3SO8_OPHHA
ID 3SO8_OPHHA Reviewed; 86 AA.
AC A8N286;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 1.
DT 25-MAY-2022, entry version 56.
DE RecName: Full=Haditoxin;
DE AltName: Full=Muscarinic toxin-like protein 3 homolog;
DE Short=MTLP-3 homolog;
DE Flags: Precursor;
OS Ophiophagus hannah (King cobra) (Naja hannah).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Ophiophagus.
OX NCBI_TaxID=8665;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=17616557; DOI=10.1096/fj.07-8658com;
RA Rajagopalan N., Pung Y.F., Zhu Y.Z., Wong P.T.H., Kumar P.P., Kini R.M.;
RT "Beta-cardiotoxin: a new three-finger toxin from Ophiophagus hannah (king
RT cobra) venom with beta-blocker activity.";
RL FASEB J. 21:3685-3695(2007).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=24297900; DOI=10.1073/pnas.1314702110;
RA Vonk F.J., Casewell N.R., Henkel C.V., Heimberg A.M., Jansen H.J.,
RA McCleary R.J., Kerkkamp H.M., Vos R.A., Guerreiro I., Calvete J.J.,
RA Wuster W., Woods A.E., Logan J.M., Harrison R.A., Castoe T.A.,
RA de Koning A.P., Pollock D.D., Yandell M., Calderon D., Renjifo C.,
RA Currier R.B., Salgado D., Pla D., Sanz L., Hyder A.S., Ribeiro J.M.,
RA Arntzen J.W., van den Thillart G.E., Boetzer M., Pirovano W., Dirks R.P.,
RA Spaink H.P., Duboule D., McGlinn E., Kini R.M., Richardson M.K.;
RT "The king cobra genome reveals dynamic gene evolution and adaptation in the
RT snake venom system.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:20651-20656(2013).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 22-86, FUNCTION, SUBUNIT,
RP DISULFIDE BONDS, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=20071329; DOI=10.1074/jbc.m109.074161;
RA Roy A., Zhou X., Chong M.Z., D'hoedt D., Foo C.S., Rajagopalan N.,
RA Nirthanan S., Bertrand D., Sivaraman J., Kini R.M.;
RT "Structural and functional characterization of a novel homodimeric three-
RT finger neurotoxin from the venom of Ophiophagus hannah (king cobra).";
RL J. Biol. Chem. 285:8302-8315(2010).
CC -!- FUNCTION: Antagonist of muscle (alpha-1-beta-1-delta-epsilon/CHRNA1-
CC CHRNB1-CHRND-CHRNE) and neuronal (alpha-7/CHRNA7, alpha-3-beta-
CC 2/CHRNA3-CHRNB2, alpha-4-beta-2/CHRNA4-CHRNB2) nicotinic acetylcholine
CC receptors (nAChR) (PubMed:20071329). The highest affinity is for human
CC alpha-7/CHRNA7 nAChRs (IC(50)=180 nM), compared to human alpha-1-beta-
CC 1-delta-epsilon/CHRNA1-CHRNB1-CHRND-CHRNE nAChR (IC(50)= 550 nM),
CC alpha-3-beta-2/CHRNA3-CHRNB2 nAChR (IC(50)=500 nM), and alpha-4-beta-
CC 2/CHRNA4-CHRNB2 nAChR (IC(50)=2.6 uM). {ECO:0000269|PubMed:20071329}.
CC -!- SUBUNIT: Homodimer; non-covalently linked.
CC {ECO:0000269|PubMed:20071329}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20071329}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:20071329}.
CC -!- SIMILARITY: Belongs to the snake three-finger toxin family. Short-chain
CC subfamily. Orphan group VIII (haditoxin) sub-subfamily. {ECO:0000305}.
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DR EMBL; DQ902575; ABK41955.1; -; mRNA.
DR PDB; 3HH7; X-ray; 1.55 A; A/B=22-86.
DR PDBsum; 3HH7; -.
DR AlphaFoldDB; A8N286; -.
DR SMR; A8N286; -.
DR TopDownProteomics; A8N286; -.
DR EvolutionaryTrace; A8N286; -.
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 SUPFAM; SSF57302; SSF57302; 1.
DR PROSITE; PS00272; SNAKE_TOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylcholine receptor inhibiting toxin; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Postsynaptic neurotoxin; Secreted;
KW Signal; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..86
FT /note="Haditoxin"
FT /evidence="ECO:0000269|PubMed:20071329"
FT /id="PRO_0000318907"
FT DISULFID 24..45
FT /evidence="ECO:0000269|PubMed:20071329,
FT ECO:0000312|PDB:3HH7"
FT DISULFID 38..62
FT /evidence="ECO:0000269|PubMed:20071329,
FT ECO:0000312|PDB:3HH7"
FT DISULFID 66..78
FT /evidence="ECO:0000269|PubMed:20071329,
FT ECO:0000312|PDB:3HH7"
FT DISULFID 79..84
FT /evidence="ECO:0000269|PubMed:20071329,
FT ECO:0000312|PDB:3HH7"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:3HH7"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:3HH7"
FT STRAND 44..52
FT /evidence="ECO:0007829|PDB:3HH7"
FT STRAND 55..65
FT /evidence="ECO:0007829|PDB:3HH7"
FT STRAND 73..79
FT /evidence="ECO:0007829|PDB:3HH7"
FT TURN 82..85
FT /evidence="ECO:0007829|PDB:3HH7"
SQ SEQUENCE 86 AA; 9893 MW; 056F1A92294F3665 CRC64;
MKTLLLTLVV VTIVYLDLGY TTKCYNHQST TPETTEICPD SGYFCYKSSW IDGREGRIER
GCTFTCPELT PNGKYVYCCR RDKCNQ
