ID   LCTA_LATTR              Reviewed;        1413 AA.
AC   Q9XZC0;
DT   16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT   09-FEB-2010, sequence version 2.
DT   02-SEP-2026, entry version 94.
DE   RecName: Full=Alpha-latrocrustotoxin-Lt1a {ECO:0000305};
DE            Short=Alpha-LCT-Lt1a {ECO:0000305};
DE   AltName: Full=Alpha-latrocrustotoxin {ECO:0000303|PubMed:34845192};
DE            Short=Alpha-LCT {ECO:0000303|PubMed:34845192};
DE   AltName: Full=Crusta1;
DE   Flags: Precursor; Fragment;
OS   Latrodectus tredecimguttatus (Mediterranean black widow spider)
OS   (Latrodectus mactans tredecimguttatus).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Araneomorphae; Entelegynae; Araneoidea; Theridiidae; Latrodectus.
OX   NCBI_TaxID=6925;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=10563207;
RA   Danilevich V.N., Luk'ianov S.A., Grishin E.V.;
RT   "Cloning and structure of gene encoded alpha-latrocrustoxin from the Black
RT   widow spider venom.";
RL   Bioorg. Khim. 25:537-547(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=11195592; DOI=10.1023/a:1026666606311;
RA   Danilevich V.N., Grishin E.V.;
RT   "The chromosomal genes for black widow spider neurotoxins do not contain
RT   introns.";
RL   Bioorg. Khim. 26:933-939(2000).
RN   [3]
RP   PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=10234443;
RA   Volynskii K.E., Volkova T.M., Galkina T.G., Krasnoperov V.G.,
RA   Pluzhnikov K.A., Khvoshchev M.V., Grishin E.V.;
RT   "Molecular cloning and primary structure of cDNA fragment for alpha-
RT   latrocrustatoxin from black widow spider venom.";
RL   Bioorg. Khim. 25:25-30(1999).
RN   [4]
RP   TOXIC DOSE.
RX   PubMed=9792186; DOI=10.1016/s0041-0101(98)00162-7;
RA   Grishin E.V.;
RT   "Black widow spider toxins: the present and the future.";
RL   Toxicon 36:1693-1701(1998).
RN   [5]
RP   STRUCTURE BY ELECTRON MICROSCOPY (4.03 ANGSTROMS) OF 48-1066 IN MONOMERIC
RP   FORM, FUNCTION, RECOMBINANT EXPRESSION, AND SUBUNIT.
RX   PubMed=34845192; DOI=10.1038/s41467-021-26562-8;
RA   Chen M., Blum D., Engelhard L., Raunser S., Wagner R., Gatsogiannis C.;
RT   "Molecular architecture of black widow spider neurotoxins.";
RL   Nat. Commun. 12:6956-6956(2021).
CC   -!- FUNCTION: Crustacean-selective presynaptic neurotoxin that induces
CC       neurotransmitter exocytosis. May bind to crustacean neurexin-1 homolog,
CC       adhesion G protein-coupled receptor L1 homolog, and receptor-type
CC       tyrosine-protein phosphatase S homolog, and induces neurotransmitter
CC       exocytosis both by forming tetrameric pores in membranes and signaling
CC       via G protein-coupled receptor (By similarity) (PubMed:34845192). This
CC       recombinant protein form channels in artificial membrane bilayers, that
CC       are stabilized by calcium ions and allow calcium flux at negative
CC       membrane potentials (PubMed:34845192). {ECO:0000250|UniProtKB:P23631,
CC       ECO:0000269|PubMed:34845192}.
CC   -!- SUBUNIT: Homotetramer in membranes. {ECO:0000269|PubMed:34845192}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:10234443}. Target
CC       cell membrane {ECO:0000269|PubMed:34845192}. Note=Forms a membrane
CC       channel in the prey. {ECO:0000269|PubMed:34845192}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:10234443}.
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:0000269|PubMed:34845192}.
CC   -!- TOXIC DOSE: LD(50) is 100 ug/kg to the crayfish Procambarus cubensis.
