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Protein

Alpha-latrotoxin-Lt1a

Gene
N/A
Organism
Latrodectus tredecimguttatus (Mediterranean black widow spider) (Latrodectus mactans tredecimguttatus)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Presynaptic neurotoxin that induces exhaustive neurotransmitter release from vertebrate (but not invertebrate) nerve terminals and endocrine cells. Binds to neurexin-1-alpha (NRXN1), adhesion G protein-coupled receptor L1 (ADGRL1, also known as latrophilin-1), and receptor-type tyrosine-protein phosphatase S (PTPRS), and induces neurotransmitter exocytosis through two calcium-dependent mechanisms (membrane pore formation and signaling via latrophilin) and a yet to be defined calcium-independent mechanism.1 Publication

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor impairing toxin, Neurotoxin, Presynaptic neurotoxin, Toxin

Keywords - Biological processi

Exocytosis

Protein family/group databases

TCDBi1.C.63.1.1. the -latrotoxin (latrotoxin) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-latrotoxin-Lt1a
Short name:
Alpha-LTX-Lt1a
Alternative name(s):
Alpha-latrotoxin
Short name:
Alpha-LTX
OrganismiLatrodectus tredecimguttatus (Mediterranean black widow spider) (Latrodectus mactans tredecimguttatus)
Taxonomic identifieri6925 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaChelicerataArachnidaAraneaeAraneomorphaeEntelegynaeAraneoideaTheridiidaeLatrodectus

Organism-specific databases

ArachnoServeriAS000060. alpha-Latrotoxin-Lt1a.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane, Secreted, Target cell membrane, Target membrane

Pathology & Biotechi

Toxic dosei

LD50is 20 µg/kg by subcutaneous injection into mice.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi34 – 341C → S: Loss of function. 1 Publication
Mutagenesisi91 – 911C → S: Loss of function. 1 Publication
Mutagenesisi413 – 4131C → S: Loss of function. 1 Publication
Mutagenesisi448 – 4481L → LVPRG: Loss of function; it however still binds to receptors and stimulates synaptic hydrolysis of phosphatidylinositolphosphates. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 20201 PublicationAdd
BLAST
Chaini21 – 11991179Alpha-latrotoxin-Lt1aPRO_0000001615Add
BLAST
Propeptidei1200 – 1401202CuratedPRO_0000391352Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi413 ↔ 1066Curated

Post-translational modificationi

Processed by furin-like proteases at both the N- and C-termini.

Keywords - PTMi

Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom gland.

Interactioni

Subunit structurei

Homotetramer; Homotetramerization is triggered by calcium and is responsible for non-vesicular release and calcium-dependent vesicular exocytosis.2 Publications

Protein-protein interaction databases

MINTiMINT-1506878.

Structurei

3D structure databases

ProteinModelPortaliP23631.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati458 – 48932ANK 1Add
BLAST
Repeati490 – 52132ANK 2Add
BLAST
Repeati525 – 55430ANK 3Add
BLAST
Repeati559 – 58931ANK 4Add
BLAST
Repeati593 – 62230ANK 5Add
BLAST
Repeati626 – 65631ANK 6Add
BLAST
Repeati660 – 69031ANK 7Add
BLAST
Repeati695 – 72329ANK 8Add
BLAST
Repeati729 – 75830ANK 9Add
BLAST
Repeati762 – 79130ANK 10Add
BLAST
Repeati795 – 82430ANK 11Add
BLAST
Repeati828 – 85730ANK 12Add
BLAST
Repeati862 – 89130ANK 13Add
BLAST
Repeati895 – 92430ANK 14Add
BLAST
Repeati928 – 95730ANK 15Add
BLAST
Repeati971 – 100333ANK 16Add
BLAST
Repeati1004 – 103330ANK 17Add
BLAST
Repeati1035 – 106430ANK 18Add
BLAST
Repeati1068 – 109730ANK 19Add
BLAST
Repeati1101 – 113131ANK 20Add
BLAST
Repeati1137 – 116630ANK 21Add
BLAST
Repeati1170 – 119930ANK 22Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni17 – 204Furin-like endopeptidase recognition region
Regioni1026 – 103274C4.1 epitope
Regioni1196 – 11994Furin-like endopeptidase recognition region

Sequence similaritiesi

Contains 22 ANK repeats.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat, Signal, Transmembrane

