3L23_NAJME
ID 3L23_NAJME Reviewed; 72 AA.
AC P0DQQ1;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 1.
DT 25-MAY-2022, entry version 4.
DE RecName: Full=Long neurotoxin Tx-NM2 {ECO:0000303|PubMed:33672715};
OS Naja melanoleuca (Forest cobra) (Black-lipped cobra).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX NCBI_TaxID=8643;
RN [1]
RP PROTEIN SEQUENCE, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND 3D-STRUCTURE
RP MODELING.
RC TISSUE=Venom;
RX PubMed=33672715; DOI=10.3390/toxins13020164;
RA Son L., Kryukova E., Ziganshin R., Andreeva T., Kudryavtsev D.,
RA Kasheverov I., Tsetlin V., Utkin Y.;
RT "Novel three-finger neurotoxins from Naja melanoleuca cobra venom interact
RT with GABAA and nicotinic acetylcholine receptors.";
RL Toxins 13:0-0(2021).
CC -!- FUNCTION: Binds with high affinity to muscular (alpha-1-beta-1-gamma-
CC delta/CHRNA1-CHRNB1-CHRNG-CHRND) and neuronal (alpha-7/CHRNA7)
CC nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine
CC from binding to the receptor, thereby impairing neuromuscular and
CC neuronal transmission (PubMed:33672715). Ranges of nAChR inhibition are
CC in nanomolar (competitive binding with alpha-bungarotoxin gives Ki=8.66
CC nM on muscle nAChR and Ki=9.47 nM on alpha-7) (PubMed:33672715). Also
CC shows moderate inhibition on GABA(A) alpha-1-beta-3-gamma-2 receptor
CC (GABRA1-GABRB3-GABRG2) (IC(50)=1.25 uM), and a lower inhibition on
CC alpha-1-beta-2-gamma-2 (GABRA1-GABRB2-GABRG2) and alpha-3-beta-2-gamma-
CC 2 (GABRA3-GABRB2-GABRG2) (PubMed:33672715).
CC {ECO:0000269|PubMed:33672715}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:33672715}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:33672715}.
CC -!- MASS SPECTROMETRY: Mass=8030.68; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:33672715};
CC -!- SIMILARITY: Belongs to the snake three-finger toxin family. Long-chain
CC subfamily. Type II alpha-neurotoxin sub-subfamily. {ECO:0000305}.
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DR AlphaFoldDB; P0DQQ1; -.
DR SMR; P0DQQ1; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR CDD; cd00206; snake_toxin; 1.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR003571; Snake_3FTx.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR InterPro; IPR018354; Snake_toxin_con_site.
DR InterPro; IPR035076; Toxin/TOLIP.
DR Pfam; PF00087; Toxin_TOLIP; 1.
DR SUPFAM; SSF57302; SSF57302; 1.
PE 1: Evidence at protein level;
KW Acetylcholine receptor inhibiting toxin; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Neurotoxin;
KW Postsynaptic neurotoxin; Secreted; Toxin.
FT CHAIN 1..72
FT /note="Long neurotoxin Tx-NM2"
FT /evidence="ECO:0000269|PubMed:33672715"
FT /id="PRO_0000453025"
FT DISULFID 3..21
FT /evidence="ECO:0000250|UniProtKB:P25671"
FT DISULFID 14..42
FT /evidence="ECO:0000250|UniProtKB:P25671"
FT DISULFID 27..31
FT /evidence="ECO:0000250|UniProtKB:P25671"
FT DISULFID 46..57
FT /evidence="ECO:0000250|UniProtKB:P25671"
FT DISULFID 58..63
FT /evidence="ECO:0000250|UniProtKB:P25671"
SQ SEQUENCE 72 AA; 8127 MW; 47F6AD9542434208 CRC64;
KRCYRTPDLK SQTCPPGEDL CYTKKWCADW CTSRGKVIEL GCVATCPTVK PYEEITCCST
DNCNPHPKMP KP