CC       {ECO:0000269|PubMed:9792186}.
CC   -!- SIMILARITY: Belongs to the cationic peptide 01 (latrotoxin) family. 01
CC       (alpha-latrocrustotoxin) subfamily. {ECO:0000305}.
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DR   EMBL; AF134162; AAD33043.1; -; Genomic_DNA.
DR   PDB; 7PTX; EM; 4.03 A; A=16-1211.
DR   AlphaFoldDB; Q9XZC0; -.
DR   EMDB; EMD-13642; -.
DR   SMR; Q9XZC0; -.
DR   ArachnoServer; AS000061; alpha-Latrocrustotoxin-Lt1a.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 5.
DR   InterPro; IPR002110; Ankyrin_rpt.
DR   InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR   PANTHER; PTHR24161; ANK_REP_REGION DOMAIN-CONTAINING PROTEIN-RELATED; 1.
DR   PANTHER; PTHR24161:SF85; PALMITOYLTRANSFERASE HIP14; 1.
DR   Pfam; PF00023; Ank; 1.
DR   Pfam; PF12796; Ank_2; 6.
DR   PRINTS; PR01415; ANKYRIN.
DR   SMART; SM00248; ANK; 20.
DR   SUPFAM; SSF48403; Ankyrin repeat; 3.
DR   PROSITE; PS50297; ANK_REP_REGION; 1.
DR   PROSITE; PS50088; ANK_REPEAT; 12.
DR   PDBsum; 7PTX; -.
PE   1: Evidence at protein level;
KW   3D-structure; ANK repeat; Cleavage on pair of basic residues; Exocytosis;
KW   Membrane; Neurotoxin; Presynaptic neurotoxin; Repeat; Secreted;
KW   Target cell membrane; Target membrane; Toxin; Transmembrane.
FT   PROPEP          <1..28
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000391353"
FT   CHAIN           29..1192
FT                   /note="Alpha-latrocrustotoxin-Lt1a"
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000067053"
FT   PROPEP          1193..1413
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000391354"
FT   REPEAT          457..490
FT                   /note="ANK 1"
FT                   /evidence="ECO:0000255"
FT   REPEAT          494..524
FT                   /note="ANK 2"
FT                   /evidence="ECO:0000255"
FT   REPEAT          528..557
FT                   /note="ANK 3"
FT                   /evidence="ECO:0000255"
FT   REPEAT          562..592
FT                   /note="ANK 4"
FT                   /evidence="ECO:0000255"
FT   REPEAT          596..625
FT                   /note="ANK 5"
FT                   /evidence="ECO:0000255"
FT   REPEAT          629..658
FT                   /note="ANK 6"
FT                   /evidence="ECO:0000255"
FT   REPEAT          664..694
FT                   /note="ANK 7"
FT                   /evidence="ECO:0000255"
FT   REPEAT          699..729
FT                   /note="ANK 8"
FT                   /evidence="ECO:0000255"
FT   REPEAT          733..762
FT                   /note="ANK 9"
FT                   /evidence="ECO:0000255"
FT   REPEAT          766..795
FT                   /note="ANK 10"
FT                   /evidence="ECO:0000255"
FT   REPEAT          799..828
FT                   /note="ANK 11"
FT                   /evidence="ECO:0000255"
FT   REPEAT          832..861
