="ECO:0000255"
FT REPEAT 1048..1077
FT /note="ANK 18"
FT /evidence="ECO:0000255"
FT REPEAT 1081..1111
FT /note="ANK 19"
FT /evidence="ECO:0000255"
FT REPEAT 1117..1146
FT /note="ANK 20"
FT /evidence="ECO:0000255"
FT REGION 218..237
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 1176..1179
FT /note="Furin-like endopeptidase recognition region"
FT /evidence="ECO:0000250|UniProtKB:P23631"
FT DISULFID 393..1046
FT /evidence="ECO:0000250|UniProtKB:P23631"
FT NON_TER 1361
FT /evidence="ECO:0000305"
SQ SEQUENCE 1361 AA; 152539 MW; 1C2C0B0A9031A8B6 CRC64;
EGEDLTLEEK AEICSELELQ QKYVDIASNI IGDLSSLPMV GKIVGTIAAA AMTVTHVASG
RLDIEQTLLG CSDLPFDQIK EILEKRFNEI DRKLESHSAA LEEITKLVEK SISAVEKTRK
QMNKRFDEVM KSIQDAKVSP IVSKINNFAR YFDTEKERIR GLKLNDYILK LEEPNGILLH
FKESRTPKDD SLQAPLFSII QERYAVPKSI DDELAFKVLX ALLYGTQTYV SVMFFLLEQY
SFLANHYYEK GDLEKYDEYF NSLNNVFLDF KSSLVGTGTS NNEGLLDRVL QVLMIVKNSE
FLKLGKNGVD EMLNSKINLF NKIKEEIEGK QRMTLSETPE NFAQISFDKD ITTPIGDWRD
GREVRYAVQY ASETLFSKIG HWSDPVNVRE RACPTLRMPV DQTRRNVLVF RKFDNSKPQL
VGEITPYLSN FIDIDRDLYN AASNPDSAVG FKEFTKLNYD GANIRATFDQ GRTVFHAAAK
SGNDKIMFGL TFLAKSTELN QPDKKGYTPI HVAADSGNAG IVNLLIQRGV SINSKTFHFL
QTPLHLAAQR GFVTTFQRLM ESPEININER DKDGFTPLHY AVRGGERILE AFMNQIDIDI
NAKSDKGLTP FHLAIIKNDW PVASTLLRSK KVDINAVDEN NMTALHYAAI LGYLEIAKQL
INLKEINANI VSSPGLLSAL HYAILYKHDD VASFLLRSSN VNVNLKALGG ITPLHLAVIQ
GRKHILSLMF XIGVNIEQQT DEKYTPLHLA AMSKYPELIQ IFLNQGSNFE AKTNSGATPL
HLATFKGKSQ AALILLNNEV NWRDTDENGQ MPIHGAAMTG LLDVAQAIIS LDATVLDIED
KNSDTPLNLA AQNFHIDAVK YFIDQGADIN TRNKKGHAPL LAFSKKGNLD MVKYLFDKNA
NVYIADNDGM NFFYYAVRNG HLNIVKYAMS EKDKFEWSNI DNNRRDECPK EECAISHFAV
CDAVQFDKIE IVKYFVGTLG NFGICGPLHQ AARYGHLHIV KYLVEEEFLS VDGSKTDTPL
CYASENGHLA VVQYLVSNGA KVNHDCDNGM TAIDKAITKN HLQVVQFLAA NGVDFRRKNS
RGATPFLTAV AENAFDIAEY LIREKRQDIN INEQNVDKDT ALHLAVYYKN LQMIKLLVKY
GIDVTIRNAY DKTALDIATD AKFSIIVEYL KTKSGKFRRE YKSSYGEPSL LQTNKISSFI
DGKNIEHDHL QFINADNESS QLFSDTVSNI DVIGTLLLVD VLIRYFSKQG YISKESDSAS
DGITQAAALS ITEKFEDVLN SLHNESVKEQ VDLAEVHGRV YAALKSGRNS RIHQILCSSL
KSISTLKPED MEELVSVIMN SQSSVSLPEV TDSANEAYGE A
