VKTHA_DENAN
ID VKTHA_DENAN Reviewed; 59 AA.
AC P00980;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 25-MAY-2022, entry version 115.
DE RecName: Full=Kunitz-type serine protease inhibitor homolog alpha-dendrotoxin;
DE Short=Alpha-DTX;
DE AltName: Full=Protease inhibitor 1 homolog;
DE AltName: Full=Toxin C13S2C3;
DE AltName: Full=Venom basic protease inhibitor 1 homolog;
OS Dendroaspis angusticeps (Eastern green mamba) (Naja angusticeps).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Dendroaspis.
OX NCBI_TaxID=8618;
RN [1]
RP PROTEIN SEQUENCE, AND PYROGLUTAMATE FORMATION AT GLN-1.
RC TISSUE=Venom;
RX PubMed=7429422; DOI=10.1515/bchm2.1980.361.1.661;
RA Joubert F.J., Taljaard N.;
RT "Snake venoms. The amino acid sequences of two proteinase inhibitor
RT homologues from Dendroaspis angusticeps venom.";
RL Hoppe-Seyler's Z. Physiol. Chem. 361:661-674(1980).
RN [2]
RP REVIEW, AND FUNCTION.
RX PubMed=10936620; DOI=10.1016/s0041-0101(00)00162-8;
RA Harvey A.L.;
RT "Twenty years of dendrotoxins.";
RL Toxicon 39:15-26(2001).
RN [3]
RP REVIEW, FUNCTION, AND SITE LYS-5; LEU-9 AND LYS-19.
RX PubMed=23771044; DOI=10.3390/md11062069;
RA Mourao C.B., Schwartz E.F.;
RT "Protease inhibitors from marine venomous animals and their counterparts in
RT terrestrial venomous animals.";
RL Mar. Drugs 11:2069-2112(2013).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=1373774; DOI=10.1016/0022-2836(92)90552-u;
RA Skarzynski T.;
RT "Crystal structure of alpha-dendrotoxin from the green mamba venom and its
RT comparison with the structure of bovine pancreatic trypsin inhibitor.";
RL J. Mol. Biol. 224:671-683(1992).
CC -!- FUNCTION: Serine protease inhibitor homolog that blocks voltage-gated
CC potassium channels (Kv1.1/KCNA1, Kv1.2/KCNA2, and Kv1.6/KCNA6)
CC (IC(50)=0.4-150 nM) and facilitates neurotransmitter release.
CC {ECO:0000269|PubMed:10936620, ECO:0000269|PubMed:23771044}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- TOXIC DOSE: LD(50) is 23 mg/kg by intravenous injection.
CC -!- MISCELLANEOUS: Does not inhibit serine proteases and voltage-gated
CC potassium channels Kvl.3/KCNA3, Kv1.4/KCNA4, Kv1.5/KCNA5, Kv3.1/KCNC1,
CC Kv3.4/KCNC4, and Kv4.1/KCND1.
CC -!- SIMILARITY: Belongs to the venom Kunitz-type family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR PIR; A01212; VIEPIA.
DR PDB; 1DTX; X-ray; 2.20 A; A=2-59.
DR PDBsum; 1DTX; -.
DR AlphaFoldDB; P00980; -.
DR SMR; P00980; -.
DR EvolutionaryTrace; P00980; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR CDD; cd00109; KU; 1.
DR Gene3D; 4.10.410.10; -; 1.
DR InterPro; IPR002223; Kunitz_BPTI.
DR InterPro; IPR036880; Kunitz_BPTI_sf.
DR InterPro; IPR020901; Prtase_inh_Kunz-CS.
DR Pfam; PF00014; Kunitz_BPTI; 1.
DR PRINTS; PR00759; BASICPTASE.
DR SMART; SM00131; KU; 1.
DR SUPFAM; SSF57362; SSF57362; 1.
DR PROSITE; PS00280; BPTI_KUNITZ_1; 1.
DR PROSITE; PS50279; BPTI_KUNITZ_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Potassium channel impairing toxin;
KW Pyrrolidone carboxylic acid; Secreted; Toxin;
KW Voltage-gated potassium channel impairing toxin.
FT CHAIN 1..59
FT /note="Kunitz-type serine protease inhibitor homolog alpha-
FT dendrotoxin"
FT /id="PRO_0000155433"
FT DOMAIN 7..57
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT SITE 5
FT /note="May be the major determinant of the binding affinity
FT for potassium channels"
FT SITE 9
FT /note="Important for binding to potassium channels"
FT SITE 19
FT /note="Not important for inhibition of potassium channels"
FT MOD_RES 1
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:7429422"
FT DISULFID 7..57
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031,
FT ECO:0000269|PubMed:7429422"
FT DISULFID 16..40
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031,
FT ECO:0000269|PubMed:7429422"
FT DISULFID 32..53
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031,
FT ECO:0000269|PubMed:7429422"
FT HELIX 5..8
FT /evidence="ECO:0007829|PDB:1DTX"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:1DTX"
FT STRAND 20..26
FT /evidence="ECO:0007829|PDB:1DTX"
FT TURN 27..30
FT /evidence="ECO:0007829|PDB:1DTX"
FT STRAND 31..37
FT /evidence="ECO:0007829|PDB:1DTX"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:1DTX"
FT HELIX 50..57
FT /evidence="ECO:0007829|PDB:1DTX"
SQ SEQUENCE 59 AA; 7071 MW; 96B60752E8AD81AE CRC64;
QPRRKLCILH RNPGRCYDKI PAFYYNQKKK QCERFDWSGC GGNSNRFKTI EECRRTCIG