Family and domain databases

Gene3Di1.25.40.20. 5 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR028047. Latrotoxin_C_dom.
[Graphical view]
PfamiPF12796. Ank_2. 6 hits.
PF15658. Latrotoxin_C. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 20 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 3 hits.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 11 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P23631-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MISVGEIMER ANHSLVRMRR EGEDLTLEEK AEICSELELQ QKYVDIASNI
60 70 80 90 100
IGDLSSLPIA GKIAGTIAAA AMTATHVASG RLDIEQTLLG CSDLPFDQIK
110 120 130 140 150
EVLENRFNEI DRKLDSHSAA LEEITKLVEK SISVVEKTRK QMNKRFDEVM
160 170 180 190 200
KSIQDAKVSP IISKINNFAR YFDTEKERIR GLKLNDYILK LEEPNGILLH
210 220 230 240 250
FKESRTPTDD SLQAPLFSII EEGYAVPKSI DDELAFKVLY ALLYGTQTYV
260 270 280 290 300
SVMFFLLEQY SFLANHYYEK GYLEKYDEYF NSLNNVFLDF KSSLVGTGTS
310 320 330 340 350
NNEGLLDRVL QVLMTVKNSE FLGLEKNGVD EMLNEKINLF NKIKEEIEGK
360 370 380 390 400
QKMTLSETPE NFAQISFDKD ITTPIGDWRD GREVRYAVQY ASETLFSKIS
410 420 430 440 450
HWSDPVSVRE KACPTLRMPV DQTRRNVLVF RKFDSSKPQL VGEITPYLSN
460 470 480 490 500
FIDIDRDLYN AASNPDSAVG FKEFTKLNYD GANIRATFDH GRTVFHAAAK
510 520 530 540 550
SGNDKIMFGL TFLAKSTELN QPDKKGYTPI HVAADSGNAG IVNLLIQRGV
560 570 580 590 600
SINSKTYHFL QTPLHLAAQR GFVTTFQRLM ESPEININER DKDGFTPLHY
610 620 630 640 650
AIRGGERILE AFLNQISIDV NAKSNTGLTP FHLAIIKNDW PVASTLLGSK
660 670 680 690 700
KVDINAVDEN NITALHYAAI LGYLETTKQL INLKEINANV VSSPGLLSAL
710 720 730 740 750
HYAILYKHDD VASFLMRSSN VNVNLKALGG ITPLHLAVIQ GRKQILSLMF
760 770 780 790 800
DIGVNIEQKT DEKYTPLHLA AMSKYPELIQ ILLDQGSNFE AKTNSGATPL
810 820 830 840 850
HLATFKGKSQ AALILLNNEV NWRDTDENGQ MPIHGAAMTG LLDVAQAIIS
860 870 880 890 900
IDATVVDIED KNSDTPLNLA AQNSHIDVIK YFIDQGADIN TRNKKGLAPL
910 920 930 940 950
LAFSKKGNLD MVKYLFDKNA NVYIADNDGM NFFYYAVQNG HLNIVKYAMS
960 970 980 990 1000
EKDKFEWSNT DNNRRDECPN EECAISHFAV CDAVQFDRIE IVKYFVGTLG
1010 1020 1030 1040 1050
NFAICGPLHQ AARYGHLDIV KYLVEEEFLS VDGSKTDTPL CYASENGHFT
1060 1070 1080 1090 1100
VVQYLVSNGA KVNHDCGNGM TAIDKAITKN HLQVVQFLAA NGVDFRRKNS
1110 1120 1130 1140 1150
RGTTPFLTAV AENALHIAEY LIREKRQDIN INEQNVDKDT ALHLAVYYKN
1160 1170 1180 1190 1200
LQMIKLLIKY GIDVTIRNAY DKTALDIAID AKFSNIVEYL KTKSGKFRRE
1210 1220 1230 1240 1250
YKSSYGERSL LQTNQISNFI DRKNIEHDHP LFINADNESS ELFSKTASNI
1260 1270 1280 1290 1300
DVIGTLLLID VLIRYFSKQG YISKESDSAS DGITQAAALS ITEKFEDVLN
1310 1320 1330 1340 1350
SLHNESAKEQ VDLAEVHGKV YAALKSGRNS QIHQILCSSL NSISTLKPED
1360 1370 1380 1390 1400
MEKLESVIMN SHSSVSLPEV TDSANEAYGE TLHLFGESCL HSDGILTKKL

