LATA_LATHE
ID LATA_LATHE Reviewed; 1418 AA.
AC P0DJE3; A0A089FYN5; L7XGA0;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2015, sequence version 2.
DT 25-MAY-2022, entry version 30.
DE RecName: Full=Alpha-latrotoxin-Lhe1a {ECO:0000303|PubMed:22001442};
DE Short=Alpha-LTX-Lhe1a {ECO:0000303|PubMed:22001442};
DE AltName: Full=Alpha-latrotoxin {ECO:0000303|PubMed:22001442};
DE Short=Alpha-LTX {ECO:0000303|PubMed:22001442};
DE Flags: Precursor;
OS Latrodectus hesperus (Western black widow spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Entelegynae; Araneoidea; Theridiidae; Latrodectus.
OX NCBI_TaxID=256737;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=25217831; DOI=10.1016/j.febslet.2014.08.034;
RA Bhere K.V., Haney R.A., Ayoub N.A., Garb J.E.;
RT "Gene structure, regulatory control, and evolution of black widow venom
RT latrotoxins.";
RL FEBS Lett. 588:3891-3897(2014).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-1390.
RC STRAIN=Riverside (California);
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 [3]
RP PROTEIN SEQUENCE OF 386-398 AND 582-590, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND SUBCELLULAR 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).
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: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 -!- 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; KM382064; AIP91371.1; -; Genomic_DNA.
DR EMBL; KC414032; AGD80166.1; -; Genomic_DNA.
DR AlphaFoldDB; P0DJE3; -.
DR SMR; P0DJE3; -.
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; PF00023; Ank; 1.
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; 11.
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..20
FT /evidence="ECO:0000250|UniProtKB:P23631"
FT CHAIN 21..1199
FT /note="Alpha-latrotoxin-Lhe1a"
FT /id="PRO_0000415932"
FT PROPEP 1200..1418
FT /evidence="ECO:0000250|UniProtKB:P23631"
FT /id="PRO_0000432877"
FT REPEAT 458..489
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 490..521
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 525..554
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 559..589
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 593..622
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REPEAT 626..656
FT /note="ANK 6"
FT /evidence="ECO:0000255"
FT REPEAT 660..690
FT /note="ANK 7"
FT /evidence="ECO:0000255"
FT REPEAT 695..723
FT /note="ANK 8"
FT /evidence="ECO:0000255"
FT REPEAT 729..758
FT /note="ANK 9"
FT /evidence="ECO:0000255"
FT REPEAT 762..791
FT /note="ANK 10"
FT /evidence="ECO:0000255"
FT REPEAT 795..824
FT /note="ANK 11"
FT /evidence="ECO:0000255"
FT REPEAT 828..857
FT /note="ANK 12"
FT /evidence="ECO:0000255"
FT REPEAT 862..891
