ID   3SOF1_NAJAT             Reviewed;          62 AA.
AC   P0DUK7;
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=Mu-elapitoxin-Na1a {ECO:0000305|PubMed:30804211};
DE            Short=Mu-EPTX-Na1a {ECO:0000303|PubMed:30804211};
OS   Naja atra (Chinese cobra).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX   NCBI_TaxID=8656;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, MASS SPECTROMETRY, AND 3D-STRUCTURE MODELING.
RC   TISSUE=Venom;
RX   PubMed=30804211; DOI=10.1074/jbc.ra118.007370;
RA   Zhang F., Zhang C., Xu X., Zhang Y., Gong X., Yang Z., Zhang H., Tang D.,
RA   Liang S., Liu Z.;
RT   "Naja atra venom peptide reduces pain by selectively blocking the voltage-
RT   gated sodium channel Nav1.8.";
RL   J. Biol. Chem. 294:7324-7334(2019).
CC   -!- FUNCTION: Potent inhibitor of hNav1.8/SCN10A (IC(50)=141-380 nM)
CC       (PubMed:30804211). Is highly selective for this channel and acts in a
CC       reversible manner (PubMed:30804211). Shows a depolarizing shift of
CC       activation and hyperpolarizing shift of inactivation (PubMed:30804211).
CC       In contrast to the very similar cytotoxin A5 (AC P62375), does not seem
CC       to bind integrin alpha-V/beta-3, since it does not promote or inhibit
CC       the proliferation of HUVECs and C-PAE cells (PubMed:30804211). In vivo,
CC       in rodent models of inflammatory and neuropathic pain, it alleviates
CC       nociceptive behaviors more potently than does morphine
CC       (PubMed:30804211). It displays no evident cytotoxic, hemolytic and
CC       cardiotoxic activities and produces no obvious adverse responses in
CC       mice even at a dose 30-fold higher than that producing a significant
CC       analgesic effect (PubMed:30804211). {ECO:0000269|PubMed:30804211}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:30804211}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:30804211}.
CC   -!- MASS SPECTROMETRY: Mass=7053.48; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:30804211};
CC   -!- MISCELLANEOUS: Is classified as a P-type cytotoxin, since a proline
CC       residue stands at position 52 (Pro-31 in standard classification).
CC       {ECO:0000250|UniProtKB:P62375}.
CC   -!- MISCELLANEOUS: Shows no or very weak inhibition of rNav1.1/SCN1A,
CC       hNav1.2/SCN2A, hNav1.3/SCN3A, hNav1.4/SCN4A (IC(50)>10 uM),
CC       hNav1.5/SCN5A (IC(50)=8.51 uM), hNav1.6/SCN8A, hNav1.7/SCN9A, and
CC       Nav1.9/SCN11A (PubMed:30804211). Has no effect on transient receptor
CC       potential cation channels TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, TRPM8,
CC       TRPC3, TRPC4, TRPC5, and TRPC6 (PubMed:30804211).
CC       {ECO:0000269|PubMed:30804211}.
CC   -!- SIMILARITY: Belongs to the snake three-finger toxin family. Short-chain
CC       subfamily. Orphan group XV sub-subfamily. {ECO:0000305}.
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DR   AlphaFoldDB; P0DUK7; -.
DR   SMR; P0DUK7; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0017080; F:sodium 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; IPR003572; Cytotoxin_Cobra.
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   PRINTS; PR00282; CYTOTOXIN.
DR   SUPFAM; SSF57302; SSF57302; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Secreted; Toxin; Voltage-gated sodium channel impairing toxin.
FT   CHAIN           1..62
FT                   /note="Mu-elapitoxin-Na1a"
FT                   /evidence="ECO:0000250|UniProtKB:P62375"
FT                   /id="PRO_0000452710"
FT   DISULFID        3..22
FT                   /evidence="ECO:0000250|UniProtKB:P62375"
FT   DISULFID        15..40
FT                   /evidence="ECO:0000250|UniProtKB:P62375"
FT   DISULFID        44..55
FT                   /evidence="ECO:0000250|UniProtKB:P62375"
FT   DISULFID        56..61
FT                   /evidence="ECO:0000250|UniProtKB:P62375"
SQ   SEQUENCE   62 AA;  7062 MW;  0E88C19BFFA7FBA5 CRC64;
     LKCHNTQLPF IYKTCPEGKN LCFKATLKKF PLKFPFKRGC ADNCPKNSAL LKYVCCSTDK
     CN