FT                   /note="ANK 12"
FT                   /evidence="ECO:0000255"
FT   REPEAT          866..895
FT                   /note="ANK 13"
FT                   /evidence="ECO:0000255"
FT   REPEAT          899..928
FT                   /note="ANK 14"
FT                   /evidence="ECO:0000255"
FT   REPEAT          965..995
FT                   /note="ANK 15"
FT                   /evidence="ECO:0000255"
FT   REPEAT          996..1026
FT                   /note="ANK 16"
FT                   /evidence="ECO:0000255"
FT   REPEAT          1031..1072
FT                   /note="ANK 17"
FT                   /evidence="ECO:0000255"
FT   REPEAT          1077..1106
FT                   /note="ANK 18"
FT                   /evidence="ECO:0000255"
FT   REPEAT          1109..1139
FT                   /note="ANK 19"
FT                   /evidence="ECO:0000255"
FT   REPEAT          1143..1172
FT                   /note="ANK 20"
FT                   /evidence="ECO:0000255"
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:0000305|PubMed:34845192"
FT   NON_TER         1
SQ   SEQUENCE   1413 AA;  158223 MW;  98E263D6CE982EC8 CRC64;
     VSIFIFHFSA NILVRNSEMK GKRVISKREM SKADQCTFLS YQSVAYGTLG DVAGDVSSIE
     GADLVATPIA AGGHLAKGAT DAAMIAMDCS SIPFDEIKQQ LNQRFNEVDK KLQKGAEALE
     NVTELAEKTY SSVEKMRVEM REGFNHVIAT IENANTKQII TGINQIIQYF NDERENINNR
     QKEDYVAKLQ EPASGNFLLY LRKSRTSEDG SLHSLLFKII NQELAIPNNA ADNNAIRALF
     ALFYGTQTFI SIMFYLVKQY SYLADYHYQN GNLAEFNSNF DHMKTVFQDF KFTLIGINTS
     NSKPLVNTVL SIIEDVKNKR FIRNLRSNLY QKIIKSTKSL LDLREKITKM DLPIIEDTPK
     SSVLINFREK SSSVPRIETP ILKWTPGTVV KYAIQYEQDG KYSKISKWSN PITVQRLANP
     YITIDKDRRN RLVFRQFGNE KPELISILDS SQNEFRDIHR DLYNAAQMPY KETALGICRK
     LIDSGAQVGA SFEMGRKSIH ASATAGNDDV ARLLLAKNNG LLNVPDKNGY TPLHIASERK
     NNDFVKFLLE KGADVNVRTF ANELTPLHLA ARQDFTIIVK TLMEKRGIDV NAKERAGFTP
     LHLSITSNSR AARTLINETP AGINIKSNSG LTPLHLAVLQ NNLSAAKVLV KSNKKVKLNE
     MDNNGMTPLH YASMLGNLEF VKYFTSEQGI DVNAKTKVKN WTPLHLAILF KKFDVAQSLL
     QVRNIDISTR ADQAITPLHL AAATGNSQIV KTILNSGAVV DQETANGFTA LHLAIMNPNT
     ETPQFLIAKG ANINAKTNDG STPLHFAAAL GKTNIFQLLM DKGANIKAEN LINQMPIHEA
     VVNGHLAIVK MLIEQDSSLM NAKNMRDEYP FYLAAEKRYK DVFNYLESKG ADVNEKNNDG
     NTLLHLFSIN GEVEVVQFLI QNGADFRLRN KERKSFFDLA VEFGHAGIVG YAIEENKVDL
     QEPYRGKTIL YHAICDSVKY DRIEVVRYFV ETLNEDQCSP LQEAAAYAHL DLVKYFVQER
     GINPTAFNND NQVSPLCIAI VGAPCGFVKS CDTPERLDVV EYLVDKTPDI NKECDTQQST
     PVSSAVYGNK VSILNYLIRN GADPNKKVRG DPPLFIAAMI GQYDIVKSLV EQHKIDVNTR
     NKEQFTPLHA AASNDHIDVV KYLIQKGADV NAKGDENLKP IDLAGEKSKA YLRSLGRRFF
     RNESPSKSFE IDKFNAIMPE VSMSGKVSHD SNFIQHISSG TRSKSNFNSA KNKMYAENSH
     VRSIDVNGAL LLLDFMVRVF SNRKMNYAAS ISGIKSRSNS EAQAEALILT ERFEHLLNAL
     IADQSIDSLD FSNVHSRIYK AIINGNPNGI SEMLCSYAKE YSELDPEKIE KLLQEFETLT
     FTKSSEIQIN EKFSHALFET CGLNRPTNVL QIK
//