FT /note="ANK 13"
FT /evidence="ECO:0000255"
FT REPEAT 895..924
FT /note="ANK 14"
FT /evidence="ECO:0000255"
FT REPEAT 928..957
FT /note="ANK 15"
FT /evidence="ECO:0000255"
FT REPEAT 971..1003
FT /note="ANK 16"
FT /evidence="ECO:0000255"
FT REPEAT 1004..1033
FT /note="ANK 17"
FT /evidence="ECO:0000255"
FT REPEAT 1035..1064
FT /note="ANK 18"
FT /evidence="ECO:0000255"
FT REPEAT 1068..1097
FT /note="ANK 19"
FT /evidence="ECO:0000255"
FT REPEAT 1101..1131
FT /note="ANK 20"
FT /evidence="ECO:0000255"
FT REPEAT 1137..1166
FT /note="ANK 21"
FT /evidence="ECO:0000255"
FT REPEAT 1170..1199
FT /note="ANK 22"
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 1026..1032
FT /note="4C4.1 epitope"
FT /evidence="ECO:0000250|UniProtKB:P23631"
FT REGION 1196..1199
FT /note="Furin-like endopeptidase recognition region"
FT /evidence="ECO:0000250|UniProtKB:P23631"
FT DISULFID 413..1066
FT /evidence="ECO:0000250|UniProtKB:P23631"
FT CONFLICT 583
FT /note="S -> P (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1192
FT /note="K -> T (in Ref. 2; AIP91371)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1418 AA; 159121 MW; 34D413B17A7ECEE4 CRC64;
MIFVGETMER ANHSLVRLRR EGEELTLDEK AEICSELELQ QKYVDIASNI IGDLSSLPMV
GKIVGTIAAA AMTVTHVASG RLDIEQTLLG CSDLPFDQIK EVLEKRFNEV DRKLESHSAA
LEEITKLVEK SISAVEKTRK QMNKRFDEVM KSIQDAKVSP IVSKINNFAR YFDTEKERIR
GLKLNDYILK LEEPNGILLH FKESRTPKDD SLQAPLFSII QEGYAVPKSI DDESAFKVLY
ALLYGTQTYI SVMFFLLEQY SFLANHYYEK GDLEKYDEYF NSLNNVFLDF KSSLVGTGTS
NNEGLIDKVL QVLMTFKNSE FLGLGKNGVD EMLNEKINLF NKIKEEIESK QRMTMSETPE
NFAQISFDKD ITTPIGDWRD GREVRYAVQY ASETLFSKIG HWSDPVSVRE KACPTLRMPV
DQTRRNVLVF RKFDNSKPQL VGEITPYLSN FIDIDRDLYN AASNPDSAVG FKEFTKLNYD
GANIRATFDQ GRTIFHAVAK SGNDKILFGL TFLVKSTELN QPDKKGYTPI HVAADSGNAG
IVNLLIQRGV SINSKTYHFL QTPLHLAAQR GFVNTFQRLM ESSEININER DKDGFTPLHY
AVRGGERILE AFMNQIGIDV NAKSNKGLTP FHLAIIKNDW QVASTLLRNK KVDINAVDEN
NMTALHYAAI LGYLETTKQL INLKEINANV VSSPGLLSAL HYAILYKHDD VASFLLRSSN
VNVNLKALGG ITPLHLAVMQ GRKQVLSLMF NIGVNIEQQT DEKYTPLHLA AMSKYPELIQ
ILLDQDSNFE AKTNSGATPL HLATFKGKSQ AALILLNNEV NWRDTDENGQ MPIHGAATTG
LLDVAQAIIS IDATVLDIED KNSDTPLNLA AQNSHIDAVK YFIDQGADIN TRNKNGHAPL
LAFSKKGNLD MVKYLFDKNA NVYIADNNGM NFFYYAVRNG HLNIIKYAMS EKDKFEWSNI
DNNRRDECPK EECAISHFAV CDAVQFDKIE IVKFFIGTLG NFNICGPLHQ AARYGHLHIV
KYLVEEEVLS VDGSKTDTPL CYASENGHLA VVQYLVSNGA KVNHDCANGM TAIDKAITKN
HLQVVQFLAA NGVDFRRKNS RGATPFLTAV AENAFDIAEY LIREKRQDIN INEQNVDKET
ALHLAVYYKN LQMIKLLVKY GIDVTIRNAY DKTVLDIATD AKFSNIVKYL KKNSGKFRRE
YKSSYGEHSF LQTNEISRFI DGKSIEHDHP QFINADNESS QLFSGTASKI DVIGTLLLID
VLIRYFSKQG YISKESDSAS DGITQAAALS ITEKFEDVLN SLPNKSAKEQ VDLADVHGKV
YAALKSGRNS QIHQILCSSL KSISTLKPED MEKLVSVIMN SHSSLSMPEA TDSANEAYGE
TLHLFGESCR HSEDYISQKF STNPFSFESE KKIQKISI