M
Length:1,401
Mass (Da):156,857
Last modified:July 11, 2002 - v2
Checksum:iB38A22083C142A98
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti60 – 601A → V in AAC78471 (PubMed:9799228).Curated
Sequence conflicti148 – 1481E → K in AAC78471 (PubMed:9799228).Curated
Sequence conflicti162 – 1621I → V in AAC78471 (PubMed:9799228).Curated
Sequence conflicti201 – 2011F → L in AAC78471 (PubMed:9799228).Curated
Sequence conflicti467 – 4671S → A in AAC78471 (PubMed:9799228).Curated
Sequence conflicti690 – 6901V → L in AAC78471 (PubMed:9799228).Curated
Sequence conflicti783 – 7831L → I in AAC78471 (PubMed:9799228).Curated
Sequence conflicti879 – 8791I → V in AAC78471 (PubMed:9799228).Curated
Sequence conflicti1116 – 11161H → D in AAC78471 (PubMed:9799228).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X55009 mRNA. Translation: CAA38753.1.
AF069521 mRNA. Translation: AAC78471.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X55009 mRNA. Translation: CAA38753.1.
AF069521 mRNA. Translation: AAC78471.1.

3D structure databases

ProteinModelPortaliP23631.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-1506878.

Protein family/group databases

TCDBi1.C.63.1.1. the -latrotoxin (latrotoxin) family.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ArachnoServeriAS000060. alpha-Latrotoxin-Lt1a.

Miscellaneous databases

PROiP23631.

Family and domain databases

Gene3Di1.25.40.20. 5 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR028047. Latrotoxin_C_dom.
[Graphical view]
PfamiPF12796. Ank_2. 6 hits.
PF15658. Latrotoxin_C. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 20 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 3 hits.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 11 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Cloning and structure of cDNA encoding alpha-latrotoxin from black widow spider venom."
    Kiyatkin N.I., Dulubova I.E., Chekhovskaya I.A., Grishin E.V.
    FEBS Lett. 270:127-131(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Venom gland.
  2. "Alpha-latrotoxin action probed with recombinant toxin: receptors recruit alpha-latrotoxin but do not transduce an exocytotic signal."
    Ichtchenko K., Khvotchev M., Kiyatkin N., Simpson L., Sugita S., Suedhof T.C.
    EMBO J. 17:6188-6199(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 21-1197, FUNCTION, MUTAGENESIS OF CYS-34; CYS-91; CYS-413 AND LEU-448.
    Tissue: Venom gland.
  3. "Structure of tryptic fragments of a neurotoxin from black widow spider venom."
    Volkova T.M., Galkina T.G., Kudelin A.B., Nazimov I.V., Grishin E.V.
    Bioorg. Khim. 17:437-441(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PARTIAL PROTEIN SEQUENCE.
    Tissue: Venom.
  4. "Black widow spider toxins: the present and the future."
    Grishin E.V.
    Toxicon 36:1693-1701(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 21-39, TOXIC DOSE.
  5. "Tetramerisation of alpha-latrotoxin by divalent cations is responsible for toxin-induced non-vesicular release and contributes to the Ca(2+)-dependent vesicular exocytosis from synaptosomes."
    Ashton A.C., Rahman M.A., Volynski K.E., Manser C., Orlova E.V., Matsushita H., Davletov B.A., van Heel M., Grishin E.V., Ushkaryov Y.A.
    Biochimie 82:453-468(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  6. "Characterization of the epitope for 4C4.1 mAb on alpha-latrotoxin using phage display-peptide libraries: prevention of toxin-dependent 45Ca(2+) uptake in non-neuronal human embryonic cells transiently expressing latrophilin."
    Pescatori M., Grasso A.
    Biochimie 82:909-914(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: EPITOPE FOR 4C4.1 MAB.
  7. Cited for: REVIEW.
  8. "Structure of alpha-latrotoxin oligomers reveals that divalent cation-dependent tetramers form membrane pores."
    Orlova E.V., Rahman M.A., Gowen B., Volynski K.E., Ashton A.C., Manser C., van Heel M., Ushkaryov Y.A.
    Nat. Struct. Biol. 7:48-53(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY ELECTRON CRYOMICROSCOPY, PROBABLE DISULFIDE BOND, SUBUNIT.

Entry informationi

Entry nameiLATA_LATTR
AccessioniPrimary (citable) accession number: P23631
Secondary accession number(s): O76456, Q25328
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: July 11, 2002
Last modified: May 11, 2016
This is version 95 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Miscellaneous

Is the main neurotoxin responsible for the human envenomation syndrome known as latrodectism that results from bites by Latrodectus species.
Anti-alpha-LTX monoclonal antibody 4C4.1 blocks neurotransmitter release induced by this protein by preventing tetramerization and ionophore activity once inserted into cell membranes. However, 4C4.1 is incapable of reversing pore formation (PubMed:11086220).1 Publication

Keywords - Technical termi

Direct protein sequencing

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.